Identification

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Name
Codeine
Accession Number
DB00318  (APRD00120, DB09471)
Type
Small Molecule
Groups
Approved, Illicit
Description

The relief of pain (analgesia) is a primary goal for enhancing the quality of life of patients and for increasing the ability of patients to engage in day to day activities. Codeine, an opioid analgesic, was originally approved in the US in 1950 and is a drug used to decrease pain by increasing the threshold for pain without impairing consciousness or altering other sensory functions. Opiates such as codeine are derived from the poppy plant, Papaver somniferum (Papaveraceae).4

Codeine is utilized as a central analgesic, sedative, hypnotic, antinociceptive, and antiperistaltic agent, and is also recommended in certain diseases with incessant coughing.Label,4

Structure
Thumb
Synonyms
  • (−)-Codeine
  • (5alpha,6alpha)-7,8-Didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol
  • 7,8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol
  • Codein
  • Codeína
  • Codéine
  • Codeine anhydrous
  • Codeine polistirex
  • Codeinum
  • L-Codeine
  • Methylmorphine
  • morphine 3-methyl ether
  • Morphine monomethyl ether
  • morphine-3-methyl ether
  • O3-Methylmorphine
External IDs
IDS-NC-005(SECT.-2)
Product Ingredients
IngredientUNIICASInChI Key
Codeine hydrochloride406LPJ779Q1422-07-7NUXLENPAZQNFAM-FFHNEAJVSA-N
Codeine monohydrateQ830PW75206059-47-8WRRSFOZOETZUPG-FFHNEAJVSA-N
Codeine phosphate2X585M1M3T52-28-8WUXLCJZUUHIXFY-FFHNEAJVSA-N
Codeine phosphate hemihydrateGSL05Y1MN641444-62-6DKSZLDSPXIWGFO-BLOJGBSASA-N
Codeine sulfate11QV9BS0CB6854-40-6BOLDZXRCJAJADM-AAXBYHQXSA-N
Codeine sulfate anhydrousAVW5HY4N2E1420-53-7BCXHDORHMMZBBZ-DORFAMGDSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Codeine 15TabletOralLaboratoire Riva Inc1994-12-31Not applicableCanada
Codeine 30TabletOralLaboratoire Riva Inc1994-12-31Not applicableCanada
Codeine Contin 100mg Controlled Release TabTablet, extended releaseOralPurdue Pharma1995-12-31Not applicableCanada
Codeine Contin 150mg Controlled Release TabTablet, extended releaseOralPurdue Pharma1995-12-31Not applicableCanada
Codeine Contin 200mg Controlled Release TabTablet, extended releaseOralPurdue Pharma1995-12-31Not applicableCanada
Codeine Contin 50mg Controlled Release TabTablet, extended releaseOralPurdue Pharma1997-03-13Not applicableCanada
Codeine Phosphate Inj 30mg/mlSolutionIntramuscular; SubcutaneousHospira Healthcare Ulc1981-12-312018-09-21Canada
Codeine Phosphate Inj 60mg/mlSolutionIntramuscular; SubcutaneousHospira Healthcare Ulc1981-12-312018-09-21Canada
Codeine Phosphate Injection USPLiquidIntramuscular; SubcutaneousSandoz Canada Incorporated1978-12-31Not applicableCanada
Codeine Phosphate SyrupSyrupOralD.C. Labs Limited1951-12-312005-07-19Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Codeine SulfateTablet30 mg/1OralLannett Company, Inc.2014-06-13Not applicableUs
Codeine SulfateTablet15 mg/1OralLannett Company, Inc.2014-06-13Not applicableUs
Codeine SulfateTablet60 mg/1OralLannett Company, Inc.2014-06-13Not applicableUs
PMS-codeineTabletOralPharmascience Inc2001-11-162019-04-04Canada
PMS-codeineTabletOralPharmascience Inc2001-12-162019-04-04Canada
Ratio-codeineSyrupOralTEVA Canada Limited1977-12-312017-05-01Canada
Teva-codeineTabletOralTEVA Canada Limited1983-12-31Not applicableCanada
Teva-codeineTabletOralTEVA Canada Limited1983-12-31Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
(extra Strength) Acetaminophen, Caffeine & 8mg Codeine Phosphate CapletsCodeine phosphate (8 mg) + Acetaminophen (500 mg) + Caffeine (15 mg)TabletOralStanley Pharmaceuticals, A Division Of Vita Health Products Inc.1998-07-222002-07-31Canada
222 TabletsCodeine phosphate (8 mg) + Acetylsalicylic acid (375 mg) + Caffeine citrate (30 mg)TabletOralMcneil Consumer Healthcare Division Of Johnson & Johnson Inc1951-12-312015-08-17Canada
282 Mep TabCodeine phosphate (15 mg) + Acetylsalicylic acid (350 mg) + Caffeine citrate (30 mg) + Meprobamate (200 mg)TabletOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1959-12-311998-08-14Canada
282 TabCodeine phosphate (15 mg) + Acetylsalicylic acid (375 mg) + Caffeine citrate (30 mg)TabletOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1951-12-311998-04-21Canada
282 TabletsCodeine phosphate (15 mg) + Acetylsalicylic acid (375 mg) + Caffeine citrate (30 mg)TabletOralPendopharm Division Of De Pharmascience Inc1998-11-01Not applicableCanada
292 TabCodeine phosphate (30 mg) + Acetylsalicylic acid (375 mg) + Caffeine citrate (30 mg)TabletOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1951-12-311998-08-14Canada
292 TabletsCodeine phosphate (30 mg) + Acetylsalicylic acid (375 mg) + Caffeine citrate (30 mg)TabletOralPendopharm Division Of De Pharmascience Inc1998-10-01Not applicableCanada
A & C Tablets With Codeine 15mgCodeine phosphate (15 mg) + Acetylsalicylic acid (375 mg) + Caffeine (15 mg)TabletOralD.C. Labs Limited1971-12-312003-07-11Canada
A & C Tablets With Codeine 30mgCodeine phosphate (30 mg) + Acetylsalicylic acid (375 mg) + Caffeine (15 mg)TabletOralD.C. Labs Limited1971-12-312003-07-11Canada
A.C. & C 8mg TabCodeine phosphate (8 mg) + Acetylsalicylic acid (375 mg) + Caffeine (15 mg)TabletOralVita Health Products Inc1970-12-312019-09-23Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AiracofCodeine phosphate hemihydrate (7.5 mg/5mL) + Diphenhydramine hydrochloride (12.5 mg/5mL) + Phenylephrine hydrochloride (7.5 mg/5mL)LiquidOralCenturion Labs2010-01-082016-05-02Us
Chlorpheniramine and CodeineCodeine phosphate hemihydrate (10 mg/5mL) + Chlorpheniramine maleate (2 mg/5mL)LiquidOralBreckenridge Pharmaceutical, Inc.2009-10-012011-02-28Us
Codeine Phosphate and Pseudoephedrine HydrochlorideCodeine phosphate hemihydrate (10 mg/5mL) + Pseudoephedrine hydrochloride (30 mg/5mL)SyrupOralBreckenridge Pharmaceutical, Inc.2009-12-012011-11-30Us
Codeine Phosphate GuaifenesinCodeine phosphate hemihydrate (10 mg/5mL) + Guaifenesin (200 mg/5mL)LiquidOralKylemore Pharmaceuticals, LLC2010-01-012012-11-30Us
Codeine SulfateCodeine sulfate (60 mg/1)TabletOralGlenmark Generics, Inc. USA2006-07-012011-08-31Us
Codeine SulfateCodeine sulfate (30 mg/1)TabletOralGlenmark Generics, Inc. USA2006-07-012011-08-31Us
Dexphen w/ CodeineCodeine phosphate hemihydrate (10 mg/5mL) + Dexchlorpheniramine maleate (1 mg/5mL) + Phenylephrine hydrochloride (5 mg/5mL)LiquidOralBreckenridge Pharmaceutical, Inc.2010-10-102010-10-10Us
EndaCof-CCodeine phosphate hemihydrate (10 mg/5mL) + Chlorpheniramine maleate (2 mg/5mL)LiquidOralLarken Laboratories, Inc.2009-05-252012-01-31Us
Endal CDCodeine phosphate hemihydrate (7.5 mg/5mL) + Diphenhydramine hydrochloride (10 mg/5mL) + Phenylephrine hydrochloride (7.5 mg/5mL)SyrupOralTiber Laboratories2009-12-092009-12-31Us
ExeClear CCodeine phosphate hemihydrate (10 mg/5mL) + Guaifenesin (2 mg/5mL)LiquidOralLarken Laboratories, Inc.2008-10-172015-11-10Us
International/Other Brands
Actacode (Sigma) / Bisoltus (Boehringer Ingelheim) / Bromophar (Qualiphar) / Bronchicum (Sanofi-Aventis) / Bronchodine (Pharmacobel) / Codant (Antigen) / Codedrill (Pierre Fabre) / Codein (Cristália) / Codeisan (Belmac) / Coderpina (Frycia Centro América) / Codicalm (Welti) / Codicept / Codinex (Pinewood) / Coducept / Cougel (Hwang's) / Coutan (Mey See) / Dinco (Center) / Farmacod (Farmacom) / Galcodine (Thornton & Ross) / Pectoral (Siphat) / Tussoret (MaxMedic)
Categories
UNII
UX6OWY2V7J
CAS number
76-57-3
Weight
Average: 299.3642
Monoisotopic: 299.152143543
Chemical Formula
C18H21NO3
InChI Key
OROGSEYTTFOCAN-DNJOTXNNSA-N
InChI
InChI=1S/C18H21NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3-6,11-13,17,20H,7-9H2,1-2H3/t11-,12+,13-,17-,18-/m0/s1
IUPAC Name
(1S,5R,13R,14S,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10,15-tetraen-14-ol
SMILES
[H][C@]12C=C[C@H](O)[C@@H]3OC4=C5C(C[C@H]1N(C)CC[C@@]235)=CC=C4OC

Pharmacology

Indication

Codeine sulfate is a form of this drug that is commonly used. It is available in tablet form Label and indicated for the relief of mild to moderately severe pain, where the use of an opioid analgesic is appropriate Label.

The solution form is used by itself or combined in a syrup with other drugs and is used as a cough suppressant in adults aged 18 and above 11, 12.

Associated Conditions
Pharmacodynamics

General effects

Codeine is a weak narcotic pain reliever and cough suppressant that is similar to morphine and hydrocodone. A small amount of ingested codeine is converted to morphine in the body. Codeine increases tolerance to pain, reducing existing discomfort. In addition to decreasing pain, codeine also causes sedation, drowsiness, and respiratory depression 4.

Antitussive activity

This drug has shown antitussive activity in clinical trials 6 and has been effective in cough secondary to tuberculosis and insomnia due to coughing 4. Codeine suppresses the cough reflex through a direct effect on the cough center in the medulla 13.

Effects on intestinal motility

Codeine may reduce intestinal motility through both a local and possibly central mechanism of action 14. This may possibly lead to constipation 13. The chronic use of opioids, including codeine sulfate, may lead to obstructive bowel disease, particularly in patients with underlying disorders of intestinal motility Label.

Effects on the central nervous system

Codeine phosphate is an opioid analgesic with uses similar to those of morphine, but is much less potent as an analgesic. Its primary site of action is at the mu opioid receptors distributed throughout the central nervous system. The sedative activities of codeine are less potent than those of morphine 13. Codeine may cause respiratory system depression by the activation of μ-opioid receptors at specific sites in the central nervous system 8.

Effects on blood pressure

This drug poses an increased risk of compromised ability to maintain blood pressure due to peripheral vasodilation and other mechanisms Label.

Effects on chronic cancer pain and other types of pain

Codeine is an opioid analgesic with similar indications to those of morphine, however, is much less potent in its pain alleviating properties. Its primary action takes place at the mu opioid receptors, which are distributed throughout the central nervous system. The average duration of action is about 4 hours 13.

Regular dosing of opioid analgesics such as codeine in patients with severe cancer pain has been well documented to improve symptoms 4, 7.

Mechanism of action

Codeine is a selective agonist for the mu opioid receptor, but with a much weaker affinity to this receptor than morphine, a more potent opioid drug. Codeine binds to mu-opioid receptors, which are involved in the transmission of pain throughout the body and central nervous system Label, 4. The analgesic properties of codeine are thought to arise from its conversion to Morphine, although the exact mechanism of analgesic action is unknown at this time Label, 13.

TargetActionsOrganism
AMu-type opioid receptor
agonist
Humans
AKappa-type opioid receptor
agonist
Humans
ADelta-type opioid receptor
agonist
Humans
Additional Data Available
Adverse Effects

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Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

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Absorption

Absorption

Codeine is absorbed from the gastrointestinal tract. The maximum plasma concentration occurs 60 minutes after administration Label.

Food Effects

When 60 mg codeine sulfate was given 30 minutes post-ingestion of a high high-calorie meal, there was no significant change in the absorption of codeine Label.

Steady-state concentration

The administration of 15 mg codeine sulfate every 4 hours for 5 days lead to steady-state concentrations of codeine, morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) within 48 hours Label.

Volume of distribution

Apparent volume of distribution: about 3-6 L/kg, showing an extensive distribution of the drug into tissues Label.

Protein binding

7-25% bound to plasma proteins Label.

Metabolism

Approximately 70 to 80% of the ingested dose of codeine is metabolized in the liver by conjugation with glucuronic acid to codeine-6­ glucuronide (C6G) and by O-demethylation to morphine (about 5-10%) and N-demethylation to norcodeine (about 10%) respectively. UDP-glucuronosyltransferase (UGT) 2B7 and 2B4 are the major metabolic enzymes mediating the glucurodination of codeine to the metabolite, codeine 6 glucuronide.

Cytochrome P450 2D6 is the major enzyme responsible for the transformation of codeine to morphine and P450 3A4 is the main enzyme mediating the conversion of codeine to norcodeine. Morphine and norcodeine are then further metabolized by conjugation with glucuronic acid. The glucuronide metabolites of morphine are morphine-3-glucuronide (M3G) and_ morphine-6-glucuronide _(M6G). Morphine and M6G have been proven to have analgesic activity in humans. The analgesic activity of C6G in humans is not known at this time. Norcodeine and M3G are generally not considered to have analgesic properties Label.

Route of elimination

About 90% of the total dose of codeine is excreted by the kidneys. Approximately 10% of the drug excreted by the kidneys is unchanged codeine Label.

The majority of the excretion products can be found in the urine within 6 hours of ingestion, and 40-60 % of the codeine is excreted free or conjugated, approximately 5 to 15 percent as free and conjugated morphine, and approximately 10-20% free and conjugated norcodeine 13.

Half life

Plasma half-lives of codeine and its metabolites have been reported to be approximately 3 hours Label.

Clearance

Renal clearance of codeine was 183 +/- 59 ml min-1 in a clinical study 5.

Renal impairment may decrease codeine clearance Label.

Toxicity

Oral LD50: 427 mg kg-1 (rat) MSDS.

Overdose/toxicity

Symptoms of opioid toxicity may include confusion, somnolence, shallow breathing, constricted pupils, nausea, vomiting, constipation and a lack of appetite. In severe cases, symptoms of circulatory and respiratory depression may ensue, which may be life-threatening or fatal 10, Label.

Teratogenic effects

This drug is classified as a pregnancy Category C drug. There are no adequate and well-controlled studies completed in pregnant women. Codeine should only be used during pregnancy if the potential benefit outweighs the potential risk of the drug to the fetus Label.

Codeine has shown embryolethal and fetotoxic effects in the hamster, rat as well as mouse models at about 2-4 times the maximum recommended human dose Label. Maternally toxic doses that were about 7 times the maximum recommended human dose of 360 mg/day, were associated with evidence of bone resorption and incomplete bone ossification. Codeine did not demonstrate evidence of embrytoxicity or fetotoxicity in the rabbit model at doses up to 2 times the maximum recommended human dose of 360 mg/day based on a body surface area comparison Label.

Nonteratogenic effects

Neonatal codeine withdrawal has been observed in infants born to addicted and non-addicted mothers who ingested codeine-containing medications in the days before delivery. Common symptoms of narcotic withdrawal include irritability, excessive crying, tremors, hyperreflexia, seizures, fever, vomiting, diarrhea, and poor feeding. These signs may be observed shortly following birth and may require specific treatment Label.

Codeine (30 mg/kg) given subcutaneously to pregnant rats during gestation and for 25 days after delivery increased the rate of neonatal mortality at birth. The dose given was 0.8 times the maximum recommended human dose of 360 mg/day Label.

The use in breastfeeding/nursing

Codeine is secreted into human milk. The maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants Label.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Codeine Metabolism PathwayDrug metabolism
Codeine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*4(A;A)A Allele, homozygoteEffect Directly StudiedPatients with this genotype have reduced metabolism of codeine.Details
Cytochrome P450 2D6CYP2D6*6(-;-)T deletion, homozygoteEffect Directly StudiedPatients with this genotype have reduced metabolism of codeine.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole gene deletion, homozygoteEffect Directly StudiedPatients with this genotype have reduced metabolism of codeine.Details
Cytochrome P450 2D6CYP2D6*3Not Available2549delAEffect Directly StudiedThe presence of this polymorphism in CYP2D6 results in non-functioning enzyme variant and may be associated with reduced drug mtabolism or reduced therapeutic response when treated with codeine.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableA alleleEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of codeine.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of codeine and lack of therapeutic response from codeine.Details
Cytochrome P450 2D6CYP2D6*6(-;T) / (-;-)1707delTEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of codeine.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*1XNNot AvailableNormal allele duplicated.ADR InferredUltra-rapid drug metabolizer. Risk of toxicity, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*2XNNot Available2850C>T / 4180G>C  … show all ADR InferredUltra-rapid drug metabolizer. Risk of toxicity, alternative drug recommended.Details
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirementsDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableG alleleEffect Directly StudiedThe presence of this polymorphism in CYP2D6 results in non-functioning enzyme variant and may be associated with reduced therapeutic response when treated with codeine.Details
Cytochrome P450 2D6CYP2D6*4Not Available3877G>AEffect Directly StudiedThe presence of this polymorphism in CYP2D6 results in non-functioning enzyme variant and may be associated with reduced therapeutic response when treated with codeine.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidineThe metabolism of Codeine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may increase the analgesic activities of Codeine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may increase the analgesic activities of Codeine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the analgesic activities of Codeine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Codeine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Codeine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Codeine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Codeine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AbacavirAbacavir may decrease the excretion rate of Codeine which could result in a higher serum level.
AbirateroneThe metabolism of Codeine can be decreased when combined with Abiraterone.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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

References

Synthesis Reference

Nagaraj R. Ayyangar, Anil R. Choudhary, Uttam R. Kalkote, Vasant K. Sharma, "Process for the preparation of codeine from morphine." U.S. Patent US4764615, issued May, 1912.

US4764615
General References
  1. Schroeder K, Fahey T: Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD001831. [PubMed:15495019]
  2. Vree TB, van Dongen RT, Koopman-Kimenai PM: Codeine analgesia is due to codeine-6-glucuronide, not morphine. Int J Clin Pract. 2000 Jul-Aug;54(6):395-8. [PubMed:11092114]
  3. Srinivasan V, Wielbo D, Tebbett IR: Analgesic effects of codeine-6-glucuronide after intravenous administration. Eur J Pain. 1997;1(3):185-90. [PubMed:15102399]
  4. Bhandari M, Bhandari A, Bhandari A: Recent updates on codeine. Pharm Methods. 2011 Jan;2(1):3-8. doi: 10.4103/2229-4708.81082. [PubMed:23781422]
  5. Chen ZR, Somogyi AA, Reynolds G, Bochner F: Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers. Br J Clin Pharmacol. 1991 Apr;31(4):381-90. [PubMed:2049245]
  6. Takahama K, Wakuda I, Fukushima H, Isohama Y, Kai H, Miyata T: Differential effect of codeine on coughs caused by mechanical stimulation of two different sites in the airway of guinea pigs. Eur J Pharmacol. 1997 Jun 18;329(1):93-7. [PubMed:9218689]
  7. Straube C, Derry S, Jackson KC, Wiffen PJ, Bell RF, Strassels S, Straube S: Codeine, alone and with paracetamol (acetaminophen), for cancer pain. Cochrane Database Syst Rev. 2014 Sep 19;(9):CD006601. doi: 10.1002/14651858.CD006601.pub4. [PubMed:25234029]
  8. Boom M, Niesters M, Sarton E, Aarts L, Smith TW, Dahan A: Non-analgesic effects of opioids: opioid-induced respiratory depression. Curr Pharm Des. 2012;18(37):5994-6004. doi: 10.2174/138161212803582469. [PubMed:22747535]
  9. Prommer E: Role of codeine in palliative care. J Opioid Manag. 2011 Sep-Oct;7(5):401-6. [PubMed:22165039]
  10. Codeine phosphate tablets, 30mg [Link]
  11. DailyMed: Codeine and promethazine syrup [Link]
  12. Codittusin, DailyMed [Link]
  13. EPAR, Codeine [File]
  14. Codeine, MedSafe NZ document [File]
External Links
Human Metabolome Database
HMDB0004995
KEGG Drug
D03580
KEGG Compound
C06174
PubChem Compound
5284371
PubChem Substance
46507764
ChemSpider
4447447
BindingDB
50105098
ChEBI
16714
ChEMBL
CHEMBL485
Therapeutic Targets Database
DAP000213
PharmGKB
PA449088
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Codeine
ATC Codes
N02AA79 — Codeine, combinations with psycholepticsR05DA04 — CodeineN02AA59 — Codeine, combinations excl. psycholepticsN02AJ08 — Codeine and ibuprofenN02AJ06 — Codeine and paracetamolN02AJ07 — Codeine and acetylsalicylic acid
AHFS Codes
  • 48:08.00 — Antitussives
  • 28:08.08 — Opiate Agonists
FDA label
Download (138 KB)
MSDS
Download (52.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedBasic ScienceDrug Biotransformation / Membrane Transport1
1CompletedBasic ScienceGenotype-related Drug Metabolism1
1CompletedTreatmentConstipation Drug Induced / Healthy Volunteers1
1CompletedTreatmentCoughing2
1CompletedTreatmentDiabetic Neuropathies / Fibromyalgia / Major Depressive Disorder (MDD) / Vasomotor Symptoms1
1CompletedTreatmentMechanically Ventilated Neonates / Painful Procedures in Newborns1
1CompletedTreatmentPain4
1Not Yet RecruitingBasic ScienceCodeine / Metformin / Organic Cation Transporter 11
1, 2CompletedTreatmentSickle Cell Disorders1
2CompletedTreatmentNeck Pain1
2CompletedTreatmentOsteoarthritis (OA)1
2CompletedTreatmentPostoperative pain1
2RecruitingTreatmentNeoplasms, Upper Aerodigestive Tract / Uterine Cervical Cancer1
2RecruitingTreatmentOrthopaedic Related Pain (Musculoskeletal Pain)1
2, 3CompletedTreatmentIdiopathic Intracranial Hypertension (IIH)1
3CompletedSupportive CareAnalgesia After ED Discharge for Extremity Injuries1
3CompletedTreatmentBreast Diseases / Pain1
3CompletedTreatmentKnee Osteoarthritis (Knee OA)1
3CompletedTreatmentMyopia1
3CompletedTreatmentPost-Operative Pain1
3CompletedTreatmentPostoperative Dental Pain1
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3TerminatedTreatmentPain1
4CompletedNot AvailableCleft Palate Repair1
4CompletedOtherEsophageal Motility Disorders1
4CompletedSupportive CarePain / Unspecified Adult Solid Tumor, Protocol Specific1
4CompletedTreatmentArthroscopic Meniscus Surgery1
4CompletedTreatmentBack Pain, Unspecified / Osteoarthritis (OA)1
4CompletedTreatmentCervical Preparation / Pain / Pregnancy Termination1
4CompletedTreatmentGastric Motility Disorder1
4CompletedTreatmentGeneral Surgery1
4CompletedTreatmentImpacted Third Molar Tooth1
4CompletedTreatmentOsteoarthritis (OA)2
4CompletedTreatmentPain2
4CompletedTreatmentPain / Tonsillitis1
4CompletedTreatmentPostcraniotomy Pain1
4CompletedTreatmentPostoperative pain2
4CompletedTreatmentTemporomandibular Disorders1
4CompletedTreatmentTo Control Pain After Third Molar Surgery1
4CompletedTreatmentTraumas1
4RecruitingSupportive CareNeoplasms, Thyroid / Parathyroid Adenomas / Parathyroid Diseases / Parathyroid Hyperplasia / Thyroid Cancers / Thyroid Diseases / Thyroid Goitre / Thyroid Nodules1
4Unknown StatusTreatmentPostoperative Laminectomy Pain / Postoperative pain1
4Unknown StatusTreatmentPostoperative Pain, PCA Contramal Consumption1
4WithdrawnBasic ScienceSickle Cell Disorders1
4WithdrawnTreatmentBreast Cancer / Postoperative pain1
4WithdrawnTreatmentPain, Chronic1
Not AvailableCompletedDiagnosticGastric Emptying / Healthy Volunteers / Motility Disorders1
Not AvailableCompletedPreventionHeadache1
Not AvailableCompletedTreatmentEdema / Pain / Trismus1
Not AvailableCompletedTreatmentFracture Bone1
Not AvailableCompletedTreatmentCaudal epidural block therapy / Mastectomy1
Not AvailableCompletedTreatmentPain2
Not AvailableCompletedTreatmentPeriapical Abscess1
Not AvailableNot Yet RecruitingBasic ScienceItching / Morphine1
Not AvailableRecruitingTreatmentBack Pain Lower Back1
Not AvailableRecruitingTreatmentPost-Operative Pain1
Not AvailableTerminatedTreatmentPain, Acute1
Not AvailableUnknown StatusTreatmentFracture Bone / Pain1

Pharmacoeconomics

Manufacturers
  • Roxane laboratories inc
Packagers
  • Actavis Group
  • Aidarex Pharmacuticals LLC
  • Amarin Pharmaceuticals
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Athlon Pharmaceuticals Inc.
  • Barr Pharmaceuticals
  • BASF Corp.
  • Blansett Pharmacal Co. Inc.
  • Blenheim Pharmacal
  • Breckenridge Pharmaceuticals
  • Bryant Ranch Prepack
  • C.O. Truxton Inc.
  • Cardinal Health
  • Carlisle Laboratories Inc.
  • Centurion Labs
  • Century Pharmaceuticals Inc.
  • Cerovene Inc.
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • D.M. Graham Laboratories Inc.
  • DAVA Pharmaceuticals
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Duramed
  • Eon Labs
  • Glenmark Generics Ltd.
  • Golden State Medical Supply Inc.
  • Great Southern Laboratories
  • H and H Laboratories
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Hi Tech Pharmacal Co. Inc.
  • Hospira Inc.
  • Innoviant Pharmacy Inc.
  • Ivax Pharmaceuticals
  • Janssen-Ortho Inc.
  • Jerome Stevens Pharmaceuticals Inc.
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Lannett Co. Inc.
  • Lehigh Valley Technologies Inc.
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mallinckrodt Inc.
  • Mckesson Corp.
  • MCR American Pharmaceuticals Inc.
  • Medvantx Inc.
  • Mikart Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Nexgen Pharma Inc.
  • Novartis AG
  • Nucare Pharmaceuticals Inc.
  • Ortho-McNeil-Janssen Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patient First Corp.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Association
  • Pharmedix
  • Pharmpak Inc.
  • Physicians Total Care Inc.
  • Poly Pharmaceuticals Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Qualitest
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Roxane Labs
  • Sandhills Packaging Inc.
  • SJ Pharmaceuticals LLC
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stanley Pharmaceuticals Ltd.
  • Stat Rx Usa
  • Talbert Medical Management Corp.
  • Teva Pharmaceutical Industries Ltd.
  • TG United Inc.
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Va Cmop Dallas
  • Valeant Ltd.
  • Vascondor Inc.
  • Veratex Corp.
  • Vintage Pharmaceuticals Inc.
  • Watson Pharmaceuticals
  • West-Ward Pharmaceuticals
  • Wockhardt Ltd.
Dosage forms
FormRouteStrength
TabletOral
SolutionOral
CapsuleOral
Tablet, extended releaseOral
Tablet, extended releaseOral
SolutionIntramuscular; Subcutaneous
LiquidIntramuscular; Subcutaneous
SyrupOral
SolutionOral15 mg/2.5mL
SolutionOral30 mg/5mL
TabletOral15 mg/1
TabletOral30 mg/1
TabletOral60 mg/1
Suspension, extended releaseOral
SolutionOral
LiquidOral
TabletOral
SyrupOral
LiquidOral
ElixirOral
KitOral
SuspensionOral
Prices
Unit descriptionCostUnit
Codeine phosphate powder8.25USD g
Codeine Phosphate 30 mg/ml1.31USD ml
Codeine sulfate 60 mg tablet0.86USD tablet
Codeine sulfate 30 mg tablet0.76USD tablet
Codeine ph 30 mg/ml syringe0.54USD ml
Codeine ph 15 mg/ml syringe0.49USD ml
Codeine sulfate 15 mg tablet0.43USD tablet
Ratio-Codeine 30 mg Tablet0.09USD tablet
Ratio-Codeine 15 mg Tablet0.07USD tablet
Ratio-Codeine 5 mg/ml Syrup0.03USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8062667No2011-11-222029-03-29Us
US8790700No2014-07-292027-03-15Us
US9066942No2015-06-302032-01-03Us
US6383471No2002-05-072019-04-06Us
US6248363No2001-06-192019-11-23Us
US9107921No2015-08-182032-01-03Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)154-156MSDS
boiling point (°C)250 http://www.chm.bris.ac.uk/webprojects2002/winder/information.htm
water solubilitysoluble in waterhttp://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con126132.pdf
logP1.39https://www.agilent.com/cs/library/applications/5990-9625EN.pdf
logS-1.52ADMET & DMPK 1(4) (2013) 48-62; doi: 10.5599/admet.1.4.24
pKa8.2http://www.inchem.org/documents/pims/pharm/codeine.htm
Predicted Properties
PropertyValueSource
Water Solubility0.577 mg/mLALOGPS
logP1.2ALOGPS
logP1.34ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)13.78ChemAxon
pKa (Strongest Basic)9.19ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.93 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity84.6 m3·mol-1ChemAxon
Polarizability31.95 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9966
Blood Brain Barrier+0.9979
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.8631
P-glycoprotein inhibitor IInhibitor0.5435
P-glycoprotein inhibitor IINon-inhibitor0.8724
Renal organic cation transporterInhibitor0.638
CYP450 2C9 substrateNon-substrate0.7698
CYP450 2D6 substrateSubstrate0.9274
CYP450 3A4 substrateSubstrate0.7796
CYP450 1A2 substrateNon-inhibitor0.6494
CYP450 2C9 inhibitorNon-inhibitor0.8866
CYP450 2D6 inhibitorInhibitor0.6978
CYP450 2C19 inhibitorNon-inhibitor0.8256
CYP450 3A4 inhibitorNon-inhibitor0.8899
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.747
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9567
BiodegradationNot ready biodegradable0.9935
Rat acute toxicity2.8450 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8556
hERG inhibition (predictor II)Non-inhibitor0.8615
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-01ot-3950000000-e80ecb11646b4da6aa92
LC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL Thermo Scientific) 60V, PositiveLC-MS/MSsplash10-0uxr-0973000000-87d07ddd2ed24b9598d7
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0009000000-d68b67071bf467a42afa
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0009000000-a298cedb776a11677cf7
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0459000000-1a92521b38ba51a7fa81
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0gc1-0940000000-68cae285315cfe9c7d0e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0uxs-0910000000-b0c288c76c616e1a54d3
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0159-0390000000-ac30542a576060b3373c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-870de7833257cd342810
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-8ece718ed46e5e439112
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0139000000-7880499a47dbd2f41229
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0973000000-87d07ddd2ed24b9598d7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-015a-0920000000-4f676c9e2b42320493af
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0910000000-e67964930533268605cd
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-99b083bf48ae39e3cec6
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0009000000-efebfbff05a4cb72fe32
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0139000000-be0f9b6eaa028b54ad6c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0973000000-89bc81638a52beefd890
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-015a-0920000000-7eccc8e19d8d88b18128
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0uxr-0910000000-5809a9ed32210bcfa231
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0159-0390000000-a7469c01c0a4ff4179bf
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0uyi-1952000000-3db61b1a0c8cde5b8c82
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0lea-1940000000-b491506c23f09adaee8c
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0lea-1930000000-48dcc53ac80bf97d1f2d

Taxonomy

Description
This compound belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Morphinans
Sub Class
Not Available
Direct Parent
Morphinans
Alternative Parents
Phenanthrenes and derivatives / Tetralins / Coumarans / Anisoles / Aralkylamines / Alkyl aryl ethers / Piperidines / Trialkylamines / Secondary alcohols / Oxacyclic compounds
show 3 more
Substituents
Morphinan / Phenanthrene / Tetralin / Coumaran / Anisole / Alkyl aryl ether / Aralkylamine / Piperidine / Benzenoid / Secondary alcohol
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
morphinane alkaloid, organic heteropentacyclic compound (CHEBI:16714) / Isoquinoline alkaloids (C06174)

Targets

Details
1. Mu-type opioid receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Voltage-gated calcium channel activity
Specific Function
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
Molecular Weight
44778.855 Da
References
  1. Takahama K, Shirasaki T: Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs. Cough. 2007 Jul 9;3:8. [PubMed:17620111]
  2. Codeine FDA label [File]
  3. EPAR, Codeine [File]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
Curator comments
This target action is based on in vitro data.
General Function
Opioid receptor activity
Specific Function
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
Molecular Weight
42644.665 Da
References
  1. Mignat C, Wille U, Ziegler A: Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes. Life Sci. 1995;56(10):793-9. [PubMed:7885194]
  2. Schmidt H, Vormfelde Sv, Klinder K, Gundert-Remy U, Gleiter CH, Skopp G, Aderjan R, Fuhr U: Affinities of dihydrocodeine and its metabolites to opioid receptors. Pharmacol Toxicol. 2002 Aug;91(2):57-63. [PubMed:12420793]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Opioid receptor activity
Specific Function
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
Gene Name
OPRD1
Uniprot ID
P41143
Uniprot Name
Delta-type opioid receptor
Molecular Weight
40368.235 Da
References
  1. Mignat C, Wille U, Ziegler A: Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes. Life Sci. 1995;56(10):793-9. [PubMed:7885194]
  2. Schmidt H, Vormfelde Sv, Klinder K, Gundert-Remy U, Gleiter CH, Skopp G, Aderjan R, Fuhr U: Affinities of dihydrocodeine and its metabolites to opioid receptors. Pharmacol Toxicol. 2002 Aug;91(2):57-63. [PubMed:12420793]
  3. ChemBL resource, opioid receptors [Link]

Enzymes

Details
1. Cytochrome P450 2D6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Zhou SF: Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet. 2009;48(11):689-723. doi: 10.2165/11318030-000000000-00000. [PubMed:19817501]
  2. Flockhart Table of Drug Interactions [Link]
  3. Codeine FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [PubMed:15304429]
  2. Yue QY, Sawe J: Different effects of inhibitors on the O- and N-demethylation of codeine in human liver microsomes. Eur J Clin Pharmacol. 1997;52(1):41-7. [PubMed:9143866]
  3. Codeine FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Coffman BL, Rios GR, King CD, Tephly TR: Human UGT2B7 catalyzes morphine glucuronidation. Drug Metab Dispos. 1997 Jan;25(1):1-4. [PubMed:9010622]
  2. Codeine FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as...
Gene Name
UGT2B4
Uniprot ID
P06133
Uniprot Name
UDP-glucuronosyltransferase 2B4
Molecular Weight
60512.035 Da
References
  1. Raungrut P, Uchaipichat V, Elliot DJ, Janchawee B, Somogyi AA, Miners JO: In vitro-in vivo extrapolation predicts drug-drug interactions arising from inhibition of codeine glucuronidation by dextropropoxyphene, fluconazole, ketoconazole, and methadone in humans. J Pharmacol Exp Ther. 2010 Aug;334(2):609-18. doi: 10.1124/jpet.110.167916. Epub 2010 May 18. [PubMed:20484152]
  2. Gelston EA, Coller JK, Lopatko OV, James HM, Schmidt H, White JM, Somogyi AA: Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects. Br J Clin Pharmacol. 2012 May;73(5):786-94. doi: 10.1111/j.1365-2125.2011.04145.x. [PubMed:22092298]
  3. Codeine FDA label [File]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Tzvetkov MV, dos Santos Pereira JN, Meineke I, Saadatmand AR, Stingl JC, Brockmoller J: Morphine is a substrate of the organic cation transporter OCT1 and polymorphisms in OCT1 gene affect morphine pharmacokinetics after codeine administration. Biochem Pharmacol. 2013 Sep 1;86(5):666-78. doi: 10.1016/j.bcp.2013.06.019. Epub 2013 Jul 5. [PubMed:23835420]
  2. Dujic T, Zhou K, Donnelly LA, Tavendale R, Palmer CN, Pearson ER: Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study. Diabetes. 2015 May;64(5):1786-93. doi: 10.2337/db14-1388. Epub 2014 Dec 15. [PubMed:25510240]
  3. Venkatasubramanian R, Fukuda T, Niu J, Mizuno T, Chidambaran V, Vinks AA, Sadhasivam S: ABCC3 and OCT1 genotypes influence pharmacokinetics of morphine in children. Pharmacogenomics. 2014 Jul;15(10):1297-309. doi: 10.2217/pgs.14.99. [PubMed:25155932]

Drug created on June 13, 2005 07:24 / Updated on November 12, 2019 22:57