Medicine Encyclopedia

Acyclovir

2008-01-23T10:17:00.000-08:00

U.S. BRAND NAMES — Zovirax®
PHARMACOLOGIC CATEGORY Antiviral Agent
DOSING: ADULTS — Note: Obese patients should be dosed using ideal body weight
Genital HSV: I.V.: Immunocompetent: Initial episode, severe: 5 mg/kg every 8 hours for 5-7 days Oral: Initial episode: 200 mg every 4 hours while awake (5 times/day) for 10 days (per manufacturer's labeling); 400 mg 3 times/day for 5-10 days has also been reported Recurrence: 200 mg every 4 hours while awake (5 times/day) for 5 days (per manufacturer's labeling; begin at earliest signs of disease); 400 mg 3 times/day for 5 days has also been reported Chronic suppression: 400 mg twice daily or 200 mg 3-5 times/day, for up to 12 months followed by re-evaluation (per manufacturer's labeling); 400-1200 mg/day in 2-3 divided doses has also been reported Topical: Immunocompromised: Ointment: Initial episode: 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Herpes labialis (cold sores): Topical: Apply 5 times/day for 4 days
Herpes zoster (shingles): Oral: Immunocompetent: 800 mg every 4 hours (5 times/day) for 7-10 days I.V.: Immunocompromised: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours for 7 days
HSV encephalitis: I.V.: 10 mg/kg/dose every 8 hours for 10 days (per manufacturer's labeling); 10-15 mg/kg/dose every 8 hours for 14-21 days also reported
Mucocutaneous HSV: I.V.: Immunocompromised: 5 mg/kg/dose every 8 hours for 7 days (per manufacturer's labeling); dosing for up to 14 days also reported Oral: Immunocompromised (unlabeled use): 400 mg 5 times a day for 7-14 days Topical: Ointment: Nonlife-threatening, immunocompromised: 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset: Oral: >40 kg (immunocompetent): 800 mg/dose 4 times a day for 5 days I.V.: Immunocompromised (unlabeled use): 1500 mg/m2/day divided every 8 hours or 10 mg/kg/dose every 8 hours for 7-10 days
Prevention of HSV reactivation in HIV-positive patients, for use only when recurrences are frequent or severe (unlabeled use): Oral: 200 mg 3 times/day or 400 mg 2 times/day
Prevention of HSV reactivation in HSCT (unlabeled use): Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days) Oral: 200 mg 3 times/day I.V.: 250 mg/m2/dose every 12 hours
Bone marrow transplant recipients (unlabeled use): I.V.: Allogeneic patients who are HSV and CMV seropositive: 500 mg/m2/dose (10 mg/kg) every 8 hours; for clinically-symptomatic CMV infection, consider replacing acyclovir with ganciclovir
DOSING: PEDIATRIC — Note: Obese patients should be dosed using ideal body weight
(For additional information see "Acyclovir: Pediatric drug information")
Genital HSV: I.V.: Children 12 years: Refer to adult dosing. Oral: Initial episode (unlabeled use): 40-80 mg/kg/day divided into 3-4 doses for 5-10 days (maximum: 1 g/day) Chronic suppression (unlabeled use; limited data): 80 mg/kg/day in 3 divided doses (maximum: 1 g/day), re-evaluate after 12 months of treatment
Herpes labialis (cold sores): Topical: Children 12 years: Refer to adult dosing.
Herpes zoster (shingles): I.V.: Children <12 years (immunocompromised): 20 mg/kg/dose every 8 hours for 7 days Children 12 years: Refer to adult dosing.
HSV encephalitis: I.V.: Children 3 months to 12 years: 20 mg/kg/dose every 8 hours for 10 days (per manufacturer's labeling); dosing for 14-21 days also reported Children 12 years: Refer to adult dosing.
Mucocutaneous HSV: I.V.: Children <12 years (immunocompromised): 10 mg/kg/dose every 8 hours for 7 days Children 12 years: Refer to adult dosing.
Neonatal HSV: I.V.: Neonate: Birth to 3 months: 10 mg/kg/dose every 8 hours for 10 days (manufacturer's labeling); 15 mg/kg/dose or 20 mg/kg/dose every 8 hours for 14-21 days has also been reported
Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset: Oral: Children 2 years and 40 kg (immunocompetent): 20 mg/kg/dose (up to 800 mg/dose) 4 times/day for 5 days Children >40 kg: Refer to adult dosing. I.V.: Children <1 year (immunocompromised, unlabeled use): 10 mg/kg/dose every 8 hours for 7-10 days Children 1 year: Refer to adult dosing.
Prevention of HSV reactivation in HIV-positive patients, for use only when recurrences are frequent or severe (unlabeled use): Oral: 80 mg/kg/day in 3-4 divided doses
Prevention of HSV reactivation in HSCT (unlabeled use): Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days): I.V.: 250 mg/m2/dose every 8 hours or 125 mg/m2/dose every 6 hours
Bone marrow transplant recipients (unlabeled use): I.V.: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Oral: Clcr 10-25 mL/minute/1.73 m2: Normal dosing regimen 800 mg every 4 hours: Administer 800 mg every 8 hours Clcr <10 mL/minute/1.73 m2: Normal dosing regimen 200 mg every 4 hours, 200 mg every 8 hours, or 400 mg every 12 hours: Administer 200 mg every 12 hours Normal dosing regimen 800 mg every 4 hours: Administer 800 mg every 12 hours
I.V.: Clcr 25-50 mL/minute/1.73 m2: Administer recommended dose every 12 hours Clcr 10-25 mL/minute/1.73 m2: Administer recommended dose every 24 hours Clcr <10 mL/minute/1.73 m2: Administer 50% of recommended dose every 24 hours
Hemodialysis: Administer dose after dialysis
Peritoneal dialysis: No supplemental dose needed
CAVH: 3.5 mg/kg/day
CVVHD/CVVH: Adjust dose based upon Clcr 30 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution, as sodium: 500 mg, 1000 mg Zovirax®: 500 mg [DSC]
Injection, solution, as sodium [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL (480 mL) Zovirax®: 200 mg/5 mL (480 mL) [banana flavor]
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
DOSAGE FORMS: CONCISE Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution: 500 mg, 1000 mg
Injection, solution [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL Zovirax®: 200 mg/5 mL
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes cream, ointment
ADMINISTRATION Oral: May be administered with or without food.
I.V.: Avoid rapid infusion; infuse over 1 hour to prevent renal damage; maintain adequate hydration of patient; check for phlebitis and rotate infusion sites
Topical: Not for use in the eye. Apply using a finger cot or rubber glove to avoid transmission to other parts of the body or to other persons.
COMPATIBILITY — Stable in D5W, D5NS, D51/4NS, D51/2NS, LR, NS.
Incompatible with blood products and protein-containing solutions.
Y-site administration: Compatible: Allopurinol, amikacin, amphotericin B cholesteryl sulfate complex, ampicillin, cefamandole, cefazolin, cefoperazone, cefotaxime, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, chloramphenicol, cimetidine, clindamycin, co-trimoxazole, dexamethasone, dimenhydrinate, diphenhydramine, docetaxel, doxorubicin liposome, doxycycline, erythromycin lactobionate, etoposide, famotidine, filgrastim, fluconazole, gatifloxacin, gentamicin, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, imipenem/cilastatin, linezolid, lorazepam, magnesium sulfate, melphalan, methylprednisolone sodium succinate, metoclopramide, metronidazole, multivitamins, nafcillin, oxacillin, paclitaxel, penicillin G potassium, pentobarbital, perphenazine, piperacillin, potassium chloride, propofol, ranitidine, remifentanil, sodium bicarbonate, tacrolimus, teniposide, theophylline, thiotepa, ticarcillin, tobramycin, vancomycin, zidovudine. Incompatible: Amifostine, amsacrine, aztreonam, cefepime, dobutamine, dopamine, fludarabine, foscarnet, gemcitabine, idarubicin, levofloxacin, ondansetron, piperacillin/tazobactam, sargramostim, vinorelbine. Variable (consult detailed reference): Cisatracurium, diltiazem, meperidine, meropenem, morphine, TPN.
Compatibility when admixed: Compatible: Fluconazole. Incompatible: Dobutamine, dopamine. Variable (consult detailed reference): Meropenem.
USE — Treatment of genital herpes simplex virus (HSV), herpes labialis (cold sores), herpes zoster (shingles), HSV encephalitis, neonatal HSV, mucocutaneous HSV in immunocompromised patients, varicella-zoster (chickenpox)
USE - UNLABELED / INVESTIGATIONAL — Prevention of HSV reactivation in HIV-positive patients; prevention of HSV reactivation in hematopoietic stem-cell transplant (HSCT); prevention of HSV reactivation during periods of neutropenia in patients with acute leukemia
ADVERSE REACTIONS SIGNIFICANT Systemic: Oral:
>10%: Central nervous system: Malaise (12%)
1% to 10%: Central nervous system: Headache (2%) Gastrointestinal: Nausea (2% to 5%), vomiting (3%), diarrhea (2% to 3%)
Systemic: Parenteral:
1% to 10%: Dermatologic: Hives (2%), itching (2%), rash (2%) Gastrointestinal: Nausea/vomiting (7%) Hepatic: Liver function tests increased (1% to 2%) Local: Inflammation at injection site or phlebitis (9%) Renal: BUN increased (5% to 10%), creatinine increased (5% to 10%), acute renal failure
Topical:
>10%: Dermatologic: Mild pain, burning, or stinging (ointment 30%)
1% to 10%: Dermatologic: Pruritus (ointment 4%), itching
All forms: <1% (Limited to important or life-threatening): Abdominal pain, aggression, agitation, alopecia, anaphylaxis, anemia, angioedema, anorexia, ataxia, coma, confusion, consciousness decreased, delirium, desquamation, diarrhea, disseminated intravascular coagulopathy (DIC), dizziness, dry lips, dysarthria, encephalopathy, erythema multiforme, fatigue, fever, gastrointestinal distress, hallucinations, hematuria, hemolysis, hepatitis, hyperbilirubinemia, hypotension, insomnia, jaundice, leukocytoclastic vasculitis, leukocytosis, leukopenia, local tissue necrosis (following extravasation), lymphadenopathy, mental depression, myalgia, neutrophilia, paresthesia, peripheral edema, photosensitization, pruritus, psychosis, renal failure, seizure, somnolence, sore throat, Stevens-Johnson syndrome, thrombocytopenia, thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), thrombocytosis, toxic epidermal necrolysis, tremor, urticaria, visual disturbances
CONTRAINDICATIONS — Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation
WARNINGS / PRECAUTIONS — Use with caution in immunocompromised patients; thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has been reported. Use caution in the elderly, pre-existing renal disease, or in those receiving other nephrotoxic drugs. Maintain adequate hydration during oral or intravenous therapy. Use I.V. preparation with caution in patients with underlying neurologic abnormalities, serious hepatic or electrolyte abnormalities, or substantial hypoxia.
Safety and efficacy of oral formulations have not been established in pediatric patients <2 years of age.
Chickenpox: Treatment should begin within 24 hours of appearance of rash; oral route not recommended for routine use in otherwise healthy children with varicella, but may be effective in patients at increased risk of moderate to severe infection (>12 years of age, chronic cutaneous or pulmonary disorders, long-term salicylate therapy, corticosteroid therapy).
Genital herpes: Physical contact should be avoided when lesions are present; transmission may also occur in the absence of symptoms. Treatment should begin with the first signs or symptoms.
Herpes labialis: For external use only to the lips and face; do not apply to eye or inside the mouth or nose. Treatment should begin with the first signs or symptoms.
Herpes zoster: Acyclovir should be started within 72 hours of appearance of rash to be effective.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Does not affect absorption of oral acyclovir.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. Acyclovir has been shown to cross the human placenta. There are no adequate and well-controlled studies in pregnant women. Results from a pregnancy registry, established in 1984 and closed in 1999, did not find an increase in the number of birth defects with exposure to acyclovir when compared to those expected in the general population. However, due to the small size of the registry and lack of long-term data, the manufacturer recommends using during pregnancy with caution and only when clearly needed. Data from the pregnancy registry may be obtained from GlaxoSmithKline.
LACTATION — Enters breast milk/use with caution (AAP rates "compatible")
BREAST-FEEDING CONSIDERATIONS — Nursing mothers with herpetic lesions near or on the breast should avoid breast-feeding. Limited data suggest exposure to the nursing infant of ~0.3 mg/kg/day following oral administration of acyclovir to the mother.
DIETARY CONSIDERATIONS — May be taken with or without food. Acyclovir 500 mg injection contains sodium ~50 mg (~2 mEq).
PRICING — (data from drugstore.com)Capsules (Acyclovir) 200 mg (30): $12.99
Capsules (Zovirax) 200 mg (30): $66.50
Cream (Zovirax) 5% (2): $42.53 5% (5): $94.81
Ointment (Zovirax) 5% (15): $105.18
Suspension (Acyclovir) 200 mg/5 mL (473): $82.68
Suspension (Zovirax) 200 mg/5 mL (473): $183.41
Tablets (Acyclovir) 400 mg (60): $28.99 800 mg (30): $24.99
Tablets (Zovirax) 400 mg (60): $242.78 800 mg (30): $236.13
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, liver enzymes, CBC
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Overdoses of up to 20 g have been reported. Symptoms of overdose include agitation, seizures, somnolence, confusion, elevated serum creatinine, and renal failure. In the event of overdose, sufficient urine flow must be maintained to avoid drug precipitation within renal tubules. Hemodialysis has resulted in up to 60% reduction in serum acyclovir levels.
CANADIAN BRAND NAMES — Apo-Acyclovir®; Gen-Acyclovir; Nu-Acyclovir; ratio-Acyclovir; Zovirax®
INTERNATIONAL BRAND NAMES — Abbovir (PL); ACERPES (DE); Acic Creme (DE); Acicloftal (IT); Aciclor (VE); Aciclosina (PE); Aciclovir (PL); Aciclovir-BC IV (AU); Acihexal (AU); Acivir Cream (IL, IN); Acivir Eye (IN); Acix (PL); Aclova (KR); Aclovir (HR, TH, TW); Aclovirax (HK); ACS (KR); Activir (FR); Acyclo-V (AU, BH); Acyclostad (PL); Acyclovir (PL); Acyclovir Stada (PL); Acyklowir (PL); Acylene (MY); Acyrova (KR); Acyvir (EC, HK, IT); Aias (KR); Antivir (PL); Apicol (CO); Apo-Acyclovir (CA, PL); Avorax (HK, MY, SG); Avorax Cream (MY); Awirol (PL); Azovir (ID); Bearax (SG); Cicloferon (MX); Cicloviral (CO); Clinovir (ID, TH); Clovicin (TW); Clovir (BR); Cloviran (CL); Colsor (TH); Cusiviral (ES, HK, MY, PL, SG); Cyclivex (ZA); Cyclomed (IL); Cyclorax (HK); Cyclostad (PH); Cyclovir (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Cyllanvir (PH); Danovir (SG); Deherp (TH, TW); Dravyr (SG); Duvimex (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Entir (SG, TH); Erlvirax (SG); Euroclovir (HK); Eurovir (PY); Exavir (BR); Expit (UY); Gen-Acyclovir (CA); Hascovir (PL); Herpefug (DE); Herpesin (PL); Herpex (BH, IN, PL); Herpoviric (DE); Herpoviric Rp Creme (DE); Heviran (PL); Inmerax (CL); Juviral (DE); Laciken (MX); Lermex (TH); Libravir (EC); Lisovyr (AR, CL); Lovir (AU, HK, MY, NZ, SG); Lovire (ZA); Marvir (TH); Matrovir (ID); Maynor (ES); Medovir (AE, BF, BG, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SG, SL, SN, SY, TZ, UG, YE, ZM, ZW); Nevirz (ID); Norum (TH); Nu-Acyclovir (CA); Olvit (MX); Oppvir (TH, TW); Opthavir (MX); Poviral (EC); Proviral (AR); Qualiclovir (HK); Quavir (ID); Ranvir (TH); Ranviran (PL); ratio-Acyclovir (CA); Skirax (TW); Supra-Vir (IL); Supraviran (DE, PL); Supraviran Creme (AE, BH, CY, DE, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Syntovir (HK); Vacrax (MY); Vermis (TH); Vicorax (TH, TW); Viraban (NZ); Viracir (PL); Viralex-DS (PH); Virax (KR); Vircella (ID); Virest (MY, SG); Virex (CO); Virless (CN, TW); Viroclear (HK); Virogon (TH); Virolan (TW); Virolex (HR, PL); Viromed (TH); Virucid (HK); Virules (HK); Vivir (KR); Warviron (HK); Zetavir (MX); Zeven Cream (MY); Zevin (HK, TH); Zoral (HK, SG); Zoral Cream (MY); Zorax (SG); Zorel (ID); Zoter (ID); Zovir (DK); Zovirax [tabs./susp./ungt.] (PL); Zovirax (AE, AN, AR, AT, AU, BB, BD, BE, BF, BG, BH, BJ, BM, BO, BR, BS, BZ, CA, CH, CI, CL, CN, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SE, SL, SN, SR, SV, SY, TR, TT, TW, TZ, UG, UY, YE, ZA, ZM, ZW); Zumasid (ID); Zyclir (AU); Zyclorax (ID); Zyvir (KE)
MECHANISM OF ACTION — Acyclovir is converted to acyclovir monophosphate by virus-specific thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA.
PHARMACODYNAMICS / KINETICS Absorption: Oral: 15% to 30%
Distribution: Vd: 0.8 L/kg (63.6 L): Widely (eg, brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, CSF)
Protein binding: 9% to 33%
Metabolism: Converted by viral enzymes to acyclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes
Bioavailability: Oral: 10% to 20% with normal renal function (bioavailability decreases with increased dose)
Half-life elimination: Terminal: Neonates: 4 hours; Children 1-12 years: 2-3 hours; Adults: 3 hours
Time to peak, serum: Oral: Within 1.5-2 hours
Excretion: Urine (62% to 90% as unchanged drug and metabolite)
PATIENT INFORMATION — This is not a cure for herpes (recurrences tend to continually reappear every 3-6 months after original infection), nor will this medication reduce the risk of transmission to others when lesions are present; avoid sexual intercourse when visible lesions are present. Take as directed for full course of therapy; do not discontinue even if feeling better. Oral doses may be taken with food.
(For additional information see "Acyclovir: Patient drug information"

Acrivastine and pseudoephedrine

2008-01-23T10:10:00.000-08:00

U.S. BRAND NAMES — Semprex®-D
PHARMACOLOGIC CATEGORY Antihistamine
DOSING: ADULTS — Rhinitis, nasal congestion, allergic symptoms: Oral: 1 capsule 3-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Do not use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: Acrivastine 8 mg and pseudoephedrine hydrochloride 60 mg
DOSAGE FORMS: CONCISE Capsule: Semprex®-D: Acrivastine 8 mg and pseudoephedrine 60 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Temporary relief of nasal congestion, decongest sinus openings, running nose, itching of nose or throat, and itchy, watery eyes due to hay fever or other upper respiratory allergies
ADVERSE REACTIONS SIGNIFICANT >10%: Central nervous system: Drowsiness, headache
1% to 10%: Cardiovascular: Tachycardia, palpitation Central nervous system: Nervousness, dizziness, insomnia, vertigo, lightheadedness, fatigue Gastrointestinal: Nausea, vomiting, xerostomia, diarrhea Genitourinary: Dysuria Neuromuscular & skeletal: Weakness Respiratory: Pharyngitis, cough increased Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to pseudoephedrine, acrivastine (or other alkylamine antihistamines), or any component of the formulation; MAO inhibitor therapy within 14 days of initiating therapy; severe hypertension, severe coronary artery disease; renal impairment (Clcr 48 mL/minute)
WARNINGS / PRECAUTIONS Disease-related concerns: Asthma: Use with caution in patients with asthma. Cardiovascular disease: Use with caution in patients with high blood pressure and/or ischemic heart disease. Diabetes: Use with caution in patients with diabetes mellitus. GI obstruction: Use with caution in patients with GI obstruction. Increased intraocular pressure: Use with caution in patients with increased intraocular pressure. Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Special populations: Elderly: Use with caution in patients >60 years of age. Pediatrics: Not recommended for use in children.
DRUG INTERACTIONS Decreased effect of guanethidine, reserpine, methyldopa, and beta-blockers
Increased toxicity with MAO inhibitors (hypertensive crisis), sympathomimetics, CNS depressants, ethanol (sedation)
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Avoid ethanol (may increase sedation)
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Enters breast milk/contraindicated
PRICING — (data from drugstore.com)Capsules (Semprex-D) 8-60 mg (30): $37.47
MECHANISM OF ACTION — Refer to Pseudoephedrine; acrivastine is an analogue of triprolidine and it is considered to be relatively less sedating than traditional antihistamines; believed to involve competitive blockade of H1-receptor sites resulting in the inability of histamine to combine with its receptor sites and exert its usual effects on target cells
PHARMACODYNAMICS / KINETICS Pseudoephedrine: See Pseudoephedrine.
Acrivastine: Metabolism: Minimally hepatic Time to peak: ~1.1 hours Excretion: Urine (84%); feces (13%)

Acitretin:

2008-01-23T09:54:00.000-08:00

U.S. BRAND NAMES — Soriatane®
PHARMACOLOGIC CATEGORY Retinoid-Like Compound
DOSING: ADULTS Psoriasis: Oral: Individualization of dosage is required to achieve maximum therapeutic response while minimizing side effects Initial therapy: Therapy should be initiated at 25-50 mg/day, given as a single dose with the main meal Maintenance: Doses of 25-50 mg/day may be given after initial response to treatment; the maintenance dose should be based on clinical efficacy and tolerability
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: 10 mg, 25 mg
DOSAGE FORMS: CONCISE Capsule: Soriatane®: 10 mg, 25 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of severe psoriasis
ADVERSE REACTIONS SIGNIFICANT >10%: Central nervous system: Hyperesthesia (10% to 25%) Dermatologic: Cheilitis (>75%), alopecia (50% to 75%), skin peeling (50% to 75%), dry skin (25% to 50%), nail disorder (25% to 50%), pruritus (25% to 50%), erythematous rash (10% to 25%), skin atrophy (10% to 25%), sticky skin (10% to 25%), paronychia (10% to 25%) Endocrine & metabolic: Hypercholesterolemia (25% to 50%), hypertriglyceridemia (50% to 75%), HDL decreased (25% to 50%), phosphorus increased (10% to 25%), potassium increased (10% to 25%), sodium increased (10% to 25%), magnesium increased/decreased (10% to 25%), fasting blood sugar increased (25% to 50%), fasting blood sugar decreased (10% to 25%) Gastrointestinal: Xerostomia (10% to 25%) Hematologic: Reticulocytes increased (25% to 50%), hematocrit decreased (10% to 25%), hemoglobin decreased (10% to 25%), WBC increased/decreased (10% to 25%), haptoglobin increased (10% to 25%), neutrophils increased (10% to 25%) Hepatic: Liver function tests increased (25% to 50%), alkaline phosphatase increased (10% to 25%), direct bilirubin increased (10% to 25%), GGTP increased (10% to 25%) Neuromuscular & skeletal: Paresthesia (10% to 25%), arthralgia (10% to 25%), rigors (10% to 25%), CPK increased (25% to 50%), spinal hyperostosis progression (10% to 25%) Ocular: Xerophthalmia (10% to 25%), Renal: Uric acid increased (10% to 25%), acetonuria (10% to 25%), hematuria (10% to 25%), RBC in urine (10% to 25%) Respiratory: Rhinitis (25% to 50%), epistaxis (10% to 25%)
1% to 10%: Cardiovascular: Flushing, edema Central nervous system: Headache, pain, depression, insomnia, somnolence, fatigue Dermatologic: Skin odor, hair texture change, bullous eruption, dermatitis, diaphoresis increased, psoriasiform rash, purpura, pyogenic granuloma, rash, seborrhea, ulcers, fissures, sunburn Endocrine & metabolic: Hot flashes, potassium decreased, phosphorus decreased, sodium decreased, calcium increased or decreased, chloride increased or decreased Gastrointestinal: Gingival bleeding, gingivitis, saliva increased, stomatitis, thirst, ulcerative stomatitis, abdominal pain, diarrhea, nausea, taste disturbance, anorexia, appetite increased, tongue disorder Hepatic: Total bilirubin increased Neuromuscular & skeletal: Arthritis, back pain, hypertonia, myalgia, osteodynia, peripheral joint hyperostosis, Bell's palsy Ocular: Blurred vision, blepharitis, conjunctivitis, night blindness, photophobia, corneal epithelial abnormality, eye pain, eyebrow or eyelash loss, diplopia, cataract Otic: Earache, tinnitus Renal: BUN increased, creatinine increased, glycosuria, proteinuria Respiratory: Sinusitis
<1% (Limited to important or life-threatening): Anxiety, bleeding time increased, chest pain, cirrhosis, conjunctival hemorrhage, constipation, corneal ulceration, cyanosis, deafness, diplopia, dizziness, dyspepsia, dysphonia, dysuria, eczema, esophagitis, fever, furunculosis, gastritis, glossitis, gum hyperplasia, hair discoloration, healing impaired, hemorrhage, hepatic dysfunction, hepatitis, hyperkeratosis, hypertrichosis, hypoesthesia, intermittent claudication, itchy eyes, jaundice, leukorrhea, malaise, melena, MI, moniliasis, myopathy, nervousness, neuritis, pancreatitis, papilledema, peripheral ischemia, photosensitivity, pseudotumor cerebri, scleroderma, skin fragility or thinning, spinal hyperostosis (new lesion), stroke, taste loss, tendonitis, thromboembolism
CONTRAINDICATIONS — Hypersensitivity to acitretin, other retinoids, or any component of the formulation; patients who are pregnant or intend on becoming pregnant; ethanol ingestion; severe hepatic or renal dysfunction; chronically-elevated blood lipid levels; concomitant use with methotrexate or tetracycline
Acitretin is contraindicated in females of childbearing potential unless all of the following conditions apply. 1) Patient has severe psoriasis unresponsive to other therapy or if clinical condition contraindicates other treatments. 2) Patient must have two negative urine or serum pregnancy tests prior to therapy. 3) Patient must commit to using two effective forms of birth control starting 1 month prior to acitretin treatment and for 3 years after discontinuation. 4) Patient is reliable in understanding and carrying out instructions. 5) Patient has received, and acknowledged, understanding of a careful oral and printed explanation of the hazards of fetal exposure to acitretin and the risk of possible contraception failure; this explanation may include showing a line drawing to the patient of an infant with the characteristic external deformities resulting from retinoid exposure during pregnancy. Patient must sign an agreement/informed consent document stating that she understands these risks and that she should not consume ethanol during therapy or for 2 months after discontinuation. 6) All patients (male and female) should not donate blood during and for 3 years following treatment with acitretin.
WARNINGS / PRECAUTIONS Box warnings: Blood donation: See "Other warnings/precautions" below. Ethanol use: See "Concurrent drug therapy issues" below. Medication guide: See "Other warnings/precautions" below. Pregnancy: See "Special populations" below.
Concerns related to adverse effects: Hepatotoxicity: Monitor for hepatotoxicity; discontinue if elevations of liver enzymes occur. Use with caution in patients at risk of hypertriglyceridemias. Pseudotumor cerebri: Rarely associated with pseudotumor cerebri. Visual disturbances: May cause a decrease in night vision or decreased tolerance to contact lenses; discontinue if visual changes occur.
Concurrent drug therapy issues: Ethanol use: [U.S. Boxed Warning]: All patients (male and female) should abstain from ethanol or ethanol-containing products during therapy and for 2 months after discontinuation.
Special populations: Pediatrics: Safety and efficacy have not been established in children; growth potential may be affected. Pregnancy: [U.S. Boxed Warning]: Not for use by women who want to become pregnant; patient should not get pregnant for at least 3 years after discontinuation.
Other warnings/precautions: Blood donation: [U.S. Boxed Warning]: All patients should be advised not to donate blood during therapy or for 3 years following completion of therapy. Medication guide: [U.S. Boxed Warning]: All patients must be provided with a medication guide each time acitretin is dispensed. Female patients must also sign an informed consent prior to therapy.
RESTRICTIONS — An FDA-approved medication guide must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm.
DRUG INTERACTIONS Ethanol: Etretinate (a retinoid with a much longer half-life) can be formed with concurrent use; contraindicated.
Methotrexate: The concomitant administration of methotrexate and etretinate has been associated with hepatitis, a similar increased hepatitis risk may be expected with the combined use of acitretin and methotrexate; concomitant use is contraindicated.
Progestins: Decreased contraceptive effect with concurrent use; use of "mini-pill" preparations are not recommended. Interactions with other progestational agents or hormonal contraceptives have not been established.
Sulfonylureas: Glucose-lowering effect may be potentiated. Effect seen with glibenclamide.
Tetracycline: Acitretin and tetracyclines may both cause increased intracranial pressure; concomitant use is contraindicated.
Vitamin A: Concomitant administration of vitamin A and other systemic retinoids must be avoided due to the risk of possible additive toxic effects.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Use leads to formation of etretinate, a teratogenic metabolite with a prolonged half-life; concomitant use of ethanol or ethanol-containing products is contraindicated.
PREGNANCY RISK FACTOR — X (show table)
PREGNANCY IMPLICATIONS — Acitretin is teratogenic in humans. Severe birth defects have been reported when conception occurred during treatment or after therapy was complete. Not for use by women who want to become pregnant; patient should not get pregnant for at least 3 years after discontinuation. In addition, because ethanol forms a teratogenic metabolite and would increase the duration of teratogenic potential, ethanol should not be consumed during treatment or for 2 months after discontinuation. Limited amounts of acitretin are found in seminal fluid; although it appears this poses little risk to a fetus, the actual risk of teratogenicity is not known. Any pregnancy which occurs during treatment, or within 3 years after treatment is discontinued, should be reported to the manufacturer at 1-888-500-3376 or to the FDA at 1-800-FDA-1088.
LACTATION — Enters breast milk/not recommended
BREAST-FEEDING CONSIDERATIONS — Acitretin should not be given prior to or during nursing due to the potential for adverse effects in the nursing infant.
DIETARY CONSIDERATIONS — Administer with food. Avoid ingestion of additional sources of exogenous vitamin A (in excess of RDA); use of ethanol and ethanol-containing products is contraindicated.
PRICING — (data from drugstore.com)Capsules (Soriatane) 10 mg (30): $451.54 25 mg (30): $573.49
MONITORING PARAMETERS — Lipid profile (baseline and at 1- to 2-week intervals for 4-8 weeks); liver function tests (baseline, and at 1- to 2-week intervals until stable, then as clinically indicated); blood glucose in patients with diabetes; bone abnormalities (with long-term use)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of acute hypervitaminosis A (headache, vertigo) would be expected; vomiting has also been reported. Pregnancy test for women of childbearing age; counseling regarding potential for birth defects and appropriate contraceptive use.
CANADIAN BRAND NAMES — Soriatane®
INTERNATIONAL BRAND NAMES — Neo-Tigason (TH); Neotigason (AN, AR, AT, AU, BB, BE, BF, BG, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CZ, DE, DK, EC, EE, EG, ES, ET, FI, GB, GH, GM, GN, GY, HU, IE, IL, IT, JM, KE, KR, LR, MA, ML, MR, MU, MW, MX, NE, NG, NL, NO, NZ, PE, PH, PL, PT, PY, SC, SD, SE, SL, SN, SR, TT, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Soriatane (CA, FR)
PHARMACODYNAMICS / KINETICS — Etretinate has been detected in serum for up to 3 years following therapy, possibly due to storage in adipose tissue.
Onset: May take 2-3 months for full effect; improvement may be seen within 8 weeks.
Absorption: Oral: ~72% absorbed when given with food
Protein binding: >99% bound, primarily to albumin
Metabolism: Metabolized to cis-acitretin; both compounds are further metabolized. Concomitant ethanol use leads to the formation of etretinate (active).
Half-life elimination: Acitretin: 49 hours (range: 33-96); cis-acitretin: 63 hours (range: 28-157); etretinate: 120 days (range: 84-168 days)
Excretion: Feces (34% to 54%); urine (16% to 53%)
PATIENT INFORMATION — Take with food. Do not drink alcohol during therapy and for 2 months after discontinuation. Use contraception for 1 month before, during, and for 3 years after discontinuation. You may not be able to tolerate contact lenses during treatment. Do not donate blood during treatment and for 3 years after discontinuation (male and female patients). Avoid exposure to sunlight. Wear protective clothing and sunscreens. Avoid use of other vitamin A products. Females: Use two effective forms of birth control. If you have had your tubes tied, then use an additional form of birth control. If you become pregnant, contact your prescriber immediately.

Acetylcysteine

2008-01-23T09:48:00.000-08:00

U.S. BRAND NAMES — Acetadote®
PHARMACOLOGIC CATEGORY AntidoteMucolytic Agent
DOSING: ADULTS Acetaminophen poisoning: Oral: 140 mg/kg; followed by 17 doses of 70 mg/kg every 4 hours; repeat dose if emesis occurs within 1 hour of administration; therapy should continue until acetaminophen levels are undetectable and there is no evidence of hepatotoxicity. I.V. (Acetadote®): Loading dose: 150 mg/kg over 60 minutes; Note: Extended infusion time recommended by manufacturer as of February, 2006. Loading dose is followed by 2 additional infusions: Initial maintenance dose of 50 mg/kg infused over 4 hours, followed by a second maintenance dose of 100 mg/kg infused over 16 hours. Total dosage: 300 mg/kg administered over 21 hours. Patients <40 kg: Reduce fluid volume according to the following table.
Acetadote® Dosing / Fluid Volume Guidelines for Patients <40 kg
Body weight 30 kg: Loading dose (150 mg/kg over 1 hour): Acetadote® 22.5 mL in D5W 100 mL Second dose (50 mg/kg over 4 hours): Acetadote® 7.5 mL in D5W 250 mL Third dose (100 mg/kg over 16 hours): Acetadote® 15 mL in D5W 500 mL
Body weight 25 kg: Loading dose (150 mg/kg over 1 hour): Acetadote® 18.75 mL in D5W 100 mL Second dose (50 mg/kg over 4 hours): Acetadote® 6.25 mL in D5W 250 mL Third dose (100 mg/kg over 16 hours): Acetadote® 12.5 mL in D5W 500 mL
Body weight 20 kg: Loading dose (150 mg/kg over 1 hour): Acetadote® 15 mL in D5W 60 mL Second dose (50 mg/kg over 4 hours): Acetadote® 5 mL in D5W 140 mL Third dose (100 mg/kg over 16 hours): Acetadote® 10 mL in D5W 280 mL
Body weight 15 kg: Loading dose (150 mg/kg over 1 hour): Acetadote® 11.25 mL in D5W 45 mL Second dose (50 mg/kg over 4 hours): Acetadote® 3.75 mL in D5W 105 mL Third dose (100 mg/kg over 16 hours): Acetadote® 7.5 mL in D5W 210 mL
Body weight 10 kg: Loading dose (150 mg/kg over 1 hour): Acetadote® 7.5 mL in D5W 130 mL Second dose (50 mg/kg over 4 hours): Acetadote® 2.5 mL in D5W 70 mL Third dose (100 mg/kg over 16 hours): Acetadote® 5 mL in D5W 140 mL Note: If commercial I.V. form is unavailable, the following dose has been reported using solution for oral inhalation (unlabeled): Loading dose: 140 mg/kg, followed by 70 mg/kg every 4 hours, for a total of 13 doses (loading dose and 48 hours of treatment); infuse each dose over 1 hour through a 0.2 micron Millipore filter (in-line). Experts suggest that the duration of acetylcysteine administration may vary depending upon serial acetaminophen levels and liver function tests obtained during treatment. In general, patients without measurable acetaminophen levels and without significant LFT elevations (>3 times the ULN) can safely stop acetylcysteine after 24 hours of treatment. The patients who still have detectable levels of acetaminophen, and/or LFT elevations (>1000 units/L) continue to benefit from additional acetylcysteine administration.
Adjuvant therapy in respiratory conditions: Note: Patients should receive bronchodilator 15 minutes prior to dose. Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted: 3-5 mL of 20% solution or 6-10 mL of 10% solution until nebulized given 3-4 times/day; dosing range: 1-10 mL of 20% solution or 2-20 mL of 10% solution every 2-6 hours Inhalation, nebulization (tent, croupette): Dose must be individualized; may require up to 300 mL solution/treatment Direct instillation: Into tracheostomy: 1-2 mL of 10% to 20% solution every 1-4 hours Through percutaneous intratracheal catheter: 1-2 mL of 20% or 2-4 mL of 10% solution every 1-4 hours via syringe attached to catheter
Diagnostic bronchogram: Nebulization or intratracheal: 1-2 mL of 20% solution or 2-4 mL of 10% solution administered 2-3 times prior to procedure
Prevention of radiocontrast-induced renal dysfunction (unlabeled use): Oral: 600 mg twice daily for 2 days (beginning the day before the procedure); may be given as powder in capsules, some centers use solution (diluted in cola beverage or juice). Hydrate patient with saline concurrently.
DOSING: PEDIATRIC
(For additional information see "Acetylcysteine: Pediatric drug information")Acetaminophen poisoning: Refer to adult dosing.
Adjuvant therapy in respiratory conditions: Note: Patients should receive an aerosolized bronchodilator 10-15 minutes prior to acetylcysteine Inhalation, nebulization (face mask, mouth piece, tracheostomy): Acetylcysteine 10% and 20% solution (dilute 20% solution with sodium chloride or sterile water for inhalation); 10% solution may be used undiluted. Infants: 1-2 mL of 20% solution or 2-4 mL 10% solution until nebulized given 3-4 times/day Children: Refer to adult dosing. Inhalation, nebulization (tent, croupette): Children: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL) [contains disodium edetate]
Solution, inhalation/oral: 10% [100 mg/mL] (4 mL, 10 mL, 30 mL); 20% [200 mg/mL] (4 mL, 10 mL, 30 mL)
DOSAGE FORMS: CONCISE Injection, solution: Acetadote®: 20% [200 mg/mL] (30 mL)
Solution, inhalation/oral: 10% [100 mg/mL]; 20% [200 mg/mL]
GENERIC EQUIVALENT AVAILABLE — Yes: Solution for inhalation
ADMINISTRATION Inhalation: Acetylcysteine is incompatible with tetracyclines, erythromycin, amphotericin B, iodized oil, chymotrypsin, trypsin, and hydrogen peroxide. Administer separately. Intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime.
Oral: For treatment of acetaminophen overdosage, administer orally as a 5% solution. Dilute the 20% solution 1:3 with a cola, orange juice, or other soft drink. Use within 1 hour of preparation. Unpleasant odor becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister.
I.V.: Intravenous formulation (Acetadote®): Administer loading dose of 150 mg/kg over 60 minutes (see "Note"), followed by 2 separate maintenance infusions: 50 mg/kg over 4 hours followed by 100 mg/kg over 16 hours. If not using commercially available I.V. formulation, use a 0.2-µ millipore filter (in-line). Note: Extended infusion time recommended by manufacturer as of February, 2006.
COMPATIBILITY Inhalation: Incompatible with rubber and metals (particularly iron, copper, and nickel); do not mix with ampicillin, tetracycline, oxytetracycline, erythromycin.
Intravenous: Compatible with D5W, 1/2NS, SWFI. Incompatible with rubber and metals (particularly iron, copper, and nickel).
USE — Adjunctive mucolytic therapy in patients with abnormal or viscid mucous secretions in acute and chronic bronchopulmonary diseases; pulmonary complications of surgery and cystic fibrosis; diagnostic bronchial studies; antidote for acute acetaminophen toxicity
USE - UNLABELED / INVESTIGATIONAL — Prevention of radiocontrast-induced renal dysfunction (oral, I.V.); distal intestinal obstruction syndrome (DIOS, previously referred to as meconium ileus equivalent)
ADVERSE REACTIONS SIGNIFICANT Inhalation: Frequency not defined. Central nervous system: Drowsiness, chills, fever Gastrointestinal: Vomiting, nausea, stomatitis Local: Irritation, stickiness on face following nebulization Respiratory: Bronchospasm, rhinorrhea, hemoptysis Miscellaneous: Acquired sensitization (rare), clamminess, unpleasant odor during administration
Intravenous:
>10%: Miscellaneous: Anaphylactoid reaction (~17%; reported as severe in 1% or moderate in 10% of patients within 15 minutes of first infusion; severe in 1% or mild to moderate in 6% to 7% of patients after 60-minute infusion)
1% to 10%: Cardiovascular: Angioedema (2% to 8%), vasodilation (1% to 6%), hypotension (1% to 4%), tachycardia (1% to 4%), syncope (1% to 3%), chest tightness (1%), flushing (1%) Central nervous system: Dysphoria (<1% to 2%) Dermatologic: Urticaria (2% to 7%), rash (1% to 5%), facial erythema (1%), palmar erythema (1%), pruritus (1% to 3%), pruritus with rash and vasodilation (2% to 9%) Gastrointestinal: Vomiting (<1% to 10%), nausea (1% to 10%), dyspepsia (1%) Neuromuscular & skeletal: Gait disturbance (<1% to 2%) Ocular: Eye pain (<1% to 3%) Otic: Ear pain (1%) Respiratory: Bronchospasm (1% to 6%), cough (1% to 4%), dyspnea (<1% to 3%), pharyngitis (1%), rhinorrhea (1%), rhonchi (1%), throat tightness (1%) Miscellaneous: Diaphoresis (1%)
CONTRAINDICATIONS — Hypersensitivity to acetylcysteine or any component of the formulation
WARNINGS / PRECAUTIONS Disease-related concerns: Acetaminophen overdose: Appropriate use: The modified Rumack-Matthew nomogram allows for stratification of patients into risk categories based on the relationship between the serum acetaminophen level and time after ingestion. There are several situations where the nomogram is of limited use. Serum acetaminophen levels obtained prior to 4-hour postingestion are not interpretable; patients presenting late may have undetectable serum concentrations, but have received a lethal dose. The nomogram is less predictive in a chronic ingestion or in an overdose with an extended release product. Acetylcysteine should be administered for any signs of hepatotoxicity even if acetaminophen serum level is low or undetectable. The nomogram also does not take into account patients at higher risk of acetaminophen toxicity (eg, alcoholics, malnourished patients).
Dosage form specific issues: Inhalation: Since increased bronchial secretions may develop after inhalation, percussion, postural drainage, and suctioning should follow. If bronchospasm occurs, administer a bronchodilator; discontinue acetylcysteine if bronchospasm progresses. Intravenous: Acute flushing and erythema have been reported; usually occurs within 30-60 minutes and may resolve spontaneously. Serious anaphylactoid reactions have also been reported. Acetylcysteine infusion may be interrupted until treatment of allergic symptoms is initiated; the infusion can then be carefully restarted. Treatment for anaphylactic reactions should be immediately available. Use caution with asthma or history of bronchospasm.
DRUG INTERACTIONS — Adsorbed by activated charcoal; clinical significance is minimal, though, once a pure acetaminophen ingestion requiring N-acetylcysteine is established; further charcoal dosing is unnecessary once the appropriate initial charcoal dose is achieved (5-10 g:g acetaminophen)
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Based on limited reports using acetylcysteine to treat acetaminophen overdose in pregnant women, acetylcysteine has been shown to cross the placenta and may provide protective levels in the fetus.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)Solution (Acetylcysteine) 10% (30): $19.56 20% (4): $7.99 20% (10): $14.99
Solution (Mucomyst) 20% (30): $18.99
Solution (Mucomyst-10) 10% (10): $11.74 10% (30): $18.99
MONITORING PARAMETERS — Acetaminophen overdose: AST, ALT, bilirubin, PT, serum creatinine, BUN, serum glucose, and electrolytes. Acetaminophen levels at ~4 hours postingestion (every 4-6 hours if extended release acetaminophen; plot on the nomogram) and every 4-6 hours to assess serum levels, and LFTs for possible hepatotoxicity. Assess patient for nausea, vomiting, and skin rash following oral administration for treatment of acetaminophen poisoning. If administered I.V., monitor for anaphylaxis/anaphylactoid reactions.
REFERENCE RANGE — Determine acetaminophen level as soon as possible, but no sooner than 4 hours after ingestion (to ensure peak levels have been obtained); administer for acetaminophen level >150 mcg/mL at 4 hours following ingestion; toxic concentration with probable hepatotoxicity: >200 mcg/mL at 4 hours or 50 mcg at 12 hours
TOXICOLOGY / OVERDOSE COMPREHENSIVE — The treatment of acetylcysteine toxicity is usually aimed at reversing anaphylactoid symptoms or controlling nausea and vomiting. The use of epinephrine, antihistamines, and steroids may be beneficial.
CANADIAN BRAND NAMES — Acetylcysteine Solution; Mucomyst®; Parvolex®
INTERNATIONAL BRAND NAMES — ACC (MX, PL); ACC 200 (EE, HU); Acetain (KR); Acetylcysteine Solution (CA); Acypront (HK, PL); Alveolex (IE); Bromuc (BR); Drenaflen (EC); Ecomucyl (CH); Eloamin (CZ); Exomuc (FR, HK); Fabrol (AT, GR); Flemex AC (TH); Fluimicil (CH); Fluimucil (BR, CN, CO, EC, HK, ID, MA, NL, PE, PL, SG, TH, TW); Fluimucil A (MY, PK); Fluimukan (HR); Flutafin (TW); Hidonac (ID, PH, TH); Libramucil (EC); Menaxol (CR, DO, GT, HN, NI, PA, SV); Mucofillin (JP); Mucolator (MY); Mucolitico (CL); Mucomiste (PT); Mucomyst (AT, AU, BE, CA, DK, FI, FR, KR, NL); Mucoserin (KR); Mucosof (CN); Mucosten (KR); Mucosys (IN); Mucoza (TH); Mukolit (ID); Muteran (KR); Parvolex (CA, GB, IE, NZ, PH); Parvolex DBL (MY); Reolin (IL); Simucin (TH); Siran 200 (IL); Solmucol (SG); Spatam (SG); Stecin (KR); Syntemucol (PL); Tussicom (PL); Zifluvis (CO)
MECHANISM OF ACTION — Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity. The exact mechanism of action in acetaminophen toxicity is unknown; thought to act by providing substrate for conjugation with the toxic metabolite.
PHARMACODYNAMICS / KINETICS Onset of action: Inhalation: 5-10 minutes
Duration: Inhalation: >1 hour
Distribution: 0.47 L/kg
Protein binding, plasma: 83%
Half-life elimination: Reduced acetylcysteine: 2 hours Total acetylcysteine: Adults: 5.5 hours; Newborns: 11 hours
Time to peak, plasma: Oral: 1-2 hours
Excretion: Urine
PATIENT INFORMATION — Clear airway by coughing deeply before using aerosol.
(For additional information see "Acetylcysteine: Patient drug information")

Acetylcholine

2008-01-23T09:45:00.000-08:00

U.S. BRAND NAMES — Miochol®-E
PHARMACOLOGIC CATEGORY Cholinergic AgonistOphthalmic Agent, Miotic
DOSING: ADULTS — To produce miosis: Intraocular: 0.5-2 mL of 1% injection (5-20 mg) instilled into anterior chamber before or after securing one or more sutures
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Powder for solution, intraocular, as chloride: Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
DOSAGE FORMS: CONCISE Powder for intraocular solution: Miochol®-E: 1:100 [20 mg; packaged with diluent (2 mL)]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Open under aseptic conditions only. Attach filter before irrigating eye.
USE — Produces complete miosis in cataract surgery, keratoplasty, iridectomy, and other anterior segment surgery where rapid miosis is required
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Bradycardia, flushing, hypotension
Central nervous system: Headache
Ocular: Clouding, corneal edema, decompensation
Respiratory: Dyspnea
Miscellaneous: Diaphoresis
CONTRAINDICATIONS — Hypersensitivity to acetylcholine chloride or any component of the formulation; acute iritis and acute inflammatory disease of the anterior chamber
WARNINGS / PRECAUTIONS — During cataract surgery, use only after lens is in place. Systemic effects rarely occur but can cause problems for patients with acute cardiac failure, bronchial asthma, peptic ulcer, hyperthyroidism, GI spasm, urinary tract obstruction, and Parkinson's disease; open under aseptic conditions only.
DRUG INTERACTIONS Decreased effect possible with flurbiprofen and suprofen, ophthalmic.
Increased effect may be prolonged or enhanced in patients receiving tacrine.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Acetylcholine is used primarily in the eye and there are no reports of its use in pregnancy. Because it is ionized at physiologic pH, transplacental passage would not be expected.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Treatment includes flushing eyes with water or normal saline and supportive measures. If accidentally ingested, induce emesis or perform gastric lavage.
CANADIAN BRAND NAMES — Miochol®-E
INTERNATIONAL BRAND NAMES — Miochol (AU, BE, FI, NL, NZ); Miochol-E (AU, CA, CL, DE, GB, HK, ID, IE, IL, KR, NL, NZ, SG)
MECHANISM OF ACTION — Causes contraction of the sphincter muscles of the iris, resulting in miosis and contraction of the ciliary muscle, leading to accommodation spasm
PHARMACODYNAMICS / KINETICS Onset of action: Rapid
Duration: ~10 minutes
PATIENT INFORMATION — Do not touch dropper to eye. May sting on instillation. Use caution while driving at night or performing hazardous tasks.
(For additional information see "Acetylcholine: Patient drug information")

Acetohydroxamic acid:

2008-01-23T09:43:00.000-08:00

U.S. BRAND NAMES — Lithostat®
PHARMACOLOGIC CATEGORY Urinary Tract Product
DOSING: ADULTS — Susceptible infections: Oral: 250 mg 3-4 times/day for a total daily dose of 10-15 mg/kg/day
DOSING: PEDIATRIC — Susceptible infections: Oral: Initial: 10 mg/kg/day
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Not recommended for use in significant renal impairment (Srcr >2.5 mg/dL).
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 250 mg
DOSAGE FORMS: CONCISE Tablet: Lithostat®: 250 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Should be administered on an empty stomach.
USE — Adjunctive therapy in chronic urea-splitting urinary infection
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Deep vein thrombosis (rare), embolism, palpitation, phlebitis
Central nervous system: Anorexia, anxiety, depression, headache, malaise, nervousness, tremor
Dermatologic: Flushing (with ethanol consumption), rash (nonpruritic, macular)
Gastrointestinal: Nausea, vomiting
Hematologic: Hemolytic anemia (15% with laboratory evidence; ~3% severe requiring discontinuation; may be accompanied by GI symptoms or systemic complaints of malaise and/or fatigue); hyperbilirubinemia
Respiratory: Pulmonary embolism (rare)
CONTRAINDICATIONS — Hypersensitivity to acetohydroxamic acid or any component of the formulation; pregnancy
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Bone marrow suppression: May suppress bone marrow function; use with caution in patients with prior bone marrow depression. Close monitoring of hematologic function is recommended. Hemolytic anemia: Has been associated with hemolytic anemia (Coombs' negative), which may be associated with gastrointestinal distress and systemic symptoms; use with caution in patients with anemia. Monitor hematologic parameters during extended therapy. Hepatotoxicity: May cause hepatic injury; close monitoring of hepatic function is recommended.
Disease-related concerns: Psychiatric disorders: Use with caution in patients with pre-existing psychiatric disorders; may be associated with nervousness, anxiety, and/or depression.
DRUG INTERACTIONS Calcium and/or magnesium products: Acetohydroxamic acid may chelate divalent metals, decreasing the absorption of both agents; avoid concurrent use.
Iron: Orally-administered iron may be chelated by acetohydroxamic acid, decreasing the absorption of both agents. To treat hypochromic anemia, parenteral iron should be used.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol (may increase incidence of rash and/or flushing).
Food: May decrease absorption of acetohydroxamic acid.
PREGNANCY RISK FACTOR — X (show table)
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Should be taken on an empty stomach, 1 hour before or 2 hours after meals.
PRICING — (data from drugstore.com)Tablets (Lithostat) 250 mg (100): $143.36
MONITORING PARAMETERS — In patients receiving therapy >2 weeks, monitor CBC with reticulocytes at 3-month intervals during the duration of treatment.
CANADIAN BRAND NAMES — Lithostat®
INTERNATIONAL BRAND NAMES — Lithostat (CA)
MECHANISM OF ACTION — Acetohydroxamic acid inhibits bacterial urease enzymes, decreasing the formation of ammonia in the urine by urea-splitting organisms. A reduction in urinary ammonia may increase the antibacterial activity of some antibiotic agents.

Acetic acid, propylene glycol diacetate, and hydrocortisone

2008-01-23T09:41:00.000-08:00

U.S. BRAND NAMES — Acetasol® HC; VoSol® HC
PHARMACOLOGIC CATEGORY Otic Agent, Anti-infective
DOSING: ADULTS — Otitis externa (superficial): Otic: Instill 3-5 drops in ear(s) every 4-6 hours
DOSING: PEDIATRIC — Children 3 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, otic drops: Acetic acid 2%, propylene glycol diacetate 3%, and hydrocortisone 1% (10 mL)
DOSAGE FORMS: CONCISE Solution, otic drops: Acetic acid 2%, propylene glycol diacetate 3%, and hydrocortisone 1% (10 mL) Acetasol® HC, VoSol® HC: Acetic acid 2%, propylene glycol diacetate 3%, and hydrocortisone 1% (10 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — After removing cerumen and debris, solution may be applied by inserting a cotton wick into the ear canal and saturating with the solution. Wick may remain in place for 24 hours and then removed; however, drops should continue to be instilled into ear canal as long as indicated.
USE — Treatment of superficial infections of the external auditory canal caused by organisms susceptible to the action of the antimicrobial, complicated by swelling
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined: Otic: Transient burning or stinging may be noticed occasionally when the solution is first instilled into the acutely inflamed ear
CONTRAINDICATIONS — Hypersensitivity to acetic acid, propylene glycol, hydrocortisone, or any component of the formulation; perforated tympanic membrane; herpes simplex; vaccinia, and varicella
DRUG INTERACTIONS — Hydrocortisone: Substrate of CYP3A4 (minor); Induces CYP3A4 (weak)
PRICING — (data from drugstore.com)Solution (Acetasol HC) 2-1% (10): $16.07
PATIENT INFORMATION — See individual agents for Acetic Acid and Hydrocortisone.
(For additional information see "Acetic acid, propylene glycol diacetate, and hydrocortisone: Patient drug information")

Acetic acid

2008-01-23T09:39:00.000-08:00

U.S. BRAND NAMES — VoSol® [DSC]
PHARMACOLOGIC CATEGORY Otic Agent, Anti-infectiveTopical Skin Product
DOSING: ADULTS Irrigation (Note: Dosage of an irrigating solution depends on the capacity or surface area of the structure being irrigated): For continuous irrigation of the urinary bladder with 0.25% acetic acid irrigation, the rate of administration will approximate the rate of urine flow; usually 500-1500 mL/24 hours For periodic irrigation of an indwelling urinary catheter to maintain patency, about 50 mL of 0.25% acetic acid irrigation is required
Otitis externa: Otic: Insert saturated wick; keep moist 24 hours; remove wick and instill 5 drops 3-4 times/day
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution for irrigation: 0.25% (250 mL, 500 mL, 1000 mL)
Solution, otic (VoSol® [DSC]): 2% (15 mL)
DOSAGE FORMS: CONCISE Solution for irrigation: 0.25% (250 mL, 500 mL, 1000 mL)
Solution, otic: 2% (15 mL)
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Not for internal intake or I.V. infusion; topical use or irrigation use only.
USE — Irrigation of the bladder; treatment of superficial bacterial infections of the external auditory canal
ADVERSE REACTIONS SIGNIFICANT — <1% (Limited to important or life-threatening): Hematuria, systemic acidosis, urologic pain
CONTRAINDICATIONS — Hypersensitivity to acetic acid or any component of the formulation; during transurethral procedures
WARNINGS / PRECAUTIONS — Not for internal intake or I.V. infusion; topical use or irrigation use only. Use of irrigation in patients with mucosal lesions of urinary bladder may cause irritation. Systemic acidosis may result from absorption.
PREGNANCY RISK FACTOR — C (show table)

Acetazolamide

2008-01-23T09:37:00.001-08:00

U.S. BRAND NAMES — Diamox® Sequels®
PHARMACOLOGIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase InhibitorOphthalmic Agent, Antiglaucoma
DOSING: ADULTS — Note: I.M. administration is not recommended.
Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg extended release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day
Edema: Oral, I.V.: 250-375 mg once daily
Epilepsy: Oral: 8-30 mg/kg/day in 1-4 divided doses, not to exceed 1 g/day. Note: Extended release capsule is not recommended for treatment of epilepsy.
Metabolic alkalosis (unlabeled use): I.V. 250 mg every 6 hours for 4 doses or 500 mg single dose; reassess need based upon acid-base status
Mountain sickness: Oral: 250 mg every 8-12 hours (or 500 mg extended release capsules every 12-24 hours). Therapy should begin 24-48 hours before and continue during ascent and for at least 48 hours after arrival at the high altitude. Note: In situations of rapid ascent (such as rescue or military operations), 1000 mg/day is recommended.
Urine alkalinization (unlabeled use): Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Respiratory stimulant in COPD (unlabeled use): Oral, I.V.: 250 mg twice daily
DOSING: PEDIATRIC — Note: I.M. administration is not recommended.
(For additional information see "Acetazolamide: Pediatric drug information")
Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/24 hours divided every 6 hours, not to exceed 1 g/day
Edema: Oral, I.V.: 5 mg/kg or 150 mg/m2 once every day
Epilepsy: Oral: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 250 mg once or twice daily; use lowest effective dose possible.
DOSING: RENAL IMPAIRMENT Clcr 10-50 mL/minute: Administer every 12 hours.
Clcr <10 mL/minute: Avoid use (ineffective).
Moderately dialyzable (20% to 50%)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
DOSAGE FORMS: CONCISE Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: May cause an alteration in taste, especially carbonated beverages. Short-acting tablets may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug; do not use fruit juices. Alternatively, submerge tablet in 10 mL of hot water and add 10 mL honey or syrup.
I.M.: I.M. administration is painful because of the alkaline pH of the drug; use by this route is not recommended.
COMPATIBILITY — Stable in dextran 6% in D5W, dextran 6% in NS, D5LR, D5NS, D51/2NS, D51/4NS, D5W, D10W, LR, NS, 1/2NS.
Y-site administration: Variable (consult detailed reference): Diltiazem, TPN.
Compatibility when admixed: Compatible: Cimetidine, ranitidine. Incompatible: Multivitamins.
USE — Treatment of glaucoma (chronic simple open-angle, secondary glaucoma, preoperatively in acute angle-closure); drug-induced edema or edema due to congestive heart failure (adjunctive therapy); centrencephalic epilepsies (immediate release dosage form); prevention or amelioration of symptoms associated with acute mountain sickness
USE - UNLABELED / INVESTIGATIONAL — Urine alkalinization; respiratory stimulant in COPD; metabolic alkalosis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Flushing
Central nervous system: Ataxia, confusion, convulsions, depression, dizziness, drowsiness, excitement, fatigue, fever, headache, malaise
Dermatologic: Allergic skin reactions, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Electrolyte imbalance, growth retardation (children), hyperglycemia, hypoglycemia, hypokalemia, hyponatremia, metabolic acidosis
Gastrointestinal: Appetite decreased, diarrhea, melena, nausea, taste alteration, vomiting
Genitourinary: Crystalluria, glycosuria, hematuria, polyuria, renal failure
Hematologic: Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura
Hepatic: Cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency, liver function tests abnormal
Local: Pain at injection site
Neuromuscular & skeletal: Flaccid paralysis, paresthesia
Ocular: Myopia
Otic: Hearing disturbance, tinnitus
Miscellaneous: Anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation; hepatic disease or insufficiency; decreased sodium and/or potassium levels; adrenocortical insufficiency, cirrhosis; hyperchloremic acidosis, severe renal disease or dysfunction; severe pulmonary obstruction; long-term use in noncongestive angle-closure glaucoma
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS effects: Impairment of mental alertness and/or physical coordination may occur. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Diabetes: Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control. Hepatic impairment: Use with caution in patients with hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Respiratory acidosis: Use with caution in patients with respiratory acidosis.
Special populations: Elderly: Use with caution in the elderly; may be more sensitive to side effects.
Other warnings/precautions: I.M. administration: Painful because of the alkaline pH of the drug; use by this route is not recommended.
DRUG INTERACTIONS — Inhibits CYP3A4 (weak)
Amphetamines: Urinary excretion of amphetamine may be decreased; magnitude and duration of effects may be enhanced.
Carbamazepine: May increase serum concentrations of carbamazepine.
Cyclosporine trough concentrations may be increased resulting in possible nephrotoxicity and neurotoxicity.
Flecainide: May decrease excretion of flecainide.
Lithium: Serum concentrations may be decreased by acetazolamide; monitor.
Memantine: May decrease excretion of memantine.
Methenamine: Urinary antiseptic effect may be prevented by acetazolamide.
Phenytoin: Serum concentrations of phenytoin may be increased; incidence of osteomalacia may be enhanced or increased in patients on chronic phenytoin therapy.
Primidone serum concentrations may be decreased; carbonic anhydrase inhibitors may enhance the adverse/toxic effects of primidone.
Quinidine: Urinary excretion of quinidine may be decreased and effects may be enhanced.
Salicylate use (high dose) may result in carbonic anhydrase inhibitor accumulation and toxicity including CNS depression and metabolic acidosis. Salicylate toxicity might also be enhanced.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic in animal studies, however, there are no adequate and well-controlled studies in pregnant women.
LACTATION — Enters breast milk/not recommended (AAP rates "compatible")
DIETARY CONSIDERATIONS — May be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Sodium content of 500 mg injection: 47.2 mg (2.05 mEq).
PRICING — (data from drugstore.com)Capsule, 12-hour (Diamox Sequels) 500 mg (60): $169.03
Tablets (AcetaZOLAMIDE) 125 mg (60): $8.98 250 mg (60): $18.99
MONITORING PARAMETERS — Intraocular pressure, potassium, serum bicarbonate; serum electrolytes, periodic CBC with differential; monitor growth in pediatric patients
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include low blood sugar, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor, and coma. Hypoglycemia should be managed with 50 mL I.V. dextrose 50% followed immediately with a continuous infusion of 10% dextrose in water (administer at a rate sufficient enough to approach a serum glucose level of 100 mg/dL). The use of corticosteroids to treat the hypoglycemia is controversial, however, the addition of 100 mg of hydrocortisone to the dextrose infusion may prove helpful. In certain instances, hemodialysis may be helpful.
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
INTERNATIONAL BRAND NAMES — Acetadiazol (MX); Albox (JP); Apo-Acetazolamide (CA, MY); Azol (TW); Carbinib (PT); Cetamid (PH); Defiltran (DE); Dehydratin (BG); Diamox (AE, AR, AT, AU, BE, BH, BR, CA, CH, CN, CO, CY, DK, EC, EG, ES, FI, FR, GB, HR, ID, IE, IN, IQ, IR, IT, JO, JP, KW, LB, LY, MX, MY, NL, NO, NZ, OM, PH, PY, QA, RU, SA, SE, SG, SY, TH, VE, YE, ZA); Diamox Sustets (CO); Diluran (CZ); Diural (UY); Diuramid (DE, PL); Edemox (ES); Evamox (PK); Genephamide (PE); Glaucomed (CO); Glaupax (CH, DK, HR, IE, JP, NO, TH); Huma-Zolamide (HU); Ledamox (JP); Lediamox (PT); Renamid (HR); Stazol (PY); Uramox (IL)
MECHANISM OF ACTION — Reversible inhibition of the enzyme carbonic anhydrase resulting in reduction of hydrogen ion secretion at renal tubule and an increased renal excretion of sodium, potassium, bicarbonate, and water to decrease production of aqueous humor; also inhibits carbonic anhydrase in central nervous system to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS / KINETICS Onset of action: Capsule, extended release: 2 hours; I.V.: 2 minutes Peak effect: Capsule, extended release: 8-12 hours; I.V.: 15 minutes; Tablet: 2-4 hours
Duration: Inhibition of aqueous humor secretion: Capsule, extended release: 18-24 hours; I.V.: 4-5 hours; Tablet: 8-12 hours
Distribution: Erythrocytes, kidneys; blood-brain barrier and placenta; distributes into milk (~30% of plasma concentrations)
Excretion: Urine (70% to 100% as unchanged drug)
PATIENT INFORMATION — Report numbness or tingling of extremities. Do not crush, chew, or swallow contents of long-acting capsule; may be opened and sprinkled on soft food. Ability to perform tasks requiring mental alertness and/or physical coordination may be impaired. Take with food; drug may cause substantial increase in blood glucose in some diabetic patients.
(For additional information see "Acetazolamide: Patient drug information")

Acetaminophen, isometheptene, and dichloralphenazone

2008-01-23T09:34:00.000-08:00

U.S. BRAND NAMES — Amidrine [DSC]; Duradrin®; Midrin®; Migquin; Migratine; Migrazone®; Migrin-A
PHARMACOLOGIC CATEGORY Analgesic, Miscellaneous
DOSING: ADULTS Migraine headache: Oral: 2 capsules to start, followed by 1 capsule every hour until relief is obtained (maximum: 5 capsules/12 hours)
Tension headache: Oral: 1-2 capsules every 4 hours (maximum: 8 capsules/24 hours)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: Acetaminophen 325 mg, isometheptene mucate 65 mg, dichloralphenazone 100 mg Amidrine [DSC], Duradrin®, Midrin®, Migquin, Migrazone®, Migratine, Migrin-A: Acetaminophen 325 mg, isometheptene mucate 65 mg, and dichloralphenazone 100 mg
DOSAGE FORMS: CONCISE Capsule: Acetaminophen 325 mg, isometheptene 65 mg, dichloralphenazone 100 mg Duradrin®, Midrin®, Migquin, Migrazone®, Migratine, Migrin-A: Acetaminophen 325 mg, isometheptene 65 mg, and dichloralphenazone 100 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of migraine and tension headache
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Central nervous system: Transient dizziness
Dermatological: Rash
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, isometheptene, dichloralphenazone, or any component of the formulation; glaucoma; severe renal disease; hypertension; organic heart disease; hepatic disease; MAO inhibitor therapy
RESTRICTIONS — C-IV
DRUG INTERACTIONS Based on acetaminophen component: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak) Decreased effect: Barbiturates, carbamazepine, hydantoins, rifampin, sulfinpyrazone may decrease the analgesic effect of acetaminophen; cholestyramine may decrease acetaminophen absorption (separate dosing by at least 1 hour) Increased toxicity: Barbiturates, carbamazepine, hydantoins, isoniazid, rifampin, sulfinpyrazone may increase the hepatotoxic potential of acetaminophen; chronic ethanol abuse increases risk for acetaminophen toxicity; effect of warfarin may be enhanced
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — Acetaminophen and dichloralphenazone are excreted in breast milk; excretion of isometheptene is not known.
PRICING — (data from drugstore.com)Capsules (Amidrine) 325-65-100 mg (30): $13.99
Capsules (Migratine) 325-65-100 mg (100): $37.57
Capsules (Migrazone) 325-65-100 mg (100): $38.99

Acetaminophen, dextromethorphan, and pseudoephedrine

2008-01-23T09:31:00.000-08:00

SPECIAL ALERTS Infant Deaths Associated with Cough and Cold Medications - January 2007
The Centers for Disease Control and Prevention (CDC) has released a report concerning the use of cough and cold medications in children <2 years of age. Products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), cough suppressants (eg, dextromethorphan), and expectorants are often used in this age group. The CDC notes that during 2004 and 2005, ~ 1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with these medications.
During this time period, 3 infants <6 months of age died. All 3 had postmortem blood levels of pseudoephedrine, ranging from 4743-7100 ng/mL (therapeutic levels for children 2-12 years: 180-500 ng/mL). In addition, 2 of the 3 infants also had detectable levels of dextromethorphan. Although dextromethorphan has been shown to be effective to reduce cough in adults, the same efficacy has not been documented in young children. The American Academy of Pediatrics and the American College of Chest Physicians do not recommend the use of dextromethorphan for over-the-counter (OTC) use in young children.
Safety and efficacy for the use of cough and cold products in children <2 years of age is limited. The Food and Drug Administration (FDA) notes that there are no approved OTC uses for these products in children <2 years of age. Clinicians are reminded to ask caregivers about the use of OTC products in order to avoid exposure to multiple medications containing the same ingredient. Caregivers are reminded that OTC cough and cold products should not be used in children <2 years of age except under specific direction by their healthcare provider.
For additional information, refer to the following CDC website: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — Comtrex® Non-Drowsy Cold and Cough Relief [OTC] [DSC]; Infants' Tylenol® Cold Plus Cough Concentrated Drops [OTC] [DSC]; Sudafed® Severe Cold [OTC]; Triaminic® Cough and Sore Throat Formula [OTC] [DSC]; Tylenol® Cold Day Non-Drowsy [OTC]; Tylenol® Flu Non-Drowsy Maximum Strength [OTC]; Vicks® DayQuil® Multi-Symptom Cold and Flu [OTC] [DSC]
PHARMACOLOGIC CATEGORY AntihistamineAntitussive
DOSING: ADULTS Pain (Analgesic): Oral: Based on acetaminophen component: 325-650 mg every 4-7 hours as needed; do not exceed 4 g/day
Cough suppressant (Antitussive): Oral: Based on dextromethorphan component: 10-20 mg every 4-8 hours or 30 mg every 8 hours; do not exceed 120 mg/24 hours
Nasal congestion (Decongestant): Oral: Based on pseudoephedrine component: 60 mg every 4 hours (maximum: 360 mg/24 hours)
Product labeling:
Sudafed® Severe Cold, Tylenol® Flu Non-Drowsy Maximum Strength: Oral: 2 doses every 6 hours (maximum: 8 doses/24 hours)
Tylenol® Cold Non-Drowsy: Oral: 2 doses every 6 hours (maximum: 8 doses/24 hours)
DOSING: PEDIATRIC Analgesic: Oral: Based on acetaminophen component: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses/24 hours.
Cough suppressant: Oral: Based on dextromethorphan component: Children 6-12 years: 15 mg every 6-8 hours; do not exceed 60 mg/24 hours Children >12 years: Refer to adult dosing.
Decongestant: Oral: Based on pseudoephedrine component: Children: 2-6 years: 15 mg every 4 hours (maximum: 90 mg/24 hours) 6-12 years: 30 mg every 4 hours (maximum: 180 mg/24 hours) Children >12 years: Refer to adult dosing.
Product labeling:
Infants' Tylenol® Cold Plus Cough Concentrated Drops: Oral: Children 2-3 years (24-55 lb): 2 dropperfuls every 4-6 hours (maximum: 4 doses/24 hours)
Sudafed® Severe Cold, Thera-Flu® Non-Drowsy Maximum Strength (gelcap), Tylenol® Flu Non-Drowsy Maximum Strength: Oral: Children >12 years: Refer to adult dosing.
Tylenol® Cold Non-Drowsy: Oral: Children 6-11 years: 1 dose every 6 hours (maximum: 4 doses/24 hours) Children 12 years: Refer to adult dosing.
Thera-Flu® Non-Drowsy Maximum Strength: Oral: Children >12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet: Comtrex® Non-Drowsy Cold and Cough Relief: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and pseudoephedrine hydrochloride 30 mg [contains benzoic acid] [DSC] Tylenol® Cold Day Non-Drowsy: Acetaminophen 325 mg dextromethorphan hydrobromide 15 mg, and pseudoephedrine hydrochloride 30 mg
Capsule, liquid: Vicks® DayQuil® Multi-Symptom Cold and Flu: Acetaminophen 250 mg, dextromethorphan hydrobromide 10 mg, and pseudoephedrine hydrochloride 30 mg [DSC]
Gelcap: Tylenol® Cold Day Non-Drowsy: Acetaminophen 325 mg, dextromethorphan hydrobromide 15 mg, and pseudoephedrine hydrochloride 30 mg [contains benzyl alcohol] [DSC] Tylenol® Flu Non-Drowsy Maximum Strength: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and pseudoephedrine hydrochloride 30 mg
Liquid: Triaminic® Cough and Sore Throat Formula: Acetaminophen 160 mg, dextromethorphan hydrobromide 7.5 mg, and pseudoephedrine hydrochloride 15 mg per 5 mL (120 mL, 240 mL) [contains benzoic acid; grape flavor] [DSC] Vicks® DayQuil® Multi-Symptom Cold and Flu: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and pseudoephedrine hydrochloride 30 mg per 15 mL (175 mL) [DSC]
Suspension, oral [drops]: Infants' Tylenol® Cold Plus Cough Concentrated Drops: Acetaminophen 160 mg, dextromethorphan hydrobromide 5 mg, and pseudoephedrine hydrochloride 15 mg per 1.6 mL (15 mL) [1.6 mL = 2 dropperfuls] [cherry flavor] [DSC]
DOSAGE FORMS: CONCISE Caplet: Sudafed® Severe Cold [OTC], Tylenol® Cold Day Non-Drowsy [OTC]: Acetaminophen 325 mg, dextromethorphan 15 mg, and pseudoephedrine 30 mg
Gelcap: Tylenol® Flu Non-Drowsy Maximum Strength [OTC]: Acetaminophen 500 mg, dextromethorphan 15 mg, and pseudoephedrine 30 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of mild-to-moderate pain and fever; symptomatic relief of cough and congestion
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, dextromethorphan, pseudoephedrine, or any component of the formulation
DRUG INTERACTIONS Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Dextromethorphan: Substrate of CYP2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 2E1 (minor), 3A4 (minor); Inhibits CYP2D6 (weak)
Also see individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
CANADIAN BRAND NAMES — Contac® Complete; Contac® Cough, Cold and Flu Day & Night™; Sudafed® Cold & Cough Extra Strength; Tylenol® Cold Daytime
INTERNATIONAL BRAND NAMES — Contac Complete (CA); Contac Cough, Cold and Flu Day & Night® (CA); Sudafed Cold & Cough Extra Strength (CA); Tylenol Cold Daytime (CA)
PHARMACODYNAMICS / KINETICS — See individual agents.

Acetaminophen, codeine, and doxylamine

2008-01-23T09:29:00.000-08:00

PHARMACOLOGIC CATEGORY Analgesic, OpioidAntihistamine
DOSING: ADULTS — Oral: 1-2 tablets every 4 hours as needed; total dose should not exceed 12 tablets in a 24-hour period
DOSING: PEDIATRIC — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment required.
DOSING: HEPATIC IMPAIRMENT Acetaminophen: Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis. However, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
Codeine: Dosage adjustment of codeine is probably necessary in hepatic insufficiency; no specific guidelines available.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Tablet: Mersyndol® With Codeine [CAN]: Acetaminophen 325 mg, codeine 8 mg, and doxylamine 5 mg [not available in the U.S.]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Tablet: Mersyndol® With Codeine [CAN]: Acetaminophen 325 mg, codeine 8 mg, and doxylamine 5 mg [not available in the U.S.]
USE — Relief of headache, cold symptoms, neuralgia, and muscular aches/pain
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine, doxylamine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: Acetaminophen may cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
Disease-related concerns: Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension/hypotension and tachycardia). CNS depression/coma: Use with caution in patients with CNS depression or coma. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Ethanol use: Use with caution in patients with alcoholic liver disease; consuming 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Gastrointestinal motility disorders: Use with caution in patients with gastrointestinal motility disorders; avoid in paralytic ileus. Glaucoma: Use with caution in patients with angle-closure glaucoma and/or increased intraocular pressure. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Pyloroduodenal obstruction: Use with caution in patients with pyloroduodenal obstruction (including stenotic peptic ulcer). Seizure disorder: Use with caution in patients with a history of seizure disorder. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Pediatrics: Safety and efficacy have not been established in children <12 years of age. Surgical patients: Use with caution in postoperative patients following thoracotomy or laparotomy due to suppression of cough.
Other warnings/precautions: Dosage limit: Limit total acetaminophen dose to <4 g/day.
RESTRICTIONS — CDSA-1; Not available in U.S.
DRUG INTERACTIONS Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Codeine: Substrate of CYP2D6 (major), 3A4 (minor); Inhibits CYP2D6 (weak)
Anticholinergic agents: Central and/or peripheral anticholinergic syndrome can occur when administered with opioid analgesics, phenothiazines and other antipsychotics (especially with high anticholinergic activity), tricyclic antidepressants, quinidine and some other antiarrhythmics, and antihistamines.
Cholinergic agents: Drugs with high anticholinergic activity may antagonize the therapeutic effect of cholinergic agents; includes donepezil, rivastigmine, and tacrine.
CNS depressants: Sedative effects may be additive with CNS depressants; includes ethanol, benzodiazepines, barbiturates, opioid analgesics, and other sedative agents; monitor for increased effect.
CYP2D6 inhibitors: May decrease the effects of codeine. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.
Warfarin: The effect of warfarin may be enhanced.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol (may increase CNS depression).
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Should not be used in pregnancy unless the potential benefit to the mother justifies possible harm to the fetus.
LACTATION — No data available.
BREAST-FEEDING CONSIDERATIONS — Doxylamine may be excreted in breast milk, potentially resulting in sedative effects in nursing infants.
MONITORING PARAMETERS — Relief of pain, respiratory and mental status, blood pressure, bowel function
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of acetaminophen overdose include hepatic necrosis and blood dyscrasias, while opiate overdose may result in respiratory depression. Anticholinergic overdose may result in death, cardiopulmonary arrest, catatonic psychosis, CNS depression or stimulation, elevated CPK, mydriasis, seizures, rhabdomyolysis, or tachycardia.
Activated charcoal is effective at binding certain chemicals, and this is especially true for acetaminophen (use within 2 hours of ingestion).
Acetylcysteine 140 mg/kg orally (loading) followed by 70 mg/kg every 4 hours for 17 doses; therapy should be initiated based upon laboratory analysis suggesting high probability of hepatotoxic potential.
Naloxone 2 mg I.V. (0.01 mg/kg for children) with repeat administration as necessary up to a total of 10 mg; can also be used to reverse the toxic effects of the opiate.
CANADIAN BRAND NAMES — Mersyndol® With Codeine
INTERNATIONAL BRAND NAMES — Mersyndol With Codeine (CA)
MECHANISM OF ACTION — Acetaminophen inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center. Codeine binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough supression by direct central action in the medulla; produces generalized CNS depression. Doxylamine competes with histamine for H1-receptor sites on effector cells; blocks chemoreceptor trigger zone, diminishes vestibular stimulation, and depresses labyrinthine function through its central anticholinergic activity.
PHARMACODYNAMICS / KINETICS — See individual agents.

Acetaminophen, chlorpheniramine, and pseudoephedrine

2008-01-23T09:27:00.000-08:00

SPECIAL ALERTS Infant Deaths Associated with Cough and Cold Medications - January 2007
The Centers for Disease Control and Prevention (CDC) has released a report concerning the use of cough and cold medications in children <2 years of age. Products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), cough suppressants (eg, dextromethorphan), and expectorants are often used in this age group. The CDC notes that during 2004 and 2005, ~ 1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with these medications.
During this time period, 3 infants <6 months of age died. All 3 had postmortem blood levels of pseudoephedrine, ranging from 4743-7100 ng/mL (therapeutic levels for children 2-12 years: 180-500 ng/mL). In one case, the infant received both a prescription product containing pseudoephedrine and an over-the-counter (OTC) product, also containing pseudoephedrine. Alternatives to nasal decongestants in this age group may be softening nasal secretions with saline drops or a cool-mist humidifier and/or the removal of nasal secretions with the use of rubber suction bulb.
Safety and efficacy for the use of cough and cold products in children <2 years of age is limited. The Food and Drug Administration (FDA) notes that there are no approved OTC uses for these products in children <2 years of age. Clinicians are reminded to ask caregivers about the use of OTC products in order to avoid exposure to multiple medications containing the same ingredient. Caregivers are reminded that OTC cough and cold products should not be used in children <2 years of age except under specific direction by their healthcare provider.
For additional information, refer to the following CDC website: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — Actifed® Cold and Sinus [OTC]; Alka-Seltzer® Plus Cold Liqui-Gels® [OTC]; Comtrex® Flu Therapy Day/Night [OTC]; Comtrex® Flu Therapy Nighttime [OTC]; Drinex [OTC]; Kolephrin® [OTC]; Sinutab® Sinus Allergy Maximum Strength [OTC]; Tylenol® Allergy Complete [OTC] [DSC]; Tylenol® Children's Plus Cold Nighttime [OTC]
PHARMACOLOGIC CATEGORY Analgesic, MiscellaneousAntihistamine
DOSING: ADULTS Pain (Analgesic): Oral: Based on acetaminophen component: 325-650 mg every 4-6 hours as needed; do not exceed 4 g/day
Rhinitis (Antihistamine): Oral: Based on chlorpheniramine maleate component: 4 mg every 4-6 hours (maximum: 24 mg/24 hours)
Nasal congestion (Decongestant): Oral: Based on pseudoephedrine component: 60 mg every 4 hours (maximum: 360 mg/24 hours)
Product labeling:
Alka-Seltzer Plus® Cold Medicine Liqui-Gels®: Oral: 2 softgels every 4 hours with water (maximum: 4 doses/24 hours)
Sinutab® Sinus Allergy Maximum Strength: Oral: 2 tablets/caplets every 6 hours (maximum: 8 doses/24 hours)
DOSING: PEDIATRIC Analgesic: Oral: Based on acetaminophen component: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses in 24 hours.
Antihistamine: Oral: Based on chlorpheniramine maleate component: 2-6 years: 1 mg every 4-6 hours (maximum: 6 mg/24 hours) 6-12 years: 2 mg every 4-6 hours (maximum: 12 mg/24 hours) Children >12 years: Refer to adult dosing.
Decongestant: Oral: Based on pseudoephedrine component: 2-6 years: 15 mg every 4 hours (maximum: 90 mg/24 hours) 6-12 years: 30 mg every 4 hours (maximum: 180 mg/24 hours) Children >12 years: Refer to adult dosing.
Product labeling:
Alka-Seltzer Plus® Cold Medicine Liqui-Gels®: Oral: Children 6-12 years: 1 softgel every 4 hours with water (maximum: 4 doses/24 hours) Children >12 years: Refer to adult dosing.
Sinutab® Sinus Allergy Maximum Strength: Oral: Children >12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet: Acetaminophen 325 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg Actifed® Cold and Sinus, Sinutab® Sinus Allergy Maximum Strength, Tylenol® Allergy Complete [DSC]: Acetaminophen 500 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg Kolephrin®: Acetaminophen 325 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg
Capsule, softgel: Alka-Seltzer® Plus Cold Liqui-Gels®: Acetaminophen 325 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg [contains potassium 25 mg]
Combination package: (Comtrex® Flu Therapy Day/Night): Caplet [Daytime]: Acetaminophen 500 mg and pseudoephedrine hydrochloride 30 mg Caplet [Nighttime]: Acetaminophen 500 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg
Liquid: Comtrex® Flu Therapy Nighttime: Acetaminophen 100 mg, chlorpheniramine maleate 4 mg, and pseudoephedrine hydrochloride 60 mg per 30 mL (240 mL) [contains alcohol; cherry flavor] Tylenol® Children's Plus Cold Nighttime: Acetaminophen 160 mg, chlorpheniramine maleate 1 mg, and pseudoephedrine hydrochloride 15 mg per 5 mL (120 mL) [contains sodium benzoate; grape flavor]
Tablet: Drinex: Acetaminophen 650 mg, chlorpheniramine maleate 4 mg, and pseudoephedrine hydrochloride 60 mg
DOSAGE FORMS: CONCISE Caplet: Acetaminophen 325 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg Actifed® Cold and Sinus [OTC], Sinutab® Sinus Allergy Maximum Strength [OTC]: Acetaminophen 500 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg Kolephrin® [OTC]: Acetaminophen 325 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg
Capsule, softgel: Acetaminophen 325 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg Alka-Seltzer® Plus Cold Liqui-Gels® [OTC]: Acetaminophen 325 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg
Combination package: Acetaminophen 500 mg and pseudoephedrine 30 mg and acetaminophen 500 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg Comtrex® Flu Therapy Day/Night [OTC]: Caplet [Daytime]: Acetaminophen 500 mg and pseudoephedrine 30 mg Caplet [Nighttime]: Acetaminophen 500 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg
Liquid: Acetaminophen 100 mg, chlorpheniramine 4 mg, and pseudoephedrine 60 mg per 30 mL; acetaminophen 160 mg, chlorpheniramine 1 mg, and pseudoephedrine 15 mg per 5 mL Comtrex® Flu Therapy Nighttime [OTC]: Acetaminophen 100 mg, chlorpheniramine 4 mg, and pseudoephedrine 60 mg per 30 mL Tylenol® Children's Plus Cold Nighttime [OTC]: Acetaminophen 160 mg, chlorpheniramine 1 mg, and pseudoephedrine 15 mg per 5 mL
Tablet: Drinex: Acetaminophen 650 mg, chlorpheniramine maleate 4 mg, and pseudoephedrine hydrochloride 60 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Temporary relief of sinus symptoms
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
DRUG INTERACTIONS Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Chlorpheniramine: Substrate of CYP2D6 (minor), 3A4 (major); Inhibits CYP2D6 (weak)
Also see individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
PREGNANCY RISK FACTOR — B (show table)
DIETARY CONSIDERATIONS Children's Tylenol® Plus Cold contains phenylalanine 6 mg/tablet.
Thera-Flu® Cold and Sore Throat Night Time contains phenylalanine 11 mg/packet.
CANADIAN BRAND NAMES — Sinutab® Sinus & Allergy; Tylenol® Allergy Sinus
INTERNATIONAL BRAND NAMES — Sinutab Sinus & Allergy (CA); Tylenol Allergy Sinus (CA)
PHARMACODYNAMICS / KINETICS — See individual agents.

Acetaminophen, caffeine, and dihydrocodeine

2008-01-23T09:26:00.000-08:00

U.S. BRAND NAMES — Panlor® DC; Panlor® SS; ZerLor™
PHARMACOLOGIC CATEGORY Analgesic Combination (Opioid)
DOSING: ADULTS — Relief of pain: Oral:
Panlor® DC: 2 capsules every 4 hours as needed; adjust dose based on severity of pain (maximum dose: 10 capsules/24 hours)
Panlor® SS, ZerLor™: 1 tablet every 4 hours as needed; adjust dose based on severity of pain (maximum dose: 5 tablets/24 hours)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: Panlor® DC: Acetaminophen 356.4 mg, caffeine 30 mg, and dihydrocodeine bitartrate 16 mg
Tablet: Panlor® SS, ZerLor™: Acetaminophen 712.8 mg, caffeine 60 mg, and dihydrocodeine bitartrate 32 mg
DOSAGE FORMS: CONCISE Capsule: Panlor® DC: Acetaminophen 356.4 mg, caffeine 30 mg, and dihydrocodeine 16 mg
Tablet: Panlor® SS, ZerLor™: Acetaminophen 712.8 mg, caffeine 60 mg, and dihydrocodeine 32 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Tablet
USE — Relief of moderate to moderately-severe pain
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined. Most common reactions with this combination include:
Central nervous system: Dizziness, drowsiness, lightheadedness, sedation
Dermatologic: Pruritus, skin reactions
Gastrointestinal: Constipation, nausea, vomiting
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, caffeine, dihydrocodeine, codeine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia; paralytic ileus
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: Acetaminophen may cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
Disease-related concerns: Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. CNS depression/coma: Use with caution in patients with CNS depression or coma. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Ethanol use: Use with caution in patients with alcoholic liver disease; consuming 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Hepatic impairment: Use with caution in patients with severe hepatic impairment. Hypotension: Use with caution in patients with hypotension. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Renal impairment: Use with caution in patients with severe renal impairment. Respiratory disease: Use with caution in patients with respiratory diseases including asthma, emphysema, and/or COPD. Seizure disorder: Use with caution in patients with a history of seizure disorder. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues: MAO inhibitors: Use with caution with concurrent use of MAO inhibitors.
Special populations: Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Caffeine: May cause CNS and cardiovascular stimulation, as well as GI irritation in high doses. Use with caution in patients with a history of peptic ulcer or GERD; avoid in patients with symptomatic cardiac arrhythmias. Dosage limit: Limit total acetaminophen dose to <4 g/day.
RESTRICTIONS — C-III
DRUG INTERACTIONS Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Caffeine: Substrate of CYP1A2 (major), 2C9 (minor), 2D6 (minor), 2E1 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 3A4 (moderate)
Dihydrocodeine: Substrate of CYP2D6 (major)
Acetaminophen: See individual agents for associated interactions.
Caffeine: CYP1A2 inhibitors: May increase the levels/effects of caffeine. Example inhibitors include amiodarone, fluvoxamine, ketoconazole, and rofecoxib. CYP3A4 substrates: Caffeine may increase the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, ergot derivatives, mirtazapine, nateglinide, nefazodone, tacrolimus, and venlafaxine. Quinolone antibiotics (specifically ciprofloxacin, norfloxacin, ofloxacin): Quinolones may increase the level/effects of caffeine.
Dihydrocodeine: CYP2D6 inhibitors: May decrease the effects of dihydrocodeine. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole. Quinidine: Quinidine may decrease the effects of dihydrocodeine.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced toxicity. Ethanol may also increase CNS depression.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Reproduction studies have not been conducted with this combination.
LACTATION — Enters breast milk/not recommended
BREAST-FEEDING CONSIDERATIONS — Acetaminophen and caffeine are both excreted in breast milk. Specific information for dihydrocodeine is not available; however, similar agents (eg, codeine, morphine) are excreted in breast milk.
PRICING — (data from drugstore.com)Capsules (Panlor DC) 356.4-30-16 mg (30): $29.99
Tablets (Panlor SS) 712.8-60-32 mg (30): $45.36
MECHANISM OF ACTION Acetaminophen inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center.
Caffeine is a CNS stimulant; use with acetaminophen and dihydrocodeine increases the level of analgesia provided by each agent.
Dihydrocodeine binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression

Acetaminophen, aspirin, caffeine

2008-01-23T09:23:00.000-08:00

U.S. BRAND NAMES — Excedrin® Extra Strength [OTC]; Excedrin® Migraine [OTC]; Fem-Prin® [OTC]; Genaced™ [OTC]; Goody's® Extra Strength Headache Powder [OTC]; Goody's® Extra Strength Pain Relief [OTC]; Pain-Off [OTC]; Vanquish® Extra Strength Pain Reliever [OTC]
PHARMACOLOGIC CATEGORY Analgesic, Miscellaneous
DOSING: ADULTS Pain management: Based on acetaminophen component: Mild-to-moderate pain: Oral: 325-650 mg every 4-6 hours as needed; do not exceed 4 g/day Mild-to-moderate pain associated with migraine headache: Oral: 500 mg/dose (in combination with 500 mg aspirin and 130 mg caffeine) every 6 hours while symptoms persist; do not use for longer than 48 hours Based on aspirin component: Mild-to-moderate pain: Oral: 325-650 mg every 4-6 hours as needed; do not exceed 4 g/day Mild-to-moderate pain associated with migraine headache: Oral: 500 mg/dose (in combination with 500 mg acetaminophen and 130 mg caffeine) every 6 hours; do not use for longer than 48 hours
Product labeling:
Excedrin® Extra Strength, Excedrin® Migraine: Oral: 2 doses every 6 hours (maximum: 8 doses/24 hours) Note: When used for migraine, do not use for longer than 48 hours
Goody's® Extra Strength Headache Powder: Oral: 1 powder, placed on tongue or dissolved in water, every 4-6 hours (maximum: 4 powders/24 hours)
Goody's® Extra Strength Pain Relief Tablets: Oral: 2 tablets every 4-6 hours (maximum: 8 tablets/24 hours)
Vanquish® Extra Strength Pain Reliever: Oral: 2 tablets every 4 hours (maximum: 12 tablets/24 hours)
DOSING: PEDIATRIC Product labeling:
Excedrin® Extra Strength, Excedrin® Migraine: Oral: Children >12 years: Refer to adult dosing
Goody's® Extra Strength Headache Powder: Oral: Children >12 years: Refer to adult dosing
Goody's® Extra Strength Pain Relief Tablets: Oral: Children >12 years: Refer to adult dosing
Vanquish® Extra Strength Pain Reliever: Oral: Children >12 years: Refer to adult dosing
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis. However, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet: Excedrin® Extra Strength, Excedrin® Migraine: Acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg Vanquish® Extra Strength Pain Reliever: Acetaminophen 194 mg, aspirin 227 mg, and caffeine 33 mg
Geltab (Excedrin® Extra Strength, Excedrin® Migraine): Acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg
Powder (Goody's® Extra Strength Headache Powder): Acetaminophen 260 mg, aspirin 520 mg, and caffeine 32.5 mg [contains lactose]
Tablet: Excedrin® Extra Strength, Excedrin® Migraine, Genaced™, Pain-Off: Acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg Fem-Prin®: Acetaminophen 194.4 mg, aspirin 226.8 mg, and caffeine 32.4 mg Goody's® Extra Strength Pain Relief: Acetaminophen 130 mg, aspirin 260 mg, and caffeine 16.25 mg
DOSAGE FORMS: CONCISE Caplet: Acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg; acetaminophen 194 mg, aspirin 227 mg, and caffeine 33 mg Excedrin® Extra Strength [OTC], Excedrin® Migraine [OTC]: Acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg Vanquish® Extra Strength Pain Reliever [OTC]: Acetaminophen 194 mg, aspirin 227 mg, and caffeine 33 mg
Geltab: Acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg Excedrin® Extra Strength [OTC], Excedrin® Migraine [OTC]: Acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg
Powder: Acetaminophen 260 mg, aspirin 520 mg, and caffeine 32.5 mg Goody's® Extra Strength Headache Powder [OTC]: Acetaminophen 260 mg, aspirin 520 mg, and caffeine 32.5 mg
Tablet: Excedrin® Extra Strength [OTC], Excedrin® Migraine [OTC], Genaced™ [OTC], Pain-Off [OTC]: Acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg Fem-Prin® [OTC]: Acetaminophen 194.4 mg, aspirin 226.8 mg, and caffeine 32.4 mg Goody's® Extra Strength Pain Relief [OTC]: Acetaminophen 130 mg, aspirin 260 mg, and caffeine 16.25 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of mild-to-moderate pain; mild-to-moderate pain associated with migraine headache
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, aspirin, salicylates, caffeine, or any component of the formulation; pregnancy
DRUG INTERACTIONS Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Aspirin: Substrate (minor) of CYP2C9
Caffeine: Substrate of CYP1A2 (major), 2C9 (minor), 2D6 (minor), 2E1 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 3A4 (moderate)
Also see individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
PREGNANCY RISK FACTOR — D (show table)
PHARMACODYNAMICS / KINETICS — See individual agents.

Acetaminophen, aspirin, and caffeine

2008-01-20T05:09:00.000-08:00

Acetaminophen and pseudoephedrine

2008-01-20T05:07:00.001-08:00

SPECIAL ALERTS Infant Deaths Associated with Cough and Cold Medications - January 2007
The Centers for Disease Control and Prevention (CDC) has released a report concerning the use of cough and cold medications in children <2 years of age. Products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), cough suppressants (eg, dextromethorphan), and expectorants are often used in this age group. The CDC notes that during 2004 and 2005, ~ 1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with these medications.
During this time period, 3 infants <6 months of age died. All 3 had postmortem blood levels of pseudoephedrine, ranging from 4743-7100 ng/mL (therapeutic levels for children 2-12 years: 180-500 ng/mL). In one case, the infant received both a prescription product containing pseudoephedrine and an over-the-counter (OTC) product, also containing pseudoephedrine. Alternatives to nasal decongestants in this age group may be softening nasal secretions with saline drops or a cool-mist humidifier and/or the removal of nasal secretions with the use of rubber suction bulb.
Safety and efficacy for the use of cough and cold products in children <2 years of age is limited. The Food and Drug Administration (FDA) notes that there are no approved OTC uses for these products in children <2 years of age. Clinicians are reminded to ask caregivers about the use of OTC products in order to avoid exposure to multiple medications containing the same ingredient. Caregivers are reminded that OTC cough and cold products should not be used in children <2 years of age except under specific direction by their healthcare provider.
For additional information, refer to the following CDC website: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — Allerest® Allergy and Sinus Relief [OTC]; Genapap™ Sinus Maximum Strength [OTC]; Mapap Sinus Maximum Strength [OTC]; Medi-Synal [OTC]; Oranyl Plus [OTC]; Ornex® Maximum Strength [OTC]; Ornex® [OTC]; Sinus-Relief [OTC] [DSC]; Sudafed® Multi-Symptom Sinus and Cold [OTC]; Tylenol® Cold Daytime, Children's [OTC]; Tylenol® Cold, Infants [OTC]; Tylenol® Sinus Daytime [OTC]
PHARMACOLOGIC CATEGORY Alpha/Beta AgonistAnalgesic, Miscellaneous
DOSING: ADULTS Pain (Analgesic): Oral; Based on acetaminophen component: 325-650 mg every 4-6 hours as needed; do not exceed 4 g/day
Decongestant: Oral: Based on pseudoephedrine component: 60 mg every 4 hours; do not exceed 360 mg/day
Product labeling: Sudafed® Multi-Symptom Sinus and Cold: 2 capsules every 4-6 hours (maximum: 8 capsules/24 hours) Tylenol® Sinus Daytime: 2 caplets or gelcaps every 4-6 hours (maximum: 8 caplets or gelcaps/24 hours)
DOSING: PEDIATRIC Analgesic: Based on acetaminophen component: Oral: Children: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses in 24 hours
Decongestant: Based on pseudoephedrine component: Oral: Children: 2-6 years: 15 mg every 4 hours; do not exceed 90 mg/day 6-12 years: 30 mg every 4 hours; do not exceed 180 mg/day Children >12 years and Adults: Refer to adult dosing.
Product labeling:
Children's Tylenol® Cold Daytime: Children: 2-5 years (24-47 lb): 1 teaspoonful every 4-6 hours (maximum: 4 doses/24 hours) 6-11 years (48-95 lb): 2 teaspoonfuls every 4-6 hours (maximum: 4 doses/24 hours)
Infants' Tylenol® Cold: Children 2-3 years (24-35 lb): 1.6 mL every 4-6 hours (maximum: 4 doses/24 hours)
Sudafed® Multi-Symptom Sinus and Cold, Tylenol® Sinus Daytime: Children 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet: Allerest® Allergy and Sinus Relief, Ornex®: Acetaminophen 325 mg and pseudoephedrine hydrochloride 30 mg Genapap™ Sinus Maximum Strength, Mapap Sinus Maximum Strength, Ornex® Maximum Strength, Tylenol® Sinus Daytime: Acetaminophen 500 mg and pseudoephedrine hydrochloride 30 mg
Capsule, liquid: Sudafed® Multi-Symptom Sinus and Cold: Acetaminophen 325 mg and pseudoephedrine hydrochloride 30 mg [contains sodium 16 mg]
Gelcap: Tylenol® Sinus Daytime: Acetaminophen 500 mg and pseudoephedrine hydrochloride 30 mg
Liquid: Childrens Tylenol® Cold Daytime: Acetaminophen 160 mg and pseudoephedrine hydrochloride 15 mg per 5 mL (120 mL) [contains sodium benzoate; fruit flavor]
Liquid, oral [drops]: Infants Tylenol® Cold: Acetaminophen 80 mg and pseudoephedrine 7.5 mg per 0.8 mL [contains sodium benzoate; bubble gum flavor]
Tablet: Medi-Synal, Sinus-Relief [DSC]: Acetaminophen 325 mg and pseudoephedrine hydrochloride 30 mg Oranyl Plus: Acetaminophen 500 mg and pseudoephedrine hydrochloride 30 mg
DOSAGE FORMS: CONCISE Caplet: Allerest® Allergy and Sinus Relief, Ornex®: Acetaminophen 325 mg and pseudoephedrine hydrochloride 30 mg Genapap™ Sinus Maximum Strength, Mapap Sinus Maximum Strength, Ornex® Maximum Strength, Tylenol® Sinus Daytime: Acetaminophen 500 mg and pseudoephedrine hydrochloride 30 mg
Capsule, liquid: Sudafed® Multi-Symptom Sinus and Cold: Acetaminophen 325 mg and pseudoephedrine hydrochloride 30 mg
Gelcap: Tylenol® Sinus Daytime: Acetaminophen 500 mg and pseudoephedrine hydrochloride 30 mg
Liquid: Childrens Tylenol® Cold Daytime: Acetaminophen 160 mg and pseudoephedrine hydrochloride 15 mg per 5 mL
Liquid, oral [drops]: Infants Tylenol® Cold: Acetaminophen 80 mg and pseudoephedrine 7.5 mg per 0.8 mL
Tablet: Medi-Synal: Acetaminophen 325 mg and pseudoephedrine hydrochloride 30 mg Oranyl Plus: Acetaminophen 500 mg and pseudoephedrine hydrochloride 30 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of mild-to-moderate pain; relief of congestion
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
DRUG INTERACTIONS — Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Also see individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
DIETARY CONSIDERATIONS Sudafed® Multi-Symptom Sinus and Cold capsule contains acetaminophen 325 mg, pseudoephedrine hydrochloride 30 mg, and sodium 16 mg.
CANADIAN BRAND NAMES — Contac® Cold and Sore Throat, Non Drowsy, Extra Strength; Dristan® N.D., Extra Strength; Dristan® N.D.; Sinutab® Non Drowsy; Sudafed® Head Cold and Sinus Extra Strength; Tylenol® Decongestant; Tylenol® Sinus
INTERNATIONAL BRAND NAMES — Contac Cold and Sore Throat, Non Drowsy, Extra Strength (CA); Dristan N.D. (CA); Dristan N.D., Extra Strength (CA); Sinutab Non Drowsy (CA); Sudafed Head Cold and Sinus Extra Strength (CA); Tylenol Decongestant (CA); Tylenol Sinus (CA)
PHARMACODYNAMICS / KINETICS — See individual agents.

Acetaminophen and phenyltoloxamine

2008-01-20T05:06:00.001-08:00

U.S. BRAND NAMES — Aceta-Gesic [OTC]; Alpain; Dologesic®; Flextra 650; Flextra-DS; Genasec™ [OTC]; Hyflex-DS®; Lagesic™; Percogesic® [OTC]; Phenagesic [OTC]; Phenylgesic [OTC]; RhinoFlex 650; RhinoFlex™; Staflex
PHARMACOLOGIC CATEGORY Analgesic, Miscellaneous
DOSING: ADULTS Pain (Analgesic): Oral: Based on acetaminophen component: 325-650 mg every 4-6 hours as needed (maximum: 4 g/day)
Product-specific labeling: Oral: Flextra-650: 1/2-1 tablet every 6 hours (maximum: 4 tablets/day) Flextra-DS, Hyflex-DS®, RhinoFlex™, RhinoFlex™-650:1/2-1 tablet every 4 hours (maximum: 5 tablets/day) Percogesic®: 1-2 tablets every 4 hours (maximum: 8 tablets/24 hours)
DOSING: PEDIATRIC Analgesic: Oral: Based on acetaminophen component: 10-15 mg/kg/dose every 4-6 hours as needed (maximum: 5 doses/24 hours)
Product-specific labeling: Oral: Flextra-650: Children 6 to <12 years: 1/2 tablet every 6 hours (maximum: 2 tablets/day) Children 12 years: Refer to adults dosing. Flextra-DS, Hyflex-DS®, RhinoFlex™, RhinoFlex™-650: Children 6 to <12 years: 1/2 tablet every 4 hours (maximum: 2.5 tablets/day) Children 12 years : Refer to adults dosing. Percogesic®: Children 6-12 years: 1 tablet every 4 hours (maximum: 4 tablets/24 hours)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Specific dosing adjustment not available. Monitor renal function with severe impairment.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet: Alpain: Acetaminophen 500 mg and phenyltoloxamine citrate 60 mg Dologesic®: Acetaminophen 500 mg and phenyltoloxamine citrate 30 mg Staflex: Acetaminophen 500 mg and phenyltoloxamine citrate 55 mg
Caplet, extended release [scored]: Lagesic™: Acetaminphen 600 mg and phenyltoloxamine citrate 66 mg
Capsule: Dologesic®: Acetaminophen 500 mg and phenyltoloxamine citrate 30 mg
Liquid: Dologesic®: Acetaminophen 500 mg and phenyltoloxamine citrate 30 mg per 15 mL (180 mL)
Tablet: Acetaminophen 325 mg and phenyltoloxamine citrate 30 mg Aceta-Gesic, Genasec™, Percogesic®, Phenagesic, Phenylgesic: Acetaminophen 325 mg and phenyltoloxamine citrate 30 mg Flextra-650: Acetaminophen 650 mg and phenyltoloxamine citrate 60 mg Flextra-DS, Hyflex-DS®, RhinoFlex™: Acetaminophen 500 mg and phenyltoloxamine citrate 50 mg RhinoFlex™-650: Acetaminophen 650 mg and phenyltoloxamine citrate 50 mg
DOSAGE FORMS: CONCISE Caplet: Alpain: Acetaminophen 500 mg and phenyltoloxamine citrate 60 mg Dologesic®: Acetaminophen 500 mg and phenyltoloxamine citrate 30 mg Staflex: Acetaminophen 500 mg and phenyltoloxamine citrate 55 mg
Caplet, extended release [scored]: Lagesic™: Acetaminphen 600 mg and phenyltoloxamine citrate 66 mg
Capsule: Dologesic®: Acetaminophen 500 mg and phenyltoloxamine citrate 30 mg
Liquid: Dologesic®: Acetaminophen 500 mg and phenyltoloxamine citrate 30 mg per 15 mg
Tablet: Acetaminophen 325 mg and phenyltoloxamine citrate 30 mg Aceta-Gesic [OTC], Genasec™ [OTC], Percogesic® [OTC], Phenagesic [OTC], Phenylgesic [OTC]: Acetaminophen 325 mg and phenyltoloxamine citrate 30 mg Flextra-650: Acetaminophen 650 mg and phenyltoloxamine citrate 60 mg Flextra-DS, Hyflex-DS®, RhinoFlex™: Acetaminophen 500 mg and phenyltoloxamine citrate 50 mg RhinoFlex™-650: Acetaminophen 650 mg and phenyltoloxamine citrate 50 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Tablet
USE — Relief of mild pain
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, phenyltoloxamine, or any component of the formulation
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: May cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients.
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Glaucoma: Use with caution in patients with glaucoma. Hepatic impairment: Use with caution in patients with hepatic impairment. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Renal impairment: Use with caution in patients with renal impairment. Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages.
Special populations: Pediatrics: Safety and efficacy have not been established in children <6 years of age.
Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>3 days or for pain lasting >10 days in adults or >5 days in children.
DRUG INTERACTIONS — Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Refer to Acetaminophen monograph.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
Food: Rate of absorption may be decreased when given with food.
PREGNANCY RISK FACTOR — C (show table)
PRICING — (data from drugstore.com)Tablets (Flextra DS) 50-500 mg (30): $22.35
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Refer to Acetaminophen monograph.
MECHANISM OF ACTION — Acetaminophen inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center. Phenyltoloxamine is an antihistamine (H1-blocking agent) which acts primarily to inhibit secretions in the nose, mouth, and pharynx, as well as causing CNS depression.

Acetaminophen and diphenhydramine

2008-01-20T05:00:00.000-08:00

U.S. BRAND NAMES — Excedrin® P.M. [OTC]; Goody's PM® [OTC]; Legatrin PM® [OTC]; Percogesic® Extra Strength [OTC]; Tylenol® PM [OTC]; Tylenol® Severe Allergy [OTC]
PHARMACOLOGIC CATEGORY Analgesic, Miscellaneous
DOSING: ADULTS — Insomnia and pain: Oral: Adults: 50 mg of diphenhydramine HCl (76 mg diphenhydramine citrate) at bedtime or as directed by physician; do not exceed recommended dosage
DOSING: PEDIATRIC — Not for use in children <12 years of age.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Excedrin® P.M.: Acetaminophen 500 mg and diphenhydramine citrate 38 mg Legatrin PM®: Acetaminophen 500 mg and diphenhydramine hydrochloride 50 mg Percogesic® Extra Strength: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [also available in vanilla caplets] Tylenol® Severe Allergy: Acetaminophen 500 mg and diphenhydramine hydrochloride 12.5 mg
Gelcap: Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg
Geltab: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Excedrin® P.M.: Acetaminophen 500 mg and diphenhydramine citrate 38 mg Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg
Liquid: Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg per 15 mL (240 mL) [contains sodium benzoate; vanilla flavor]
Powder for oral solution: Goody's PM®: Acetaminophen 500 mg and diphenhydramine citrate 38 mg [contains potassium 41.9 mg and sodium 3.15 mg per powder]
Tablet: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Excedrin® P.M.: Acetaminophen 500 mg and diphenhydramine citrate 38 mg
DOSAGE FORMS: CONCISE Caplet: Acetaminophen 500 mg and diphenhydramine 25 mg Excedrin® P.M. [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg Legatrin PM® [OTC]: Acetaminophen 500 mg and diphenhydramine 50 mg Percogesic® Extra Strength [OTC], Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg Tylenol® Severe Allergy [OTC]: Acetaminophen 500 mg and diphenhydramine 12.5 mg
Gelcap: Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg
Geltab: Acetaminophen 500 mg and diphenhydramine 25 mg Excedrin® P.M. [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg
Liquid: Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg per 15 mL
Powder for oral solution: Goody's PM® [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg
Tablet: Acetaminophen 500 mg and diphenhydramine 25 mg Excedrin® P.M. [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes gelcap, powder, and liquid
USE — Aid in the relief of insomnia accompanied by minor pain
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
DRUG INTERACTIONS Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Diphenhydramine: Inhibits CYP2D6 (moderate)
Also see individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
PHARMACODYNAMICS / KINETICS — See individual agents.

Acetaminophen and codeine

2008-01-20T04:59:00.000-08:00

U.S. BRAND NAMES — Capital® and Codeine; Tylenol® With Codeine
PHARMACOLOGIC CATEGORY Analgesic, Opioid
DOSING: ADULTS — Doses should be adjusted according to severity of pain and response of the patient. Adult doses 60 mg codeine fail to give commensurate relief of pain but merely prolong analgesia and are associated with an appreciably increased incidence of side effects.
Cough (Antitussive): Oral: Based on codeine (15-30 mg/dose) every 4-6 hours (maximum: 360 mg/24 hours based on codeine component)
Pain (Analgesic): Oral: Based on codeine (30-60 mg/dose) every 4-6 hours (maximum: 4000 mg/24 hours based on acetaminophen component) 1-2 tablets every 4 hours to a maximum of 12 tablets/24 hours
DOSING: PEDIATRIC
(For additional information see "Acetaminophen and codeine: Pediatric drug information")Analgesic: Oral: Codeine: 0.5-1 mg codeine/kg/dose every 4-6 hours Acetaminophen: 10-15 mg/kg/dose every 4 hours up to a maximum of 2.6 g/24 hours for children <12>12 years: 15 mL every 4 hours as needed of elixir
DOSING: ELDERLY — Doses should be titrated to appropriate analgesic effect.
1 Tylenol® [#3] or 2 Tylenol® [#2] tablets every 4 hours; do not exceed 4 g/day acetaminophen.
DOSING: RENAL IMPAIRMENT — See individual agents.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name
Caplet: ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.]
Elixir, oral [C-V]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (5 mL, 10 mL, 12.5 mL, 15 mL, 120 mL, 480 mL) [contains alcohol 7%] Tylenol® with Codeine [DSC]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [contains alcohol 7%; cherry flavor] Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine phosphate 8 mg per 5 mL (500 mL) [contains alcohol 7%, sucrose 31%; cherry flavor; not available in the U.S.]
Suspension, oral [C-V] (Capital® and Codeine): Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [alcohol free; fruit punch flavor]
Tablet [C-III]: Acetaminophen 300 mg and codeine phosphate 15 mg; acetaminophen 300 mg and codeine phosphate 30 mg; acetaminophen 300 mg and codeine phosphate 60 mg ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine phosphate 30 mg [not available in the U.S.] ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 2 [CAN], Tylenol No. 2 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 15 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 3 [CAN], Tylenol No. 3 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 30 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 4 [CAN], Tylenol No. 4 with Codeine [CAN]: Acetaminophen 300 mg and codeine phosphate 60 mg [not available in the U.S.] Triatec-8 [CAN]: Acetaminophen 325 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.] Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine phosphate 30 mg [contains sodium metabisulfite] Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine phosphate 60 mg [contains sodium metabisulfite]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Caplet: ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine 8 mg, and caffeine 15 mg [not available in the U.S.] Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine 8 mg, and caffeine 15 mg [not available in the U.S.]
Elixir, oral [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine 8 mg per 5 mL [not available in the U.S.]
Suspension, oral [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL Capital® and Codeine [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL
Tablet [C-III]: Acetaminophen 300 mg and codeine 15 mg; acetaminophen 300 mg and codeine 30 mg; acetaminophen 300 mg and codeine 60 mg ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine 30 mg [not available in the U.S.] ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine 8 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 2 [CAN], Tylenol No. 2 with Codeine [CAN]: Acetaminophen 300 mg, codeine 15 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 3 [CAN], Tylenol No. 3 with Codeine [CAN]: Acetaminophen 300 mg, codeine 30 mg, and caffeine 15 mg [not available in the U.S.] ratio-Lenoltec No. 4 [CAN], Tylenol No. 4 with Codeine [CAN]: Acetaminophen 300 mg and codeine 60 mg [not available in the U.S.] Triatec-8 [CAN]: Acetaminophen 325 mg, codeine 8 mg, and caffeine 30 mg [not available in the U.S.] Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine 8 mg, and caffeine 30 mg [not available in the U.S.] Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine 30 mg Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine 60 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of mild-to-moderate pain
ADVERSE REACTIONS SIGNIFICANT >10%: Central nervous system: Lightheadedness, dizziness, sedation Gastrointestinal: Nausea, vomiting Respiratory: Dyspnea
1% to 10%: Central nervous system: Euphoria, dysphoria Dermatologic: Pruritus Gastrointestinal: Constipation, abdominal pain Miscellaneous: Histamine release
<1% (Limited to important or life-threatening): Antidiuretic hormone release, biliary tract spasm, bradycardia, hypotension, intracranial pressure increased, physical and psychological dependence, respiratory depression, urinary retention
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia; paralytic ileus
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: May cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
Disease-related concerns: Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions. Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. CNS depression/coma: Use with caution in patients with CNS depression or coma. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Ethanol use: Use with caution in patients with alcoholic liver disease; consuming 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Hepatic impairment: Use with caution in patients with severe hepatic impairment. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Renal impairment: Use with caution in patients with renal impairment. Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages. Seizure disorder: Use with caution in patients with a history of seizure disorder. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose.
Dosage form specific issues: Metabisulfite: Tablets contain metabisulfite which may cause allergic reactions. Non-U.S. formulations: Some non-U.S. formulations (including most Canadian formulations) may contain caffeine as an additional ingredient. Caffeine may cause CNS and cardiovascular stimulation, as well as GI irritation in high doses. Use with caution in patients with a history of peptic ulcer or GERD; avoid in patients with symptomatic cardiac arrhythmias.
Other warnings/precautions: Dosage limit: Limit total acetaminophen dose to <4 g/day. Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms.
RESTRICTIONS — C-III; C-V
Note: In countries outside of the U.S., some formulations of Tylenol® with Codeine (eg, Tylenol® No. 3) include caffeine.
DRUG INTERACTIONS — Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Increased toxicity: CNS depressants, phenothiazines, tricyclic antidepressants, guanabenz, MAO inhibitors (may also decrease blood pressure); effect of warfarin may be enhanced.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Enters breast milk/use caution
DIETARY CONSIDERATIONS — May be taken with food.
PRICING — (data from drugstore.com)Solution (Acetaminophen-Codeine) 120-12 mg/5 mL (118): $8.99 120-12 mg/5 mL (240): $8.98
Tablets (Acetaminophen-Codeine #2) 300-15 mg (30): $7.99
Tablets (Acetaminophen-Codeine #3) 300-30 mg (30): $7.99
Tablets (Acetaminophen-Codeine #4) 300-60 mg (30): $11.99
Tablets (Tylenol/Codeine #3) 300-30 mg (30): $17.69
Tablets (Tylenol/Codeine #4) 300-60 mg (30): $30.54
MONITORING PARAMETERS — Relief of pain, respiratory and mental status, blood pressure, bowel function
TOXICOLOGY / OVERDOSE COMPREHENSIVE Symptoms include hepatic necrosis, blood dyscrasias, respiratory depression.
Acetylcysteine 140 mg/kg orally (loading) followed by 70 mg/kg every 4 hours for 17 doses; therapy should be initiated based upon laboratory analysis suggesting high probability of hepatotoxic potential.
Naloxone 2 mg I.V. (0.01 mg/kg for children) with repeat administration as necessary up to a total of 10 mg; can also be used to reverse the toxic effects of the opiate.
Activated charcoal is effective at binding certain chemicals, and this is especially true for acetaminophen (use within 2 hours of ingestion).
CANADIAN BRAND NAMES — ratio-Emtec; ratio-Lenoltec; Triatec-30; Triatec-8 Strong; Triatec-8; Tylenol Elixir with Codeine; Tylenol No. 1 Forte; Tylenol No. 1; Tylenol No. 2 with Codeine; Tylenol No. 3 with Codeine; Tylenol No. 4 with Codeine
INTERNATIONAL BRAND NAMES — Algesidal (FR); Algimide (CO); Algimide F (CO); Chemists Own Dolased Day Pain Relief (AU); Claradol Codeine (FR); Co-Cadamol (SG); Cod-Acamol Forte (IL); Codabrol (IL); Codalgin (AU, NZ); Codapane (AU); Codeidol (CO); Codeidol F (CO); Codeipar (CL); Codicet (TH); Codilprane Enfant (FR); Codipar (GB, IE); Coditam (ID); Codoliprane (FR); Codoliprane Enfant (FR); Codral Pain Relief (AU); Dafalgan Codeine (FR); Dolorol Forte (ZA); Dymadon Co (AU, NZ); Dymadon Forte (AU); Efferalgan Codeine (PY); Febricod (AU); Liquigesic Co (AU); Maxadol (ZA); Nasa w/codeine (TH); Paceco (MY, SG); Panadeine (AN, AU, BB, BM, BS, BZ, CZ, GY, HK, HU, JM, MY, NZ, SR, TT); Panadeine Co (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Panadeine Forte (AU); Panadiene (AN, AU, BB, BM, BS, BZ, CZ, GY, HK, HU, JM, JP, MY, NZ, SR, TT); Panado-Co Caplets (ZA); Panadol Ultra (HK); Panamax (AU); Paracodol (ZA); Paradine (MY); Paramax (EE); Parcono (TH); Parcoten (HK); Perdolan codeine (BE); Prodeine Forte (AU); Prodeine-15 (AU); ratio-Emtec (CA); ratio-Lenoltec (CA); Rokamol Plus (IL); Solpadeine (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Solpadol (GB, IE); Triatec-30 (CA); Triatec-8 (CA); Triatec-8 Strong (CA); TWC 30 (IN); Tylenol Elixir with Codeine (CA); Tylenol No. 1 (CA); Tylenol No. 1 Forte (CA); Tylenol No. 2 with Codeine (CA); Tylenol No. 3 with Codeine (CA); Tylenol No. 4 with Codeine (CA); Tylex CD (CR, DO, GT, HN, MX, NI, PA, SV); Winadol Forte (CO); Zapain (GB, IE)
MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center; binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough supression by direct central action in the medulla; produces generalized CNS depression. Caffeine (contained in some non-U.S. formulations) is a CNS stimulant; use with acetaminophen and codeine increases the level of analgesia provided by each agent.
PHARMACODYNAMICS / KINETICS — See individual agents.

Acetaminophen

2008-01-20T04:55:00.000-08:00

(For additional information see "Acetaminophen: Patient drug information" and see "Acetaminophen: Pediatric drug information")
U.S. BRAND NAMES — Acephen™ [OTC]; Apra Children's [OTC]; Aspirin Free Anacin® Maximum Strength [OTC]; Cetafen Extra® [OTC]; Cetafen® [OTC]; Comtrex® Sore Throat Maximum Strength [OTC]; FeverALL® [OTC]; Genapap™ Children [OTC]; Genapap™ Extra Strength [OTC]; Genapap™ Infant [OTC]; Genapap™ [OTC]; Genebs Extra Strength [OTC]; Genebs [OTC]; Infantaire [OTC]; Mapap Children's [OTC]; Mapap Extra Strength [OTC]; Mapap Infants [OTC]; Mapap [OTC]; Nortemp Children's [OTC]; Pain Eze [OTC]; Silapap® Children's [OTC]; Silapap® Infants [OTC]; Tycolene Maximum Strength [OTC]; Tycolene [OTC]; Tylenol® 8 Hour [OTC]; Tylenol® Arthritis Pain [OTC]; Tylenol® Children's with Flavor Creator [OTC]; Tylenol® Children's [OTC]; Tylenol® Extra Strength [OTC]; Tylenol® Infants [OTC]; Tylenol® Junior [OTC]; Tylenol® [OTC]; Valorin Extra [OTC]; Valorin [OTC]
PHARMACOLOGIC CATEGORY Analgesic, Miscellaneous
DOSING: ADULTS — Pain or fever: Oral, rectal: 325-650 mg every 4-6 hours or 1000 mg 3-4 times/day; do not exceed 4 g/day.
DOSING: PEDIATRIC — Pain or fever: Oral, rectal: Children <12 years: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses (2.6 g) in 24 hours; alternatively, the following doses may be used; see table.
(For additional information see "Acetaminophen: Pediatric drug information")
Acetaminophen Dosing 0-3 months: 40 mg 4-11 months: 80 mg 1-2 years: 120 mg 2-3 years: 160 mg 4-5 years: 240 mg 6-8 years: 320 mg 9-10 years: 400 mg 11 years: 480 mg
Note: Higher rectal doses have been studied for use in preoperative pain control in children. However, specific guidelines are not available and dosing may be product dependent. The safety and efficacy of alternating acetaminophen and ibuprofen dosing has not been established.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Clcr 10-50 mL/minute: Administer every 6 hours.
Clcr <10 mL/minute: Administer every 8 hours (metabolites accumulate).
Moderately dialyzable (20% to 50%)
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis. However, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet: 500 mg Cetafen Extra® Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Tycolene Maximum Strength, Tylenol® Extra Strength: 500 mg
Caplet, extended release: Tylenol® 8 Hour, Tylenol® Arthritis Pain: 650 mg
Capsule: 500 mg
Elixir: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) Apra Children's: 160 mg/5 mL (120 mL, 480 mL, 3780 mL) [alcohol free; contains benzoic acid; cherry and grape flavors] Mapap Children's: 160 mg/5 mL (120 mL) [alcohol free; contains benzoic acid and sodium benzoate; cherry flavor]
Gelcap: Mapap Extra Strength, Tylenol® Extra Strength: 500 mg
Geltab: Tylenol® Extra Strength: 500 mg
Geltab, extended release: Tylenol® 8 Hour: 650 mg [DSC]
Liquid, oral: 500 mg/15 mL (240 mL) Comtrex® Sore Throat Maximum Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; honey lemon flavor] Genapap™ Children: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry and grape flavors] Silapap®: 160 mg/5 mL (120 mL, 240 mL, 480 mL) [sugar free; contains sodium benzoate; cherry flavor] Tylenol® Extra Strength: 500 mg/15 mL (240 mL) [contains sodium benzoate; cherry flavor]
Solution, oral: 160 mg/5 mL (120 mL, 480 mL)
Solution, oral [drops]: 80 mg/0.8 mL (15 mL) [droppers are marked at 0.4 mL (40 mg) and at 0.8 mL (80 mg)] Genapap™ Infant: 80 mg/0.8 mL (15 mL) [fruit flavor] Infantaire: 80 mg/0.8mL (15 mL, 30 mL) Silapap® Infant's: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor]
Suppository, rectal: 120 mg, 325 mg, 650 mg Acephen™: 120 mg, 325 mg, 650 mg FeverALL®: 80 mg, 120 mg, 325 mg, 650 mg Mapap: 125 mg, 650 mg
Suspension, oral: Mapap Children's: 160 mg/5 mL (120 mL) [contains sodium benzoate; cherry flavor] Nortemp Children's: 160 mg/5 mL (120 mL) [alcohol free; contains sodium benzoate; cotton candy flavor] Tylenol® Children's: 160 mg/5 mL (120 mL, 240 mL) [contains sodium benzoate; bubble gum yum, cherry blast, dye free cherry, grape splash, and very berry strawberry flavors] Tylenol® Children's with Flavor Creator: 160 mg/5 mL (120 mL) [contains sodium 2 mg/5 mL and sodium benzoate; cherry blast flavor; packaged with apple (4), bubblegum (8), chocolate (4), & strawberry (4) sugar free flavor packets]
Suspension, oral [drops]: Mapap Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry flavor] Tylenol® Infants: 80 mg/0.8 mL (15 mL, 30 mL) [contains sodium benzoate; cherry, dye free cherry, and grape flavors]
Tablet: 325 mg, 500 mg Aspirin Free Anacin® Extra Strength, Genapap™ Extra Strength, Genebs Extra Strength, Mapap Extra Strength, Pain Eze, Tylenol® Extra Strength, Valorin Extra: 500 mg Cetafen®, Genapap™, Genebs, Mapap, Tycolene, Tylenol®, Valorin: 325 mg
Tablet, chewable: 80 mg Genapap™ Children: 80 mg [contains phenylalanine 6 mg/tablet; fruit and grape flavors] Mapap Children's: 80 mg [contains phenylalanine 3 mg/tablet; bubble gum, fruit, and grape flavors] Mapap Junior Strength: 160 mg [contains phenylalanine 12 mg/tablet; grape flavor]
Tablet, orally disintegrating: 80 mg, 160 mg Tylenol® Children's Meltaways: 80 mg [bubble gum, grape, and watermelon flavors] Tylenol® Junior Meltaways: 160 mg [bubble gum and grape flavors]
DOSAGE FORMS: CONCISE Caplet: 500 mg Cetafen Extra® Strength [OTC], Genapap™ Extra Strength [OTC], Genebs Extra Strength [OTC], Mapap Extra Strength [OTC], Tycolene Maximum Strength [OTC], Tylenol® Extra Strength [OTC]: 500 mg
Caplet, extended release: Tylenol® 8 Hour [OTC], Tylenol® Arthritis Pain [OTC]: 650 mg
Capsule: 500 mg
Elixir: 160 mg/5 mL Apra Children's [OTC]: 160 mg/5 mL Mapap Children's [OTC]: 160 mg/5 mL
Gelcap: 500 mg Mapap Extra Strength [OTC], Tylenol® Extra Strength [OTC]: 500 mg
Geltab: 500 mg Tylenol® Extra Strength [OTC]: 500 mg
Liquid, oral: 500 mg/15 mL Comtrex® Sore Throat Maximum Strength [OTC], Tylenol® Extra Strength [OTC]: 500 mg/15 mL Genapap™ Children [OTC], Silapap® [OTC]: 160 mg/5 mL
Solution, oral: 160 mg/5 mL
Solution, oral [drops]: 80 mg/0.8 mL Genapap™ Infant [OTC], Infantaire [OTC], Silapap® Infant's [OTC]: 80 mg/0.8 mL
Suppository, rectal: 120 mg, 325 mg, 650 mg Acephen® [OTC]: 120 mg, 325 mg, 650 mg FeverALL® [OTC]: 80 mg, 120 mg, 325 mg, 650 mg Mapap [OTC]: 125 mg, 650 mg
Suspension, oral: 160 mg/5 mL Mapap Children's [OTC], Nortemp Children's [OTC], Tylenol® Children's [OTC], Tylenol® Children's with Flavor Creator [OTC]: 160 mg/5 mL
Suspension, oral [drops]: 80 mg/0.8 mL Mapap Infants [OTC], Tylenol® Infants [OTC]: 80 mg/0.8 mL
Tablet: 325 mg, 500 mg Aspirin Free Anacin® Extra Strength [OTC], Genapap™ Extra Strength [OTC], Genebs Extra Strength [OTC], Mapap Extra Strength [OTC], Redutemp® [OTC], Tylenol® Extra Strength [OTC], Valorin Extra [OTC]: 500 mg Cetafen® [OTC], Genapap™ [OTC], Genebs [OTC], Mapap [OTC], Tylenol® [OTC], Valorin [OTC]: 325 mg
Tablet, chewable: 80 mg Genapap™ Children [OTC], Mapap Children's [OTC]: 80 mg Mapap Junior Strength [OTC]: 160 mg
Tablet, orally disintegrating: 80 mg, 160 mg Tylenol® Children's Meltaways [OTC]: 80 mg Tylenol® Junior Meltaways [OTC]: 160 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes extended release products
ADMINISTRATION Suppositories: Do not freeze.
Suspension, oral: Shake well before pouring a dose.
USE — Treatment of mild-to-moderate pain and fever (antipyretic/analgesic); does not have antirheumatic or anti-inflammatory effects
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Dermatologic: Rash
Endocrine & metabolic: May increase chloride, uric acid, glucose; may decrease sodium, bicarbonate, calcium
Hematologic: Anemia, blood dyscrasias (neutropenia, pancytopenia, leukopenia)
Hepatic: Bilirubin increased, alkaline phosphatase increased
Renal: Ammonia increased, nephrotoxicity with chronic overdose, analgesic nephropathy
Miscellaneous: Hypersensitivity reactions (rare)
CONTRAINDICATIONS — Hypersensitivity to acetaminophen or any component of the formulation
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Hepatotoxicity: May cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients.
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency.
Other warnings/precautions: Dosage limit: Limit dose to <4>3 days or for pain lasting >10 days in adults or >5 days in children.
DRUG INTERACTIONS — Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Decreased effect: Barbiturates, carbamazepine, hydantoins, rifampin, sulfinpyrazone may decrease the analgesic effect of acetaminophen. Cholestyramine may decrease acetaminophen absorption (separate dosing by at least 1 hour).
Increased toxicity: Barbiturates, carbamazepine, hydantoins, isoniazid, rifampin, sulfinpyrazone may increase the hepatotoxic potential of acetaminophen. Chronic ethanol abuse increases risk for acetaminophen toxicity; effect of warfarin may be enhanced.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
Food: Rate of absorption may be decreased when given with food.
Herb/Nutraceutical: St John's wort may decrease acetaminophen levels.
PREGNANCY RISK FACTOR — B (show table)
LACTATION — Enters breast milk/compatible
DIETARY CONSIDERATIONS — Chewable tablets may contain phenylalanine (amount varies, ranges between 3-12 mg/tablet); consult individual product labeling.
PRICING — (data from drugstore.com)Tablets (Tylenol) 325 mg (30): $7.99 500 mg (30): $7.99
MONITORING PARAMETERS — Relief of pain or fever
REFERENCE RANGE Therapeutic concentration (analgesic/antipyretic): 10-30 mcg/mL
Toxic concentration (acute ingestion) with probable hepatotoxicity: >200 mcg/mL at 4 hours or 50 mcg/mL at 12 hours after ingestion
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include hepatic necrosis, transient azotemia, renal tubular necrosis with acute toxicity, anemia, and GI disturbances with chronic toxicity. Acetylcysteine 140 mg/kg orally (loading) followed by 70 mg/kg every 4 hours for 17 doses. Therapy should be initiated based upon laboratory analysis suggesting high probability of hepatotoxic potential. Activated charcoal is very effective at binding acetaminophen.
CANADIAN BRAND NAMES — Abenol®; Apo-Acetaminophen®; Atasol®; Novo-Gesic; Pediatrix; Tempra®; Tylenol®
INTERNATIONAL BRAND NAMES — A-Mol (TH); Abenol (CA); Acamol (CL, IL); Acamoli Baby (IL); Acamoli Forte suppositories for Kids (IL); Acenol (PL); Acet (MY, PH); ACET suppositories (SG); Acetalgin (CH); Acetamol (IT); Adorem (CO); Afebrin (HK, ID); Alvedon (SE); Amol (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Anadin (PL); Anadin dla dzieci (PL); Analgiser (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Antidol (PL); APAP (PL); Apo-Acetaminophen (CA); Arfen (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, MY, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Atamel (PE); Atasol (CA); Ben-U-Ron (PT); Benuron (JP, PL); Biogesic (ID, PH, TH); Biogesic Suspension (HK); Bodrex (ID); Calapol (ID); Calodol (PH); Calpol (AE, AN, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IE, IN, IQ, IR, JM, JO, JP, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, PL, QA, SA, SC, SD, SL, SN, SR, SY, TH, TT, TZ, UG, YE, ZM, ZW); Causalon (AR); Cemol (TH); Christamol (HK); Claradol (MA); Codipar (PL); Crocin (IN); Dafalgan (PL); Daga (TH); Denamol (TH); Dirox (AR); Dismifen (MX); Dolex (UY); Doliprane (FR, MA, PL); Dolitabs (FR); Dolofen (CO); Dolomol (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Dolorol (ZA); Dolotemp (MX); Dymadon (AU); Efferalgan (PL); Efferalgan 500 (CR, DO, EE, GT, HN, NI, PA, SV); Efferalganodis (FR); Eraldor (EC); Etoran (PL); Europain (HK); Expandol (FR); Febridol (AU); Fepril (MY); Fervex (BR); Fortolin (CN); Gelocatil (ES); Geluprane 500 (FR); Grippostad (PL); Gunaceta (ID); Itamol (ID); Itamol Forte (ID); Kamolas (ID); Kyofen (CO); Lekadol (HR, PL); Lemgrip (BE); Lexalgin (PH); Lotemp (TH); Lupocet (HR); Maganol (ID); Malidens (IN); Mebinol (PE); Medgenol (PH); Metagesic (PH); Mexalen (AT, CZ, HU); Milidon 500 (SG); Minopan (KR); Mypara (TH); Nalgesik (ID); Napamol (ZA); Naprex (ID); NEBS (JP); Nektol 500 (PH); Nilapur (ID); Novo-Gesic (CA, PL); Pacimol (IN); Pamol (DK, NZ); Panadol (AE, AU, BE, BF, BG, BH, BJ, CH, CI, CL, CY, EE, EG, ET, FI, FR, GB, GH, GM, GN, GR, HK, ID, IE, IL, IQ, IR, JO, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NL, NZ, OM, PK, PL, QA, SA, SC, SD, SL, SN, SY, TH, TW, TZ, UG, UY, YE, ZM, ZW); Panadol Actifast (MY, SG); Panadon (HR); Panamax (AU); Panodil (DK, NO, SE); Paracemol (PL); Paracenol (PL); Paracet (NO); Paracetamol (HR, PL); Parageniol (PY); Paragin (TH); Paralief (IE); Paramidol (PE); Paramol (IL, PL, TW); Parapaed (DE); Parapaed Junior (NZ); Parapaed Six Plus (NZ); Paratabs (NZ); Parcemol (HK); Parcemol Forte (HK); Parvid (PH); Paximol (SG); Pediatrix (CA); Pedipan (KR); Penral-Night (KR); Perfalgan (PL); Pinex (NO); Plicet (HR, PL); Poro (MY); Puernol (IT); Raperon (KR); Rapidol (CL); Reliv (SE); Remedol (AN, BB, BM, BS, BZ, GY, JM, SR, TT); Revanin (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Rhinapen elixir (KR); Salzone (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Saridon (CO); Sensamol (IL); Serimol (HK); Sinedol (DO); Stone (TW); Suspen ER (KR); Tabcin (PL); Tamifen (EC); Tazamol (PL); Tempra (BE, CA, EC, ES, GR, ID, JP, TH); Tempte (TW); Temzzard (MX); Turpan (ID); Tylenol (AT, AU, BG, BR, CA, CH, CN, DE, ES, FR, JP, KR, MX, PH, PT, TH, VE); Tylenol Extra Fuerte (PY); Tylenol Forte (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, PL, QA, SA, SY, YE); Tylex (CR, DO, GT, HN, NI, PA, SV); Winadol (CO, VE); Xebramol (TH); Zydinol (PH)
MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center
PHARMACODYNAMICS / KINETICS Onset of action: <1 hour
Duration: 4-6 hours
Absorption: Incomplete; varies by dosage form
Protein binding: 8% to 43% at toxic doses
Metabolism: At normal therapeutic dosages, hepatic to sulfate and glucuronide metabolites, while a small amount is metabolized by CYP to a highly reactive intermediate (acetylimidoquinone) which is conjugated with glutathione and inactivated; at toxic doses (as little as 4 g daily) glutathione conjugation becomes insufficient to meet the metabolic demand causing an increase in acetylimidoquinone concentration, which may cause hepatic cell necrosis
Half-life elimination: Prolonged following toxic doses Neonates: 2-5 hours Adults: 1-3 hours (may be increased in elderly; however, this should not affect dosing)
Time to peak, serum: Oral: 10-60 minutes; may be delayed in acute overdoses
Excretion: Urine (2% to 5% unchanged; 55% as glucuronide metabolites; 30% as sulphate metabolites)

Acenocoumarol

2008-01-20T04:53:00.000-08:00

PHARMACOLOGIC CATEGORY Anticoagulant, Coumarin Derivative
DOSING: ADULTS — Note: Dosage must be individualized. The following information is based on the manufacturer's labeling in Canada.
Oral: Initial: 8-12 mg on day 1, followed by 4-8 mg on day 2. Subsequent dosage should be based on PT/INR measurements. Usual range of maintenance doses: 1-10 mg/day. Tapering of dosage is recommended prior to discontinuation.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Tablet: Sintrom® [CAN]: 1 mg, 4 mg [not available in the U.S.]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Tablet: Sintrom® [CAN]: 1 mg, 4 mg [not available in the U.S.]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer at the same time each day.
USE — Prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders; atrial fibrillation with risk of embolism; adjunct in the prophylaxis of coronary occlusion and transient ischemic attacks
ADVERSE REACTIONS SIGNIFICANT — As with all anticoagulants, bleeding is the major adverse effect of acenocoumarol. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the intensity of anticoagulation and patient susceptibility.
Frequency not defined. Cardiovascular: Hemorrhagic shock Central nervous system: Fever, headache, stroke (hemorrhagic) Dermatologic: Rash, urticaria, skin necrosis Skin necrosis/gangrene, due to paradoxical local thrombosis, is a known but rare risk of oral anticoagulant therapy. Its onset is usually within the first few days of therapy and is frequently localized to the limbs, breast, or penis. The risk of this effect is increased in patients with protein C or S deficiency.
Additional adverse reactions associated with warfarin, but likely to also occur with indanediones, include priapism and skin necrosis ("purple toe" syndrome or cutaneous gangrene). Gastrointestinal: Gastrointestinal bleeding, melena Genitourinary: Hematuria Hematologic: Hemorrhage, retroperitoneal hematoma, unrecognized bleeding sites (eg, colon cancer) may be uncovered by anticoagulation. Other hematologic reactions reported with coumarin derivatives include agranulocytosis, red cell aplasia, anemia, thrombocytopenia, eosinophilia. Hepatic: Hepatitis, hepatotoxicity, hematobilia Ocular: Ocular hemorrhage Respiratory: Epistaxis, hemoptysis, pulmonary hemorrhage Miscellaneous: Hypersensitivity/allergic reactions
CONTRAINDICATIONS — Hypersensitivity to acenocoumarol or any component of the formulation; hemorrhagic tendencies; hemophilia; thrombocytopenia purpura; leukemia; recent or potential surgery of the eye or CNS; major regional lumbar block anesthesia or surgery resulting in large, open surfaces; bleeding from the GI, respiratory, or GU tract; threatened abortion; aneurysm; prolonged dietary insufficiencies (vitamin K deficiency); ascorbic acid deficiency; history of bleeding diathesis; prostatectomy; continuous tube drainage of the small intestine; polyarthritis; diverticulitis; emaciation; malnutrition; cerebrovascular hemorrhage; eclampsia/pre-eclampsia; blood dyscrasias; severe uncontrolled or malignant hypertension; severe hepatic disease; pericarditis or pericardial effusion; subacute bacterial endocarditis; visceral carcinoma; following spinal puncture and other diagnostic or therapeutic procedures with potential for significant bleeding; history of warfarin-induced necrosis; an unreliable, noncompliant patient; alcoholism; patient who has a history of falls or is a significant fall risk; pregnancy
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Anaphylaxis/hypersensitivity: May cause hypersensitivity reactions, including anaphylaxis; use with caution in patients with anaphylactic disorders. Bleeding: May cause major or fatal bleeding. Risk factors for bleeding include high intensity anticoagulation (INR >4), age (>65 years), variable INRs, history of GI bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, severe diabetes, malignancy, trauma, renal insufficiency, polycythemia vera, vasculitis, open wound, history of PUD, indwelling catheters, menstruating and postpartum women, drug-drug interactions and long duration of therapy. Patient must be instructed to report bleeding, accidents, or falls as well as any new or discontinued medications, herbal or alternative products used, significant changes in smoking or dietary habits. Skin necrosis/gangrene: Necrosis or gangrene of the skin and other tissues can occur (rarely) due to early hypercoagulability; risk is increased in patients with protein C deficiency. "Purple toe" syndrome, due to cholesterol microembolization, has been described with coumarin-type anticoagulants.
Disease-related concerns: Infection: Use with caution in patients with acute infection or active TB; antibiotics and fever may alter response to acenocoumarol. Renal impairment: Use with caution in patients with renal impairment. Thyroid disease: Use with caution in patients with thyroid disease.
Special populations: Elderly: The elderly may be more sensitive to anticoagulant therapy. Ovulating women: May be at risk of developing ovarian hemorrhage at the time of ovulation. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Patient selection: Use care in the selection of patients appropriate for this treatment; ensure patient cooperation especially from the alcoholic, illicit drug user, demented, or psychotic patient.
RESTRICTIONS — Not available in U.S.
DRUG INTERACTIONS Substrate of CYP1A2 (major), 2C9 (major), 2C19 (minor)
Note: As an oral coumarin derivative, acenocoumarol is likely subject to the same pharmacodynamic drug-drug interactions as warfarin.
Acetaminophen: May increase the effects of acenocoumarol.
Amiodarone: May increase the level/effects of acenocoumarol.
Anticoagulants: May increase the effects of acenocoumarol.
Antiplatelet agents: May increase the effects of acenocoumarol.
CYP1A2 inducers may decrease the levels/effects of acenocoumarol. Example inducers include aminoglutethimide, carbamazepine, phenobarbital, and rifampin.
CYP1A2 inhibitors may increase the levels/effects of acenocoumarol. Example inhibitors include ciprofloxacin, fluvoxamine, ketoconazole, norfloxacin, ofloxacin, and rofecoxib.
CYP2C9 inducers may decrease the levels/effects of acenocoumarol. Example inducers include carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine, and secobarbital.
CYP2C9 inhibitors may increase the levels/effects of acenocoumarol. Example inhibitors include delavirdine, fluconazole, gemfibrozil, ketoconazole, nicardipine, NSAIDs, pioglitazone, and sulfonamides.
Miconazole: May increase the level/effects of acenocoumarol.
NSAIDs: May increase the level/effects of acenocoumarol.
Salicylates: May increase the effects of acenocoumarol.
Sulfamethoxazole: May increase the effects of acenocoumarol.
Sulfinpyrazone: May increase the effects of acenocoumarol.
Tetracycline antibiotics: May increase the effects of acenocoumarol.
Trimethoprim: May increase the effects of acenocoumarol.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol. Acute ethanol ingestion (binge drinking) decreases the metabolism of oral anticoagulants and increases PT/INR. Chronic daily ethanol use increases the metabolism of oral anticoagulants and decreases PT/INR.
Food: The anticoagulant effects of acenocoumarol may be decreased if taken with foods rich in vitamin K. Vitamin E may increase anticoagulant effect.
Herb/Nutraceutical: St John's wort may decrease oral anticoagulant levels. Alfalfa contains large amounts of vitamin K as do many enteral products. Coenzyme Q10 may decrease response to oral anticoagulants. Avoid cat's claw, dong quai, evening primrose, feverfew, red clover, horse chestnut, garlic, green tea, ginseng, and ginkgo (all have additional antiplatelet activity).
PREGNANCY IMPLICATIONS — Oral anticoagulants cross the placenta and produce fetal abnormalities. Fatal hemorrhage in the fetus has been reported even when the mother's acenocoumarol levels were in the therapeutic range. Acenocoumarol should not be used during pregnancy because of significant risks. Adjusted-dose heparin can be given safely throughout pregnancy in patients with venous thromboembolism. Women of childbearing potential are advised to use effective contraception during treatment.
LACTATION — Enters breast milk/not recommended (per manufacturer)
DIETARY CONSIDERATIONS — Foods high in vitamin K (eg, beef liver, pork liver, green tea, and leafy green vegetables) inhibit anticoagulant effect. Do not change dietary habits once stabilized on acenocoumarol therapy. A balanced diet with a consistent intake of vitamin K is essential. Avoid large amounts of alfalfa, asparagus, broccoli, Brussels sprouts, cabbage, cauliflower, green teas, kale, lettuce, spinach, turnip greens, watercress; these decrease efficacy of oral anticoagulants. It is recommended that the diet contain a CONSISTENT vitamin K content of 70-140 mcg/day. Check with healthcare provider before changing diet. Avoid using multivitamins that contain vitamin K.
MONITORING PARAMETERS — PT/INR; hepatic function, CBC, urinalysis (for albuminuria/proteinuria)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of overdose include internal or external hemorrhage and hematuria. Avoid emesis and lavage to avoid possible trauma and incidental bleeding. When an overdose occurs, the drug should be immediately discontinued and vitamin K1 (phytonadione) may be administered, up to 40 mg I.V. for adults. When hemorrhage occurs, fresh frozen plasma transfusions can help control bleeding by replacing clotting factors. In urgent bleeding, prothrombin complex concentrates may be needed.
CANADIAN BRAND NAMES — Sintrom®
INTERNATIONAL BRAND NAMES — Acenocoumarol (PL); Acenocumarol (PL); Acenox (CL); Acitrom (IN); Coarol (CL); Isquelium (CL); Mini-Sintrom (FR); Neo-Sintrom (CL); Sinthrome (GB); Sintrom (AR, AT, BE, CA, CH, ES, FR, GR, IL, IT, MX, NL, PL, PT); Syncumar (PL)
MECHANISM OF ACTION — Interferes with hepatic synthesis of vitamin K-dependent coagulation factors (II, VII, IX, X)
PHARMACODYNAMICS / KINETICS Onset of action: Peak anticoagulant effect: Oral: 36-48 hours
Absorption: Oral: 60%
Protein binding: 99%
Metabolism: Hepatic, via oxidation (possibly by CYP1A2, 2C9, and 2C19) to inactive metabolites
Half-life elimination: 8-11 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (60%) and feces (29%) as metabolites

Acebutolol

2008-01-20T04:51:00.000-08:00

U.S. BRAND NAMES — Sectral®
PHARMACOLOGIC CATEGORY Antiarrhythmic Agent, Class IIBeta Blocker With Intrinsic Sympathomimetic Activity
DOSING: ADULTS Angina, ventricular arrhythmia: Oral: 400 mg/day in divided doses; maintenance: 600-1200 mg/day in divided doses; maximum: 1200 mg/day
Hypertension: Oral: 400-800 mg/day (larger doses may be divided); maximum: 1200 mg/day; usual dose range (JNC 7): 200-800 mg/day in 2 divided doses
DOSING: ELDERLY — Oral: Initial: 200-400 mg/day; dose reduction due to age-related decrease in Clcr will be necessary; do not exceed 800 mg/day.
DOSING: RENAL IMPAIRMENT Clcr 25-49 mL/minute/1.73 m2: Reduce dose by 50%.
Clcr <25 mL/minute/1.73 m2: Reduce dose by 75%.
DOSING: HEPATIC IMPAIRMENT — Use with caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, as hydrochloride: 200 mg, 400 mg Sectral®: 200 mg, 400 mg
DOSAGE FORMS: CONCISE Capsule, as hydrochloride: 200 mg, 400 mg Sectral®: 200 mg, 400 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — To discontinue therapy, taper dose gradually. May be administered without regard to meals.
USE — Treatment of hypertension, ventricular arrhythmias, angina
ADVERSE REACTIONS SIGNIFICANT >10%: Central nervous system: Fatigue (11%)
1% to 10%: Cardiovascular: Chest pain (2%), edema (2%), bradycardia, hypotension, CHF Central nervous system: Headache (6%), dizziness (6%), insomnia (3%), depression (2%), abnormal dreams (2%), anxiety, hyperesthesia, hypoesthesia, impotence Dermatologic: Rash (2%), pruritus Gastrointestinal: Constipation (4%), diarrhea (4%), dyspepsia (4%), nausea (4%), flatulence (3%), vomiting, abdominal pain Genitourinary: Micturition frequency (3%), dysuria, nocturia, impotence (2%) Neuromuscular & skeletal: Arthralgia (2%), myalgia (2%), back pain, joint pain Ocular: Abnormal vision (2%), conjunctivitis, dry eyes, eye pain Respiratory: Dyspnea (4%), rhinitis (2%), cough (1%), pharyngitis, wheezing
<1% (Limited to important or life-threatening): AV block, exacerbation of pre-existing renal insufficiency, hepatotoxic reaction, impotence, lichen planus, pleurisy, pneumonitis, pulmonary granulomas, systemic lupus erythematosus, urinary retention, ventricular arrhythmia
Potential adverse effects (based on experience with other beta-blocking agents) include reversible mental depression, disorientation, catatonia, short-term memory loss, emotional lability, slightly clouded sensorium, laryngospasm, respiratory distress, allergic reactions, erythematous rash, agranulocytosis, purpura, thrombocytopenia, mesenteric artery thrombosis, ischemic colitis, alopecia, Peyronie's disease, claudication
CONTRAINDICATIONS — Hypersensitivity to beta-blocking agents; uncompensated congestive heart failure; cardiogenic shock; bradycardia or second- and third-degree heart block (except in patients with a functioning artificial pacemaker); sinus node dysfunction; pregnancy (2nd and 3rd trimesters)
WARNINGS / PRECAUTIONS Disease-related concerns: Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring. CHF: Use with caution in patients with compensated heart failure and monitor for a worsening of the condition (beta-blockers with intrinsic sympathomimetic activity have not been demonstrated to be of value in CHF). Conduction ABNL: Consider pre-existing conditions such as sick sinus syndrome before initiating. Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms. Hepatic impairment: Use with caution in patients with hepatic impairment. Myasthenia gravis: Use with caution in patients with myasthenia gravis. Peripheral vascular disease (PVD): Use with caution in patients with PVD (including Raynaud's). Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker. Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression. Renal impairment: Use with caution in patients with renal impairment, especially the elderly.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia.
DRUG INTERACTIONS — Inhibits CYP2D6 (weak)
Alpha-blockers (prazosin, terazosin): Concurrent use of beta-blockers may increase risk of orthostasis.
Clonidine: Hypertensive crisis after or during withdrawal of either agent.
Drugs which slow AV conduction (digoxin): Effects may be additive with beta-blockers.
Glucagon: Acebutolol may blunt the hyperglycemic action of glucagon.
Insulin and oral hypoglycemics: Acebutolol masks the tachycardia from hypoglycemia.
NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam) may reduce the antihypertensive effects of beta-blockers.
Salicylates may reduce the antihypertensive effects of beta-blockers.
Sulfonylureas: Beta-blockers may alter response to hypoglycemic agents.
Verapamil or diltiazem may have synergistic or additive pharmacological effects when taken concurrently with beta-blockers.
ETHANOL / NUTRITION / HERB INTERACTIONS Food: Peak serum acebutolol levels may be slightly decreased if taken with food.
Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid yohimbe, ginseng (may worsen hypertension).
PREGNANCY RISK FACTOR — B (show table) (manufacturer); D (2nd and 3rd trimesters - expert analysis)
PREGNANCY IMPLICATIONS — Acebutolol crosses the placenta. Beta-blockers have been associated with persistent bradycardia, hypotension, and IUGR; IUGR is probably related to maternal hypertension. Available evidence suggests beta-blockers are generally safe during pregnancy (JNC 7). Cases of neonatal hypoglycemia have been reported following maternal use of beta-blockers at parturition or during breast-feeding. Monitor breast-fed infant for symptoms of beta-blockade.
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Hypotension, bradycardia, and tachypnea have been reported in nursing infants.
DIETARY CONSIDERATIONS — May be taken without regard to meals.
PRICING — (data from drugstore.com)Capsules (Acebutolol HCl) 200 mg (60): $32.99 400 mg (30): $21.99
Capsules (Sectral) 200 mg (60): $169.99 400 mg (30): $124.99
MONITORING PARAMETERS — Blood pressure, orthostatic hypotension, heart rate, CNS effects, ECG
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include cardiac disturbances, CNS toxicity, bronchospasm, hypoglycemia, and hyperkalemia. The most common cardiac symptoms include hypotension and bradycardia. Atrioventricular block, intraventricular conduction disturbances, cardiogenic shock, and asystole may occur with severe overdose, especially with membrane-depressant drugs (eg, propranolol). CNS effects include convulsions, coma, and respiratory arrest is commonly seen with propranolol and other membrane-depressant and lipid-soluble drugs. Treatment is symptomatic for seizures, hypotension, hyperkalemia, and hypoglycemia. Bradycardia and hypotension resistant to atropine, isoproterenol or pacing, may respond to glucagon. Wide QRS defects caused by membrane-depressant poisoning may respond to hypertonic sodium bicarbonate. Repeat-dose charcoal, hemoperfusion, or hemodialysis may be helpful.
CANADIAN BRAND NAMES — Apo-Acebutolol®; Gen-Acebutolol; Monitan®; Novo-Acebutolol; Nu-Acebutolol; Rhotral; Rhoxal-acebutolol; Sandoz-Acebutolol; Sectral®
INTERNATIONAL BRAND NAMES — Abutol (PL); ACB (NZ, SG); Acebutolol (PL); Acecor (PL); Apo-Acebutolol (CA); Beloc (CL); Cetolol (PL); Diasectral (DK, FI); Flebutol (VE); Gen-Acebutolol (CA); Grifobutol (CL); Monitan (CA); Novo-Acebutolol (CA); Nu-Acebutolol (CA); Prent (DE, IT, PT); Rhotral (CA); Rhoxal-acebutolol (CA); Sandoz-Acebutolol (CA); Sectral (AE, AN, BB, BE, BG, BH, BM, BS, BZ, CA, CH, CY, CZ, EG, ES, FR, GB, GY, HK, IE, IL, IQ, IR, IT, JM, JO, KW, LB, LY, MY, NL, OM, PL, QA, SA, SR, SY, TT, TW, YE, ZA); Sectral LP (FR)
MECHANISM OF ACTION — Competitively blocks beta1-adrenergic receptors with little or no effect on beta2-receptors except at high doses; exhibits membrane stabilizing and intrinsic sympathomimetic activity
PHARMACODYNAMICS / KINETICS Onset of action: 1-2 hours
Duration: 12-24 hours
Absorption: Oral: 40%
Protein binding: 5% to 15%
Metabolism: Extensive first-pass effect
Half-life elimination: 6-7 hours
Time to peak: 2-4 hours
Excretion: Feces (~55%); urine (35%)
PATIENT INFORMATION — Do not discontinue abruptly. Consult pharmacist or prescriber before taking with other adrenergic drugs (eg, cold medications). Take at the same time each day. May be taken without regard to meals. Use with caution while driving or performing tasks requiring alertness. Notify prescriber if CHF symptoms become worse or if other side effects occur. May mask signs of hypoglycemia in diabetics.
(For additional information see "Acebutolol: Patient drug information")

Acarbose

2008-01-20T04:48:00.000-08:00

U.S. BRAND NAMES — Precose®
PHARMACOLOGIC CATEGORY Antidiabetic Agent, Alpha-Glucosidase Inhibitor
DOSING: ADULTS — Type 2 diabetes: Oral:
Initial: 25 mg 3 times/day
Maintenance dose: Should be adjusted at 4- to 8-week intervals based on 1-hour postprandial glucose levels and tolerance until maintenance dose is reached; maintenance dose: 50-100 mg 3 times/day. Dosage must be individualized on the basis of effectiveness and tolerance while not exceeding the maximum recommended dose.
Maximum: 60 kg: 50 mg 3 times/day >60 kg: 100 mg 3 times/day
Patients receiving sulfonylureas: Acarbose given in combination with a sulfonylurea will cause a further lowering of blood glucose and may increase the hypoglycemic potential of the sulfonylurea. If hypoglycemia occurs, appropriate adjustments in the dosage of these agents should be made.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — Clcr <25 mL/minute: Peak plasma concentrations were 5 times higher and AUCs were 6 times larger than in volunteers with normal renal function; however, long-term clinical trials in diabetic patients with significant renal dysfunction have not been conducted and treatment of these patients with acarbose is not recommended
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 25 mg, 50 mg, 100 mg
DOSAGE FORMS: CONCISE Tablet: Precose®: 25 mg, 50 mg, 100 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Should be administered with the first bite of each main meal.
USE Monotherapy, as indicated as an adjunct to diet to lower blood glucose in patients with type 2 diabetes mellitus (noninsulin dependent, NIDDM) whose hyperglycemia cannot be managed on diet alone
Combination with a sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus (noninsulin dependent, NIDDM) when diet plus acarbose do not result in adequate glycemic control. The effect of acarbose to enhance glycemic control is additive to that of other hypoglycemic agents when used in combination.
ADVERSE REACTIONS SIGNIFICANT >10%: Gastrointestinal: Abdominal pain (21%) and diarrhea (33%) tend to return to pretreatment levels over time, and the frequency and intensity of flatulence (77%) tend to abate with time Hepatic: Transaminases increased
<1% (Limited to important or life-threatening): Severe gastrointestinal distress
CONTRAINDICATIONS — Hypersensitivity to acarbose or any component of the formulation; patients with diabetic ketoacidosis or cirrhosis; patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction, or in patients predisposed to intestinal obstruction; patients who have chronic intestinal diseases associated with marked disorders of digestion or absorption, and in patients who have conditions that may deteriorate as a result of increased gas formation in the intestine
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Elevated serum transaminases: Treatment-emergent elevations of serum transaminases (AST and/or ALT) occurred in 15% of acarbose-treated patients in long-term studies. These serum transaminase elevations appear to be dose related. At doses >100 mg 3 times/day, the incidence of serum transaminase elevations greater than 3 times the upper limit of normal was 2-3 times higher in the acarbose group than in the placebo group. These elevations were asymptomatic, reversible, more common in females, and, in general, were not associated with other evidence of liver dysfunction.
Disease-related concerns: Stress-related states: It may be necessary to discontinue acarbose and administer insulin if the patient is exposed to stress (ie, fever, trauma, infection, surgery).
Concurrent drug therapy issues: Sulfonylureas: In combination with a sulfonylurea will cause a further lowering of blood glucose and may increase the hypoglycemic potential of the sulfonylurea.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
DRUG INTERACTIONS Calcium channel blocking agents: May decrease the efficacy of acarbose due to hyperglycemic effects.
Corticosteroids: May decrease the efficacy of acarbose due to hyperglycemic effects.
Digoxin: Acarbose decreases the bioavailability of digoxin, resulting in lower serum concentrations.
Diuretics (including thiazides): May decrease the efficacy of acarbose due to hyperglycemic effects.
Enzyme replacement (pancrelipase, amylase): May decrease the efficacy of acarbose due to effects on carbohydrate metabolism.
Estrogens: May decrease the efficacy of acarbose due to hyperglycemic effects.
Insulin: Acarbose may increase the hypoglycemic potential of insulin. Oral glucose (dextrose) should be used in the treatment of mild-to-moderate hypoglycemia; severe hypoglycemia may require the use of either intravenous glucose infusion or glucagon injection.
Isoniazid: May decrease the efficacy of acarbose due to hyperglycemic effects.
Nicotinic acid: May decrease the efficacy of acarbose due to hyperglycemic effects.
Oral contraceptives: May decrease the efficacy of acarbose due to hyperglycemic effects.
Phenothiazines: May decrease the efficacy of acarbose due to hyperglycemic effects.
Sulfonylureas: Acarbose may increase the hypoglycemic potential of sulfonylureas. Oral glucose (dextrose) should be used in the treatment of mild-to-moderate hypoglycemia; severe hypoglycemia may require the use of either intravenous glucose infusion or glucagon injection.
Thyroid hormones: May decrease the efficacy of acarbose due to hyperglycemic effects.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Limit ethanol.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Abnormal blood glucose levels are associated with a higher incidence of congenital abnormalities. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.
LACTATION — Excretion in breast milk unknown/use caution
PRICING — (data from drugstore.com)Tablets (Precose) 25 mg (90): $79.17 50 mg (90): $81.95 100 mg (90): $94.45
MONITORING PARAMETERS — Postprandial glucose, glycosylated hemoglobin levels, serum transaminase levels should be checked every 3 months during the first year of treatment and periodically thereafter.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — An overdose of acarbose will not result in hypoglycemia. An overdose may result in transient increases in flatulence, diarrhea, and abdominal discomfort which shortly subside. However, acarbose may complicate the treatment of hypoglycemia from other causes, since it will inhibit the absorption of oral disaccharides (sucrose). Oral glucose (dextrose) should be used in mild-to-moderate hypoglycemia; severe hypoglycemia should be treated with I.V. glucose. In cases of overdosage, the patient should not be given fluids or food containing carbohydrates (polysaccharides, oligosaccharides, or disaccharides) for 4-6 hours following overdose.
CANADIAN BRAND NAMES — Prandase®
INTERNATIONAL BRAND NAMES — Deglu (TW); Glibose (TW); Glicobase (IT); Glucobay (AE, AN, AR, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CY, CZ, DE, DK, DO, EC, EG, ES, ET, FI, GB, GH, GM, GN, GT, GY, HK, HN, HR, HU, ID, IN, IQ, IR, IT, JM, JO, JP, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PL, PT, PY, QA, SA, SC, SD, SE, SG, SL, SN, SR, SV, SY, TH, TT, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Gluconase (PH); Glucor (FR); Glumida (ES); Prandase (CA, IL); Rebose (IN)
MECHANISM OF ACTION — Competitive inhibitor of pancreatic alpha-amylase and intestinal brush border alpha-glucosidases, resulting in delayed hydrolysis of ingested complex carbohydrates and disaccharides and absorption of glucose; dose-dependent reduction in postprandial serum insulin and glucose peaks; inhibits the metabolism of sucrose to glucose and fructose
PHARMACODYNAMICS / KINETICS Absorption: <2% as active drug
Metabolism: Exclusively via GI tract, principally by intestinal bacteria and digestive enzymes; 13 metabolites identified
Bioavailability: Low systemic bioavailability of parent compound; acts locally in GI tract
Excretion: Urine (~34%)
PATIENT INFORMATION — Take this medication exactly as directed, with the first bite of each main meal. It is important to continue to adhere to dietary instructions, a regular exercise program, and regular testing of urine and/or blood glucose. The risk of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be well understood by patients and responsible family members. A source of glucose (dextrose) should be readily available to treat symptoms of low blood glucose when taking acarbose in combination with a sulfonylurea or insulin. If side effects occur, they usually develop during the first few weeks of therapy and are most often mild-to-moderate gastrointestinal effects, such as flatulence, diarrhea, or abdominal discomfort and generally diminish in frequency and intensity with time.
(For additional information see "Acarbose: Patient drug information")

Acamprosate

2008-01-20T04:46:00.000-08:00

U.S. BRAND NAMES — Campral®
PHARMACOLOGIC CATEGORY GABA Agonist/Glutamate Antagonist
DOSING: ADULTS — Alcohol abstinence: Oral: 666 mg 3 times/day (a lower dose may be effective in some patients). Adjustment in patients with low body weight (unlabeled): A lower dose (4 tablets/day) may be considered in patients with low body weight (eg, <60 kg).
Note: Treatment should be initiated as soon as possible following the period of alcohol withdrawal, when the patient has achieved abstinence.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Clcr 30-50 mL/minute: Initial dose should be reduced to 333 mg 3 times/day.
Clcr <30 mL/minute: Contraindicated in severe renal impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, enteric coated, delayed release, as calcium: 333 mg [contains calcium 33 mg and sulfites]
DOSAGE FORMS: CONCISE Tablet, enteric coated, delayed release: Campral®: 333 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered without regard to meals. Tablet should be swallowed whole; do not crush or chew.
USE — Maintenance of alcohol abstinence
ADVERSE REACTIONS SIGNIFICANT Note: Many adverse effects associated with treatment may be related to alcohol abstinence; reported frequency range may overlap with placebo.
>10%: Gastrointestinal: Diarrhea (10% to 17%)
1% to 10%: Cardiovascular: Syncope, palpitation, edema (peripheral) Central nervous system: Insomnia (6% to 9%), anxiety (5% to 8%), depression (4% to 8%), dizziness (3% to 4%), pain (2% to 4%), paresthesia (2% to 3%), headache, somnolence, amnesia, tremor, chills Dermatologic: Pruritus (3% to 4%), rash Endocrine and metabolic: Weight gain, libido decreased Gastrointestinal: Anorexia (2% to 5%), flatulence (1% to 3%), nausea (3% to 4%), abdominal pain, dry mouth (1% to 3%), vomiting, dyspepsia, constipation, appetite increased, taste perversion Genitourinary: Impotence Neuromuscular & skeletal: Weakness (5% to 7%), back pain, myalgia, arthralgia Ocular: Abnormal vision Respiratory: Rhinitis, dyspnea, pharyngitis, bronchitis Miscellaneous: Diaphoresis (2% to 3%), suicide attempt
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Angina, asthma, exfoliative dermatitis, gastrointestinal hemorrhage, hallucinations, hypothyroidism, MI, ophthalmitis, pancreatitis, photosensitivity, psychosis, pulmonary embolus, renal calculus, renal failure, seizure, suicidal ideation, suicide attempts, suicide completion
CONTRAINDICATIONS — Hypersensitivity to acamprosate or any component of the formulation; severe renal impairment (Clcr <30 mL/minute)
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Suicidal ideation/attempt: Attempted and completed suicides have occurred in acamprosate-treated patients; use with caution in suicidal ideation. Monitor for depression and/or suicidal thinking.
Disease-related concerns: Alcohol dependence: Appropriate use: Should be used as part of a comprehensive program to treat alcohol dependence. Treatment should be initiated as soon as possible following the period of alcohol withdrawal, when the patient has achieved abstinence. Acamprosate does not eliminate or diminish the symptoms of alcohol withdrawal. Renal impairment: Use with caution in patients with moderate renal impairment (Clcr 30-50 mL/minute).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Dosage form specific issues: Sulfites: Traces of sulfites may be present in the formulation.
DRUG INTERACTIONS — No clinically-significant drug-to-drug interactions have been identified.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Abstinence is required during treatment. Ethanol does not affect the pharmacokinetics of acamprosate; however, the continued use of ethanol will decrease desired efficacy of acamprosate.
Food: Food decreases absorption of acamprosate (not clinically significant).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic in animal studies. No adequate or well-controlled studies in pregnant women; use only if potential benefit outweighs possible risk to the fetus.
LACTATION — Excretion in breast milk unknown/use caution
DIETARY CONSIDERATIONS — May be taken without regard to meals. Each 333 mg tablet contains 33 mg of elemental calcium.
PRICING — (data from drugstore.com)Tablet, EC (Campral) 333 mg (180): $121.36
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms may include diarrhea and (in chronic overdose) hypercalcemia. Treatment is symptom-directed and supportive.
INTERNATIONAL BRAND NAMES — Acampral (KR); Aotal (FR); Campral (AR, AT, AU, BE, BR, CH, CL, DE, DK, ES, GB, HU, IE, NL, PL, RU, SE); Sobrial (ZA)
MECHANISM OF ACTION — Mechanism not fully defined. Structurally similar to gamma-amino butyric acid (GABA), acamprosate appears to increase the activity of the GABA-ergic system, and decreases activity of glutamate within the CNS, including a decrease in activity at N-methyl D-aspartate (NMDA) receptors; may also affect CNS calcium channels. Restores balance to GABA and glutamate activities which appear to be disrupted in alcohol dependence. During therapeutic use, reduces alcohol intake, but does not cause a disulfiram-like reaction following alcohol ingestion.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 1 L/kg
Protein binding: Negligible
Metabolism: Not metabolized
Bioavailability: 11%
Half-life elimination: 20-33 hours
Excretion: Urine (as unchanged drug)

Absorbable gelatin

2008-01-20T04:44:00.000-08:00

U.S. BRAND NAMES — Gelfilm®; Gelfoam®
PHARMACOLOGIC CATEGORY Hemostatic Agent
DOSING: ADULTS — Hemostasis: Local: Apply packs or sponges dry or saturated with sodium chloride. When applied dry, hold in place with moderate pressure. When applied wet, squeeze to remove air bubbles. The powder is applied as a paste prepared by adding approximately 4 mL of sterile saline solution to the powder.
DOSING: PEDIATRIC — Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Film, ophthalmic (Gelfilm®): 25 mm x 50 mm (6s)
Film, topical (Gelfilm®): 100 mm x 125 mm (1s)
Powder, topical (Gelfoam®): 1 g
Sponge, dental (Gelfoam®): Size 4 (12s)
Sponge, topical (Gelfoam®): Size 50 (4s) Size 100 (6s) Size 200 (6s) Size 2 cm (1s) Size 6 cm (6s) Size 12-7 mm (12s)
DOSAGE FORMS: CONCISE Film, ophthalmic: Gelfilm®: 25 mm x 50 mm (6s)
Film, topical: Gelfilm®: 100 mm x 125 mm (1s)
Powder, topical: Gelfoam®: 1 g
Sponge, dental: Gelfoam®: Size 4 (12s)
Sponge, topical: Gelfoam®: Size 50 (4s) Size 100 (6s) Size 200 (6s) Size 2 cm (1s) Size 6 cm (6s) Size 12-7 mm (12s)
GENERIC EQUIVALENT AVAILABLE — No
USE — Adjunct to provide hemostasis in surgery; open prostatic surgery
ADVERSE REACTIONS SIGNIFICANT — 1% to 10%: Local: Infection and abscess formation
CONTRAINDICATIONS — Should not be used in closure of skin incisions since they may interfere with the healing of skin edges
WARNINGS / PRECAUTIONS — Do not sterilize by heat; do not use in the presence of infection
DRUG INTERACTIONS — No data reported
PREGNANCY RISK FACTOR — No (show table) data reported

Absorbable collagen

2008-01-20T04:43:00.000-08:00

U.S. BRAND NAMES — CollaCote®; CollaPlug®; CollaTape®
PHARMACOLOGIC CATEGORY Hemostatic Agent
DOSING: ADULTS — Control of bleeding: Topical: A sufficiently large dressing should be selected so as to completely cover the oral wound
DOSING: PEDIATRIC — Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Wound dressing:
3/8" x 3/4"
3/4" x 1 1/2"
1" x 3"
DOSAGE FORMS: CONCISE Wound dressing: Generics: 3/8" x 3/4" 3/4" x 1 1/2" 1" x 3" Brands: CollaCote®, CollaPlug®, CollaTape®: 3/8" x 3/4" 3/4" x 1 1/2" 1" x 3"
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Hemostatic
ADVERSE REACTIONS SIGNIFICANT — No data reported.
CONTRAINDICATIONS — No data reported
WARNINGS / PRECAUTIONS — Should not be used on infected or contaminated wounds
DRUG INTERACTIONS — No data reported
LACTATION — Compatible
MECHANISM OF ACTION — The highly porous sponge structure absorbs blood and wound exudate. The collagen component causes aggregation of platelets which bind to collagen fibrils. The aggregated platelets degranulate, releasing coagulation factors that promote the formation of fibrin.

Abciximab

2008-01-20T04:42:00.000-08:00

U.S. BRAND NAMES — ReoPro®
PHARMACOLOGIC CATEGORY Antiplatelet Agent, Glycoprotein IIb/IIIa Inhibitor
DOSING: ADULTS Prevention of restenosis (patients at high risk for abrupt closure): I.V.: 0.25 mg/kg bolus administered 10-60 minutes before the start of intervention followed by an infusion of 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours
Patients with unstable angina not responding to conventional medical therapy and with planned percutaneous coronary intervention within 24 hours: I.V.: 0.25 mg/kg intravenous bolus followed by an 18- to 24-hour intravenous infusion of 10 mcg/minute, concluding 1 hour after the percutaneous coronary intervention.
Acute MI combination regimen (unlabeled): Half-dose tenecteplase (15-25 mg based on weight), abciximab 0.25 mg/kg bolus then 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours and heparin dosing as follows: Concurrent bolus of 40 units/kg (maximum: 3000 units), then 7 units/kg/hour (maximum: 800 units/hour) as continuous infusion. Adjust to aPTT target of 50-70 seconds.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: 2 mg/mL (5 mL)
DOSAGE FORMS: CONCISE Injection, solution: ReoPro®: 2 mg/mL (5 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Abciximab is intended for coadministration with aspirin postangioplasty and heparin infused and weight adjusted to maintain a therapeutic bleeding time (eg, ACT 300-500 seconds). Solution must be filtered prior to administration. Do not shake the vial.
Bolus dose: Aseptically withdraw the necessary amount of abciximab for the bolus dose into a syringe using a 0.2 or 5 micron low protein-binding syringe filter (or equivalent); the bolus should be administered 10-60 minutes before the procedure.
Continuous infusion: Aseptically withdraw 4.5 mL (9 mg) of abciximab for the infusion through a 0.2 or 5 micron low protein-binding syringe filter into a syringe; inject this into 250 mL of NS or D5W to make a solution with a final concentration of 35 mcg/mL. Infuse at a rate of 17 mL/hour (10 mcg/minute) for 12 hours via pump. If a syringe filter was not used when preparing the infusion, administer using an in-line 0.02 or 0.22 low protein-binding filter.
COMPATIBILITY — Abciximab should be administered in a separate intravenous line. No incompatibilities have been observed with glass bottles or PVC bags.
USE — Prevention of acute cardiac ischemic complications in patients at high risk for abrupt closure of the treated coronary vessel and patients at risk of restenosis; an adjunct with heparin to prevent cardiac ischemic complications in patients with unstable angina not responding to conventional therapy when a percutaneous coronary intervention (PCI) is scheduled within 24 hours
USE - UNLABELED / INVESTIGATIONAL — Acute MI - combination regimen of abciximab (full dose), tenecteplase (half dose), and heparin (unlabeled dose)
ADVERSE REACTIONS SIGNIFICANT — As with all drugs which may affect hemostasis, bleeding is associated with abciximab. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the concurrent use of multiple agents which alter hemostasis and patient susceptibility.
>10%: Cardiovascular: Hypotension (14.4%), chest pain (11.4%) Gastrointestinal: Nausea (13.6%) Hematologic: Minor bleeding (4.0% to 16.8%) Neuromuscular & skeletal: Back pain (17.6%)
1% to 10%: Cardiovascular: Bradycardia (4.5%), peripheral edema (1.6%) Central nervous system: Headache (6.45) Gastrointestinal: Vomiting (7.3%), abdominal pain (3.1%) Hematologic: Major bleeding (1.1% to 14%), thrombocytopenia: <100,000 cells/mm3 (2.5% to 5.6%); <50,000 cells/mm3 (0.4% to 1.7%) Local: Injection site pain (3.6%)
<1% (Limited to important or life-threatening): Abnormal thinking, allergic reactions/anaphylaxis (possible), AV block, bronchospasm, bullous eruption, coma, confusion, diabetes mellitus, embolism, hyperkalemia, ileus, inflammation, intracranial hemorrhage, myalgia, nodal arrhythmia, pleural effusion, pulmonary embolism, prostatitis, pruritus, stroke, urinary retention, ventricular tachycardia, xerostomia
CONTRAINDICATIONS — Hypersensitivity to abciximab, to murine proteins, or any component of the formulation; active internal hemorrhage or recent (within 6 weeks) clinically-significant GI or GU bleeding; history of cerebrovascular accident within 2 years or cerebrovascular accident with significant neurological deficit; clotting abnormalities or administration of oral anticoagulants within 7 days unless prothrombin time (PT) is 1.2 times control PT value; thrombocytopenia (<100,000 cells/µL); recent (within 6 weeks) major surgery or trauma; intracranial tumor, arteriovenous malformation, or aneurysm; severe uncontrolled hypertension; history of vasculitis; use of dextran before PTCA or intent to use dextran during PTCA; concomitant use of another parenteral GP IIb/IIIa inhibitor
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: Administration may result in human antichimeric antibody formation that can cause hypersensitivity reactions (including anaphylaxis). Bleeding: The most common complication is bleeding, including retroperitoneal, pulmonary, and spontaneous GI and/or GU bleeding; watch closely for bleeding, especially the arterial access site for the cardiac catheterization. Use with extreme caution in patients with platelet counts <150,000/mm3,>70 minutes duration, or PTCA performed within 12 hours of symptom onset for acute myocardial infarction. Thrombocytopenia: Administration may result in human antichimeric antibody formation that can cause thrombocytopenia; readministration within 30 days or in patients with human antichimeric antibodies (HACA) increases the incidence and severity of thrombocytopenia.
Special populations: Elderly: Use with caution in patients >65 years of age; increased risk of bleeding. Low weight patients: Use with caution in patients weighing <75 kg; increased risk of bleeding. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Diminished efficacy: Administration may result in human antichimeric antibody formation that can cause diminished efficacy. Sheath removal: Prior to pulling the sheath, heparin should be discontinued for 3-4 hours and ACT 175 seconds or aPTT 50 seconds. Use standard compression techniques after sheath removal. Watch the site closely afterwards for further bleeding.
DRUG INTERACTIONS Heparin and aspirin: Use with aspirin and heparin may increase bleeding over aspirin and heparin alone. However, aspirin and heparin were used concurrently in the majority of patients in the major clinical studies of abciximab.
Monoclonal antibodies: Allergic reactions may be increased in patients who have received diagnostic or therapeutic monoclonal antibodies due to the presence of HACA antibodies.
Thrombolytic agents theoretically may increase the risk of bleeding; use with caution.
Warfarin and oral anticoagulants: Risk of bleeding may be increased during concurrent therapy.
Other IIb/IIIa antagonists: Avoid concomitant use of other glycoprotein IIb/IIIa antagonists (see Contraindications).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal reproduction studies have not been conducted. In vitro studies have shown only small amounts of abciximab to cross the placenta. It is not known whether abciximab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — Prothrombin time, activated partial thromboplastin time (aPTT), hemoglobin, hematocrit, platelet count, fibrinogen, fibrin split products, transfusion requirements, signs of hypersensitivity reactions, guaiac stools, Hemastix® urine. Platelet count should be monitored at baseline, 2-4 hours following bolus infusion, and at 24 hours (or prior to discharge, if before 24 hours). To minimize risk of bleeding: Abciximab initiated 18-24 hours prior to PCI: Maintain aPTT between 60-85 seconds during the heparin/abciximab infusion period During PCI: Maintain ACT between 200-300 seconds Following PCI (if anticoagulation is maintained): Maintain aPTT between 50-75 seconds
Sheath removal should not occur until aPTT is 50 seconds or ACT 175 seconds.
Maintain bleeding precautions, avoid unnecessary arterial and venous punctures, use saline or heparin lock for blood drawing, assess sheath insertion site and distal pulses of affected leg every 15 minutes for the first hour and then every 1 hour for the next 6 hours. Arterial access site care is important to prevent bleeding. Care should be taken when attempting vascular access that only the anterior wall of the femoral artery is punctured, avoiding a Seldinger (through and through) technique for obtaining sheath access. Femoral vein sheath placement should be avoided unless needed. While the vascular sheath is in place, patients should be maintained on complete bedrest with the head of the bed at a 30º angle and the affected limb restrained in a straight position.
Observe patient for mental status changes, hemorrhage; assess nose and mouth mucous membranes, puncture sites for oozing, ecchymosis, and hematoma formation; and examine urine, stool, and emesis for presence of occult or frank blood; gentle care should be provided when removing dressings.
TOXICOLOGY / OVERDOSE COMPREHENSIVE — The antiplatelet effects can be quickly reversed with the administration of platelets.
CANADIAN BRAND NAMES — Reopro®
INTERNATIONAL BRAND NAMES — ReoPro (AT, AU, BE, BR, CA, CH, CL, CZ, DE, DK, ES, FI, FR, GB, IE, IN, IT, KR, MX, MY, NL, NO, NZ, PE, PK, PL, SE, SG, TH, TW, ZA)
MECHANISM OF ACTION — Fab antibody fragment of the chimeric human-murine monoclonal antibody 7E3; this agent binds to platelet IIb/IIIa receptors, resulting in steric hindrance, thus inhibiting platelet aggregation
PHARMACODYNAMICS / KINETICS — Half-life elimination: ~30 minutes

Abatacept

2008-01-20T04:40:00.002-08:00

U.S. BRAND NAMES — Orencia®
PHARMACOLOGIC CATEGORY Antirheumatic, Disease Modifying
DOSING: ADULTS — Rheumatoid arthritis: I.V.: Dosing is according to body weight. Repeat dose at 2 weeks and 4 weeks after initial dose, and every 4 weeks thereafter: <60>100 kg: 1000 mg
DOSING: ELDERLY — Refer to adult dosing. Due to potential for higher rates of infections and malignancies, use caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution [preservative free]: 250 mg
DOSAGE FORMS: CONCISE Injection, powder for reconstitution [preservative free]: Orencia®: 250 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Infuse over 30 minutes. Administer through a 0.2-1.2 micron low protein-binding. filter
COMPATIBILITY — Stable in NS.
USE — Treatment of rheumatoid arthritis not responsive to other disease-modifying antirheumatic drugs (DMARD); may be used as monotherapy or in combination with other DMARDs (not in combination with TNF-blocking agents)
ADVERSE REACTIONS SIGNIFICANT — Note: Percentages not always reported; COPD patients experienced a higher frequency of COPD-related adverse reactions (COPD exacerbation, cough, dyspnea, pneumonia, rhonchi)
>10%: Central nervous system: Headache (18%) Gastrointestinal: Nausea Respiratory: Nasopharyngitis (12%), upper respiratory tract infection Miscellaneous: Infection
1% to 10%: Cardiovascular: Hypertension (7%) Central nervous system: Dizziness (9%) Dermatologic: Rash (4%) Gastrointestinal: Dyspepsia (6%) Genitourinary: Urinary tract infection (6%) Neuromuscular & skeletal: Back pain (7%), limb pain (3%) Respiratory: Cough (8%), bronchitis, pneumonia, rhinitis, sinusitis Miscellaneous: Infusion-related reactions (9%), herpes simplex, influenza
<1% (Limited to important or life-threatening): Anaphylaxis, anaphylactoid reactions, cellulitis, diverticulitis, dyspnea, flushing, hypersensitivity, hypotension, lung cancer, lymphoma, pruritus, pyelonephritis, urticaria, wheezing
CONTRAINDICATIONS — Hypersensitivity to abatacept or any component of the formulation; concurrent use with tumor necrosis factor (TNF) blocking agents (eg, adalimumab, etanercept, infliximab)
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: May cause hypersensitivity, anaphylaxis, or anaphylactoid reactions; medication for the treatment of hypersensitivity reactions should be available for immediate use. Infections: Caution should be exercised when considering the use in patients with a history of new/recurrent infections, with conditions that predispose them to infections, or with chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued. Malignancy: Use may affect defenses against malignancies; impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma.
Disease-related concerns: COPD: Use caution with chronic obstructive pulmonary disease (COPD), higher incidences of adverse effects (COPD exacerbation, cough, rhonchi, dyspnea) have been observed; monitor closely.
Concurrent drug therapy issues: Anakinra: The manufacturer does not recommend concurrent use with anakinra. TNF-blocking agents: Patients receiving therapy in combination with TNF-blocking agents had higher rates of infections (including serious infections) than patients on TNF-blocking agents alone.
Special populations: Pediatrics: Safety and efficacy have not been established in children. Tuberculosis-positive patients: Safety has not been established in tuberculosis-positive patients; screen patients for latent tuberculosis infection prior to initiating therapy.
Other warnings/precautions: Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.
DRUG INTERACTIONS TNF-blocking agents: Concurrent use with abatacept may increase risk of infections; contraindicated.
Vaccines, live: Concomitant use has not be studied; currently recommended not to administer live vaccines during or for 3 months after the completion of abatacept treatment.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Due to the potential risk for development of autoimmune disease in the fetus, use during pregnancy only if clearly needed.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions and possible effects on the developing immune system, breast-feeding is not recommended.
PRICING — (data from drugstore.com)Injection (reconstituted) (Orencia) 250 mg (1): $498.99
MONITORING PARAMETERS — Signs and symptoms of infection
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Doses up to 50 mg/kg have been tolerated. In the event of an overdose, monitor for signs and symptoms of adverse reactions; treatment should be symptom-directed and supportive.
MECHANISM OF ACTION — Selective costimulation modulator; inhibits T-cell (T-lymphocyte) activation by binding to CD80 and CD86 on antigen presenting cells (APC), thus blocking the required CD28 interaction between APCs and T cells. Activated T lymphocytes are found in the synovium of rheumatoid arthritis patients.
PHARMACODYNAMICS / KINETICS Distribution: Vss: 0.02-0.13 L/kg
Half-life elimination: 8-25 days
PATIENT INFORMATION — This drug can only be administered by infusion. Do not have any vaccinations while using this medication without consulting prescriber first. You will be more prone to infection. Avoid crowds and wash your hands frequently. Report infections (local or in your whole body) to prescriber immediately. You will need an overall health assessment prior to each treatment to ensure that you do not have an active infection. You may experience headache or dizziness (use caution when driving) or nausea (small frequent meals or sucking lozenges may help).
(For additional information see "Abatacept: Patient drug information")

Abarelix

2008-01-20T04:40:00.001-08:00

U.S. BRAND NAMES — Plenaxis™ [DSC]
PHARMACOLOGIC CATEGORY Gonadotropin Releasing Hormone Antagonist
DOSING: ADULTS — Male prostate cancer: I.M.: 100 mg administered on days 1, 15, 29 (week 4), then every 4 weeks
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product.
Injection, powder for reconstitution [preservative free]: 113 mg [provides 100 mg/2 mL depot suspension when reconstituted; packaged with diluent and syringe] [DSC]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer intramuscularly (to the buttock).
USE — Palliative treatment of advanced prostate cancer; treatment is limited to men who are not candidates for LHRH therapy, refuse surgical castration, and have one or more of the following complications due to metastases or local encroachment: 1) risk of neurological compromise, 2) ureteral or bladder outlet obstruction, or 3) severe bone pain (persisting despite narcotic analgesia)
ADVERSE REACTIONS SIGNIFICANT >10%: Cardiovascular: Hot flushes (79%), peripheral edema (15%) Central nervous system: Sleep disturbance (44%), pain (31%), dizziness (12%), headache (12%) Endocrine & metabolic: Breast enlargement (30%), nipple discharge/tenderness (20%) Gastrointestinal: Constipation (15%), diarrhea (11%) Neuromuscular & skeletal: Back pain (17%) Respiratory: Upper respiratory infection (12%)
1% to 10%: Central nervous system: Fatigue (10%) Endocrine & metabolic: Serum triglycerides increased (10%) Gastrointestinal: Nausea (10%) Genitourinary: Dysuria (10%), micturition frequency (10%), urinary retention (10%), urinary tract infection (10%) Hepatic: Transaminases increased (2% to 8%) Miscellaneous: Allergic reactions (urticaria, pruritus, syncope, hypotension); risk increases with prolonged treatment
CONTRAINDICATIONS — Hypersensitivity to abarelix or any component of the formulation
WARNINGS / PRECAUTIONS Box warnings: Allergic reactions: See "Concerns related to adverse effects" below. Diminished efficacy: See "Other warnings/precautions" below. Plenaxis™ Plus Program: See "Other warnings/precautions" below.
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Allergic reactions: [U.S. Boxed Warning]: Has been associated with immediate-onset allergic reactions; may occur with initial dose and risk increases with duration of treatment. Observe for signs/symptoms of allergic reactions (which may include hypotension and/or syncope) for at least 30 minutes following each injection. Decreased bone mineral density: Extended treatment may result in a decrease in bone mineral density. QT prolongation: May cause prolongation of the QT interval; consider risk:benefit in patients with baseline QTc values >450 msec or patients receiving concurrent medications which prolong the QTc interval (class Ia and class III antiarrhythmics).
Other warnings/precautions: Diminished efficacy: [U.S. Boxed Warning]: Efficacy may diminish during prolonged treatment, particularly in patients weighing >225 pounds; monitor serum testosterone levels to identify treatment failures. Monitoring: Monitor transaminase levels and hepatic function during therapy. Plenaxis™ Plus Program: [U.S. Boxed Warning]: May only be prescribed by physicians enrolled in the Plenaxis™ Plus Program.
RESTRICTIONS — Abarelix is not distributed through retail pharmacies. Prior to its discontinuation, prescribing and distribution of abarelix was limited to physicians and hospital pharmacies participating in the Plenaxis™ PLUS program. Additional information may be obtained by calling 1-877-772-3247 or 1-866-753-2947.
DRUG INTERACTIONS — No formal drug interaction studies have been conducted.
QTc-prolonging agents: Additive QTc prolongation may occur. Life-threatening ventricular arrhythmias may result. Example drugs include class Ia and class III antiarrhythmics, cisapride, selected quinolones, erythromycin, pimozide, mesoridazine, and thioridazine.
PREGNANCY RISK FACTOR — X (show table)
PREGNANCY IMPLICATIONS — Not indicated for use in women; may cause fetal harm if administered to a pregnant woman.
LACTATION — Excretion in breast milk unknown/not indicated in women
BREAST-FEEDING CONSIDERATIONS — Not indicated for use in women
MONITORING PARAMETERS — Signs/symptoms of allergic reaction (for at least 30 minutes after each injection). Obtain transaminase levels at baseline and periodically during treatment. Serum testosterone (to identify treatment failure) just prior to abarelix administration, beginning on day 29 and every 8 weeks thereafter. PSA and bone mineral density may be monitored as needed.
REFERENCE RANGE — Efficacy may be monitored by suppression of serum testosterone <50 ng/dL
TOXICOLOGY / OVERDOSE COMPREHENSIVE — No experience in overdose. Treatment is symptomatic and supportive.
MECHANISM OF ACTION — Competes with naturally-occurring GnRH for binding on receptors of the pituitary. Suppresses LH and FSH, resulting in decreased testosterone.
PHARMACODYNAMICS / KINETICS Distribution: Vd: 4040 L (+/- 1607)
Metabolism: Hepatic, via peptide hydrolysis
Half-life elimination: 13 days
Time to peak, serum: 3 days (following I.M. administration)
Excretion: Urine (13% as unchanged drug)

Abacavir, lamivudine, and zidovudine

2008-01-19T23:09:00.000-08:00

(For additional information see "Abacavir, lamivudine, and zidovudine: Patient drug information" and see "Abacavir, lamivudine, and zidovudine: Pediatric drug information")
U.S. BRAND NAMES — Trizivir®
PHARMACOLOGIC CATEGORY Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV treatment: Oral: 1 tablet twice daily. Note: Not recommended for patients <40 kg.
DOSING: PEDIATRIC — HIV treatment: Adolescents: Refer to adult dosing (not recommended for patients <40 kg).
(For additional information see "Abacavir, lamivudine, and zidovudine: Pediatric drug information")
DOSING: ELDERLY — Use with caution.
DOSING: RENAL IMPAIRMENT — Clcr 50 mL/minute: Avoid use.
DOSING: HEPATIC IMPAIRMENT — Use contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
DOSAGE FORMS: CONCISE Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer without regard to food or water.
USE — Treatment of HIV infection (either alone or in combination with other antiretroviral agents) in patients whose regimen would otherwise contain the components of Trizivir®
ADVERSE REACTIONS SIGNIFICANT — Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out.
The following information is based on CNA3005 study data concerning effects noted in patients receiving abacavir, lamivudine, and zidovudine. See individual agents for additional information.
>10%: Central nervous system: Headache (13%), malaise (12%), fatigue (12%) Gastrointestinal: Nausea (19%)
1% to 10%: Central nervous system: Fever/chills (6%), depression (6%), anxiety (5%) Dermatologic: Rash (5%) Endocrine & metabolic: Triglycerides increased (2% grade 3-4) Gastrointestinal: Nausea and vomiting (10%), diarrhea (7%), amylase increased (2%) Hematologic: Neutropenia (5%) Hepatic: ALT increased (6%) Neuromuscular & skeletal: CPK increased (7%) Otic: Ear infection (5%) Respiratory: Nose/throat infection (5%) Miscellaneous: Hypersensitivity (2% to 9% based on abacavir component), viral infection (5%)
Other (frequency unknown): Pancreatitis, GGT increased, fat redistribution, immune reconstitution syndrome
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component of the formulation; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity to abacavir.
WARNINGS / PRECAUTIONS Box warnings: Chronic hepatitis B: See "Disease-related concerns" below. Hematologic toxicity: See "Concerns related to adverse effects" below. HIV: Appropriate use: See "Disease-related concerns" below. Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: See "Concerns related to adverse effects" below. Myopathy: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hematologic toxicity: [U.S. Boxed Warning]: Zidovudine has been associated with hematologic toxicities (eg, neutropenia, anemia); use with caution in patients with bone marrow compromise. Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). Patients exhibiting symptoms of fever, skin rash, fatigue, respiratory symptoms (eg, pharyngitis, dyspnea, cough) and/or GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea) should discontinue therapy immediately and call for medical attention. Trizivir® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Trizivir® SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (eg, interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (eg, acute onset respiratory diseases, gastroenteritis, reactions to other medications). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out. To report these events on Trizivir® hypersensitivity, a registry has been established (1-800-270-0425). Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required. Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis). Myopathy: [U.S. Boxed Warning]: Prolonged use of zidovudine has been associated with symptomatic myopathy and myositis.
Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Exacerbation of hepatitis B has been reported with discontinuation of lamivudine in coinfected HIV/HBV patients; monitor hepatic function closely for several months after discontinuing Trizivir® in coinfected patients. HIV: Appropriate use: [U.S. Boxed Warning]: This combination should only be used as part of a multidrug regimen for which the individual components are indicated. Renal impairment: Trizivir®, as a fixed-dose combination tablet, should not be used in patients with Clcr 50 mL/minute.
Concurrent drug therapy issues: Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident.
Special populations: Adults <40 kg: Trizivir®, as a fixed-dose combination tablet, should not be used in patients <40 kg or those requiring dosage adjustment. Pediatrics: Trizivir®, as a fixed-dose combination tablet, should not be used in children.
RESTRICTIONS — An FDA-approved medication guide and warning card (summarizing symptoms of hypersensitivity) must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm.
DRUG INTERACTIONS — See individual agents.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — See individual agents.
BREAST-FEEDING CONSIDERATIONS — See individual agents.
DIETARY CONSIDERATIONS — May be taken without regard to food or water.
PRICING — (data from drugstore.com)Tablets (Trizivir) 300-150-300 mg (60): $1154.51
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of overdose with zidovudine include nausea, vomiting, headache, dizziness, drowsiness, lethargy, confusion, and hematologic changes. Myocardial degeneration has been documented in animals during long-term high-dose toxicology studies; clinical relevance is unknown. Treatment is symptom-directed and supportive. Peritoneal dialysis and hemodialysis have little to no effect on the removal of the components of Trizivir®.
MECHANISM OF ACTION — The combination of abacavir, lamivudine, and zidovudine is believed to act synergistically to inhibit reverse transcriptase via DNA chain termination after incorporation of the nucleoside analogue as well as to delay the emergence of mutations conferring resistance.
PHARMACODYNAMICS / KINETICS — Bioavailability studies of Trizivir® show no difference in AUC or Cmax when compared to abacavir, lamivudine, and zidovudine given together as individual agents. See individual agents.

Abacavir and lamivudine

2008-01-19T23:06:00.000-08:00

U.S. BRAND NAMES — Epzicom™
PHARMACOLOGIC CATEGORY Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV: Oral: One tablet (abacavir 600 mg and lamivudine 300 mg) once daily
DOSING: RENAL IMPAIRMENT — Clcr <50 mL/minute: Use not recommended
DOSING: HEPATIC IMPAIRMENT — Use contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: Epzicom™: Abacavir 600 mg and lamivudine 300 mg
DOSAGE FORMS: CONCISE Tablet: Epzicom™: Abacavir 600 mg and lamivudine 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food.
USE — Treatment of HIV infections in combination with other antiretroviral agents
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
Postmarketing and/or case reports: Alopecia, anaphylaxis, anemia, aplastic anemia, breath sounds abnormal, CPK increased, erythema multiforme, fat redistribution, hepatic steatosis, hepatitis B exacerbation, hyperglycemia, hypersensitivity reaction, lactic acidosis, lymphadenopathy, muscle weakness, pancreatitis, paresthesia, peripheral neuropathy, rhabdomyolysis, seizure, splenomegaly, Stevens-Johnson syndrome, stomatitis, urticaria, weakness, wheezing
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, or any component of the formulation; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity to abacavir.
WARNINGS / PRECAUTIONS Box warnings: Chronic hepatitis B: . HIV: Appropriate use: . Hypersensitivity reactions: . Lactic acidosis/hepatomegaly: .
Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Epzicom™). Patients exhibiting symptoms of fever, skin rash, fatigue, respiratory symptoms (eg, pharyngitis, dyspnea, cough) and/or GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea) should discontinue therapy immediately and call for medical attention. Epzicom™ should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Epzicom™ SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (eg, interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (eg, acute onset respiratory diseases, gastroenteritis, reactions to other medications). If Epzicom™ is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out. To report these events on Epzicom™ hypersensitivity, a registry has been established (1-800-270-0425). Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required. Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Following discontinuation of lamivudine, severe acute exacerbations of hepatitis B in patients coinfected with HBV and HIV have been reported. Monitor patients closely for several months following discontinuation of therapy for chronic hepatitis B; clinical exacerbations may occur. HIV: Appropriate use: [U.S. Boxed Warning]: This combination should only be used as part of a multidrug regimen for which the individual components are indicated. Renal impairment: Due to fixed dose of combination product, use is not recommended with renal impairment (Clcr <50 mL/minute).
Concurrent drug therapy issues: Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident.
Special populations: Pediatrics: Due to fixed dose of combination product, use is not recommended in children.
RESTRICTIONS — An FDA-approved medication guide and warning card (summarizing symptoms of hypersensitivity) must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm.
DRUG INTERACTIONS See individual agents.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — See individual agents.
BREAST-FEEDING CONSIDERATIONS — HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV. See individual agents.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)Tablets (Epzicom) 600-300 mg (30): $790.34
MONITORING PARAMETERS — Amylase, bilirubin, liver enzymes, hematologic parameters, viral load, and CD4 count
TOXICOLOGY / OVERDOSE COMPREHENSIVE — See individual agents.
CANADIAN BRAND NAMES — Kivexa™
INTERNATIONAL BRAND NAMES — Kivexa (AR, AT, BE, BG, CA, CH, CL, CZ, DE, DK, ES, FI, FR, GB, GR, HU, IE, IT, NL, NO, PT, RU, SE, TR)
MECHANISM OF ACTION — Nucleoside reverse transcriptase inhibitor combination.
Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
Lamivudine is a cytosine analog. After lamivudine is triphosphorylated, the principle mode of action is inhibition of HIV reverse transcription via viral DNA chain termination; inhibits RNA-dependent DNA polymerase activities of reverse transcriptase.
PHARMACODYNAMICS / KINETICS — See individual agents.

Abacavir

2008-01-19T23:04:00.000-08:00

Copyright 1978-2006 Lexi-Comp, Inc. All rights reserved.

(For additional information see "Abacavir: Patient drug information" and see "Abacavir: Pediatric drug information")
U.S. BRAND NAMES — Ziagen®
PHARMACOLOGIC CATEGORY Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV treatment: Oral: 300 mg twice daily or 600 mg once daily in combination with other antiretroviral agents
DOSING: PEDIATRIC — HIV treatment: Oral: 3 months to 16 years: 8 mg/kg body weight twice daily (maximum: 300 mg twice daily) in combination with other antiretroviral agents
(For additional information see "Abacavir: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT Mild dysfunction (Child-Pugh score 5-6): 200 mg twice daily (oral solution is recommended)
Moderate-to-severe dysfunction: Use is contraindicated by the manufacturer
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, oral: Ziagen®: 20 mg/mL (240 mL) [strawberry-banana flavor]
Tablet: 300 mg
DOSAGE FORMS: CONCISE Solution, oral: Ziagen®: 20 mg/mL
Tablet: Ziagen®: 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food.
USE — Treatment of HIV infections in combination with other antiretroviral agents
ADVERSE REACTIONS SIGNIFICANT — Hypersensitivity reactions (which may be fatal) occur in ~5% of patients (see Warnings/Precautions). Symptoms may include anaphylaxis, fever, rash (including erythema multiforme), fatigue, diarrhea, abdominal pain; respiratory symptoms (eg, pharyngitis, dyspnea, cough, adult respiratory distress syndrome, or respiratory failure); headache, malaise, lethargy, myalgia, myolysis, arthralgia, edema, paresthesia, nausea and vomiting, mouth ulcerations, conjunctivitis, lymphadenopathy, hepatic failure, and renal failure.
Note: Rates of adverse reactions were defined during combination therapy with other antiretrovirals (lamivudine and efavirenz or lamivudine and zidovudine). Only reactions which occurred at a higher frequency in adults (except where noted) than in the comparator group are noted. Adverse reaction rates attributable to abacavir alone are not available.
>10%: Central nervous system: Headache (7% to 13%) Gastrointestinal: Nausea (7% to 19%, children 9%)
1% to 10%: Central nervous system: Depression (6%), fever/chills (6%, children 9%), anxiety (5%) Dermatologic: Rash (5% to 6%, children 7%) Endocrine & metabolic: Triglycerides increased (2% to 6%) Gastrointestinal: Diarrhea (7%), vomiting (children 9%), amylase increased (2%) Hematologic: Thrombocytopenia (1%) Hepatic: AST increased (6%) Neuromuscular and skeletal: Musculoskeletal pain (5% to 6%) Miscellaneous: Hypersensitivity reactions (2% to 9%; may include reactions to other components of antiretroviral regimen), infection (EENT 5%)
<1% (Limited to important or life-threatening): Erythema multiforme, fat redistribution, GGT increased, hepatic steatosis, hepatomegaly, hepatotoxicity, lactic acidosis, pancreatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis
CONTRAINDICATIONS — Hypersensitivity to abacavir or any component of the formulation (do not rechallenge patients who have experienced hypersensitivity to abacavir); moderate-to-severe hepatic impairment
WARNINGS / PRECAUTIONS Box warnings: Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hypersensitivity reactions: [U.S. Boxed Warning]: Serious and sometimes fatal hypersensitivity reactions have occurred. Patients exhibiting symptoms from two or more of the following: Fever, skin rash, constitutional symptoms (malaise, fatigue, aches), respiratory symptoms (eg, pharyngitis, dyspnea, cough), and GI symptoms (eg, abdominal pain, diarrhea, nausea, vomiting) should discontinue therapy immediately and call for medical attention. Abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Abacavir SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (ie, interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (eg, acute onset respiratory diseases, gastroenteritis, reactions to other medications). If abacavir is restarted following an interruption in therapy, evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out. To report these events on abacavir hypersensitivity, a registry has been established (1-800-270-0425). Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required. Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
Disease-related concerns: Hepatic impairment: Use with caution in patients with mild hepatic dysfunction (contraindicated in moderate-to-severe dysfunction). HIV: Appropriate use: Abacavir should always be used as a component of a multidrug regimen.
Special populations: Pediatrics: Safety and efficacy have not been established in children <3 months of age.
RESTRICTIONS — An FDA-approved medication guide and warning card (summarizing symptoms of hypersensitivity) must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm.
DRUG INTERACTIONS Ganciclovir, valganciclovir: May increase the adverse/toxic effects of nucleoside reverse transcriptase inhibitors.
Ribavirin: Concomitant use of ribavirin and nucleoside analogues may increase the risk of developing hepatic decompensation or other signs of mitochondrial toxicity, including pancreatitis or lactic acidosis.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Ethanol may increase the risk of toxicity.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — It is not known if abacavir crosses the human placenta. No increased risk of overall birth defects has been observed following 1st trimester exposure according to data collected by the antiretroviral pregnancy registry. Cases of lactic acidosis/hepatic steatosis syndrome have been reported in pregnant women receiving nucleoside analogues. It is not known if pregnancy itself potentiates this known side effect; however, pregnant women may be at increased risk of lactic acidosis and liver damage. Hepatic enzymes and electrolytes should be monitored frequently during the 3rd trimester of pregnancy in women receiving nucleoside analogues. Dose adjustment is not needed for pregnancy. The Perinatal HIV Guidelines Working Group considers abacavir to be an alternative NRTI in dual nucleoside combination regimens. Health professionals are encouraged to contact the antiretroviral pregnancy registry to monitor outcomes of pregnant women exposed to antiretroviral medications (1-800-258-4263 or www.APRegistry.com).
LACTATION — Excretion in breast milk unknown/contraindicated
BREAST-FEEDING CONSIDERATIONS — HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)Solution (Ziagen) 20 mg/mL (240): $113.54
Tablets (Ziagen) 300 mg (60): $466.91
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Treatment should be symptom-directed and supportive. Benefit of dialysis is unknown.
CANADIAN BRAND NAMES — Ziagen®
INTERNATIONAL BRAND NAMES — Abamune (IN); Filabac (AR); Zepril (AR); Ziagen (AN, AT, AU, BB, BE, BG, BM, BS, BZ, CA, CH, CL, CO, CR, CZ, DE, DK, DO, ES, FI, FR, GB, GR, GT, GY, HK, HN, HU, IE, IL, IT, JM, KR, NI, NL, NO, NZ, PA, PE, PL, PT, RU, SE, SG, SR, SV, TR, TT, TW, VE); Ziagenavir (AR, BR, MX, TH, UY)
MECHANISM OF ACTION — Nucleoside reverse transcriptase inhibitor. Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
PHARMACODYNAMICS / KINETICS Absorption: Rapid and extensive absorption
Distribution: Vd: 0.86 L/kg
Protein binding: 50%
Metabolism: Hepatic via alcohol dehydrogenase and glucuronyl transferase to inactive carboxylate and glucuronide metabolites
Bioavailability: 83%
Half-life elimination: 1.5 hours
Time to peak: 0.7-1.7 hours
Excretion: Primarily urine (as metabolites, 1.2% as unchanged drug); feces (16% total dose)
PATIENT INFORMATION — If you experience any of the following: Fever, skin rash, fatigue, nausea, vomiting, diarrhea, abdominal pain, contact your prescriber immediately. This drug is not a cure for HIV infection, nor will it reduce the risk of transmission to others. You will need frequent blood tests to adjust dosage for maximum therapeutic effect. Take as directed; do not discontinue (even if feeling better). You may experience headache or muscle pain or weakness. If you are instructed to stop the medication, do not take this medication in the future. Do not restart without specific instructions by your prescriber.