Acetaminophen

Pronunciation (a seet a MIN oh fen)

• Acetaminophen Toxicity Nomogram

U.S. Brand Names Acephen® [OTC]; Aspirin Free Anacin® Maximum Strength [OTC]; Cetafen® [OTC]; Cetafen Extra® [OTC]; Feverall® [OTC]; Genapap® [OTC]; Genapap® Children [OTC]; Genapap® Extra Strength [OTC]; Genapap® Infant [OTC]; Genebs® [OTC]; Genebs® Extra Strength [OTC]; Infantaire [OTC]; Liquiprin® for Children [OTC]; Mapap® [OTC]; Mapap® Children's [OTC]; Mapap® Extra Strength [OTC]; Mapap® Infants [OTC]; Redutemp® [OTC]; Silapap® Children's [OTC]; Silapap® Infants [OTC]; Tylenol® [OTC]; Tylenol® Arthritis Pain [OTC]; Tylenol® Children's [OTC]; Tylenol® Extra Strength [OTC]; Tylenol® Infants [OTC]; Tylenol® Junior Strength [OTC]; Tylenol® Sore Throat [OTC]; Valorin [OTC]; Valorin Extra [OTC]

Synonyms APAP; N-Acetyl-P-Aminophenol; Paracetamol

Generic Available Yes

Canadian Brand Names Abenol®; Apo®-Acetaminophen; Atasol®; Pediatrix; Tempra®; Tylenol®

Pharmacologic Category Analgesic, Miscellaneous

Use Treatment of mild to moderate pain and fever; does not have antirheumatic effects (analgesic)

Use - Dental Treatment of postoperative pain

Pregnancy Risk Factor B

Lactation Enters breast milk/compatible

Contraindications Hypersensitivity to acetaminophen or any component of the formulation; patients with known G6PD deficiency

Warnings/Precautions May cause severe hepatic toxicity on overdose; use with caution in patients with alcoholic liver disease; chronic daily dosing in adults of 5-8 g of acetaminophen over several weeks or 3-4 g/day of acetaminophen for 1 year have resulted in liver damage

Frequency not defined:

<1%: Rash, nausea, vomiting, blood dyscrasias (neutropenia, pancytopenia, leukopenia), anemia, analgesic nephropathy, nephrotoxicity with chronic overdose, hypersensitivity reactions (rare)

Overdosage/Toxicology Symptoms of overdose include hepatic necrosis, transient azotemia, renal tubular necrosis with acute toxicity, anemia, and GI disturbances with chronic toxicity. Treatment consists of 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 a high probability of hepatotoxic potential. Activated charcoal is very effective at binding acetaminophen. Intravenous acetylcysteine should be reserved for patients unable to take oral forms.

Drug Interactions CYP1A2 enzyme substrate (minor), CYP2E1 and 3A3/4 enzyme substrate

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: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.

Food: May slightly delay absorption of extended-release preparations; rate of absorption may be decreased when given with food high in carbohydrates.

Herb/Nutraceutical: St John's wort may decrease acetaminophen levels.

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

Onset of action: <1 hour

Duration: 4-6 hours

Protein binding: 20% to 50%

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:

Time to peak, serum: Oral: 10-60 minutes; may be delayed in acute overdoses

Excretion: Urine

Dosage Oral, rectal (if fever not controlled with acetaminophen alone, administer with full doses of aspirin on an every 4- to 6-hour schedule, if aspirin is not otherwise contraindicated):

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 age-based doses may be used. See table.

Adults: 325-650 mg every 4-6 hours or 1000 mg 3-4 times/day; do not exceed 4 g/day

Dosing interval in renal impairment:

Hemodialysis: Moderately dialyzable (20% to 50%)

Dosing adjustment/comments in 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.

Monitoring Parameters Relief of pain or fever

Therapeutic concentration (analgesic/antipyretic): 10-30 g/mL

Toxic concentration (acute ingestion) with probable hepatotoxicity: >200 g/mL at 4 hours or 50 g/mL at 12 hours after ingestion

Patient Information Take exactly as directed (do not increase dose or frequency); most adverse effects are related to excessive use. Take with food or milk. While using this medication, avoid or limit alcohol to <3 drinks/day and avoid other prescription or OTC medications that contain acetaminophen. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). This medication will not reduce inflammation; consult prescriber for anti-inflammatory, if needed. Report unusual bleeding (stool, mouth, urine) or bruising; unusual fatigue and weakness; change in elimination patterns; or change in color of urine or stool.

Suppositories: Do not freeze

Suspension, oral: Shake well before pouring a dose

Anesthesia and Critical Care Concerns/Other Considerations Has no significant anti-inflammatory effect

Dental Health: Effects on Dental Treatment No effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions No information available to require special precautions

Dental Comment Doses of acetaminophen >5 g/day for several weeks can produce severe, often fatal liver damage. Hepatotoxicity caused by acetaminophen is potentiated by chronic ethanol consumption. It has been reported that a combination of two quarts of whiskey a day with 8-10 acetaminophen tablets daily resulted in severe liver toxicity. People who consume ethanol at the same time that they use acetaminophen, even in therapeutic doses, are at risk of developing hepatotoxicity.

A study by Hylek, et al, suggested that the combination of acetaminophen with warfarin (Coumadin®) may cause enhanced anticoagulation. The following recommendations have been made by Hylek, et al, and supported by an editorial in JAMA by Bell.

The study by Hylek reported the following:

Mental Health: Effects on Mental Status None reported

Mental Health: Effects on Psychiatric Treatment Barbiturates and carbamazepine may increase the hepatotoxic potential of acetaminophen

Caplet (Genapap® Extra Strength, Genebs® Extra Strength, Tylenol® Extra Strength): 500 mg

Caplet, extended release (Tylenol® Arthritis Pain): 650 mg

Capsule (Mapap® Extra Strength): 500 mg

Elixir: 160 mg/5 mL (5 mL, 10 mL, 20 mL, 120 mL, 240 mL, 500 mL, 3780 mL)

Gelcap (Genapap® Extra Strength, Tylenol® Extra Strength): 500 mg

Geltab (Tylenol® Extra Strength): 500 mg

Liquid, oral: 160 mg/5 mL (120 mL, 240 mL, 480 mL, 3870 mL); 500 mg/15 mL (240 mL)

Solution, oral drops: 100 mg/mL (15 mL, 30 mL) [droppers are marked at 0.4 mL (40 mg) and at 0.8 mL (80 mg)]

Suppository, rectal: 80 mg, 120 mg, 325 mg, 650 mg

Suspension, oral: 160 mg/5 mL (120 mL)

Suspension, oral drops: 100 mg/mL (15 mL, 30 mL) [droppers are marked at 0.4 mL (40 mg) and at 0.8 mL (80 mg)]

Syrup, oral: 160 mg/5 mL (120 mL)

Tablet: 160 mg, 325 mg, 500 mg

Tablet, chewable: 80 mg, 160 mg

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Bizovi K, Keys N, Rivas J, et al, "Tylenol® ER, Late Rise in APAP Level After Overdose,"Clin Toxicol, 1995, 33(5):510.

Burkhart KK, Janco N, Kulig KW, et al, "Cimetidine as Adjunctive Treatment for Acetaminophen Overdose,"Hum Exp Toxicol, 1995, 14(3):299-304.

Cetaruk E, Horowitz R, Hurlburt K, et al, "Tylenol® Extended Relief Overdose: A New Headache?"Clin Toxicol, 1995, 33(5):511.

Dionne RA, Campbell RA, Cooper SA, et al, "Suppression of Postoperative Pain by Preoperative Administration of Ibuprofen in Comparison to Placebo, Acetaminophen, and Acetaminophen Plus Codeine,"J Clin Pharmacol, 1983, 23(1):37-43.

Douglas DR, Smilkstein MJ, and Sholar JB, "Overdose With Extended-Relief Acetaminophen: Is a New Approach Necessary?"Acad Emerg Med, 1995, 2:397.

"Drugs for Pain,"Med Lett Drugs Ther, 1998, 40(1033):79-84.

Graudins A, Aaron CK, and Linden CH, "Overdose of Extended-Release Acetaminophen,"N Engl J Med, 1995, 333(3):196.

Harrison PM, Keays R, Bray GP, et al, "Improved Outcome of Paracetamol-Induced Fulminant Hepatic Failure by Late Administration of Acetylcysteine,"Lancet, 1990, 335(8705):1572-3.

Hochberg MC, Altman RD, Brandt KD, et al, "Guidelines for the Medical Management of Osteoarthritis. Part I. Osteoarthritis of the Hip. American College of Rheumatology,"Arthritis Rheum, 1995, 38(11):1535-40.

Hochberg MC, Altman RD, Brandt KD, et al, "Guidelines for the Medical Management of Osteoarthritis. Part II. Osteoarthritis of the Knee. American College of Rheumatology,"Arthritis Rheum, 1995, 38(11):1541-6.

Janes J and Routledge PA, "Recent Developments in the Management of Paracetamol (Acetaminophen) Poisoning,"Drug Saf, 1992, 7(3):170-7.

Jones AL, "Mechanism of Action and Value of N-acetylcysteine in the Treatment of Early and Late Acetaminophen Poisoning: A Critical Review,"J Tox Clin Tox, 1998, 36(4):277-85.

Katzir Z, Baruch O, Hochman B, et al, "Spontaneous Remission of Paracetamol Induced Acute Renal Failure,"Clin Nephrol, 1995, 43(5):346.

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Licht H, Seeff LB, and Zimmerman HJ, "Apparent Potentiation of Acetaminophen Hepatotoxicity by Alcohol,"Ann Intern Med, 1980, 92(4):511.

McClain CJ, et al, "Potentiation of Acetaminophen Hepatotoxicity by Alcohol,"JAMA, 1980, 244:251.

Murphy R, Swartz R, and Watkins PB, "Severe Acetaminophen Toxicity in a Patient Receiving Isoniazid,"Ann Intern Med, 1990, 113(110):799-800.

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International Brand Names Abenol® (CA); Abrol® (IL); Abrolet® (IL); Acamol® (AR, CL, IL); Acenol® (CZ, PL); Acertol® (ES); Acetalgin® (CH); Acetalgine (CH); Acetaminophen-Odan® (CA); Acetamol (BR, IT); Acetofen® (BR); Acetolit® (AR); Actron® (ES); 222 AF® (CA); A.F. Anacin® (CA); Afebrin® (HK); Afebryl® (BE, LU); Aferadol (FR); Aféradol® (FR); Akindol® (FR, ES); Aldolor® (IL); Algiafin® (CL); Algina® (IN); Alginina (ES); Algitrin® (MX); Algomol® (TR); Alpiny® (JP); Alvedon® (GB, NO, SE); Anadin® (PL); Anadin dla dzieci® (PL); Anaflon (DE); Analphen (MX); Analter (ES); Anatyl (BR); Andox® (MX); Anhiba® (JP); Antalgic (ZA); Anti-Algos (DE); Antidol (ES); Antipanin N (DE); Antipanin P (DE); APA® (AT); Apacet (AT); APAP® (PL); A-Per® (TR); Apiretal (ES); Apirex® (FR); Apo-Acetaminophen® (CA); Apo-Paradex® (NZ); Arcanagesic (ZA); Arfen® (HK); Asetam® (TR); Asomal® (TR); Aspac® (ES); Asplin (ES); Asprol (AU); Atasol® (CA); Atralidon® (PT); Auxidor (ES); Babikan® (TR); Baicurina (BR); Bandol (ES); Bebesan N (CH); Becetamol (CH); Benmyo® (AT); Ben-u-ron (AT, DE); ben-u-ron® (HU, PL, PT, CH); Brunomol (ZA); Cadafen® (VE); Calapol® (ID); Calmanticold (ES); Calpol (BR, CZ, GB, HK, IN, IE, IT, PL, ZA, TR); Captin® (DE); Causalon® (AR); Ceetamol (AU); Cefalex® (BR); Cetamol (IE); Cetapon (ZA); Chemists Own Pain & Fever (AU); Children's Acetaminophen Elixir Drops® (CA); Children's Acetaminophen Oral Solution® (CA); Children's Chewable Acetaminophen® (CA); Childrens Panadol (AU); Children's Tylenol® (AU); Cilag® (MX); Claradol® (FR); Cofamol® (IN); Compralsol (FR); Comprimes analgesiques no 534 (CH); Compu-Pain (ZA); Contac® (DE); Contac Erkaltungs-Trunk (DE); Contra-Schmerz P® (CH); Contre-Douleurs P (CH); Crocin® (IN); Croix Blanche® (BE, LU); Croix Blanche N.F.® (BE); Cupanol® (GB, ES); Curadon (SE); Curpol (BE, LU); Custodial® (AR); Dafalgan® (BE, CZ, FR, LU, PL); Dafalgan (ES, CH); Daro (NL); Darocet® (NL); Datril® (MX); Daygrip® (AR); Deminofen® (TR); Democyl® (CH); Demogripal (CH); Desfebre® (ES); Dhamol® (HK); Dignocetamol (DE); Dirox® (AR); Disprol® (GB); Disprol (IE); Docpara® (BE); Dolarist (DE); Dolefin® (ES); Dolflash (FR); Dolgesic (ES); Doliprane® (FR, PL); Dolitabs (FR); Dolko® (FR); Dolofugin (DE); Doloreduct® (DE); Dolorfug® (DE); Dolorol (ZA); Dolostop® (ES); Dolotec (FR); Dolprone® (BE, LU, CH); Dol-Stop® (LU); Dorcol® (DE); Dordendril (BR); Doregrippin® (DE); Dorico (BR); Dorocoff® (DE); Dorocoff-Paracetamol (DE); Doxypol (ZA); Drazin (ES); Dristancito® (AR); Duaneo (AT); Duorol (ES); duracetamol (DE); Durapan® (TR); Dymadon® (AU); Dynadol (ZA); Efferalgan® (BE, CZ); Efferalgan (FR, HK, HU, IT, LU, PL, PT, ES, CH, YU); Ekosetol® (TR); Empaped (ZA); Enelfa (AT, DE, LU); Ennagesic (ZA); Entalgic (ZA); Eu-Med P mono (DE); Eu-Med Schmerzzapfschen (DE); Excipain® (CH); Exdol® (CA); Expandol® (FR); Expandox (FR); Extra Strength Acetaminophen® (CA); Fanalgic® (GB); Farmacetamol (ZA); Farmadol® (ID); Fébrectol® (FR); Febranine® (ES); Febrectal® (ES); Febrectal Simple (ES); Febrectol (FR); Febrex® (IN); Febricet® (YU); Febridol® (AU); Febrin® (MX, ES); Fensum® (DE); Fevamol (ZA); Fiebrolito® (AR); Finiweh (DE); Fluparmol® (TR); Fortalidon P (CH); Freka-cetamol (DE); Gardan P (DE); Gelo (ES); Geluprane (FR); Gepodan (DE); Geralgine-P® (TR); Gripeonil (BR); Gripin Bebe® (TR); Grippostad® (DE); Grippostad Heissget (DE); Gynospasmine® (FR); Hedex (IE, NL); Herron Paracetamol® (AU); Ildamol® (AT, IL); Inalgex® (HK); Infadrops® (GB); Influbene N® (CH); Junior Disprol (AU, HK, IE); Kataprin® (TR); Kiddy Calm (AU); Kinder Finimal® (NL); Kratofin simplex (AT); Labamol® (IL); Lekadol® (HR, PL); Lemgrip (BE, LU); Lemsip (AU, GB, SE); Lemsip Headcold (AU); Lemsip Max (AU); Levadol (IT); Lonarid Mono (BE); Lonarid mono® (LU); Lupocet® (HR); Lyteca (ZA); Magnidol® (MX); Malex N® (CH); Malgis (FR); Malidens® (IN); Maxadol-P (ZA); Medinol Paediatric® (GB); Medpramol (ZA); Merck-Gesic (ZA); Mexalen® (AT, HU); Minafen® (TR); Minofen® (MX); Minoset® (TR); Miralgin® (YU); Momentum (AT, LU, NL); Napamol (ZA); NeoCitran® (LU); Neodol (MX); Neodolito® (MX); Neo-Fepramol® (IT); Neo-Treupine (CH); Neuridon (BE, LU); New Cortal for Children® (HK); Nina® (CH); Nodolex® (AR); No-Febril® (AR); Nomal® (BE); Noral® (TR); Oralgan (FR); Ordov Febrigesic (AU); Ortensan (CH); Pacemol (BR); Pacet® (IL); Pacimol® (IN); Pacimol (ZA); Painamol (ZA); Paldesic® (GB); Pamol (DK, NO, ZA); Panacete (AU); Panado (ZA); Panadol® (AU); Panadol (BE, CA, CZ, FI, FR, GB, HK, HU, IE, IT, LU, NL, PL, PT, CH, TR); Panadon® (HR, PL); Panaleve® (IE); Panamax (AU); Panasorbe (PT); Panodil (DK, NO, SE); Pantalgin® (BE); Para (FR); Paracemol® (PL); Paracenol® (PL); Paracet® (NO, TR, YU); Paracetamol® (AR, AU, HR, PL, TR, YU); Paracetamol Fecofar® (AR); Paracetamol Genericon® (AT); Paracetamol Hänseler® (CH); Paracetamol Nycomed® (AT); Paracetamolo® (IT); Paracetamol Pharmavit® (HU); Paracetamol Raffo® (AR); Paracetamol-ratiopharm® (LU, PL); Paracetamol Ratiopharm® (PT); Paracetamol Rösch® (AT); Paracetamol Tablets® (AU); Paracetol® (TR); Paracin® (IN); Paracétamol SmithKline Beecham® (FR); Parador (BR); Paradrops® (IE); Parahexal® (AU); Parakapton (AT); Paralen® (CZ); Paralgin® (AU, CA); Paralief® (IE); Paralink® (IE); Paralyoc (FR); Paramol® (GB, IE); Paramolan (PT); Paranox® (TR); Parapaed (IE); Paraphar® (BE); Parasedol® (TR); Parasin (AU); Parasol (IE); Paraspen (AU); Para-Suppo® (FI); Para-Tabs® (FI); Parazine® (IN); Parcetol® (TR); Parmol® (AU); Parogal® (YU); Parol® (TR); Paroma® (TR); Parsel (PT); Pediatrix® (CA); Peinfort® (AT); Perdolan Mono (BE, LU); Pe-Tam® (BE, LU); Pharmadol® (TR); Phenipirin® (TR); Pinex (DK, NO); Piramin® (BR); Plicet® (HR); PMS-Acetaminophen® (CA); Polmofen® (TR); Predimol® (IN); Predualito® (AR); Prodol® (TR); Progesic® (HK); Prolief (ZA); Puernol (IT); Pulmofen® (TR); Pyradol (ZA); Pyragesic (ZA); Pyrigesic® (IN); Regular Strength Acetaminophen® (CA); Reliv® (SE); Remedol® (CY); Rivodol® (CH); Rounox® (CA); Rubophen® (HU); Rupemol® (AR); Salzone® (GB); Sanicet® (YU); Sanicopyrine (BE); Sanipirina (IT); Scanol® (PL); Scentalgyl® (IT); Schmer (CH); Sedalito® (MX); Sedalon® (TR); Semolacin® (TR); Servigesic® (HK); Seskamol® (TR); Setakop® (TR); Setamol (AU, ZA, SE, TR); Setol® (TR); Sifenol® (TR); Sinaspril® (NL); Sinaspril-Paracetamol (NL); Sinedol (MX); Sinedol 500 (MX); Suotex (IE); Supadol mono® (BE, LU); Supofen (PT); Supramol-M® (IL); Tachipirina® (IT); Tantaphen® (CA); Tazamol® (PL); Temol (ZA); Temperal® (MX); Tempra® (AR, AU, BE, CA, CN, LU, MX); Termofren® (AR); Tiffy® (HK); Tylenex® (BR); Tylenol (AU, AT, BR, CA, CZ, HK, IE, PL, PT, ZA); Tylephen (BR); Tylex® (MX); Tylex 750 (MX); Ultragin® (IN); Veralgina® (BR); Viclor Richet® (AR); Winasorb (MX); Winpain (ZA); Zaramol (PT)