Drug/Small Molecule:
codeine

last updated 01/24/2014

CPIC Dosing Guideline for codeine and CYP2D6

Summary

Alternate analgesics are recommended for CYP2D6 ultrarapid and poor metabolizers. A label recommended age- or weight-specific codeine dose is warranted for CYP2D6 extensive and intermediate metabolizers.

Annotation

Please see below for full details of these guidelines, with supporting evidence and disclaimers.

Guidelines regarding the use of pharmacogenomic tests in dosing for codeine have been published in 2012 in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and have been updated in 2014.

Download updated guideline: article (update) and supplement (update)
Download original guideline: article and supplement

Excerpt from the codeine dosing guidelines:

The table below summarizes the therapeutic recommendations for codeine based on CYP2D6 phenotype. A standard starting dose of codeine, as recommended in the product label, is warranted in patients with an extensive metabolizer phenotype (i.e., a CYP2D6 activity score of 1.0 to 2.0). Likewise, a standard starting dose of codeine is warranted in patients with an intermediate metabolizer phenotype (i.e., a CYP2D6 activity score of 0.5); these patients should be monitored closely for less than optimal response and should be offered an alternative analgesic if required. If the CYP2D6 substrate tramadol is selected as alternative therapy in intermediate metabolizers, close monitoring should be carried out because of the possibility of low response.

If clinical genotyping identifies a patient as a CYP2D6 poor metabolizer (i.e., a CYP2D6 activity score of 0), current evidence suggests that the use of codeine be avoided because of the possibility of lack of effect, and that an alternative analgesic should be used. That is, it may be preferable to use alternative analgesics that are not affected by this CYP2D6 phenotype, including morphine and non-opioid analgesics, in poor metabolizers. There is insufficient evidence in the literature to recommend a higher dose of codeine in poor metabolizers, especially given that adverse effects do not differ between poor metabolizers and extensive metabolizers.

In a patient identified as a CYP2D6 ultrarapid metabolizer (i.e., a CYP2D6 activity score of >2.0), the choice of an alternative analgesic should be made to avoid the risk of severe toxicity associated with a "normal" dose of codeine. That is, it may be preferable to use alternative analgesics that are not affected by this CYP2D6 phenotype, including morphine and non-opioid analgesics, in ultrarapid metabolizers.

Recommended dosing of codeine by CYP2D6 Phenotype

CYP2D6 genotype is expected to be equally reliable for inferring phenotype status from genotype in children as in adults. Codeine is not recommended in children less than 2 years of age, but presumably would carry additional dangers in neonates and young children who are ultrarapid metabolizers. The codeine drug label includes a black box warning against codeine use to manage post-operative pain in children following tonsillectomy with or without adenoidectomy.

Please see below for full details of these guidelines, with supporting evidence and disclaimers.

Likely phenotype* Activity score Genotypes Examples of diplotypes Implications for codeine metabolism Recommendations for codeine therapy Classification of recommendation for codeine therapy Considerations for alternative opioids
Ultrarapid metabolizer (~1-2% of patients) >2.0 An individual carrying more than two copies of functional alleles *1/*1xN, *1/*2xN Increased formation of morphine following codeine administration, leading to higher risk of toxicity Avoid codeine use due to potential for toxicity. Strong Alternatives that are not affected by this CYP2D6 phenotype include morphine and non-opioid analgesics. Tramadol, and to a lesser extent hydrocodone and oxycodone, are not good alternatives because their metabolism is affected by CYP2D6 activity.1,2
Extensive metabolizer (~77-92% of patients) 1.0-2.0** An individual carrying two alleles encoding full or reduced function or one full function allele together with either one nonfunctional or one reduced-function allele *1/*1, *1/*2, *2/*2, *1/*41, *1/*4, *2/*5, *10/*10 Normal morphine formation Use label recommended age- or weight-specific dosing. Strong
Intermediate metabolizer (~2-11% of patients) 0.5** An individual carrying one reduced and one nonfunctional allele *4/*10, *5/*41 Reduced morphine formation Use label recommended age- or weight-specific dosing. If no response, consider alternative analgesics such as morphine or a non-opioid. Moderate Monitor tramadol use for response.
Poor metabolizer (~5-10% of patients) 0 An individual carrying no functional alleles *4/*4, *4/*5, *5/*5, *4/*6 Greatly reduced morphine formation following codeine administration, leading to insufficient pain relief Avoid codeine use due to lack of efficacy. Strong Alternatives that are not affected by this CYP2D6 phenotype include morphine and non-opioid analgesics. Tramadol, and to a lesser extent hydrocodone and oxycodone, are not good alternatives because their metabolism is affected by CYP2D6 activity; these agents should be avoided.1,2

*Frequency estimates are based on data from Caucasians and may differ substantially for other ethnicities. See Supplementary Data for estimates of phenotype frequencies among different ethnic/geographic groups.

**Note that some investigators define patients with an activity score of 0.5 and 1.0 as intermediate metabolizers and define patients with an activity score of 1.5 and 2.0 as extensive metabolizers. Classifying patients with an activity score of 1.0 as extensive metabolizers in this guideline is based on data specific for formation of morphine from codeine in these patients.

1 There is substantial evidence for decreased efficacy of tramadol in poor metabolizers and a single case report of toxicity in an ultrarapid metabolizer with renal impairment following tramadol post-surgery. Use of other analgesics in CYP2D6 poor and ultrarapid metabolizers may therefore be preferable (see updated guideline).
2 Some other opioid analgesics are metabolized by CYP2D6, such as hydrocodone and oxycodone. To avoid treatment complications, opioids that are not metabolized by CYP2D6, including morphine, oxymorphone, buprenorphine, fentanyl, methadone and hydromorphone, along with non-opioid analgesics, may be considered as alternatives for use in CYP2D6 poor and ultrarapid metabolizers.


last updated 08/10/2011

Dutch Pharmacogenetics Working Group Guideline for codeine and CYP2D6

Summary

Select alternative analgesics for patients who are CYP2D6 poor metabolizers, intermediate metabolizers, or ultrarapid metabolizers.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for codeine based on CYP2D6 genotypes (PMID:21412232). They recommend alternative analgesics for patients carrying the poor metabolizer (PM) alleles, intermediate metabolizer (IM) alleles or ultrarapid metabolizer (UM) allleles.

Phenotype (Genotype) Therapeutic Dose Recommendation Level of Evidence Clinical Relevance
PM (two inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) alleles) Analgesia: select alternative drug (e.g., acetaminophen, NSAID, morphine-not tramadol or oxycodone) or be alert to symptoms of insufficient pain relief. Cough: no. Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): short-lived discomfort (< 48 hr) without permanent injury: e.g. reduced decrease in resting heart rate; reduction in exercise tachycardia; decreased pain relief from oxycodone; ADE resulting from increased bioavailability of atomoxetine (decreased appetite, insomnia, sleep disturbance etc); neutropenia > 1.5x109/l; leucopenia > 3.0x109/l; thrombocytopenia > 75x109/l; moderate diarrhea not affecting daily activities; reduced glucose increase following oral glucose tolerance test.
IM (two decreased-activity (*9, *10, *17, *29, *36, *41) alleles or carrying one active (*1, *2, *33, *35) and one inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) allele, or carrying one decreased-activity (*9, *10, *17, *29, *36, *41) allele and one inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) allele) Analgesia: select alternative drug (e.g., acetaminophen, NSAID, morphine-not tramadol or oxycodone) or be alert to symptoms of insufficient pain relief. Cough: no Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Minor clinical effect (S): QTc prolongation (<450 ms female, <470 ms male); INR increase < 4.5; Kinetic effect (S).
UM (a gene duplication in absence of inactive (*3-*8, *11-*16, *19-*21, *38, *40, *42) or decreased-activity (*9, *10, *17, *29, *36, *41) alleles) Analgesia: select alternative drug (e.g., acetaminophen, NSAID, morphine-not tramadol or oxycodone) or be alert to ADE. Cough: be extra alert to ADEs due to increased morphine plasma concentration. Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): death; arrhythmia; unanticipated myelosuppression.
  • *See Methods or PMID: 18253145 for definition of "good" and "moderate" quality.
  • S: statistically significant difference.
  • Please see attached PDF for detailed information about the evaluated studies: Codeine CYP2D6

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.


last updated 10/25/2013

FDA Label for codeine and CYP2D6

This label is on the FDA Biomarker List
Actionable PGx

Summary

CYP2D6 ultra-rapid metabolizers may experience overdose symptoms such as extreme sleepiness, confusion, or shallow breathing at normal dosing regimens. Mothers who are ultra-rapid metabolizers and breast-feeding have higher-than-expected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants, potentially leading to serious adverse reactions, including death, in nursing infants. However, no recommendations for testing for CYP2D6 metabolizer status are provided on the label.

Annotation

Codeine is an opiod analgesic pro-drug, typically used for pain relief. It is metabolized by CYP2D6 into morphine, which is the active drug form. CYP2D6 poor and ultra-rapid metabolizers may experience different efficacy. Mothers who are ultra-rapid metabolizers and breast-feeding should be particularly aware of potential danger to breastfed infants. The FDA added a boxed warning to the label for children who receive codeine following tonsillectomy and/or adenoidectomy who may be rapid metabolizers.

Excerpts from the codeine sulfate drug label:

Some individuals may be ultra-rapid metabolizers due to a specific CYP2D6*2x2 genotype. These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may experience overdose symptoms such as extreme sleepiness, confusion, or shallow breathing.

Codeine is secreted into human milk...some women are ultra-rapid metabolizers of codeine. These women achieve higher-than-expected serum levels of codeine's active metabolite, morphine, leading to higher-than-expected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants. Therefore, maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the codeine sulfate drug label.

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

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Pain
    • Warnings section
    • source: PHONT
  • CYP2D6
    • Boxed warning section, Drug interactions section, Clinical pharmacology section, Pharmacokinetics section, Use in specific populations section, Warnings and precautions section, toxicity, metabolism/PK
    • source: FDA Label
  • CYP3A4
    • Drug interactions section, Clinical pharmacology section, Pharmacokinetics section, metabolism/PK
    • source: FDA Label
  • UGT2B4
    • Clinical pharmacology section, Pharmacokinetics section, metabolism/PK
    • source: FDA Label
  • UGT2B7
    • Clinical pharmacology section, Pharmacokinetics section, metabolism/PK
    • source: FDA Label

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below.

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

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
Roche AmpliChip CYP450 Test CYP2D6*1, CYP2D6*10A, CYP2D6*10B, CYP2D6*11, CYP2D6*15, CYP2D6*17, CYP2D6*19, CYP2D6*20, CYP2D6*29, CYP2D6*2A, CYP2D6*2B, CYP2D6*2D, CYP2D6*3, CYP2D6*40, CYP2D6*41, CYP2D6*4A, CYP2D6*4B, CYP2D6*4D, CYP2D6*4J, CYP2D6*4K, CYP2D6*5, CYP2D6*6A, CYP2D6*6B, CYP2D6*6C, CYP2D6*7, CYP2D6*8, CYP2D6*9 , CYP2D6*1XN , CYP2D6*2XN , CYP2D6*4XN , CYP2D6*10XN , CYP2D6*17XN , CYP2D6*35XN , CYP2D6*41XN , *35 , *36
DMET Plus (Affymetrix, Inc) Variant in CYP2D6
VeraCode ADME Core Panel (Illumina, Inc) Variant in CYP2D6
TaqMan Drug Metabolism Genotyping Assay Sets (Applied Biosystems, Inc) Variant in CYP2D6
Laboratory Corporation of America Variant in CYP2D6
Quest Diagnostics, Inc Variant in CYP2D6
iPLEX ADME PGx (Sequenom, Inc) CYP2D6*11, CYP2D6*12, CYP2D6*14A, CYP2D6*14B, CYP2D6*15, CYP2D6*17, CYP2D6*18, CYP2D6*19, CYP2D6*1A, CYP2D6*20, CYP2D6*21A, CYP2D6*21B, CYP2D6*3, CYP2D6*30, CYP2D6*38, CYP2D6*4, CYP2D6*40, CYP2D6*41, CYP2D6*42, CYP2D6*44, CYP2D6*4M, CYP2D6*56A, CYP2D6*56B, CYP2D6*58, CYP2D6*6, CYP2D6*64, CYP2D6*69, CYP2D6*7, CYP2D6*8, CYP2D6*9 , Indistinguishable haplotypes with the current ADME core SNP: (CYP2D6*2A,CYP2D6*31,CYP2D6*51), (CYP2D6*2L,CYP2D6*35,CYP2D6*71), (CYP2D6*10,CYP2D6*36,CYP2D6*37,CYP2D6*47,CYP2D6*49,CYP2D6*52,CYP2D6*54,CYP2D6*57,CYP2D6*65,CYP2D6*72), CNV Assay: CYP2D6*5, CYP2D6*NxN (Haplotypes are identified manually)
Luminex xTAG CYP2D6 Assay CYP2D6*1, CYP2D6*10, CYP2D6*11, CYP2D6*15, CYP2D6*17, CYP2D6*2, CYP2D6*29, CYP2D6*3, CYP2D6*4, CYP2D6*41, CYP2D6*5, CYP2D6*6, CYP2D6*7, CYP2D6*8, CYP2D6*9 , CYP2D6*XN , *35
Cytochrome P450 2D6 (CYP2D6) CYP2D6*2, CYP2D6*5, CYP2D6*8 , rs28371725 , rs5030867 , rs5030656 , rs35742686 , rs3892097 , rs5030865 , rs5030655 , rs61736512 , rs28371706 , rs5030862 , rs1065852
GenoChip CYP2D6 (PharmGenomics, GmbH) CYP2D6*5 , rs59421388 , rs28371725 , rs5030867 , rs5030656 , rs35742686 , rs3892097 , rs5030865 , rs5030655 , rs28371706 , rs5030863 , rs1065852 , *xN (gene duplication)
INFINITI CYP450 2D6I (AutoGenomics, Inc) CYP2D6*10, CYP2D6*12, CYP2D6*17, CYP2D6*2, CYP2D6*29, CYP2D6*3, CYP2D6*4, CYP2D6*41, CYP2D6*5, CYP2D6*6, CYP2D6*7, CYP2D6*8, CYP2D6*9 , rs28371725 , rs5030867 , rs5030656 , rs35742686 , rs3892097 , rs5030865 , rs5030655 , rs61736512 , rs28371706 , rs5030862 , rs1065852 , CYP2D6*XN , *14

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.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
VIP CA VA CYP2D6 *1 N/A N/A N/A
No VIP available CA VA CYP2D6 *1XN N/A N/A N/A
VIP CA VA CYP2D6 *2 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *2A N/A N/A N/A
No VIP available CA VA CYP2D6 *2XN N/A N/A N/A
VIP CA VA CYP2D6 *3 N/A N/A N/A
VIP CA VA CYP2D6 *4 N/A N/A N/A
No VIP available CA VA CYP2D6 *5 N/A N/A N/A
VIP CA VA CYP2D6 *6 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *9 N/A N/A N/A
VIP CA VA CYP2D6 *10 N/A N/A N/A
VIP CA VA CYP2D6 *17 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *24 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *26 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *27 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *29 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *36 N/A N/A N/A
No VIP available CA VA CYP2D6 *40 N/A N/A N/A
VIP CA VA CYP2D6 *41 N/A N/A N/A
No VIP available No Clinical Annotations available VA
rs1045642 208920T>A, 208920T>C, 25171488A>G, 25171488A>T, 3435T>A, 3435T>C, 87138645A>G, 87138645A>T, ABCB1*6, ABCB1: 3435C>T, ABCB1: C3435T, ABCB1: c.3435C>T, ABCB1:3435C>T, Ile1145=, Ile1145Ile, MDR1 3435C>T, MDR1 C3435T, PGP C3435T, c.3435C>T, mRNA 3853C>T
A > T
A > G
Synonymous
Ile1145Ile
rs1065852 100C>T, 21917263G>A, 42526694G>A, 5190C>T, CYP2D6:100C>T, Pro34Ser, part of CYP2D6*4 and CYP2D6*10
G > A
Missense
Pro34Ser
No VIP available No Clinical Annotations available VA
rs1128503 1236T>C, 167964T>C, 25212444A>G, 87179601A>G, ABCB1 1236C>T, ABCB1*8, ABCB1: c.1236T>C, ABCB1:1236C>T, ABCB1:1236T>C, Gly412=, Gly412Gly, mRNA 1654T>C, p.Gly412Gly
A > G
Synonymous
Gly412Gly
VIP No Clinical Annotations available No Variant Annotations available
rs16947 21914512A>G, 42523943A>G, 733C>C, 7941C>C, 886C>C, Arg245=, Arg296=, CYP2D6:2850C>T
A > G
Not Available
No VIP available No Clinical Annotations available VA
rs1799971 -11+28644A>G, 118A>G, 154360797A>G, 34162A>G, 397A>G, 47+29103A>G, 58530254A>G, Asn133Asp, Asn40Asp, OPRM1: A118G
A > G
Missense
Asn40Asp
No VIP available No Clinical Annotations available VA
rs2032582 186947T>A, 186947T>G, 25193461A>C, 25193461A>T, 2677A, 2677G, 2677T, 2677T>A, 2677T>G, 3095G>T/A, 87160618A>C, 87160618A>T, 893 Ala, 893 Ser, 893 Thr, ABCB1*7, ABCB1: 2677G>T/A, ABCB1: 2677T/A>G, ABCB1: A893S, ABCB1: G2677T/A, ABCB1: c.2677G>T/A, ABCB1:2677G>A/T, ABCB1:2677G>T/A, ABCB1:A893T, Ala893Ser/Thr, MDR1, MDR1 G2677T/A, Ser893Ala, Ser893Thr, mRNA 3095G>T/A, p.Ala893Ser/Thr
A > C
A > T
Missense
Ser893Ala
Ser893Thr
rs28371706 21916341G>A, 320C>T, 42525772G>A, 6112C>T, CYP2D6:1023 C>T, Thr107Ile
G > A
Missense
Thr107Ile
rs28371725 21914374C>T, 42523805C>T, 8079G>A, 832+39G>A, 985+39G>A, CYP2D6*41, CYP2D6:2988G>A, part of CYP2D6*41
C > T
Intronic
rs35742686 21914813delT, 42524244delT, 622delA, 7640delA, 775delA, Arg208Glyfs, Arg259Glyfs
A > T
A > -
Frameshift
Arg208Gly
rs3892097 21915516C>T, 353-1G>A, 42524947C>T, 506-1G>A, 6937G>A, CYP2D6*4, CYP2D6:1846G>A, part of CYP2D6*4
C > T
Acceptor
rs5030655 21915655delA, 353-140delT, 42525086delA, 454delT, 6798delT, CYP2D6*6, CYP2D6:1707 del T, Trp152Glyfs, part of CYP2D6*6
T > A
T > -
Intronic
Trp152Gly
rs5030656 21914745_21914747delCTT, 42524176_42524178delCTT, 688_690delAAG, 7706_7708delAAG, 841_843delAAG, Lys230del, Lys281del
CTT > -
CTT > TTC
Non-synonymous
rs59421388 1012G>A, 21914179C>T, 3271G>A, 42523610C>T, 8274G>A, 859G>A, CYP2D6: 3183G>A, Val287Met, Val338Met
G > T
G > C
Missense
Val287Met
rs61736512 1747G>A, 21915703C>T, 353-188G>A, 406G>A, 42525134C>T, 6750G>A, CYP2D6: 1659G>A, Val136Met
G > T
G > C
Intronic
Val136Met
No VIP available No Clinical Annotations available VA
rs61737947
T > C
Not Available
No VIP available No Clinical Annotations available VA
rs7439366 10175005T>C, 69964338T>C, 802T>C, Tyr268His, UGT2B7*2, UGT2B7:802C>T, UGT2B7:H268Y, UGT2B7Y
T > C
Missense
Tyr268His
VIP No Clinical Annotations available No Variant Annotations available
rs776746 12083G>A, 219-237G>A, 321-1G>A, 37303382C>T, 581-237G>A, 689-1G>A, 99270539C>T, CYP3A5*1, CYP3A5*3, CYP3A5*3C, CYP3A5:6986A>G, g.6986A>G, intron 3 splicing defect, rs776746 A>G
C > T
Acceptor
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Codeine anhydrous
  • L-Codeine
  • Methylmorphine
  • Morphine monomethyl ether
  • Norcodeine, N-Methyl
  • Norcodine, N-Methyl
Trade Names
  • Codicept
  • Coducept
Brand Mixture Names

PharmGKB Accession Id:
PA449088

Description

An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough.

Source: Drug Bank

Indication

For treatment and management of pain (Systemic), also used as an Antidiarrheal and as a cough suppressant.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Codeine's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.

Source: Drug Bank

Pharmacology

Codeine, an opiate agonist in the CNS, is similar to other phenanthrene derivatives such as morphine. Codeine, in combination with guaifenesin or iodinated glycerol, is used as a cough suppressant and, as a single agent or in combination with acetaminophen or other products, is used for pain control and as an antidiarrheal agent.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Take with food, food reduces irritation.|To avoid constipation: increase your daily intake of fiber (beans, whole grains, vegetables).

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Codeine is a prodrug, itself inactive, but demethylated to the active morphine by the liver enzyme CYP2D6.

Source: Drug Bank

Protein Binding

7-25%

Source: Drug Bank

Absorption

Well absorbed following oral administration with a bioavailability of approximately 90%.

Source: Drug Bank

Half-Life

2-4 hours

Source: Drug Bank

Toxicity

Respiratory depression, sedation and miosis and common symptoms of overdose. Other symptoms include nausea, vomiting, skeletal muscle flaccidity, bradycardia, hypotension, and cool, clammy skin. Apnea and death may ensue.

Source: Drug Bank

Chemical Properties

Chemical Formula

C18H21NO3

Source: Drug Bank

Isomeric SMILES

CN1CC[C@]23c4c5ccc(c4O[C@H]2[C@H](C=C[C@H]3[C@H]1C5)O)OC

Source: OpenEye

Canonical SMILES

COC1=C2O[C@H]3[C@@H]

Source: Drug Bank

Average Molecular Weight

299.3642

Source: Drug Bank

Monoisotopic Molecular Weight

299.152143543

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Codeine and Morphine Pathway, Pharmacokinetics
    Representation of the candidate genes involved in metabolism of codeine and morphine.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

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
OPRD1 (source: Drug Bank)
OPRK1 (source: Drug Bank)
OPRM1 (source: Drug Bank)

Drug Interactions

Drug Description
codeine Increases the effect of the narcotic (source: Drug Bank)
codeine Increases the effect of the narcotic (source: Drug Bank)
cimetidine Cimetidine increases the effect of the narcotic (source: Drug Bank)
cimetidine Cimetidine increases the effect of the narcotic (source: Drug Bank)
naltrexone Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individual (source: Drug Bank)
naltrexone Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individual (source: Drug Bank)
quinidine Quinidine decreases the analgesic effect of codeine (source: Drug Bank)
quinidine Quinidine decreases the analgesic effect of codeine (source: Drug Bank)
quinidine Quinidine decreases the analgesic effect of codeine (source: Drug Bank)
codeine Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
codeine Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals (source: Drug Bank)
codeine Quinidine decreases the analgesic effect of codeine (source: Drug Bank)
codeine Quinidine decreases the analgesic effect of codeine (source: Drug Bank)
codeine Terbinafine may decrease the efficacy of Codeine by inhibiting active metabolite production. Consider an alternate analgesic or monitor for effectiveness of Codeine. (source: Drug Bank)
codeine The CNS depressants, Triprolidine and Codeine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank)
codeine The CNS depressants, Triprolidine and Codeine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank)

Curated Information ?

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

May Treat
Contraindicated With

Publications related to codeine: 82

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
The impact of CYP2D6 polymorphisms on the pharmacokinetics of codeine and its metabolites in Mongolian Chinese subjects. European journal of clinical pharmacology. 2013. Wu Xiujun, 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
New evidence about an old drug--risk with codeine after adenotonsillectomy. The New England journal of medicine. 2013. Racoosin Judith 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
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, 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
First demonstration that brain CYP2D-mediated opiate metabolic activation alters analgesia in vivo. Biochemical pharmacology. 2013. Zhou Kaidi, 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
Codeine-associated pediatric deaths despite using recommended dosing guidelines: three case reports. Journal of opioid management. 2013. Friedrichsdorf Stefan 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
Cytochrome P450-mediated drug metabolism in the brain. Journal of psychiatry & neuroscience : JPN. 2012. Miksys Sharon, 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
Apnea and oxygen desaturations in children treated with opioids after adenotonsillectomy for obstructive sleep apnea syndrome: a prospective pilot study. Paediatric drugs. 2012. Khetani Justin 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
A Clinician-Driven Automated System for Integration of Pharmacogenetic Interpretations Into an Electronic Medical Record. Clinical pharmacology and therapeutics. 2012. Hicks J K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenetics and genomics. 2012. Lamba Jatinder, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
More codeine fatalities after tonsillectomy in North American children. Pediatrics. 2012. Kelly Lauren E, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Prediction of codeine toxicity in infants and their mothers using a novel combination of maternal genetic markers. Clinical pharmacology and therapeutics. 2012. Sistonen 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
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype. Clinical pharmacology and therapeutics. 2011. Crews K R, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
CYP2D6 polymorphisms and codeine analgesia in postpartum pain management: a pilot study. Therapeutic drug monitoring. 2011. VanderVaart Sondra, 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 testing: time for clinical practice guidelines. Clinical pharmacology and therapeutics. 2011. Amstutz U, 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
Uniform assessment and ranking of opioid μ receptor binding constants for selected opioid drugs. Regulatory toxicology and pharmacology : RTP. 2011. Volpe Donna 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
Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J 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
Copy number variants in pharmacogenetic genes. Trends in molecular medicine. 2011. He Yijing, 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
Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse. Pharmacogenomics. 2011. Meyer Markus 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
The communication of pharmacogenetic research results: participants weigh in on their informational needs in a pilot study. Journal of population therapeutics and clinical pharmacology = Journal de la thérapeutique des populations et de la pharamcologie clinique. 2011. Madadi Parvaz, 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
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, 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
Maternal-fetal and neonatal pharmacogenomics: a review of current literature. Journal of perinatology : official journal of the California Perinatal Association. 2010. Blumenfeld Y 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
Personalized therapy in pain management: where do we stand?. Pharmacogenomics. 2010. Stamer Ulrike 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
Clinical implementation of pharmacogenomics: overcoming genetic exceptionalism. The lancet oncology. 2010. Relling Mary V, 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
Nationwide drug-dispensing data reveal important differences in adherence to drug label recommendations on CYP2D6-dependent drug interactions. British journal of clinical pharmacology. 2010. Mannheimer Buster, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Influence of the CYP2D6 polymorphism and hemodialysis on codeine disposition in patients with end-stage renal disease. European journal of clinical pharmacology. 2010. Molanaei Hadi, 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
Risk to the breast-fed neonate from codeine treatment to the mother: a quantitative mechanistic modeling study. Clinical pharmacology and therapeutics. 2009. Willmann S, 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
Guidelines for maternal codeine use during breastfeeding. Canadian family physician Médecin de famille canadien. 2009. Madadi Parvaz, et al. PubMed
No Dosing Guideline available No Drug Label available CA 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 CA VA No VIP available No VIP available
Codeine, ultrarapid-metabolism genotype, and postoperative death. The New England journal of medicine. 2009. Ciszkowski Catherine, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
The pharmacokinetics of codeine and its metabolites in Blacks with sickle cell disease. European journal of clinical pharmacology. 2009. Shord Stacy S, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Can extremely low or high morphine formation from codeine be predicted prior to therapy initiation?. Pain. 2009. Lötsch Jörn, 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
Codeine and morphine pathway. Pharmacogenetics and genomics. 2009. Thorn Caroline F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Cytochrome P450 2D6. Pharmacogenetics and genomics. 2009. Owen Ryan 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
Cross-sectional analysis of the influence of currently known pharmacogenetic modulators on opioid therapy in outpatient pain centers. Pharmacogenetics and genomics. 2009. Lötsch Jörn, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study. Clinical pharmacology and therapeutics. 2009. Madadi P, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Expression and functional analysis of CYP2D6.24, CYP2D6.26, CYP2D6.27, and CYP2D7 isozymes. Drug metabolism and disposition: the biological fate of chemicals. 2009. Zhang Wei-Yan, 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 CA VA No VIP available No VIP available
Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication. Anesthesia and analgesia. 2008. Stamer Ulrike 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
Pharmacogenetic insights into codeine analgesia: implications to pediatric codeine use. Pharmacogenomics. 2008. Madadi Parvaz, 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 analgesics: toward the individualization of prescription. Pharmacogenomics. 2008. Rollason Victoria, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17. Drug metabolism and disposition: the biological fate of chemicals. 2007. Shen Hongwu, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication. The pharmacogenomics journal. 2007. Kirchheiner J, 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 CA VA No VIP available No VIP available
The effect of CYP2D6 polymorphisms on the response to pain treatment for pediatric sickle cell pain crisis. The Journal of pediatrics. 2007. Brousseau David C, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Response to hydrocodone, codeine and oxycodone in a CYP2D6 poor metabolizer. Progress in neuro-psychopharmacology & biological psychiatry. 2006. Susce Margaret T, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet. 2006. Koren Gideon, 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
Evidence for morphine-independent central nervous opioid effects after administration of codeine: contribution of other codeine metabolites. Clinical pharmacology and therapeutics. 2006. Lötsch Jörn, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Codeine intoxication associated with ultrarapid CYP2D6 metabolism. The New England journal of medicine. 2004. Gasche Yvan, 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
Evaluation of 3'-azido-3'-deoxythymidine, morphine, and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B7*2 polymorphism. Drug metabolism and disposition: the biological fate of chemicals. 2003. Court Michael H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Adverse drug reactions to oxycodone and hydrocodone in CYP2D6 ultrarapid metabolizers. Journal of clinical psychopharmacology. 2003. de Leon Jose, 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 codeine metabolism in an urban population of children and its implications for analgesic reliability. British journal of anaesthesia. 2002. Williams D G, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Expression, purification, biochemical characterization, and comparative function of human cytochrome P450 2D6.1, 2D6.2, 2D6.10, and 2D6.17 allelic isoforms. The Journal of pharmacology and experimental therapeutics. 2002. Yu Aiming, 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
Treatment of codeine dependence with inhibitors of cytochrome P450 2D6. Journal of clinical psychopharmacology. 2002. Fernandes Leona 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
The African-specific CYP2D617 allele encodes an enzyme with changed substrate specificity. Clinical pharmacology and therapeutics. 2002. Wennerholm Agneta, 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
No pain relief from codeine...? An introduction to pharmacogenomics. Acta anaesthesiologica Scandinavica. 2001. Fagerlund T 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
Codeine analgesia is due to codeine-6-glucuronide, not morphine. International journal of clinical practice. 2000. Vree T B, 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
Codeine in post-operative pain. Study of the influence of sparteine phenotype and serum concentrations of morphine and morphine-6-glucuronide. European journal of clinical pharmacology. 1998. Poulsen 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
Same incidence of adverse drug events after codeine administration irrespective of the genetically determined differences in morphine formation. Pain. 1998. Eckhardt K, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A combination of mutations in the CYP2D6*17 (CYP2D6Z) allele causes alterations in enzyme function. Molecular pharmacology. 1997. Oscarson 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
Urinary excretion of codeine, ethylmorphine, and their metabolites: relation to the CYP2D6 activity. Therapeutic drug monitoring. 1997. Hedenmalm 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
Genetically deficient CYP2D6 metabolism provides protection against oral opiate dependence. Pharmacogenetics. 1997. Tyndale R F, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA 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 CA VA No VIP available No VIP available
Effect of codeine on gastrointestinal motility in relation to CYP2D6 phenotype. Clinical pharmacology and therapeutics. 1997. Mikus 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
Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability. The Journal of pharmacology and experimental therapeutics. 1997. Kaplan H 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
Pharmacogenetic determinants of codeine induction by rifampin: the impact on codeine's respiratory, psychomotor and miotic effects. The Journal of pharmacology and experimental therapeutics. 1997. Caraco 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
Human UGT2B7 catalyzes morphine glucuronidation. Drug metabolism and disposition: the biological fate of chemicals. 1997. Coffman B 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
The effect of codeine on gastrointestinal transit in extensive and poor metabolisers of debrisoquine. European journal of clinical pharmacology. 1997. Hasselström 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
Pharmacogenetic determination of the effects of codeine and prediction of drug interactions. The Journal of pharmacology and experimental therapeutics. 1996. Caraco Y, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Formation of morphine from codeine in Chinese subjects of different CYP2D6 genotypes. Clinical pharmacology and therapeutics. 1996. Tseng C 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
Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects. European journal of clinical pharmacology. 1996. Poulsen 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
Patient-controlled analgesia (PCA) with codeine for postoperative pain relief in ten extensive metabolisers and one poor metaboliser of dextromethorphan. British journal of clinical pharmacology. 1995. Persson 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
Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes. Life sciences. 1995. Mignat 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
The influence of pharmacogenetics on opioid analgesia: studies with codeine and oxycodone in the Sprague-Dawley/Dark Agouti rat model. The Journal of pharmacology and experimental therapeutics. 1994. Cleary 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
Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers. British journal of clinical pharmacology. 1991. Chen Z 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
Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine. Clinical pharmacology and therapeutics. 1990. Sindrup S H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Impact of environmental and genetic factors on codeine analgesia. European journal of clinical pharmacology. 1991. Desmeules 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
Polymorphic formation of morphine from codeine in poor and extensive metabolizers of dextromethorphan: relationship to the presence of immunoidentified cytochrome P-450IID1. Clinical pharmacology and therapeutics. 1990. Mortimer O, 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
Codeine O-demethylation co-segregates with polymorphic debrisoquine hydroxylation. British journal of clinical pharmacology. 1989. Yue Q 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
Polymorphic O-demethylation of codeine. Lancet. 1988. Chen Z 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
Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P-450 dbl/bufI). Biochemical and biophysical research communications. 1988. Dayer 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
http://www.sciencenews.org/sn_arc97/9_13_97/fob2.htm. [URL:http://www.sciencenews.org/sn_arc97/9_13_97/fob2.htm]

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00318
ChEBI:
16714
KEGG Compound:
C06174
PubChem Compound:
5284371
PubChem Substance:
149398
46507764
IUPHAR Ligand:
1673
Drugs Product Database (DPD):
593451
ChemSpider:
4447447
Therapeutic Targets Database:
DAP000213

Clinical Trials

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

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.