Chemical: Drug
acetaminophen

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.


last updated 07/12/2016

1. HCSC Label for acetaminophen,tramadol and CYP2D6

Actionable PGx

Summary

The product monographs for tramadol and acetaminophen (APO-TRAMADOL/ACET) and tramadol (APO-TRAMADOL) note that patients who are CYP2D6 poor metabolizers may have increased tramadol concentrations as compared to those who are CYP2D6 extensive metabolizers.

Annotation

Tramadol/acetaminophen (APO-TRAMADOL/ACET) and tramadol (APO-TRAMADOL) are used to manage moderate to moderately severe pain in adults. Excerpt from the APO-TRAMADOL/ACET and APO-TRAMADOL product monographs:

Approximately 7% of the population has reduced activity of the CYP2D6 isoenzyme of cytochrome P450. These individuals are "poor metabolizers"... Based on a population PK analysis of Phase I studies in healthy subjects, concentrations of tramadol were approximately 20% higher in "poor metabolizers" versus "extensive metabolizers", while M1 concentrations were 40% lower... The full pharmacological impact of these alterations in terms of either efficacy or safety is unknown.

For the complete product monograph text with sections containing pharmacogenetic information highlighted, see the tramadol and acetaminophen product monograph and the tramadol product monograph

*Disclaimer: The contents of this page have not been endorsed by HCSC and are the sole responsibility of PharmGKB.


PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for acetaminophen

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA CYP2D6 *1 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *2 N/A N/A N/A
No VIP available No VIP available VA CYP2E1 *1 N/A N/A N/A
No VIP available No VIP available VA CYP2E1 *5B N/A N/A N/A
No VIP available No VIP available VA G6PD Canton, Taiwan-Hakka, Gifu-like, Agrigento-like N/A N/A N/A
No VIP available No VIP available VA HLA-A *33:03 N/A N/A N/A
No VIP available No VIP available VA HLA-B *41:01 N/A N/A N/A
No VIP available No VIP available VA HLA-B *58:01 N/A N/A N/A
No VIP available No VIP available VA HLA-C *03:02 N/A N/A N/A
No VIP available No VIP available VA HLA-C *08:01 N/A N/A N/A
No VIP available CA VA HLA-DQB1 *02:02 N/A N/A N/A
No VIP available No VIP available VA HLA-DRB1 *04:05:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DRB1 *11:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DRB1 *13:02:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DRB1 *15:02:01 N/A N/A N/A
No VIP available No VIP available VA UGT1A1 *1 N/A N/A N/A
No VIP available No VIP available VA UGT1A1 *28 N/A N/A N/A
No VIP available No VIP available VA UGT1A6 *1a N/A N/A N/A
No VIP available No VIP available VA UGT1A6 *2a N/A N/A N/A
No VIP available No VIP available VA UGT2B15 *1 N/A N/A N/A
No VIP available No VIP available VA UGT2B15 *2 N/A N/A N/A
No VIP available CA VA
rs1042640 NC_000002.11:g.234681544G>C, NC_000002.12:g.233772898G>C, NG_002601.2:g.188155G>C, NG_033238.1:g.17626G>C, NM_000463.2:c.*339G>C, NM_001072.3:c.*339G>C, NM_007120.2:c.*339G>C, NM_019075.2:c.*339G>C, NM_019076.4:c.*339G>C, NM_019077.2:c.*339G>C, NM_019078.1:c.*339G>C, NM_019093.2:c.*339G>C, NM_021027.2:c.*339G>C, NM_205862.1:c.*339G>C, XR_241238.1:n.2134G>C, rs17190748, rs35909575, rs61636700
G > C
SNP
No VIP available CA VA
rs10929303 NC_000002.11:g.234681416T>C, NC_000002.12:g.233772770T>C, NG_002601.2:g.188027T>C, NG_033238.1:g.17498T>C, NM_000463.2:c.*211T>C, NM_001072.3:c.*211T>C, NM_007120.2:c.*211T>C, NM_019075.2:c.*211T>C, NM_019076.4:c.*211T>C, NM_019077.2:c.*211T>C, NM_019078.1:c.*211T>C, NM_019093.2:c.*211T>C, NM_021027.2:c.*211T>C, NM_205862.1:c.*211T>C, XR_241238.1:n.2006T>C, XR_241239.1:n.1969T>C, XR_241240.1:n.2105T>C, XR_241241.1:n.2024T>C, rs35926297, rs59599681
T > C
SNP
No VIP available CA VA
rs12746200 NC_000001.10:g.186849186A>G, NC_000001.11:g.186880054A>G, NG_012203.1:g.56155A>G, NM_001311193.1:c.115+9538A>G, NM_024420.2:c.115+9538A>G, XM_005245267.1:c.4+9310A>G, XM_005245267.2:c.4+9310A>G, XM_005245268.1:c.115+9538A>G, XM_011509641.1:c.136+9538A>G, XM_011509642.1:c.115+9538A>G, XM_011509643.1:c.115+9538A>G, XR_921838.1:n.176+9538A>G, rs17591911
A > G
SNP
No VIP available No Clinical Annotations available VA
rs1799971 NC_000006.11:g.154360797A>G, NC_000006.12:g.154039662A>G, NG_021208.1:g.34162A>G, NM_000914.4:c.118A>G, NM_001008503.2:c.118A>G, NM_001008504.3:c.118A>G, NM_001008505.2:c.118A>G, NM_001145279.3:c.397A>G, NM_001145280.3:c.-11+28644A>G, NM_001145281.2:c.47+29103A>G, NM_001145282.2:c.118A>G, NM_001145283.2:c.118A>G, NM_001145284.3:c.118A>G, NM_001145285.2:c.118A>G, NM_001145286.2:c.118A>G, NM_001285522.1:c.118A>G, NM_001285523.1:c.118A>G, NM_001285524.1:c.397A>G, NP_000905.3:p.Asn40Asp, NP_001008503.2:p.Asn40Asp, NP_001008504.2:p.Asn40Asp, NP_001008505.2:p.Asn40Asp, NP_001138751.1:p.Asn133Asp, NP_001138754.1:p.Asn40Asp, NP_001138755.1:p.Asn40Asp, NP_001138756.1:p.Asn40Asp, NP_001138757.1:p.Asn40Asp, NP_001138758.1:p.Asn40Asp, NP_001272451.1:p.Asn40Asp, NP_001272452.1:p.Asn40Asp, NP_001272453.1:p.Asn133Asp, NR_104348.1:n.252A>G, NR_104349.1:n.252A>G, NR_104350.1:n.252A>G, NR_104351.1:n.252A>G, XM_005267002.1:c.304A>G, XM_006715497.2:c.304A>G, XM_011535849.1:c.397A>G, XP_005267059.1:p.Asn102Asp, XP_006715560.1:p.Asn102Asp, XP_011534151.1:p.Asn133Asp, XR_245534.1:n.304A>G, XR_245535.1:n.304A>G, XR_245536.1:n.304A>G, XR_245537.1:n.304A>G, rs17181017, rs52818856, rs61596185
A > -
A > G
SNP
N40D
VIP No Clinical Annotations available No Variant Annotations available
rs1801030 NC_000016.10:g.28606164C>T, NC_000016.9:g.28617485C>T, NG_028128.1:g.22382G>A, NM_001055.3:c.667G>A, NM_001310136.1:c.121-139262G>A, NM_177529.2:c.667G>A, NM_177530.2:c.667G>A, NM_177534.2:c.667G>A, NM_177536.3:c.433G>A, NP_001046.2:p.Val223Met, NP_803565.1:p.Val223Met, NP_803566.1:p.Val223Met, NP_803878.1:p.Val223Met, NP_803880.1:p.Val145Met, XM_005255522.1:c.667G>A, XP_005255579.1:p.Val223Met, rs61167940, rs8054402
C > T
SNP
V223M
No VIP available CA VA
rs1805034 NC_000018.10:g.62360008C>T, NC_000018.9:g.60027241C>T, NG_008098.1:g.39694C>T, NM_001270949.1:c.575C>T, NM_001270950.1:c.575C>T, NM_001270951.1:c.575C>T, NM_001278268.1:c.533C>T, NM_003839.2:c.575C>T, NM_003839.3:c.575C>T, NP_001257878.1:p.Ala192Val, NP_001257879.1:p.Ala192Val, NP_001257880.1:p.Ala192Val, NP_001265197.1:p.Ala178Val, NP_003830.1:p.Ala192Val, XM_005266777.1:c.575C>T, XM_011526244.1:c.590C>T, XM_011526245.1:c.467C>T, XP_005266834.1:p.Ala192Val, XP_011524546.1:p.Ala197Val, XP_011524547.1:p.Ala156Val, XR_935263.1:n.605C>T, rs57818955
C > T
SNP
A192V
No VIP available CA VA
rs2228246 NC_000020.10:g.39792063A>G, NC_000020.11:g.41163423A>G, NM_002660.2:c.835A>G, NM_182811.1:c.835A>G, NP_002651.2:p.Ser279Gly, NP_877963.1:p.Ser279Gly, XM_005260438.1:c.835A>G, XM_005260438.2:c.835A>G, XM_011528865.1:c.298A>G, XM_011528866.1:c.835A>G, XM_011528867.1:c.835A>G, XP_005260495.1:p.Ser279Gly, XP_011527167.1:p.Ser100Gly, XP_011527168.1:p.Ser279Gly, XP_011527169.1:p.Ser279Gly, XR_244143.1:n.956A>G, XR_936550.1:n.956A>G, rs52803627, rs57350391, rs8192707
A > G
SNP
S279G
No VIP available No Clinical Annotations available VA
rs2231142 NC_000004.11:g.89052323G>T, NC_000004.12:g.88131171G>T, NG_032067.2:g.105152C>A, NM_001257386.1:c.421C>A, NM_004827.2:c.421C>A, NP_001244315.1:p.Gln141Lys, NP_004818.2:p.Gln141Lys, XM_005263354.1:c.421C>A, XM_005263354.2:c.421C>A, XM_005263355.1:c.421C>A, XM_005263355.2:c.421C>A, XM_005263356.1:c.421C>A, XM_005263356.2:c.421C>A, XM_011532420.1:c.421C>A, XP_005263411.1:p.Gln141Lys, XP_005263412.1:p.Gln141Lys, XP_005263413.1:p.Gln141Lys, XP_011530722.1:p.Gln141Lys, rs12721641, rs28365035, rs3736117, rs52809243, rs58973676
G > T
SNP
Q141K
VIP No Clinical Annotations available No Variant Annotations available
rs3760091 NC_000016.10:g.28609479C>G, NC_000016.9:g.28620800C>G, NG_028128.1:g.19067G>C, NM_001055.3:c.-5+452G>C, NM_001310136.1:c.121-142577G>C, NM_177529.2:c.-36+452G>C, NM_177530.2:c.-425G>C, NM_177534.2:c.-624G>C, NM_177536.3:c.139-2402G>C, XM_005255522.1:c.-5+452G>C, rs117385979, rs60448308
C > G
C > T
SNP
VIP No Clinical Annotations available No Variant Annotations available
rs750155 NC_000016.10:g.28609251C>T, NC_000016.9:g.28620572C>T, NG_028128.1:g.19295G>A, NM_001055.3:c.-4-392G>A, NM_001310136.1:c.121-142349G>A, NM_177529.2:c.-35-361G>A, NM_177530.2:c.-197G>A, NM_177534.2:c.-396G>A, NM_177536.3:c.139-2174G>A, XM_005255522.1:c.-4-392G>A
C > T
SNP
No VIP available CA VA
rs8330 NC_000002.11:g.234681645G>C, NC_000002.12:g.233772999G>C, NG_002601.2:g.188256G>C, NG_033238.1:g.17727G>C, NM_000463.2:c.*440G>C, NM_001072.3:c.*440G>C, NM_007120.2:c.*440G>C, NM_019075.2:c.*440G>C, NM_019076.4:c.*440G>C, NM_019077.2:c.*440G>C, NM_019078.1:c.*440G>C, NM_019093.2:c.*440G>C, NM_021027.2:c.*440G>C, NM_205862.1:c.*440G>C, XR_241238.1:n.2235G>C, rs3182134, rs35609787, rs386496306, rs57500970
G > C
SNP
VIP No Clinical Annotations available No Variant Annotations available
rs9282861 NC_000016.10:g.28606193C>T, NC_000016.9:g.28617514C>T, NG_028128.1:g.22353G>A, NM_001055.3:c.638G>A, NM_001310136.1:c.121-139291G>A, NM_177529.2:c.638G>A, NM_177530.2:c.638G>A, NM_177534.2:c.638G>A, NM_177536.3:c.404G>A, NP_001046.2:p.Arg213His, NP_803565.1:p.Arg213His, NP_803566.1:p.Arg213His, NP_803878.1:p.Arg213His, NP_803880.1:p.Arg135His, XM_005255522.1:c.638G>A, XP_005255579.1:p.Arg213His, rs17844870, rs17857585
C > T
SNP
R213H
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • APAP
  • Acetaminofen
  • Paracetamol
  • Paracetamolo
  • Paracetanol
Trade Names
  • Abenol
  • Abensanil
  • Acamol
  • Accu-Tap
  • Acephen
  • Aceta Elixir
  • Aceta Tablets
  • Acetagesic
  • Acetalgin
  • Actamin
  • Actimol
  • Algotropyl
  • Allay
  • Alpiny
  • Alpinyl
  • Alvedon
  • Amadil
  • Aminofen
  • Anacin
  • Anacin-3
  • Anaflon
  • Anapap
  • Anelix
  • Anhiba
  • Apacet
  • Apadon
  • Apamid
  • Apamide
  • Atasol
  • Banesin
  • Bayer Select
  • Bickie-mol
  • Bucet
  • Butapap
  • Calpol
  • Captin
  • Cetadol
  • Clixodyne
  • Co-Gesic
  • Conacetol
  • Dafalgan
  • Dapa
  • Dapa X-S
  • Darvocet
  • Datril
  • Dimindol
  • Dirox
  • Disprol
  • Dolene AP-65
  • Doliprane
  • Dolprone
  • Drixoral Plus
  • Dularin
  • Dymadon
  • Dypap
  • Elixodyne
  • Enelfa
  • Eneril
  • Eu-Med
  • Excedrin
  • Exdol
  • Febridol
  • Febrilix
  • Febrinol
  • Febro-Gesic
  • Febrolin
  • Fendon
  • Feverall
  • Fevor
  • Finimal
  • Gelocatil
  • Genapap
  • Genebs
  • Hedex
  • Homoolan
  • Hy-Phen
  • Injectapap
  • Janupap
  • Korum
  • Lestemp
  • Liquagesic
  • Liquiprin
  • Lonarid
  • Lyteca
  • Momentum
  • Multin
  • NAPA
  • Napafen
  • Napap
  • Naprinol
  • Nealgyl
  • Nebs
  • Neopap
  • Neotrend
  • Nobedon
  • Norco
  • Oraphen-PD
  • Ortensan
  • Pacemo
  • Painex
  • Paldesic
  • Panadol
  • Panaleve
  • Panasorb
  • Panets
  • Panex
  • Panofen
  • Papa-Deine
  • Paracet
  • Parapan
  • Paraspen
  • Parelan
  • Parmol
  • Pasolind
  • Pasolind N
  • Pedric
  • Phenaphen
  • Phenaphen Caplets
  • Phendon
  • Phrenilin
  • Phrenilin Forte
  • Prompt
  • Propacet 100
  • Proval #3
  • Pyrinazine
  • Redutemp
  • Rivalgyl
  • Robigesic
  • Rounox
  • SK-Apap
  • Salzone
  • Sedapap
  • Servigesic
  • Snaplets-FR
  • St. Joseph Fever Reducer
  • Suppap
  • Synalgos-Dc-A
  • Tabalgin
  • Talacen
  • Tapanol
  • Tapar
  • Tavist Allergy/Sinus/Headache
  • Temlo
  • Tempanal
  • Tempra
  • Tencon
  • Tibinide
  • Tibizide
  • Tisin
  • Tisiodrazida
  • Tizide
  • Tralgon
  • Triaprin
  • Tussapap
  • Tycolet
  • Tylenol
  • Ultracet
  • Valadol
  • Valgesic
  • Valorin
  • Valorin Extra
  • Wygesic
Brand Mixture Names
  • Amacodone (acetaminophen + hydrocodone bitartrate)
  • Anexsia (acetaminophen + hydrocodone bitartrate)
  • Anodynos (acetaminophen + hydrocodone bitartrate)
  • Anolor (acetaminophen + butalbital + caffeine)
  • Bancap (acetaminophen + hydrocodone bitartrate)
  • CoGesic (acetaminophen + hydrocodone bitartrate)
  • Dolacet (acetaminophen + hydrocodone bitartrate)
  • Duradyne (acetaminophen + hydrocodone bitartrate)
  • Endolor (acetaminophen + butalbital + caffeine)
  • Esgic (acetaminophen + butalbital + caffeine)
  • Fioricet (acetaminophen + butalbital + caffeine)
  • Hydrocet (acetaminophen + hydrocodone bitartrate)
  • Hydrogesic (acetaminophen + hydrocodone bitartrate)
  • Lorcet (acetaminophen + hydrocodone bitartrate)
  • Lortab (acetaminophen + hydrocodone bitartrate)
  • Margesic (acetaminophen + hydrocodone bitartrate)
  • Norcet (acetaminophen + hydrocodone bitartrate)
  • Oxycet (acetaminophen + oxycodone hydrochloride)
  • Percocet (acetaminophen + oxycodone hydrochloride)
  • Roxicet (acetaminophen + oxycodone hydrochloride)
  • Roxilox (acetaminophen + oxycodone hydrochloride)
  • Stagesic (acetaminophen + hydrocodone bitartrate)
  • TGesic (acetaminophen + hydrocodone bitartrate)
  • Tylox (acetaminophen + oxycodone hydrochloride)
  • Vicodin (acetaminophen + hydrocodone bitartrate)
  • Zebutal (acetaminophen + butalbital + caffeine)
  • Zydone (acetaminophen + hydrocodone bitartrate)

PharmGKB Accession Id

PA448015

Type(s):

Drug

Description

Acetaminophen, also known as paracetamol, is commonly used for its analgesic and antipyretic effects. Its therapeutic effects are similar to salicylates, but it lacks anti-inflammatory, antiplatelet, and gastric ulcerative effects.

Source: Drug Bank

Indication

For temporary relief of fever and minor aches and pains.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Acetaminophen is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin (PG) synthesis. Unlike NSAIDs, acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects. While aspirin acts as an irreversible inhibitor of COX and directly blocks the enzyme's active site, studies have found that acetaminophen indirectly blocks COX, and that this blockade is ineffective in the presence of peroxides. This might explain why acetaminophen is effective in the central nervous system and in endothelial cells but not in platelets and immune cells which have high levels of peroxides. Studies also report data suggesting that acetaminophen selectively blocks a variant of the COX enzyme that is different from the known variants COX-1 and COX-2. This enzyme is now referred to as COX-3. Its exact mechanism of action is still poorly understood, but future research may provide further insight into how it works. The antipyretic properties of acetaminophen are likely due to direct effects on the heat-regulating centres of the hypothalamus resulting in peripheral vasodilation, sweating and hence heat dissipation.

Source: Drug Bank

Pharmacology

Acetaminophen (USAN) or Paracetamol (INN) is a widely used analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains. It is a major ingredient in numerous cold and flu medications and many prescription analgesics. It is extremely safe in standard doses, but because of its wide availability, deliberate or accidental overdoses are not uncommon. Acetaminophen, unlike other common analgesics such as aspirin and ibuprofen, has no anti-inflammatory properties or effects on platelet function, and it is not a member of the class of drugs known as non-steroidal anti-inflammatory drugs or NSAIDs. At therapeutic doses acetaminophen does not irritate the lining of the stomach nor affect blood coagulation, kidney function, or the fetal ductus arteriosus (as NSAIDs can). Like NSAIDs and unlike opioid analgesics, acetaminophen does not cause euphoria or alter mood in any way. Acetaminophen and NSAIDs have the benefit of being completely free of problems with addiction, dependence, tolerance and withdrawal. Acetaminophen is used on its own or in combination with pseudoephedrine, dextromethorphan, chlorpheniramine, diphenhydramine, doxylamine, codeine, hydrocodone, or oxycodone.

Source: Drug Bank

Food Interaction

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

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Approximately 90 to 95% of a dose is conjugated in the liver with glucuronic acid and sulfuric acid. A small percentage of acetaminophen is oxidized by CYP2E1 to form N-acetyl-p-benzo-quinone imine (NAPQI), a toxic metabolite which is then conjugated to glutathione and excreted renally. Accumulation of NAPQI may occur if primary metabolic pathways are saturated.

Source: Drug Bank

Protein Binding

25%

Source: Drug Bank

Absorption

Rapid and almost complete

Source: Drug Bank

Half-Life

1 to 4 hours

Source: Drug Bank

Toxicity

Oral, mouse: LD50 = 338 mg/kg; Oral, rat: LD50 = 1944 mg/kg. Acetaminophen is metabolized primarily in the liver, where most of it is converted to inactive compounds by conjugation with glucuronic acid and, to a lesser extent, sulfuric acid. Conjugates are then excreted by the kidneys. Only a small portion is excreted in unchanged in urine or oxidized via the hepatic cytochrome P450 enzyme system (CYP2E1). Metabolism via CYP2E1 produces a toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI). The toxic effects of acetaminophen are due to NAPQI, not acetaminophen itself nor any of the major metabolites. At therapeutic doses, NAPQI reacts with the sulfhydryl group of glutathione to produce a non-toxic conjugate that is excreted by the kidneys. High doses of acetaminophen may cause glutathione depletion, accumulation of NAPQI and hepatic necrosis. The maximum daily dose of acetaminophen is 4 g. Liver failure has been observed at doses as low as 6 g per day. As such, the maximum daily and single dose of acetaminophen is currently being reviewed in some countries. N-acetyl-cysteine, a precursor of glutathione, may be administered in the event of acetaminophen toxicity.

Source: Drug Bank

Route of Elimination

Approximately 80% of acetaminophen is excreted in the urine after conjugation and about 3% is excreted unchanged.

Source: Drug Bank

Chemical Properties

Chemical Formula

C8H9NO2

Source: Drug Bank

Isomeric SMILES

CC(=O)Nc1ccc(cc1)O

Source: OpenEye

Canonical SMILES

CC(=O)NC1=CC=C(O)C=C1

Source: Drug Bank

Average Molecular Weight

151.1626

Source: Drug Bank

Monoisotopic Molecular Weight

151.063328537

Source: Drug Bank

SMILES

CC(=O)NC1=CC=C(O)C=C1

Source: Drug Bank

InChI String

InChI=1S/C8H9NO2/c1-6(10)9-7-2-4-8(11)5-3-7/h2-5,11H,1H3,(H,9,10)

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Acetaminophen Pathway (therapeutic doses), Pharmacokinetics
    Stylized diagram showing acetaminophen metabolism and transport in the liver.
  1. Acetaminophen Pathway (toxic doses), Pharmacokinetics
    Stylized diagram showing acetaminophen metabolism at higher acetaminophen doses (toxic doses) in the liver

External Pathways

Links to non-PharmGKB pathways.

  1. mechanism of acetaminophen activity and toxicity - (BioCarta via Pathway Interaction Database)

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
PTGS1 (source: Drug Bank)
PTGS2 (source: Drug Bank)

Curated Information ?

Drug Interactions

Interaction Description
acetaminophen - acenocoumarol Increases the anticoagulant effect (source: Drug Bank)
acetaminophen - dicumarol Increases the anticoagulant effect (source: Drug Bank)
acetaminophen - imatinib Increased hepatic toxicity of both agents (source: Drug Bank)
acetaminophen - isoniazid Risk of hepatotoxicity (source: Drug Bank)
acetaminophen - warfarin Acetaminophen increases the anticoagulant effect (source: Drug Bank)
imatinib - acetaminophen Increased hepatic toxicity of both agents (source: Drug Bank)
imatinib - acetaminophen Increased hepatic toxicity of both agents (source: Drug Bank)
isoniazid - acetaminophen Risk of hepatotoxicity (source: Drug Bank)
isoniazid - acetaminophen Risk of hepatotoxicity (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to acetaminophen: 71

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Can Paracetamol (Acetaminophen) be administered to Patients with Liver Impairment?. British journal of clinical pharmacology. 2015. Hayward Kelly L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association study of genetic variants in PLA2G4A, PLCG1, LAT, SYK, and TNFRS11A genes in NSAIDs-induced urticaria and/or angioedema patients. Pharmacogenetics and genomics. 2015. Ayuso Pedro, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenetics and genomics. 2015. Mazaleuskaya Liudmila L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Liver injury with novel oral anticoagulants: assessing post-marketing reports in the US Food and Drug Administration Adverse Event Reporting System. British journal of clinical pharmacology. 2015. Raschi Emanuel, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Increased bioavailability of phenylephrine by co-administration of acetaminophen: results of four open-label, crossover pharmacokinetic trials in healthy volunteers. European journal of clinical pharmacology. 2015. Atkinson Hartley C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Prenatal and infant exposure to acetaminophen and ibuprofen and the risk for wheeze and asthma in children. The Journal of allergy and clinical immunology. 2015. Sordillo Joanne E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetic insights into migraine treatment in children. Pharmacogenomics. 2014. Gentile Giovanna, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic Factors Affecting Gene Transcription and Catalytic Activity of UDP-Glucuronosyltransferases in Human Liver. Human molecular genetics. 2014. Liu Wanqing, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Candidate Gene Polymorphisms in Patients with Acetaminophen-Induced Acute Liver Failure. Drug metabolism and disposition: the biological fate of chemicals. 2013. Court Michael H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharmaceutical research. 2013. McGill Mitchell R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Glutathione transferases, regulators of cellular metabolism and physiology. Biochimica et biophysica acta. 2013. Board Philip G, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
The UDP-glucuronosyltransferase (UGT) 1A polymorphism c.2042C>G (rs8330) is associated with increased human liver acetaminophen glucuronidation, increased UGT1A exon 5a/5b splice variant mRNA ratio, and decreased risk of unintentional acetaminophen-induced acute liver failure. The Journal of pharmacology and experimental therapeutics. 2013. Court Michael H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Acetaminophen administration in a patient with Gilbert's syndrome. Pediatrics international : official journal of the Japan Pediatric Society. 2012. Nakagawa Taku, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A review of acetaminophen poisoning. Critical care clinics. 2012. Hodgman Michael J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Human mu-opioid receptor gene A118G polymorphism predicts the efficacy of tramadol/acetaminophen combination tablets (ultracet) in oxaliplatin-induced painful neuropathy. Cancer. 2012. Liu Yu-Chang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
UGT1A6 and UGT2B15 polymorphisms and acetaminophen conjugation in response to a randomized, controlled diet of select fruits and vegetables. Drug metabolism and disposition: the biological fate of chemicals. 2011. Navarro Sandi L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A study of HLA class I and class II 4-digit allele level in Stevens-Johnson syndrome and toxic epidermal necrolysis. International journal of immunogenetics. 2011. Cristallo A F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Acetaminophen-NAPQI Hepatotoxicity: A Cell Line Model System Genome-Wide Association Study. Toxicological sciences : an official journal of the Society of Toxicology. 2011. Moyer Ann M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Pharmacokinetics of intravenous paracetamol in elderly patients. Clinical pharmacokinetics. 2011. Liukas Antti, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacometabonomics as an effector for personalized medicine. Pharmacogenomics. 2011. Nicholson Jeremy K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Methylxanthines and pain. Handbook of experimental pharmacology. 2011. Sawynok Jana. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. Drug safety : an international journal of medical toxicology and drug experience. 2010. Youngster Ilan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Use of pharmaco-metabonomics for early prediction of acetaminophen-induced hepatotoxicity in humans. Clinical pharmacology and therapeutics. 2010. Winnike J H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The influence of ondansetron on the analgesic effect of acetaminophen after laparoscopic hysterectomy. Clinical pharmacology and therapeutics. 2010. Jokela R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Use of transcriptomics in understanding mechanisms of drug-induced toxicity. Pharmacogenomics. 2010. Cui Yuxia, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
An integrative genomic analysis identifies Bhmt2 as a diet-dependent genetic factor protecting against acetaminophen-induced liver toxicity. Genome research. 2010. Liu Hong-Hsing, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Developmental pharmacogenetics: a general paradigm for application to neonatal pharmacology and toxicology. Clinical pharmacology and therapeutics. 2009. Leeder J S. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Warfarin interactions with substances listed in drug information compendia and in the FDA-approved label for warfarin sodium. Clinical pharmacology and therapeutics. 2009. Anthony M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
O-demethylation of codeine to morphine inhibited by low-dose levomepromazine. European journal of clinical pharmacology. 2009. Vevelstad M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proceedings of the National Academy of Sciences of the United States of America. 2009. Clayton T Andrew, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
In vivo glucuronidation activity of drugs in neonates: extensive interindividual variability despite their young age. Therapeutic drug monitoring. 2009. Allegaert Karel, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Very important pharmacogene summary: sulfotransferase 1A1. Pharmacogenetics and genomics. 2009. Hildebrandt Michelle, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Acetaminophen hepatotoxicity and acute liver failure. Journal of clinical gastroenterology. 2009. Chun Linda J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. Xenobiotica; the fate of foreign compounds in biological systems. 2009. Laine J E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Acetaminophen-associated hepatic injury: evaluation of acetaminophen protein adducts in children and adolescents with acetaminophen overdose. Clinical pharmacology and therapeutics. 2008. James L P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Acetaminophen reinforces descending inhibitory pain pathways. Clinical pharmacology and therapeutics. 2008. Pickering G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interindividual variability in acetaminophen sulfation by human fetal liver: implications for pharmacogenetic investigations of drug-induced birth defects. Birth defects research. Part A, Clinical and molecular teratology. 2008. Adjei Araba A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008. Cappellini M D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Complicated pain management in a CYP450 2D6 poor metabolizer. Pain practice : the official journal of World Institute of Pain. 2007. Foster Adriana, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Induction of hepatobiliary efflux transporters in acetaminophen-induced acute liver failure cases. Drug metabolism and disposition: the biological fate of chemicals. 2007. Barnes Sarah N, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Apnea in a child after oral codeine: a genetic variant - an ultra-rapid metabolizer. Paediatric anaesthesia. 2007. Voronov Polina, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Disposition of acetaminophen at 4, 6, and 8 g/day for 3 days in healthy young adults. Clinical pharmacology and therapeutics. 2007. Gelotte C K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of opioids. Clinical pharmacology and therapeutics. 2007. Somogyi Andrew A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Safety and pharmacokinetics of paracetamol following intravenous administration of 5 g during the first 24 h with a 2-g starting dose. Clinical pharmacology and therapeutics. 2007. Gregoire N, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Effects of combined UDP-glucuronosyltransferase (UGT) 1A1*28 and 1A6*2 on paracetamol pharmacokinetics in beta-thalassemia/HbE. Pharmacology. 2007. Tankanitlert Jeeranut, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Kinetics of acetaminophen glucuronidation by UDP-glucuronosyltransferases 1A1, 1A6, 1A9 and 2B15. Potential implications in acetaminophen-induced hepatotoxicity. Chemical research in toxicology. 2006. Mutlib Abdul E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Profound metoprolol-induced bradycardia precipitated by acetaminophen-propoxyphene. Clinical pharmacology and therapeutics. 2006. Marraffa Jeanna M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Phenobarbital and phenytoin increased acetaminophen hepatotoxicity due to inhibition of UDP-glucuronosyltransferases in cultured human hepatocytes. Toxicological sciences : an official journal of the Society of Toxicology. 2005. Kostrubsky Seva E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Idiosyncratic drug hepatotoxicity. Nature reviews. Drug discovery. 2005. Kaplowitz Neil. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). The Journal of pharmacology and experimental therapeutics. 2005. Krishnaswamy Soundararajan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Human UGT1A6 pharmacogenetics: identification of a novel SNP, characterization of allele frequencies and functional analysis of recombinant allozymes in human liver tissue and in cultured cells. Pharmacogenetics. 2004. Nagar Swati, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Glucuronidation of acetaminophen is independent of UGT1A1 promotor genotype. International journal of clinical pharmacology and therapeutics. 2004. Rauchschwalbe S K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Glutathione, glutathione-dependent enzymes and antioxidant status in erythrocytes from children treated with high-dose paracetamol. British journal of clinical pharmacology. 2003. Kozer Eran, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Reduction of toxic metabolite formation of acetaminophen. Biochemical and biophysical research communications. 2002. Hazai Eszter, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Med-psych drug-drug interactions update. Psychosomatics. 2002. Armstrong Scott C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms. The Journal of pharmacology and experimental therapeutics. 2001. Court M H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches. Critical reviews in toxicology. 2001. Bessems J G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Involvement of human cytochrome P450 2D6 in the bioactivation of acetaminophen. Drug metabolism and disposition: the biological fate of chemicals. 2000. Dong H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6. Chemical research in toxicology. 1998. Chen W, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Quick onset of severe abdominal pain after codeine in an ultrarapid metabolizer of debrisoquine. Therapeutic drug monitoring. 1997. Dalén P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Acetaminophen metabolism in patients with different cytochrome P-4502E1 genotypes. Alcoholism, clinical and experimental research. 1996. Ueshima Y, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Paracetamol glucuronidation by recombinant rat and human phenol UDP-glucuronosyltransferases. Biochemical pharmacology. 1993. Bock K W, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Concise review: methemoglobinemia. American journal of hematology. 1993. Mansouri A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). The New England journal of medicine. 1988. Smilkstein M J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Deficiency in bilirubin UDP-glucuronyl transferase as a genetic determinant of acetaminophen toxicity. The Journal of pharmacology and experimental therapeutics. 1988. de Morais S M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Plasma glutathione S-transferase measurements after paracetamol overdose: evidence for early hepatocellular damage. Gut. 1985. Beckett G J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Paracetamol overdosage. Pharmacological considerations and clinical management. Drugs. 1983. Prescott L F. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Treatment of severe acetaminophen poisoning with intravenous acetylcysteine. Archives of internal medicine. 1981. Prescott L F. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Drug-induced haemolysis in glucose-6-phosphate dehydrogenase deficiency. British medical journal. 1976. Chan T K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The effects of hepatic and renal damage on paracetamol metabolism and excretion following overdosage. A pharmacokinetic study. British journal of pharmacology. 1973. Prescott L F, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
50580-508-20
DrugBank:
DB00316
ChEBI:
2386
KEGG Compound:
C06804
KEGG Drug:
D00217
PubChem Compound:
1983
PubChem Substance:
46506142
7847284
Drugs Product Database (DPD):
2269120
BindingDB:
26197
ChemSpider:
1906
Therapeutic Targets Database:
DAP001436
FDA Drug Label at DailyMed:
45e3d38a-1e8b-4071-8f42-532e04f5b953

Clinical Trials

These are trials that mention acetaminophen and are related to either pharmacogenetics or pharmacogenomics.

No trials found.

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Sources for PharmGKB drug information: DrugBank, PubChem.