Acetaminophen

(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)