Description

Simple

A medication used to reduce fever and treat pain.

Clinical

An analgesic drug used alone or in combination with opioids for pain management, and as an antipyretic agent.

Overview

Acetaminophen (paracetamol), also commonly known as _Tylenol_, is the most commonly taken analgesic worldwide and is recommended as first-line therapy in pain conditions by the World Health Organization (WHO).[10] It is also used for its antipyretic effects, helping to reduce fever.[22] This drug was initially approved by the U.S. FDA in 1951 and is available in a variety of forms including syrup form, regular tablets, effervescent tablets, injection, suppository, and other forms.[15,16,22,Label]

Acetaminophen is often found combined with other drugs in more than 600 over the counter (OTC) allergy medications, cold medications, sleep medications, pain relievers, and other products.[19] Confusi... Read more

Pharmacology

Indication

In general, acetaminophen is used for the treatment of mild to moderate pain and reduction of fever.[22] It is available over the counter in various forms, the most common being oral forms.

Acetamino... Read more

Pharmacodynamic

Animal and clinical studies have determined that acetaminophen has both antipyretic and analgesic effects. This drug has been shown to lack anti-inflammatory effects. As opposed to the _salicylate_ drug class, acetaminophen does not disrupt tubular secretion of uric acid and does not affect acid-bas... Read more

Mechanism of action

Although acetaminophen's exact mechanism of action has not been fully established, according to the FDA label, it is categorized as an NSAID (a nonsteroidal anti-inflammatory drug) due to that fact that it inhibits the cyclooxygenase (COX) pathways, and it is thought to exert central actions which u... Read more

Absorption

Acetaminophen has 88% oral bioavailability and reaches its highest plasma concentration 90 minutes after ingestion.[ Read more

Protein binding

The binding of acetaminophen to plasma proteins is low (ranging from 10% to 25%), when given at therapeutic doses.[Label]

Volume of distribution

Volume of distribution is about 0.9L/kg. 10 to 20% of the drug is bound to red blood cells.[11 Read more

Clearance

Adults: 0.27 L/h/kg following a 15 mg/kg intravenous (IV) dose.[Label]Children: 0.34 L/h/kg following a 15 mg/kg intravenous (IV dose).[Label]

Half life

The half-life for adults is 2.5 h after an intravenous dose of 15 mg/kg.[Label] After an overdose, the half-life can range from 4 to 8 hours depending on the severity of injury to the liver, as it heavily metabolizes acetaminophen.[ Read more

Route of elimination

Acetaminophen metabolites are mainly excreted in the urine. Less than 5% is excreted in the urine as free (unconjugated) acetaminophen and at least 90% of the administered dose is excreted within 24 hours.[... Read more

Toxicity

LD50 = 338 mg/kg (oral, mouse); LD50 = 1944 mg/kg (oral, rat)[23]

**Overdose and liver toxicity**

Acetaminophen overdose may be manifested by renal tubular necrosis, hypoglycemic coma, and thrombo... Read more

Adverse Effects

Contraindications

  • Hypersensitivity:
    • Acetaminophen
  • Sex Group: all
  • Regions: US
  • Patient Conditions:
      • Name: Drug Hypersensitivity
      • Drugbank Id: DBCOND0032673
  • Regions: US
  • Patient Conditions:
      • Name: Hepatic Impairment
      • Drugbank Id: DBCOND0031585
  • Regions: US
  • Patient Conditions:
      • Name: Severe active liver disease
      • Drugbank Id: DBCOND0108539
      • Modification Of:
        • Condition Status: active
        • Base:
          • Name: Liver Disease
          • Drugbank Id: DBCOND0028338
        • Severity:
          • Includes:
            • severe

Food Interactions

  • Avoid alcohol (may increase risk of hepatotoxicity).
  • Take without regard to meals.

Interactions

Type in a drug name to check for interaction with Acetaminophen
Type a drug name in the box above to get started
  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of (R)-warfarin can be increased when combined with Acetaminophen.
(S)-Warfarin
The metabolism of (S)-Warfarin can be increased when combined with Acetaminophen.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Acetaminophen can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be increased when combined with Acetaminophen.
4-Methoxyamphetamine
The metabolism of 4-Methoxyamphetamine can be decreased when combined with Acetaminophen.
5-methoxy-N,N-dimethyltryptamine
The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Acetaminophen.
6-O-benzylguanine
The metabolism of 6-O-benzylguanine can be decreased when combined with Acetaminophen.
8-azaguanine
The metabolism of 8-azaguanine can be decreased when combined with Acetaminophen.
8-chlorotheophylline
The metabolism of 8-chlorotheophylline can be decreased when combined with Acetaminophen.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be increased when combined with Acetaminophen.
9-Deazaguanine
The metabolism of 9-Deazaguanine can be decreased when combined with Acetaminophen.
9-Methylguanine
The metabolism of 9-Methylguanine can be decreased when combined with Acetaminophen.
Abacavir
Acetaminophen may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abatacept
The metabolism of Acetaminophen can be increased when combined with Abatacept.
Abemaciclib
The serum concentration of Abemaciclib can be increased when it is combined with Acetaminophen.
Abiraterone
The serum concentration of Acetaminophen can be increased when it is combined with Abiraterone.
Acalabrutinib
The serum concentration of Acetaminophen can be increased when it is combined with Acalabrutinib.
Acarbose
Acarbose may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Acebutolol
The serum concentration of Acebutolol can be increased when it is combined with Acetaminophen.
Aceclofenac
The risk or severity of adverse effects can be increased when Acetaminophen is combined with Aceclofenac.
24 References
  1. 1 . Kis B, Snipes JA, Busija DW: Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties. J Pharmacol Exp Ther. 2005 Oct;315(1):1-7. Epub 2005 May 6.PubMed: 15879007
  2. 2 . Aronoff DM, Oates JA, Boutaud O: New insights into the mechanism of action of acetaminophen: Its clinical pharmacologic characteristics reflect its inhibition of the two prostaglandin H2 synthases. Clin Pharmacol Ther. 2006 Jan;79(1):9-19.PubMed: 16413237
  3. 3 . Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S: Paracetamol: new vistas of an old drug. CNS Drug Rev. 2006 Fall-Winter;12(3-4):250-75.PubMed: 17227290
  4. 4 . Graham GG, Scott KF: Mechanism of action of paracetamol. Am J Ther. 2005 Jan-Feb;12(1):46-55.PubMed: 15662292
  5. 5 . Ohki S, Ogino N, Yamamoto S, Hayaishi O: Prostaglandin hydroperoxidase, an integral part of prostaglandin endoperoxide synthetase from bovine vesicular gland microsomes. J Biol Chem. 1979 Feb 10;254(3):829-36.PubMed: 104998
  6. 6 . Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL: COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13926-31. Epub 2002 Sep 19.PubMed: 12242329
  7. 7 . Adjei AA, Gaedigk A, Simon SD, Weinshilboum RM, Leeder JS: Interindividual variability in acetaminophen sulfation by human fetal liver: implications for pharmacogenetic investigations of drug-induced birth defects. Birth Defects Res A Clin Mol Teratol. 2008 Mar;82(3):155-65. doi: 10.1002/bdra.20535.PubMed: 18232020
  8. 8 . Hazai E, Vereczkey L, Monostory K: Reduction of toxic metabolite formation of acetaminophen. Biochem Biophys Res Commun. 2002 Mar 8;291(4):1089-94.PubMed: 11866476
  9. 9 . Mazaleuskaya LL, Sangkuhl K, Thorn CF, FitzGerald GA, Altman RB, Klein TE: PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26. doi: 10.1097/FPC.0000000000000150.PubMed: 26049587
  10. 10 . Ennis ZN, Dideriksen D, Vaegter HB, Handberg G, Pottegard A: Acetaminophen for Chronic Pain: A Systematic Review on Efficacy. Basic Clin Pharmacol Toxicol. 2016 Mar;118(3):184-9. doi: 10.1111/bcpt.12527. Epub 2015 Dec 28.PubMed: 26572078
  11. 11 . Bannwarth B, Pehourcq F: [Pharmacologic basis for using paracetamol: pharmacokinetic and pharmacodynamic issues]. Drugs. 2003;63 Spec No 2:5-13.PubMed: 14758786
  12. 12 . Forrest JA, Clements JA, Prescott LF: Clinical pharmacokinetics of paracetamol. Clin Pharmacokinet. 1982 Mar-Apr;7(2):93-107.PubMed: 7039926
  13. 13 . Ricciotti E, FitzGerald GA: Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011 May;31(5):986-1000. doi: 10.1161/ATVBAHA.110.207449.PubMed: 21508345
  14. 14 . Valerie Gerriets; Thomas M. Nappe (2019). Acetaminophen. StatPearls publishing.
  15. 15 . Acetaminophen tablet, DailyMed Link
  16. 16 . Acetaminophen effervescent tablets, Cleveland Clinic Link
  17. 17 . FDA safety communication: FDA has reviewed possible risks of pain medicine use during pregnancy Link
  18. 18 . U.S. National Medical Library: MedlinePlus- Acetaminophen dosing for children Link
  19. 19 . FDA consumer health information: Acetaminophen Link
  20. 20 . FDA : Acetaminophen Information Link
  21. 21 . Using Acetaminophen and Nonsteroidal Anti-inflammatory Drugs Safely Link
  22. 22 . Acetaminophen monograph, suppository File
  23. 23 . Acetaminophen data sheet, ebi.ac.uk File
  24. 24 . Tylenol arthritis pain label, OTC File