Acetaminophen


Description

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) [

Read more

Pharmacology

Indication

In general, acetaminophen is used for the treatment of mild to moderate pain and reduction of fever... Read more

Pharmacodynamic

Animal and clinical studies have determined that acetaminophen has both antipyretic and analgesic ef... Read more

Mechanism of action

Although acetaminophen's exact mechanism of action has not been fully established, according to the... Read more

Absorption

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

Protein binding

The binding of acetaminophen to plasma proteins is low (ranging from 10% to 25%), when given at ther... Read more

Volume of distribution

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

Clearance

Adults: 0.27 L/h/kg following a 15 mg/kg intravenous (IV) dose [FDA label].Children: 0.34 L/h/kg fol... Read more

Half life

The half-life for adults is 2.5 h after an intravenous dose of 15 mg/kg [FDA label]. After an over... Read more

Route of elimination

Acetaminophen metabolites are mainly excreted in the urine. Less than 5% is excreted in the urine as... Read more

Toxicity

LD50 = 338 mg/kg (oral, mouse); LD50 = 1944 mg/kg (oral, rat) [ Read more


Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Nausea US
  • adult
  • Kind: experimental
    • Percent: 34%
  • Kind: placebo
    • Percent: 31%
  • Clinical Trial
    Vomiting US
    • adult
  • Kind: experimental
    • Percent: 15%
  • Kind: placebo
    • Percent: 11%
  • Clinical Trial
    Pyrexia US
    • adult
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 14%
  • Clinical Trial
    Headache US
    • adult
  • Kind: experimental
    • Percent: 10%
  • Kind: placebo
    • Percent: 9%
  • Clinical Trial
    Insomnia US
    • adult
  • Kind: experimental
    • Percent: 7%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Atelectasis US
    • pediatric
  • Kind: experimental
    • Percent: ≥ 5
  • Agitation US
    • pediatric
  • Kind: experimental
    • Percent: ≥ 5
  • Nausea US
    • pediatric
  • Kind: experimental
    • Percent: ≥ 5
  • Vomiting US
    • pediatric
  • Kind: experimental
    • Percent: ≥ 5
  • Nausea US
    • pediatric
  • Kind: experimental
    • Percent: ≥ 5
  • Constipation US
    • pediatric
  • Kind: experimental
    • Percent: ≥ 5
  • Pruritis US
    • pediatric
  • Kind: experimental
    • Percent: ≥ 5
  • Nausea US
    • pediatric
  • Kind: experimental
    • Percent: >5%
  • Clinical Trial
    Constipation US
    • pediatric
  • Kind: experimental
    • Percent: >5%
  • Clinical Trial
    Pruritus US
    • pediatric
  • Kind: experimental
    • Percent: >5%
  • Clinical Trial
    Vomiting US
    • pediatric
  • Kind: experimental
    • Percent: >5%
  • Clinical Trial
    Hypotension US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Hypertension(HTN) US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Rash US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Periorbital edema US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Wheezing US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Stridor US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Pleural Effusion US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Hypoxia US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Edema, Pulmonary US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Oliguria US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Insomnia US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Headache US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Pain in extremity US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Muscle Spasm US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Hypervolemia US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Hypophosphatemia US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Hypomagnesemia US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Hypokalemia US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Albumin decreased US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Hepatic enzyme increase US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Pyrexia US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Edema peripheral US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Diarrhea US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Tachycardia US
    • pediatric
  • Kind: experimental
    • Percent: >1
  • Hypokalemia US
    • adult
  • Kind: experimental
    • Value: >0.05%
  • Kind: experimental
    • Percent: 1%
    • Value: >0.05%
  • Clinical Trial
    Muscle Spasms US
    • adult
  • Kind: experimental
    • Value: >0.05%
  • Kind: experimental
    • Percent: 1%
    • Value: >0.05%
  • Clinical Trial
    Aspartate aminotransferase increased US
    • adult
  • Kind: experimental
    • Value: >0.05%
  • Kind: experimental
    • Percent: 1%
    • Value: >0.05%
  • Clinical Trial
    Breath sounds abnormal US
    • adult
  • Kind: experimental
    • Percent: 1%
    • Value: >0.05%
  • Kind: experimental
    • Value: >0.05%
  • Clinical Trial
    Infusion site pain US
    • adult
  • Kind: experimental
    • Value: >0.05%
  • Kind: experimental
    • Percent: 1%
    • Value: >0.05%
  • Clinical Trial
    Edema peripheral US
    • adult
  • Kind: experimental
    • Percent: 1%
    • Value: >0.05%
  • Kind: experimental
    • Value: >0.05%
  • Clinical Trial
    Anemia US
    • adult
  • Kind: experimental
    • Value: >0.05%
  • Kind: experimental
    • Percent: 1%
    • Value: >0.05%
  • Clinical Trial
    Fatigue US
    • adult
  • Kind: experimental
    • Percent: 1%
    • Value: >0.05%
  • Kind: experimental
    • Value: >0.05%
  • Clinical Trial
    Anxiety US
    • adult
  • Kind: experimental
    • Value: >0.05%
  • Kind: experimental
    • Percent: 1%
    • Value: >0.05%
  • Clinical Trial
    Trismus US
    • adult
  • Kind: experimental
    • Percent: 1%
    • Value: >0.05%
  • Kind: experimental
    • Value: >0.05%
  • Clinical Trial

    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

    The metabolism of (R)-warfarin can be increased when combined with Acetaminophen.
    The metabolism of (S)-Warfarin can be increased when combined with Acetaminophen.
    The metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Acetaminophen.
    The metabolism of 4-hydroxycoumarin can be increased when combined with Acetaminophen.
    The metabolism of 4-Methoxyamphetamine can be decreased when combined with Acetaminophen.
    The metabolism of 5-androstenedione can be increased when combined with Acetaminophen.
    The metabolism of Acetaminophen can be decreased when combined with 6-Deoxyerythronolide B.
    The metabolism of 6-O-benzylguanine can be decreased when combined with Acetaminophen.
    The metabolism of 7-ethyl-10-hydroxycamptothecin can be increased when combined with Acetaminophen.
    The metabolism of 8-azaguanine can be decreased when combined with Acetaminophen.
    The metabolism of 8-chlorotheophylline can be decreased when combined with Acetaminophen.
    The metabolism of 9-aminocamptothecin can be increased when combined with Acetaminophen.
    The metabolism of 9-Deazaguanine can be decreased when combined with Acetaminophen.
    The metabolism of 9-Methylguanine can be decreased when combined with Acetaminophen.
    Acetaminophen may decrease the excretion rate of Abacavir which could result in a higher serum level.
    The metabolism of Acetaminophen can be increased when combined with Abatacept.
    The serum concentration of Abemaciclib can be increased when it is combined with Acetaminophen.
    The serum concentration of Acetaminophen can be increased when it is combined with Abiraterone.
    The serum concentration of Acetaminophen can be increased when it is combined with Acalabrutinib.
    Acarbose may decrease the excretion rate of Acetaminophen which could result in a higher serum level.

    References

    • 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 . 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 . 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 . Graham GG, Scott KF: Mechanism of action of paracetamol. Am J Ther. 2005 Jan-Feb;12(1):46-55. [PubMed: 15662292]
    • 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 . 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 . 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 . 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 . 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 . 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 . Bannwarth B, Pehourcq F: [Pharmacologic basis for using paracetamol: pharmacokinetic and pharmacodynamic issues]. Drugs. 2003;63 Spec No 2:5-13. [PubMed: 14758786]
    • 12 . Forrest JA, Clements JA, Prescott LF: Clinical pharmacokinetics of paracetamol. Clin Pharmacokinet. 1982 Mar-Apr;7(2):93-107. [PubMed: 7039926]
    • 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 . Valerie Gerriets; Thomas M. Nappe (2019). Acetaminophen. StatPearls publishing.
    • 15 . Acetaminophen tablet, DailyMed [Link]
    • 16 . Acetaminophen effervescent tablets, Cleveland Clinic [Link]
    • 17 . FDA safety communication: FDA has reviewed possible risks of pain medicine use during pregnancy [Link]
    • 18 . U.S. National Medical Library: MedlinePlus- Acetaminophen dosing for children [Link]
    • 19 . FDA consumer health information: Acetaminophen [Link]
    • 20 . FDA : Acetaminophen Information [Link]
    • 21 . Using Acetaminophen and Nonsteroidal Anti-inflammatory Drugs Safely [Link]
    • 22 . Acetaminophen monograph, suppository [File]
    • 23 . Acetaminophen data sheet, ebi.ac.uk [File]
    • 24 . Tylenol arthritis pain label, OTC [File]

    Recent Questions