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)
Wednesday, January 23, 2008
Acetazolamide
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")
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
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
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
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.
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
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.
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
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.
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
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
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
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