Identification

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

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

Structure
Thumb
Synonyms
  • (−)-Codeine
  • (5alpha,6alpha)-7,8-Didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol
  • (5α,6α)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol
  • 3-Methylmorphin
  • 3-methylmorphine
  • 7,8-didehydro-4,5alpha-epoxy-3-methoxy-17-methylmorphinan-6alpha-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 monomethyl ether
  • morphine-3-methyl ether
  • O(3)-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 sulfateAVW5HY4N2E1420-53-7BCXHDORHMMZBBZ-DORFAMGDSA-N
Codeine sulfate trihydrate11QV9BS0CB6854-40-6BOLDZXRCJAJADM-AAXBYHQXSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Codeine 15Tablet15 mgOralLaboratoire Riva Inc1994-12-31Not applicableCanada
Codeine 30Tablet30 mgOralLaboratoire Riva Inc1994-12-31Not applicableCanada
Codeine Contin 100mg Controlled Release TabTablet, extended release100 mgOralPurdue Pharma1995-12-31Not applicableCanada
Codeine Contin 150mg Controlled Release TabTablet, extended release150 mgOralPurdue Pharma1995-12-31Not applicableCanada
Codeine Contin 200mg Controlled Release TabTablet, extended release200 mgOralPurdue Pharma1995-12-31Not applicableCanada
Codeine Contin 50mg Controlled Release TabTablet, extended release50 mgOralPurdue Pharma1997-03-13Not applicableCanada
Codeine Phosphate Inj 30mg/mlSolution30 mgIntramuscular; SubcutaneousHospira, Inc.1981-12-31Not applicableCanada
Codeine Phosphate Inj 60mg/mlSolution60 mgIntramuscular; SubcutaneousHospira, Inc.1981-12-31Not applicableCanada
Codeine Phosphate Injection USPLiquid30 mgIntramuscular; SubcutaneousSandoz Canada Incorporated1978-12-31Not applicableCanada
Codeine Phosphate SyrupSyrup5 mgOralD.C. Labs Limited1951-12-312005-07-19Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Acetaminophen and Codeine PhosphateTablet300 mg/1OralRemedy Repack2013-04-042017-01-20Us
Codeine SulfateTablet15 mg/1OralLannett Company, Inc.2014-06-13Not applicableUs
Codeine SulfateTablet30 mg/1OralLannett Company, Inc.2014-06-13Not applicableUs
Codeine SulfateTablet60 mg/1OralLannett Company, Inc.2014-06-13Not applicableUs
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)
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. 8 mgCodeine phosphate (8 mg) + Acetylsalicylic acid (375 mg) + Caffeine (15 mg)TabletOralLaboratoires Confab IncNot applicableNot applicableCanada
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[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10,15-tetraen-14-ol
SMILES
[H][[email protected]@]12OC3=C(OC)C=CC4=C3[[email protected]@]11CCN(C)[[email protected]]([H])(C4)[[email protected]]1([H])C=C[[email protected]@H]2O

Pharmacology

Indication

For treatment and management of pain (systemic). It is also used as an antidiarrheal and as a cough suppressant.

Structured Indications
Pharmacodynamics

Codeine, an opiate agonist in the CNS, is similar to other phenanthrene derivatives such as morphine. It is selective for the mu receptor, but with a much weaker affinity than morphine. The analgesic properties of codeine have been speculated to come from its conversion to morphine. The principle therapeutic action is analgesia. Codeine concentrations do not correlate with brain concentration or relief of pain. The minimum effective concentration is highly variable is influenced by numerous factors, including but not limited to, age, previous opioid use, age, and general medical condition. However, the effective dose for patients that have developed tolerance is significantly higher than the opioid-naive patients.

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.

TargetActionsOrganism
AMu-type opioid receptor
partial agonist
Human
AKappa-type opioid receptor
partial agonist
Human
ADelta-type opioid receptor
agonist
Human
Absorption

Well absorbed following oral administration with a bioavailability of approximately 90%. Maximum plasma concentration occurs 60 minutes post-administration. Food does not effect the rate or extent of absorption of codeine.

Volume of distribution

Apparent volume of distribution = 3-6 L/kg

Protein binding

7-25% bound to plasma proteins.

Metabolism

Hepatic. Codeine is a prodrug, itself inactive, but demethylated to the active morphine by the liver enzyme CYP2D6 to morphine. 70-80% of the dose undergoes glucuronidation to form codeine-6-glucuronide. This process is mediated by UDP-glucuronosyltransferase UGT2B7 and UGT2B4. 5-10% of the dose undergoes O-demethylation to morphine and 10% undergoes N-demethylation to form norcodeine. CYP2D6 mediates the biotransformation to morphine. CYP3A4 is the enzymes that mediates the conversion to norcodiene. Morphine and norcodeine are further metabolized and undergo glucuronidation. The glucuronide metabolites of morphine are morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Both morphine and morphine-6-glucuronide are active and have analgesic activity. Norcodiene and M3G do not have any analgesic properties.

Route of elimination

90% of the total dose of codeine is excreted through the kidneys, of which 10% is unchanged codeine.

Half life

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

Clearance
Not Available
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.

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
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may increase the analgesic activities of Codeine.Experimental, Illicit
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may increase the analgesic activities of Codeine.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the analgesic activities of Codeine.Experimental, Illicit
7-NitroindazoleThe risk or severity of adverse effects can be increased when Codeine is combined with 7-Nitroindazole.Experimental
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.Experimental
AbirateroneThe serum concentration of Codeine can be increased when it is combined with Abiraterone.Approved
AcepromazineThe risk or severity of adverse effects can be increased when Codeine is combined with Acepromazine.Approved, Vet Approved
AceprometazineThe risk or severity of adverse effects can be increased when Codeine is combined with Aceprometazine.Approved
AcetazolamideThe risk or severity of adverse effects can be increased when Codeine is combined with Acetazolamide.Approved, Vet Approved
AclidiniumThe risk or severity of adverse effects can be increased when Aclidinium is combined with Codeine.Approved
AdipiplonThe risk or severity of adverse effects can be increased when Codeine is combined with Adipiplon.Investigational
AgomelatineThe risk or severity of adverse effects can be increased when Codeine is combined with Agomelatine.Approved, Investigational
AlaproclateCodeine may increase the serotonergic activities of Alaproclate.Experimental
AlcuroniumThe risk or severity of adverse effects can be increased when Alcuronium is combined with Codeine.Experimental
AlfaxaloneThe risk or severity of adverse effects can be increased when Codeine is combined with Alfaxalone.Vet Approved
AlfentanilThe risk or severity of adverse effects can be increased when Codeine is combined with Alfentanil.Approved, Illicit
AlimemazineAlimemazine may increase the hypotensive activities of Codeine.Approved, Vet Approved
AllopregnanoloneThe risk or severity of adverse effects can be increased when Codeine is combined with Allopregnanolone.Investigational
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Codeine is combined with Alphacetylmethadol.Experimental, Illicit
AlphaprodineThe risk or severity of adverse effects can be increased when Codeine is combined with Alphaprodine.Illicit
AlprazolamThe risk or severity of adverse effects can be increased when Codeine is combined with Alprazolam.Approved, Illicit, Investigational
AlvimopanThe risk or severity of adverse effects can be increased when Codeine is combined with Alvimopan.Approved
AmilorideThe risk or severity of adverse effects can be increased when Codeine is combined with Amiloride.Approved
AmiodaroneThe therapeutic efficacy of Codeine can be decreased when used in combination with Amiodarone.Approved, Investigational
AmisulprideThe risk or severity of adverse effects can be increased when Codeine is combined with Amisulpride.Approved, Investigational
AmitriptylineThe risk or severity of adverse effects can be increased when Codeine is combined with Amitriptyline.Approved
Ammonium chlorideAmmonium chloride may increase the excretion rate of Codeine which could result in a lower serum level and potentially a reduction in efficacy.Approved, Vet Approved
AmobarbitalThe risk or severity of adverse effects can be increased when Codeine is combined with Amobarbital.Approved, Illicit
AmoxapineThe risk or severity of adverse effects can be increased when Codeine is combined with Amoxapine.Approved
AmperozideThe risk or severity of adverse effects can be increased when Codeine is combined with Amperozide.Experimental
AmphetamineAmphetamine may increase the analgesic activities of Codeine.Approved, Illicit
Anisotropine MethylbromideThe risk or severity of adverse effects can be increased when Anisotropine Methylbromide is combined with Codeine.Approved
AprepitantThe serum concentration of Codeine can be increased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe therapeutic efficacy of Codeine can be decreased when used in combination with Artemether.Approved
ArticaineThe risk or severity of adverse effects can be increased when Codeine is combined with Articaine.Approved
AsenapineThe risk or severity of adverse effects can be increased when Codeine is combined with Asenapine.Approved
AtazanavirThe metabolism of Codeine can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe therapeutic efficacy of Codeine can be decreased when used in combination with Atomoxetine.Approved
AtracuriumThe risk or severity of adverse effects can be increased when Atracurium is combined with Codeine.Experimental
Atracurium besylateThe risk or severity of adverse effects can be increased when Atracurium besylate is combined with Codeine.Approved
AtropineThe risk or severity of adverse effects can be increased when Atropine is combined with Codeine.Approved, Vet Approved
AzaperoneThe risk or severity of adverse effects can be increased when Codeine is combined with Azaperone.Vet Approved
AzelastineCodeine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.Approved
AzosemideThe risk or severity of adverse effects can be increased when Codeine is combined with Azosemide.Investigational
BaclofenThe risk or severity of adverse effects can be increased when Codeine is combined with Baclofen.Approved
BarbitalThe risk or severity of adverse effects can be increased when Codeine is combined with Barbital.Illicit
BenactyzineThe risk or severity of adverse effects can be increased when Benactyzine is combined with Codeine.Withdrawn
BendroflumethiazideThe risk or severity of adverse effects can be increased when Codeine is combined with Bendroflumethiazide.Approved
BenmoxinThe risk or severity of adverse effects can be increased when Codeine is combined with Benmoxin.Withdrawn
BenperidolThe risk or severity of adverse effects can be increased when Codeine is combined with Benperidol.Investigational
BenzatropineThe risk or severity of adverse effects can be increased when Benzatropine is combined with Codeine.Approved
BenzocaineThe risk or severity of adverse effects can be increased when Codeine is combined with Benzocaine.Approved
BenzphetamineBenzphetamine may increase the analgesic activities of Codeine.Approved, Illicit
Benzyl alcoholThe risk or severity of adverse effects can be increased when Codeine is combined with Benzyl alcohol.Approved
BetaxololThe therapeutic efficacy of Codeine can be decreased when used in combination with Betaxolol.Approved
BiperidenThe risk or severity of adverse effects can be increased when Biperiden is combined with Codeine.Approved
BL-1020BL-1020 may increase the hypotensive activities of Codeine.Investigational
BoceprevirThe metabolism of Codeine can be decreased when combined with Boceprevir.Withdrawn
BornaprineThe risk or severity of adverse effects can be increased when Bornaprine is combined with Codeine.Experimental
BortezomibThe metabolism of Codeine can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Codeine can be decreased when it is combined with Bosentan.Approved, Investigational
BrexpiprazoleThe risk or severity of adverse effects can be increased when Codeine is combined with Brexpiprazole.Approved
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Codeine.Approved
BrofaromineThe risk or severity of adverse effects can be increased when Codeine is combined with Brofaromine.Experimental
BromazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Bromazepam.Approved, Illicit
BromisovalThe risk or severity of adverse effects can be increased when Codeine is combined with Bromisoval.Experimental
BromperidolThe risk or severity of adverse effects can be increased when Codeine is combined with Bromperidol.Investigational
BrompheniramineThe risk or severity of adverse effects can be increased when Codeine is combined with Brompheniramine.Approved
BrotizolamThe risk or severity of adverse effects can be increased when Codeine is combined with Brotizolam.Approved, Withdrawn
BumetanideThe risk or severity of adverse effects can be increased when Codeine is combined with Bumetanide.Approved
BupivacaineThe risk or severity of adverse effects can be increased when Codeine is combined with Bupivacaine.Approved, Investigational
BuprenorphineCodeine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BupropionThe therapeutic efficacy of Codeine can be decreased when used in combination with Bupropion.Approved
BuspironeThe risk or severity of adverse effects can be increased when Codeine is combined with Buspirone.Approved, Investigational
ButabarbitalThe risk or severity of adverse effects can be increased when Butabarbital is combined with Codeine.Approved, Illicit
ButacaineThe risk or severity of adverse effects can be increased when Codeine is combined with Butacaine.Vet Approved
ButalbitalThe risk or severity of adverse effects can be increased when Codeine is combined with Butalbital.Approved, Illicit
ButambenThe risk or severity of adverse effects can be increased when Codeine is combined with Butamben.Approved
ButethalThe risk or severity of adverse effects can be increased when Codeine is combined with Butethal.Approved, Illicit
ButorphanolThe risk or severity of adverse effects can be increased when Codeine is combined with Butorphanol.Approved, Illicit, Vet Approved
CanertinibThe risk or severity of adverse effects can be increased when Codeine is combined with Canertinib.Investigational
Canrenoic acidThe risk or severity of adverse effects can be increased when Codeine is combined with Canrenoic acid.Approved, Withdrawn
CanrenoneThe risk or severity of adverse effects can be increased when Codeine is combined with Canrenone.Investigational
CarbamazepineThe metabolism of Codeine can be increased when combined with Carbamazepine.Approved, Investigational
CarbinoxamineThe risk or severity of adverse effects can be increased when Codeine is combined with Carbinoxamine.Approved
CarfentanilThe risk or severity of adverse effects can be increased when Codeine is combined with Carfentanil.Illicit, Vet Approved
CarisoprodolThe risk or severity of adverse effects can be increased when Codeine is combined with Carisoprodol.Approved
CaroxazoneThe risk or severity of adverse effects can be increased when Codeine is combined with Caroxazone.Withdrawn
CelecoxibThe therapeutic efficacy of Codeine can be decreased when used in combination with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Codeine can be increased when it is combined with Ceritinib.Approved
CetirizineThe risk or severity of adverse effects can be increased when Codeine is combined with Cetirizine.Approved
Chloral hydrateThe risk or severity of adverse effects can be increased when Codeine is combined with Chloral hydrate.Approved, Illicit, Vet Approved
ChlordiazepoxideThe risk or severity of adverse effects can be increased when Codeine is combined with Chlordiazepoxide.Approved, Illicit
ChlormezanoneThe risk or severity of adverse effects can be increased when Codeine is combined with Chlormezanone.Approved, Withdrawn
ChloroprocaineThe risk or severity of adverse effects can be increased when Codeine is combined with Chloroprocaine.Approved
ChloroquineThe therapeutic efficacy of Codeine can be decreased when used in combination with Chloroquine.Approved, Vet Approved
ChlorothiazideThe risk or severity of adverse effects can be increased when Codeine is combined with Chlorothiazide.Approved, Vet Approved
ChlorphenamineThe risk or severity of adverse effects can be increased when Codeine is combined with Chlorphenamine.Approved
ChlorphenoxamineThe risk or severity of adverse effects can be increased when Chlorphenoxamine is combined with Codeine.Withdrawn
ChlorphentermineChlorphentermine may increase the analgesic activities of Codeine.Illicit, Withdrawn
ChlorproethazineChlorproethazine may increase the hypotensive activities of Codeine.Experimental
ChlorpromazineThe therapeutic efficacy of Codeine can be decreased when used in combination with Chlorpromazine.Approved, Vet Approved
ChlorprothixeneThe risk or severity of adverse effects can be increased when Codeine is combined with Chlorprothixene.Approved, Withdrawn
ChlorthalidoneThe risk or severity of adverse effects can be increased when Codeine is combined with Chlorthalidone.Approved
ChlorzoxazoneThe risk or severity of adverse effects can be increased when Codeine is combined with Chlorzoxazone.Approved
CholecalciferolThe therapeutic efficacy of Codeine can be decreased when used in combination with Cholecalciferol.Approved, Nutraceutical
CicletanineThe risk or severity of adverse effects can be increased when Codeine is combined with Cicletanine.Investigational
CimetidineThe therapeutic efficacy of Codeine can be decreased when used in combination with Cimetidine.Approved
CinacalcetThe therapeutic efficacy of Codeine can be decreased when used in combination with Cinacalcet.Approved
CinchocaineThe risk or severity of adverse effects can be increased when Codeine is combined with Cinchocaine.Approved, Vet Approved
CitalopramThe therapeutic efficacy of Codeine can be decreased when used in combination with Citalopram.Approved
ClarithromycinThe metabolism of Codeine can be decreased when combined with Clarithromycin.Approved
ClemastineThe therapeutic efficacy of Codeine can be decreased when used in combination with Clemastine.Approved
ClidiniumThe risk or severity of adverse effects can be increased when Codeine is combined with Clidinium.Approved
ClobazamThe therapeutic efficacy of Codeine can be decreased when used in combination with Clobazam.Approved, Illicit
ClofenamideThe risk or severity of adverse effects can be increased when Codeine is combined with Clofenamide.Experimental
clomethiazoleThe risk or severity of adverse effects can be increased when Codeine is combined with clomethiazole.Investigational
ClomipramineThe therapeutic efficacy of Codeine can be decreased when used in combination with Clomipramine.Approved, Vet Approved
ClonazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Clonazepam.Approved, Illicit
ClonidineThe risk or severity of adverse effects can be increased when Codeine is combined with Clonidine.Approved
ClopamideThe risk or severity of adverse effects can be increased when Codeine is combined with Clopamide.Experimental
ClopenthixolThe risk or severity of adverse effects can be increased when Codeine is combined with Clopenthixol.Experimental
ClorazepateThe risk or severity of adverse effects can be increased when Codeine is combined with Clorazepate.Approved, Illicit
ClorexoloneThe risk or severity of adverse effects can be increased when Codeine is combined with Clorexolone.Experimental
ClothiapineThe risk or severity of adverse effects can be increased when Codeine is combined with Clothiapine.Experimental
ClotrimazoleThe therapeutic efficacy of Codeine can be decreased when used in combination with Clotrimazole.Approved, Vet Approved
ClozapineThe therapeutic efficacy of Codeine can be decreased when used in combination with Clozapine.Approved
CobicistatThe therapeutic efficacy of Codeine can be decreased when used in combination with Cobicistat.Approved
CocaineThe therapeutic efficacy of Codeine can be decreased when used in combination with Cocaine.Approved, Illicit
ConivaptanThe serum concentration of Codeine can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Codeine can be decreased when combined with Crizotinib.Approved
CyclizineThe risk or severity of adverse effects can be increased when Codeine is combined with Cyclizine.Approved
CyclobenzaprineThe risk or severity of adverse effects can be increased when Codeine is combined with Cyclobenzaprine.Approved
CyclopenthiazideThe risk or severity of adverse effects can be increased when Codeine is combined with Cyclopenthiazide.Experimental
CyclopentolateThe risk or severity of adverse effects can be increased when Cyclopentolate is combined with Codeine.Approved
CyclosporineThe metabolism of Codeine can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CyclothiazideThe risk or severity of adverse effects can be increased when Codeine is combined with Cyclothiazide.Approved
CyproheptadineThe risk or severity of adverse effects can be increased when Codeine is combined with Cyproheptadine.Approved
DabrafenibThe serum concentration of Codeine can be decreased when it is combined with Dabrafenib.Approved
DantroleneThe risk or severity of adverse effects can be increased when Codeine is combined with Dantrolene.Approved
DapiprazoleThe risk or severity of adverse effects can be increased when Codeine is combined with Dapiprazole.Approved
DapoxetineCodeine may increase the serotonergic activities of Dapoxetine.Investigational
DarifenacinThe therapeutic efficacy of Codeine can be decreased when used in combination with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Codeine can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Codeine can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Codeine can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe therapeutic efficacy of Codeine can be decreased when used in combination with Delavirdine.Approved
DeramciclaneThe risk or severity of adverse effects can be increased when Codeine is combined with Deramciclane.Investigational
DesfluraneThe risk or severity of adverse effects can be increased when Codeine is combined with Desflurane.Approved
DesipramineThe therapeutic efficacy of Codeine can be decreased when used in combination with Desipramine.Approved
DesloratadineThe risk or severity of adverse effects can be increased when Codeine is combined with Desloratadine.Approved, Investigational
DesmopressinThe risk or severity of adverse effects can be increased when Codeine is combined with Desmopressin.Approved
DesvenlafaxineCodeine may increase the serotonergic activities of Desvenlafaxine.Approved
DetomidineThe risk or severity of adverse effects can be increased when Codeine is combined with Detomidine.Vet Approved
DexbrompheniramineThe risk or severity of adverse effects can be increased when Codeine is combined with Dexbrompheniramine.Approved
DexetimideThe risk or severity of adverse effects can be increased when Dexetimide is combined with Codeine.Withdrawn
DexmedetomidineThe risk or severity of adverse effects can be increased when Codeine is combined with Dexmedetomidine.Approved, Vet Approved
DextroamphetamineDextroamphetamine may increase the analgesic activities of Codeine.Approved, Illicit
DextromoramideThe risk or severity of adverse effects can be increased when Codeine is combined with Dextromoramide.Experimental, Illicit
DextropropoxypheneThe risk or severity of adverse effects can be increased when Codeine is combined with Dextropropoxyphene.Approved, Illicit, Withdrawn
DezocineThe risk or severity of adverse effects can be increased when Codeine is combined with Dezocine.Approved
DiazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Diazepam.Approved, Illicit, Vet Approved
DicyclomineThe risk or severity of adverse effects can be increased when Dicyclomine is combined with Codeine.Approved
Diethyl etherThe risk or severity of adverse effects can be increased when Codeine is combined with Diethyl ether.Experimental
DiethylpropionDiethylpropion may increase the analgesic activities of Codeine.Approved, Illicit
DifenoxinThe risk or severity of adverse effects can be increased when Codeine is combined with Difenoxin.Approved, Illicit
DihydrocodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Dihydrocodeine.Approved, Illicit
DihydroergotamineThe metabolism of Codeine can be decreased when combined with Dihydroergotamine.Approved
DihydroetorphineThe risk or severity of adverse effects can be increased when Codeine is combined with Dihydroetorphine.Experimental, Illicit
DihydromorphineThe risk or severity of adverse effects can be increased when Codeine is combined with Dihydromorphine.Experimental, Illicit
DiltiazemThe metabolism of Codeine can be decreased when combined with Diltiazem.Approved
DimenhydrinateThe risk or severity of adverse effects can be increased when Codeine is combined with Dimenhydrinate.Approved
DiphenhydramineThe therapeutic efficacy of Codeine can be decreased when used in combination with Diphenhydramine.Approved
DiphenoxylateThe risk or severity of adverse effects can be increased when Codeine is combined with Diphenoxylate.Approved, Illicit
DixyrazineThe risk or severity of adverse effects can be increased when Codeine is combined with Dixyrazine.Experimental
DoramectinThe risk or severity of adverse effects can be increased when Codeine is combined with Doramectin.Vet Approved
DosulepinThe therapeutic efficacy of Codeine can be decreased when used in combination with Dosulepin.Approved
DoxepinThe risk or severity of adverse effects can be increased when Codeine is combined with Doxepin.Approved
DoxycyclineThe metabolism of Codeine can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Codeine.Approved, Vet Approved
DPDPEThe risk or severity of adverse effects can be increased when Codeine is combined with DPDPE.Investigational
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Codeine.Approved, Illicit
DronedaroneThe therapeutic efficacy of Codeine can be decreased when used in combination with Dronedarone.Approved
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Codeine.Approved, Vet Approved
DrospirenoneThe risk or severity of adverse effects can be increased when Codeine is combined with Drospirenone.Approved
DrotebanolThe risk or severity of adverse effects can be increased when Codeine is combined with Drotebanol.Experimental, Illicit
DuloxetineThe therapeutic efficacy of Codeine can be decreased when used in combination with Duloxetine.Approved
DyclonineThe risk or severity of adverse effects can be increased when Codeine is combined with Dyclonine.Approved
EcgonineThe risk or severity of adverse effects can be increased when Codeine is combined with Ecgonine.Experimental, Illicit
EcopipamThe risk or severity of adverse effects can be increased when Codeine is combined with Ecopipam.Investigational
EfavirenzThe risk or severity of adverse effects can be increased when Codeine is combined with Efavirenz.Approved, Investigational
EfonidipineThe risk or severity of adverse effects can be increased when Codeine is combined with Efonidipine.Approved
EliglustatThe therapeutic efficacy of Codeine can be decreased when used in combination with Eliglustat.Approved
EltanoloneThe risk or severity of adverse effects can be increased when Codeine is combined with Eltanolone.Investigational
EluxadolineCodeine may increase the constipating activities of Eluxadoline.Approved
EmeproniumThe risk or severity of adverse effects can be increased when Emepronium is combined with Codeine.Experimental
EnfluraneThe risk or severity of adverse effects can be increased when Codeine is combined with Enflurane.Approved, Vet Approved
EntacaponeThe risk or severity of adverse effects can be increased when Codeine is combined with Entacapone.Approved, Investigational
EnzalutamideThe serum concentration of Codeine can be decreased when it is combined with Enzalutamide.Approved
EplerenoneThe risk or severity of adverse effects can be increased when Codeine is combined with Eplerenone.Approved
ErythromycinThe metabolism of Codeine can be decreased when combined with Erythromycin.Approved, Vet Approved
EscitalopramCodeine may increase the serotonergic activities of Escitalopram.Approved, Investigational
EstazolamThe risk or severity of adverse effects can be increased when Codeine is combined with Estazolam.Approved, Illicit
EszopicloneThe risk or severity of adverse effects can be increased when Codeine is combined with Eszopiclone.Approved
Etacrynic acidThe risk or severity of adverse effects can be increased when Codeine is combined with Etacrynic acid.Approved
EtanautineThe risk or severity of adverse effects can be increased when Etanautine is combined with Codeine.Experimental
EthanolCodeine may increase the central nervous system depressant (CNS depressant) activities of Ethanol.Approved
EthchlorvynolThe risk or severity of adverse effects can be increased when Codeine is combined with Ethchlorvynol.Approved, Illicit, Withdrawn
EthopropazineThe risk or severity of adverse effects can be increased when Ethopropazine is combined with Codeine.Approved
EthosuximideThe risk or severity of adverse effects can be increased when Codeine is combined with Ethosuximide.Approved
EthotoinThe risk or severity of adverse effects can be increased when Codeine is combined with Ethotoin.Approved
EthoxzolamideThe risk or severity of adverse effects can be increased when Codeine is combined with Ethoxzolamide.Withdrawn
Ethyl carbamateThe risk or severity of adverse effects can be increased when Codeine is combined with Ethyl carbamate.Withdrawn
Ethyl chlorideThe risk or severity of adverse effects can be increased when Codeine is combined with Ethyl chloride.Experimental
Ethyl loflazepateThe risk or severity of adverse effects can be increased when Codeine is combined with Ethyl loflazepate.Approved, Illicit
EthylmorphineThe risk or severity of adverse effects can be increased when Codeine is combined with Ethylmorphine.Approved, Illicit
EtidocaineThe risk or severity of adverse effects can be increased when Codeine is combined with Etidocaine.Approved
EtifoxineThe risk or severity of adverse effects can be increased when Codeine is combined with Etifoxine.Withdrawn
EtizolamThe risk or severity of adverse effects can be increased when Codeine is combined with Etizolam.Approved
EtomidateThe risk or severity of adverse effects can be increased when Codeine is combined with Etomidate.Approved
EtoperidoneCodeine may increase the serotonergic activities of Etoperidone.Approved
EtorphineThe risk or severity of adverse effects can be increased when Codeine is combined with Etorphine.Illicit, Vet Approved
EtybenzatropineThe risk or severity of adverse effects can be increased when Etybenzatropine is combined with Codeine.Experimental
EzogabineThe risk or severity of adverse effects can be increased when Codeine is combined with Ezogabine.Approved
FelbamateThe risk or severity of adverse effects can be increased when Codeine is combined with Felbamate.Approved
FencamfamineThe risk or severity of adverse effects can be increased when Codeine is combined with Fencamfamine.Approved, Illicit, Withdrawn
FenquizoneThe risk or severity of adverse effects can be increased when Codeine is combined with Fenquizone.Experimental
FentanylThe risk or severity of adverse effects can be increased when Codeine is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Codeine.Approved
FexofenadineThe risk or severity of adverse effects can be increased when Codeine is combined with Fexofenadine.Approved
FlibanserinThe risk or severity of adverse effects can be increased when Codeine is combined with Flibanserin.Approved
FluanisoneThe risk or severity of adverse effects can be increased when Codeine is combined with Fluanisone.Experimental
FluconazoleThe metabolism of Codeine can be decreased when combined with Fluconazole.Approved
FludiazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Fludiazepam.Approved, Illicit
FlunarizineThe risk or severity of adverse effects can be increased when Codeine is combined with Flunarizine.Approved
FlunitrazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Flunitrazepam.Approved, Illicit
FluoxetineThe therapeutic efficacy of Codeine can be decreased when used in combination with Fluoxetine.Approved, Vet Approved
FlupentixolThe risk or severity of adverse effects can be increased when Codeine is combined with Flupentixol.Approved, Withdrawn
FluphenazineThe risk or severity of adverse effects can be increased when Codeine is combined with Fluphenazine.Approved
FlurazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Flurazepam.Approved, Illicit
FluspirileneThe risk or severity of adverse effects can be increased when Codeine is combined with Fluspirilene.Approved
Fluticasone propionateThe risk or severity of adverse effects can be increased when Codeine is combined with Fluticasone propionate.Approved
FluvoxamineThe therapeutic efficacy of Codeine can be decreased when used in combination with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Codeine can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Codeine can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Codeine can be increased when combined with Fosphenytoin.Approved
FospropofolThe risk or severity of adverse effects can be increased when Codeine is combined with Fospropofol.Approved, Illicit
FurazolidoneThe risk or severity of adverse effects can be increased when Codeine is combined with Furazolidone.Approved, Vet Approved
FurosemideThe risk or severity of adverse effects can be increased when Codeine is combined with Furosemide.Approved, Vet Approved
Fusidic AcidThe serum concentration of Codeine can be increased when it is combined with Fusidic Acid.Approved
GabapentinThe risk or severity of adverse effects can be increased when Codeine is combined with Gabapentin.Approved, Investigational
Gabapentin EnacarbilThe risk or severity of adverse effects can be increased when Codeine is combined with Gabapentin Enacarbil.Approved
GallamineThe risk or severity of adverse effects can be increased when Gallamine is combined with Codeine.Experimental
Gallamine TriethiodideThe risk or severity of adverse effects can be increased when Gallamine Triethiodide is combined with Codeine.Approved
Gamma Hydroxybutyric AcidThe risk or severity of adverse effects can be increased when Codeine is combined with Gamma Hydroxybutyric Acid.Approved, Illicit
GepefrineGepefrine may increase the analgesic activities of Codeine.Experimental
GepironeThe risk or severity of adverse effects can be increased when Codeine is combined with Gepirone.Investigational
GlutethimideThe risk or severity of adverse effects can be increased when Codeine is combined with Glutethimide.Approved, Illicit
GlycopyrroniumThe risk or severity of adverse effects can be increased when Glycopyrronium is combined with Codeine.Approved, Investigational, Vet Approved
GuanfacineThe risk or severity of adverse effects can be increased when Codeine is combined with Guanfacine.Approved, Investigational
HalazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Halazepam.Approved, Illicit, Withdrawn
HaloperidolThe therapeutic efficacy of Codeine can be decreased when used in combination with Haloperidol.Approved
HalothaneThe risk or severity of adverse effects can be increased when Codeine is combined with Halothane.Approved, Vet Approved
HarmalineThe risk or severity of adverse effects can be increased when Codeine is combined with Harmaline.Experimental
HeroinThe risk or severity of adverse effects can be increased when Codeine is combined with Heroin.Approved, Illicit
HexamethoniumThe risk or severity of adverse effects can be increased when Hexamethonium is combined with Codeine.Experimental
HexobarbitalThe risk or severity of adverse effects can be increased when Codeine is combined with Hexobarbital.Approved
HomatropineThe risk or severity of adverse effects can be increased when Homatropine is combined with Codeine.Approved
HydracarbazineThe risk or severity of adverse effects can be increased when Codeine is combined with Hydracarbazine.Experimental
HydrochlorothiazideThe risk or severity of adverse effects can be increased when Codeine is combined with Hydrochlorothiazide.Approved, Vet Approved
HydrocodoneCodeine may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.Approved, Illicit
HydroflumethiazideThe risk or severity of adverse effects can be increased when Codeine is combined with Hydroflumethiazide.Approved
HydromorphoneThe risk or severity of adverse effects can be increased when Codeine is combined with Hydromorphone.Approved, Illicit
HydroxyamphetamineHydroxyamphetamine may increase the analgesic activities of Codeine.Approved
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Codeine.Approved
HyoscyamineThe risk or severity of adverse effects can be increased when Hyoscyamine is combined with Codeine.Approved
IbopamineThe risk or severity of adverse effects can be increased when Codeine is combined with Ibopamine.Experimental
IdelalisibThe serum concentration of Codeine can be increased when it is combined with Idelalisib.Approved
IloperidoneThe risk or severity of adverse effects can be increased when Codeine is combined with Iloperidone.Approved
ImatinibThe metabolism of Codeine can be decreased when combined with Imatinib.Approved
ImipramineThe therapeutic efficacy of Codeine can be decreased when used in combination with Imipramine.Approved
IndalpineCodeine may increase the serotonergic activities of Indalpine.Investigational, Withdrawn
IndapamideThe risk or severity of adverse effects can be increased when Codeine is combined with Indapamide.Approved
IndinavirThe therapeutic efficacy of Codeine can be decreased when used in combination with Indinavir.Approved
IndiplonThe risk or severity of adverse effects can be increased when Codeine is combined with Indiplon.Investigational
Iofetamine I-123Iofetamine I-123 may increase the analgesic activities of Codeine.Approved
Ipratropium bromideThe risk or severity of adverse effects can be increased when Ipratropium bromide is combined with Codeine.Approved
IproclozideThe risk or severity of adverse effects can be increased when Codeine is combined with Iproclozide.Withdrawn
IproniazidThe risk or severity of adverse effects can be increased when Codeine is combined with Iproniazid.Withdrawn
IsavuconazoniumThe metabolism of Codeine can be decreased when combined with Isavuconazonium.Approved, Investigational
IsocarboxazidThe risk or severity of adverse effects can be increased when Codeine is combined with Isocarboxazid.Approved
IsofluraneThe risk or severity of adverse effects can be increased when Codeine is combined with Isoflurane.Approved, Vet Approved
IsoniazidThe therapeutic efficacy of Codeine can be decreased when used in combination with Isoniazid.Approved
IsosorbideThe risk or severity of adverse effects can be increased when Codeine is combined with Isosorbide.Approved
IsradipineThe metabolism of Codeine can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Codeine can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Codeine can be increased when it is combined with Ivacaftor.Approved
KetamineThe risk or severity of adverse effects can be increased when Codeine is combined with Ketamine.Approved, Vet Approved
KetazolamThe risk or severity of adverse effects can be increased when Codeine is combined with Ketazolam.Approved
KetobemidoneThe risk or severity of adverse effects can be increased when Codeine is combined with Ketobemidone.Approved
KetoconazoleThe therapeutic efficacy of Codeine can be decreased when used in combination with Ketoconazole.Approved, Investigational
LamotrigineThe risk or severity of adverse effects can be increased when Codeine is combined with Lamotrigine.Approved, Investigational
LanreotideThe metabolism of Codeine can be decreased when combined with Lanreotide.Approved
LevetiracetamThe risk or severity of adverse effects can be increased when Codeine is combined with Levetiracetam.Approved, Investigational
LevobupivacaineThe risk or severity of adverse effects can be increased when Codeine is combined with Levobupivacaine.Approved
LevocabastineThe risk or severity of adverse effects can be increased when Codeine is combined with Levocabastine.Approved
LevocetirizineThe risk or severity of adverse effects can be increased when Codeine is combined with Levocetirizine.Approved
LevodopaThe risk or severity of adverse effects can be increased when Codeine is combined with Levodopa.Approved
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Codeine is combined with Levomethadyl Acetate.Approved
LevomilnacipranCodeine may increase the serotonergic activities of Levomilnacipran.Approved
LevorphanolThe risk or severity of adverse effects can be increased when Codeine is combined with Levorphanol.Approved
LidocaineThe risk or severity of adverse effects can be increased when Codeine is combined with Lidocaine.Approved, Vet Approved
LisdexamfetamineLisdexamfetamine may increase the analgesic activities of Codeine.Approved, Investigational
LithiumThe risk or severity of adverse effects can be increased when Codeine is combined with Lithium.Approved
LofentanilThe risk or severity of adverse effects can be increased when Codeine is combined with Lofentanil.Illicit
LopinavirThe therapeutic efficacy of Codeine can be decreased when used in combination with Lopinavir.Approved
LoprazolamThe risk or severity of adverse effects can be increased when Codeine is combined with Loprazolam.Experimental
LoratadineThe risk or severity of adverse effects can be increased when Codeine is combined with Loratadine.Approved
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Codeine.Approved
LorcaserinThe therapeutic efficacy of Codeine can be decreased when used in combination with Lorcaserin.Approved
LormetazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Lormetazepam.Approved
LovastatinThe metabolism of Codeine can be decreased when combined with Lovastatin.Approved, Investigational
LoxapineThe risk or severity of adverse effects can be increased when Codeine is combined with Loxapine.Approved
LuliconazoleThe serum concentration of Codeine can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Codeine can be increased when combined with Lumacaftor.Approved
LumefantrineThe therapeutic efficacy of Codeine can be decreased when used in combination with Lumefantrine.Approved
LurasidoneThe risk or severity of adverse effects can be increased when Codeine is combined with Lurasidone.Approved
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Codeine.Approved, Vet Approved
ManidipineThe therapeutic efficacy of Codeine can be decreased when used in combination with Manidipine.Approved
MannitolThe risk or severity of adverse effects can be increased when Codeine is combined with Mannitol.Approved, Investigational
MaprotilineThe risk or severity of adverse effects can be increased when Codeine is combined with Maprotiline.Approved
MazaticolThe risk or severity of adverse effects can be increased when Mazaticol is combined with Codeine.Experimental
MebanazineThe risk or severity of adverse effects can be increased when Codeine is combined with Mebanazine.Withdrawn
MebicarThe risk or severity of adverse effects can be increased when Codeine is combined with Mebicar.Experimental
MebutizideThe risk or severity of adverse effects can be increased when Codeine is combined with Mebutizide.Experimental
MecamylamineThe risk or severity of adverse effects can be increased when Mecamylamine is combined with Codeine.Approved
MeclizineThe risk or severity of adverse effects can be increased when Codeine is combined with Meclizine.Approved
MedazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Medazepam.Experimental
MedetomidineThe risk or severity of adverse effects can be increased when Codeine is combined with Medetomidine.Vet Approved
MefrusideThe risk or severity of adverse effects can be increased when Codeine is combined with Mefruside.Experimental
MelatoninThe risk or severity of adverse effects can be increased when Codeine is combined with Melatonin.Approved, Nutraceutical, Vet Approved
MelperoneThe risk or severity of adverse effects can be increased when Codeine is combined with Melperone.Approved
MephedroneMephedrone may increase the analgesic activities of Codeine.Investigational
MephentermineMephentermine may increase the analgesic activities of Codeine.Approved
MepivacaineThe risk or severity of adverse effects can be increased when Codeine is combined with Mepivacaine.Approved, Vet Approved
MeprobamateThe risk or severity of adverse effects can be increased when Codeine is combined with Meprobamate.Approved, Illicit
MeptazinolThe risk or severity of adverse effects can be increased when Codeine is combined with Meptazinol.Experimental
MersalylThe risk or severity of adverse effects can be increased when Codeine is combined with Mersalyl.Approved
MesoridazineThe risk or severity of adverse effects can be increased when Codeine is combined with Mesoridazine.Approved
MetaxaloneThe risk or severity of adverse effects can be increased when Codeine is combined with Metaxalone.Approved
MethadoneThe therapeutic efficacy of Codeine can be decreased when used in combination with Methadone.Approved
Methadyl AcetateThe risk or severity of adverse effects can be increased when Codeine is combined with Methadyl Acetate.Approved, Illicit
MethamphetamineMethamphetamine may increase the analgesic activities of Codeine.Approved, Illicit
MethanthelineThe risk or severity of adverse effects can be increased when Methantheline is combined with Codeine.Approved
MethapyrileneThe risk or severity of adverse effects can be increased when Codeine is combined with Methapyrilene.Withdrawn
MethaqualoneThe risk or severity of adverse effects can be increased when Codeine is combined with Methaqualone.Illicit, Withdrawn
MethazolamideThe risk or severity of adverse effects can be increased when Codeine is combined with Methazolamide.Approved
MethocarbamolThe risk or severity of adverse effects can be increased when Codeine is combined with Methocarbamol.Approved, Vet Approved
MethohexitalThe risk or severity of adverse effects can be increased when Codeine is combined with Methohexital.Approved
MethotrimeprazineCodeine may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.Approved
MethoxyfluraneThe risk or severity of adverse effects can be increased when Codeine is combined with Methoxyflurane.Approved, Vet Approved
MethoxyphenamineMethoxyphenamine may increase the analgesic activities of Codeine.Experimental
MethsuximideThe risk or severity of adverse effects can be increased when Codeine is combined with Methsuximide.Approved
MethyclothiazideThe risk or severity of adverse effects can be increased when Codeine is combined with Methyclothiazide.Approved
MethylecgonineThe risk or severity of adverse effects can be increased when Codeine is combined with Methylecgonine.Experimental
Methylene blueMethylene blue may increase the hypotensive activities of Codeine.Investigational
MethylphenobarbitalThe risk or severity of adverse effects can be increased when Codeine is combined with Methylphenobarbital.Approved
MeticraneThe risk or severity of adverse effects can be increased when Codeine is combined with Meticrane.Experimental
MetixeneThe risk or severity of adverse effects can be increased when Metixene is combined with Codeine.Approved
MetolazoneThe risk or severity of adverse effects can be increased when Codeine is combined with Metolazone.Approved
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Codeine.Approved, Investigational
MetyrosineCodeine may increase the sedative activities of Metyrosine.Approved
MidazolamThe risk or severity of adverse effects can be increased when Codeine is combined with Midazolam.Approved, Illicit
Midomafetamine3,4-Methylenedioxymethamphetamine may increase the analgesic activities of Codeine.Experimental, Illicit
MidostaurinThe therapeutic efficacy of Codeine can be decreased when used in combination with Midostaurin.Approved
MifepristoneThe serum concentration of Codeine can be increased when it is combined with Mifepristone.Approved, Investigational
MilnacipranCodeine may increase the serotonergic activities of Milnacipran.Approved
MinaprineThe risk or severity of adverse effects can be increased when Codeine is combined with Minaprine.Approved
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Codeine.Approved, Investigational
MirabegronThe therapeutic efficacy of Codeine can be decreased when used in combination with Mirabegron.Approved
MirtazapineCodeine may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.Approved
MitotaneThe serum concentration of Codeine can be decreased when it is combined with Mitotane.Approved
MMDAMMDA may increase the analgesic activities of Codeine.Experimental, Illicit
MoclobemideThe risk or severity of adverse effects can be increased when Codeine is combined with Moclobemide.Approved
MolindoneThe risk or severity of adverse effects can be increased when Codeine is combined with Molindone.Approved
MoricizineMoricizine may increase the hypotensive activities of Codeine.Approved, Withdrawn
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Codeine.Approved, Investigational
MuzolimineThe risk or severity of adverse effects can be increased when Codeine is combined with Muzolimine.Experimental
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Codeine.Approved, Investigational
NalbuphineThe risk or severity of adverse effects can be increased when Codeine is combined with Nalbuphine.Approved
NaltrexoneThe therapeutic efficacy of Codeine can be decreased when used in combination with Naltrexone.Approved, Investigational, Vet Approved
NefazodoneThe metabolism of Codeine can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Codeine can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Codeine can be increased when it is combined with Netupitant.Approved
NevirapineThe therapeutic efficacy of Codeine can be decreased when used in combination with Nevirapine.Approved
NialamideThe risk or severity of adverse effects can be increased when Codeine is combined with Nialamide.Withdrawn
NicardipineThe therapeutic efficacy of Codeine can be decreased when used in combination with Nicardipine.Approved
NilotinibThe therapeutic efficacy of Codeine can be decreased when used in combination with Nilotinib.Approved, Investigational
NitrazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Nitrazepam.Approved
Nitrous oxideThe risk or severity of adverse effects can be increased when Codeine is combined with Nitrous oxide.Approved, Vet Approved
NorfluraneThe risk or severity of adverse effects can be increased when Codeine is combined with Norflurane.Investigational
NormethadoneThe risk or severity of adverse effects can be increased when Codeine is combined with Normethadone.Approved, Illicit
NortriptylineThe risk or severity of adverse effects can be increased when Codeine is combined with Nortriptyline.Approved
OctamoxinThe risk or severity of adverse effects can be increased when Codeine is combined with Octamoxin.Withdrawn
OctreotideThe metabolism of Codeine can be decreased when combined with Octreotide.Approved, Investigational
OlanzapineThe risk or severity of adverse effects can be increased when Codeine is combined with Olanzapine.Approved, Investigational
OlaparibThe metabolism of Codeine can be decreased when combined with Olaparib.Approved
OlopatadineThe risk or severity of adverse effects can be increased when Codeine is combined with Olopatadine.Approved
OndansetronThe risk or severity of adverse effects can be increased when Codeine is combined with Ondansetron.Approved
OpiumThe risk or severity of adverse effects can be increased when Codeine is combined with Opium.Approved, Illicit
OrphenadrineCodeine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.Approved
OsanetantThe risk or severity of adverse effects can be increased when Codeine is combined with Osanetant.Investigational
OsimertinibThe serum concentration of Codeine can be increased when it is combined with Osimertinib.Approved
OtiloniumThe risk or severity of adverse effects can be increased when Otilonium is combined with Codeine.Experimental
OxazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Oxazepam.Approved
OxethazaineThe risk or severity of adverse effects can be increased when Codeine is combined with Oxethazaine.Investigational
OxitropiumThe risk or severity of adverse effects can be increased when Oxitropium is combined with Codeine.Investigational
OxprenololThe risk or severity of adverse effects can be increased when Codeine is combined with Oxprenolol.Approved
OxybuprocaineThe risk or severity of adverse effects can be increased when Codeine is combined with Oxybuprocaine.Approved
OxybutyninThe risk or severity of adverse effects can be increased when Oxybutynin is combined with Codeine.Approved, Investigational
OxycodoneThe risk or severity of adverse effects can be increased when Codeine is combined with Oxycodone.Approved, Illicit, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Codeine is combined with Oxymorphone.Approved, Investigational, Vet Approved
OxyphenoniumThe risk or severity of adverse effects can be increased when Oxyphenonium is combined with Codeine.Approved
PalbociclibThe serum concentration of Codeine can be increased when it is combined with Palbociclib.Approved
PaliperidoneThe risk or severity of adverse effects can be increased when Codeine is combined with Paliperidone.Approved
PancuroniumThe risk or severity of adverse effects can be increased when Pancuronium is combined with Codeine.Approved
PanobinostatThe serum concentration of Codeine can be increased when it is combined with Panobinostat.Approved, Investigational
ParaldehydeCodeine may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.Approved
PargylineThe risk or severity of adverse effects can be increased when Codeine is combined with Pargyline.Approved
ParoxetineThe therapeutic efficacy of Codeine can be decreased when used in combination with Paroxetine.Approved, Investigational
PasireotideThe metabolism of Codeine can be decreased when combined with Pasireotide.Approved
Peginterferon alfa-2bThe serum concentration of Codeine can be decreased when it is combined with Peginterferon alfa-2b.Approved
PegvisomantThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Codeine.Approved
PenfluridolThe risk or severity of adverse effects can be increased when Codeine is combined with Penfluridol.Experimental
PentazocineThe risk or severity of adverse effects can be increased when Codeine is combined with Pentazocine.Approved, Vet Approved
PentobarbitalThe metabolism of Codeine can be increased when combined with Pentobarbital.Approved, Vet Approved
PentoliniumThe risk or severity of adverse effects can be increased when Pentolinium is combined with Codeine.Approved
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Codeine.Approved
PerazineThe risk or severity of adverse effects can be increased when Codeine is combined with Perazine.Investigational
PerospironeThe risk or severity of adverse effects can be increased when Codeine is combined with Perospirone.Approved
PerphenazineThe risk or severity of adverse effects can be increased when Codeine is combined with Perphenazine.Approved
PethidineThe risk or severity of adverse effects can be increased when Codeine is combined with Pethidine.Approved
PhenazocineThe risk or severity of adverse effects can be increased when Codeine is combined with Phenazocine.Experimental
PhenelzineThe risk or severity of adverse effects can be increased when Codeine is combined with Phenelzine.Approved
PhenglutarimideThe risk or severity of adverse effects can be increased when Phenglutarimide is combined with Codeine.Experimental
PhenibutThe risk or severity of adverse effects can be increased when Codeine is combined with Phenibut.Experimental
PheniprazineThe risk or severity of adverse effects can be increased when Codeine is combined with Pheniprazine.Withdrawn
PhenobarbitalThe metabolism of Codeine can be increased when combined with Phenobarbital.Approved
PhenoperidineThe risk or severity of adverse effects can be increased when Codeine is combined with Phenoperidine.Experimental
PhenoxyethanolThe risk or severity of adverse effects can be increased when Codeine is combined with Phenoxyethanol.Approved
PhenoxypropazineThe risk or severity of adverse effects can be increased when Codeine is combined with Phenoxypropazine.Withdrawn
PhenterminePhentermine may increase the analgesic activities of Codeine.Approved, Illicit
PhenytoinThe metabolism of Codeine can be increased when combined with Phenytoin.Approved, Vet Approved
PimozideThe risk or severity of adverse effects can be increased when Codeine is combined with Pimozide.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Codeine is combined with Pipamperone.Approved
PipecuroniumThe risk or severity of adverse effects can be increased when Pipecuronium is combined with Codeine.Approved
PipotiazineThe risk or severity of adverse effects can be increased when Codeine is combined with Pipotiazine.Approved
PirenzepineThe risk or severity of adverse effects can be increased when Pirenzepine is combined with Codeine.Approved
PiretanideThe risk or severity of adverse effects can be increased when Codeine is combined with Piretanide.Experimental
PiritramideThe risk or severity of adverse effects can be increased when Codeine is combined with Piritramide.Investigational
PirlindoleThe risk or severity of adverse effects can be increased when Codeine is combined with Pirlindole.Approved
PivhydrazineThe risk or severity of adverse effects can be increased when Codeine is combined with Pivhydrazine.Withdrawn
PizotifenThe risk or severity of adverse effects can be increased when Codeine is combined with Pizotifen.Approved
PolythiazideThe risk or severity of adverse effects can be increased when Codeine is combined with Polythiazide.Approved
PomalidomideThe risk or severity of adverse effects can be increased when Codeine is combined with Pomalidomide.Approved
PosaconazoleThe metabolism of Codeine can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PotassiumThe risk or severity of adverse effects can be increased when Codeine is combined with Potassium.Approved
Potassium CitrateThe risk or severity of adverse effects can be increased when Codeine is combined with Potassium Citrate.Approved, Vet Approved
PramipexoleCodeine may increase the sedative activities of Pramipexole.Approved, Investigational
PramocaineThe risk or severity of adverse effects can be increased when Codeine is combined with Pramocaine.Approved
PrazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Prazepam.Approved, Illicit
PregabalinThe risk or severity of adverse effects can be increased when Pregabalin is combined with Codeine.Approved, Illicit, Investigational
PrilocaineThe risk or severity of adverse effects can be increased when Codeine is combined with Prilocaine.Approved
PrimidoneThe metabolism of Codeine can be increased when combined with Primidone.Approved, Vet Approved
ProcaineThe risk or severity of adverse effects can be increased when Codeine is combined with Procaine.Approved, Investigational, Vet Approved
ProchlorperazineThe risk or severity of adverse effects can be increased when Codeine is combined with Prochlorperazine.Approved, Vet Approved
ProcyclidineThe risk or severity of adverse effects can be increased when Procyclidine is combined with Codeine.Approved
PromazineThe therapeutic efficacy of Codeine can be decreased when used in combination with Promazine.Approved, Vet Approved
PromethazineThe risk or severity of adverse effects can be increased when Codeine is combined with Promethazine.Approved
PropanididThe risk or severity of adverse effects can be increased when Codeine is combined with Propanidid.Experimental
PropanthelineThe risk or severity of adverse effects can be increased when Propantheline is combined with Codeine.Approved
ProparacaineThe risk or severity of adverse effects can be increased when Codeine is combined with Proparacaine.Approved, Vet Approved
PropiopromazinePropiopromazine may increase the hypotensive activities of Codeine.Vet Approved
PropiverineThe risk or severity of adverse effects can be increased when Propiverine is combined with Codeine.Investigational
PropofolThe risk or severity of adverse effects can be increased when Codeine is combined with Propofol.Approved, Investigational, Vet Approved
PropoxycaineThe risk or severity of adverse effects can be increased when Codeine is combined with Propoxycaine.Approved
ProtriptylineThe risk or severity of adverse effects can be increased when Codeine is combined with Protriptyline.Approved
ProxibarbalThe risk or severity of adverse effects can be increased when Codeine is combined with Proxibarbal.Experimental
PSD502The risk or severity of adverse effects can be increased when Codeine is combined with PSD502.Investigational
PseudoephedrinePseudoephedrine may increase the analgesic activities of Codeine.Approved
QuazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Quazepam.Approved, Illicit
QuetiapineThe risk or severity of adverse effects can be increased when Codeine is combined with Quetiapine.Approved
QuinethazoneThe risk or severity of adverse effects can be increased when Codeine is combined with Quinethazone.Approved
QuinidineThe therapeutic efficacy of Codeine can be decreased when used in combination with Quinidine.Approved
QuinineThe therapeutic efficacy of Codeine can be decreased when used in combination with Quinine.Approved
QuinisocaineThe risk or severity of adverse effects can be increased when Codeine is combined with Quinisocaine.Experimental
RacloprideThe risk or severity of adverse effects can be increased when Codeine is combined with Raclopride.Investigational
RamelteonThe risk or severity of adverse effects can be increased when Codeine is combined with Ramelteon.Approved, Investigational
RamosetronCodeine may increase the constipating activities of Ramosetron.Approved
RanolazineThe therapeutic efficacy of Codeine can be decreased when used in combination with Ranolazine.Approved, Investigational
RasagilineThe risk or severity of adverse effects can be increased when Codeine is combined with Rasagiline.Approved
RemifentanilThe risk or severity of adverse effects can be increased when Codeine is combined with Remifentanil.Approved
RemoxiprideThe risk or severity of adverse effects can be increased when Codeine is combined with Remoxipride.Approved, Withdrawn
ReserpineThe risk or severity of adverse effects can be increased when Reserpine is combined with Codeine.Approved
RifabutinThe metabolism of Codeine can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Codeine can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Codeine can be increased when combined with Rifapentine.Approved
RisperidoneThe risk or severity of adverse effects can be increased when Codeine is combined with Risperidone.Approved, Investigational
RitanserinThe risk or severity of adverse effects can be increased when Codeine is combined with Ritanserin.Investigational
RitobegronRitobegron may increase the analgesic activities of Codeine.Investigational
RitonavirThe therapeutic efficacy of Codeine can be decreased when used in combination with Ritonavir.Approved, Investigational
RolapitantThe therapeutic efficacy of Codeine can be decreased when used in combination with Rolapitant.Approved
RolofyllineThe risk or severity of adverse effects can be increased when Codeine is combined with Rolofylline.Investigational
RomifidineThe risk or severity of adverse effects can be increased when Codeine is combined with Romifidine.Vet Approved
RopiniroleThe therapeutic efficacy of Codeine can be decreased when used in combination with Ropinirole.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Codeine is combined with Ropivacaine.Approved
RotigotineCodeine may increase the sedative activities of Rotigotine.Approved
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Codeine.Approved
SafrazineThe risk or severity of adverse effects can be increased when Codeine is combined with Safrazine.Withdrawn
SaquinavirThe metabolism of Codeine can be decreased when combined with Saquinavir.Approved, Investigational
ScopolamineThe risk or severity of adverse effects can be increased when Codeine is combined with Scopolamine.Approved
Scopolamine butylbromideThe risk or severity of adverse effects can be increased when Scopolamine butylbromide is combined with Codeine.Approved, Vet Approved
SecobarbitalThe risk or severity of adverse effects can be increased when Codeine is combined with Secobarbital.Approved, Vet Approved
SelegilineThe risk or severity of adverse effects can be increased when Codeine is combined with Selegiline.Approved, Investigational, Vet Approved
SepranoloneThe risk or severity of adverse effects can be increased when Codeine is combined with Sepranolone.Investigational
SertindoleThe risk or severity of adverse effects can be increased when Codeine is combined with Sertindole.Approved, Withdrawn
SertralineThe therapeutic efficacy of Codeine can be decreased when used in combination with Sertraline.Approved
SevofluraneThe risk or severity of adverse effects can be increased when Codeine is combined with Sevoflurane.Approved, Vet Approved
SildenafilThe metabolism of Codeine can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Codeine can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Codeine can be increased when it is combined with Simeprevir.Approved
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Codeine.Approved
SolifenacinThe risk or severity of adverse effects can be increased when Solifenacin is combined with Codeine.Approved
SomatostatinThe metabolism of Codeine can be decreased when combined with Somatostatin.Approved
SpiradolineThe risk or severity of adverse effects can be increased when Codeine is combined with Spiradoline.Investigational
SpironolactoneThe risk or severity of adverse effects can be increased when Codeine is combined with Spironolactone.Approved
St. John's WortThe serum concentration of Codeine can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Codeine can be increased when it is combined with Stiripentol.Approved
SuccinylcholineSuccinylcholine may increase the bradycardic activities of Codeine.Approved
SufentanilThe risk or severity of adverse effects can be increased when Codeine is combined with Sufentanil.Approved, Investigational
SulfisoxazoleThe metabolism of Codeine can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SulpirideThe risk or severity of adverse effects can be increased when Codeine is combined with Sulpiride.Approved
SultoprideThe risk or severity of adverse effects can be increased when Codeine is combined with Sultopride.Experimental
SuvorexantCodeine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.Approved
TandospironeThe risk or severity of adverse effects can be increased when Codeine is combined with Tandospirone.Investigational
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Codeine.Approved
TasimelteonThe risk or severity of adverse effects can be increased when Codeine is combined with Tasimelteon.Approved
TelaprevirThe metabolism of Codeine can be decreased when combined with Telaprevir.Withdrawn
TelithromycinThe metabolism of Codeine can be decreased when combined with Telithromycin.Approved
TemazepamThe risk or severity of adverse effects can be increased when Temazepam is combined with Codeine.Approved
TerbinafineThe therapeutic efficacy of Codeine can be decreased when used in combination with Terbinafine.Approved, Investigational, Vet Approved
TetrabenazineThe risk or severity of adverse effects can be increased when Codeine is combined with Tetrabenazine.Approved
TetracaineThe risk or severity of adverse effects can be increased when Codeine is combined with Tetracaine.Approved, Vet Approved
TetrahydropalmatineThe risk or severity of adverse effects can be increased when Codeine is combined with Tetrahydropalmatine.Investigational
TetrodotoxinThe risk or severity of adverse effects can be increased when Codeine is combined with Tetrodotoxin.Investigational
ThalidomideCodeine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.Approved, Investigational, Withdrawn
TheobromineThe risk or severity of adverse effects can be increased when Codeine is combined with Theobromine.Approved
ThiamylalThe risk or severity of adverse effects can be increased when Codeine is combined with Thiamylal.Approved, Vet Approved
ThiazinamThiazinam may increase the hypotensive activities of Codeine.Experimental
ThiethylperazineThiethylperazine may increase the hypotensive activities of Codeine.Withdrawn
ThiopentalThe risk or severity of adverse effects can be increased when Codeine is combined with Thiopental.Approved, Vet Approved
ThioridazineThe therapeutic efficacy of Codeine can be decreased when used in combination with Thioridazine.Withdrawn
ThiothixeneThe risk or severity of adverse effects can be increased when Codeine is combined with Thiothixene.Approved
TiagabineThe risk or severity of adverse effects can be increased when Codeine is combined with Tiagabine.Approved
TiaprideThe risk or severity of adverse effects can be increased when Codeine is combined with Tiapride.Approved, Investigational
TiclopidineThe therapeutic efficacy of Codeine can be decreased when used in combination with Ticlopidine.Approved
TicrynafenThe risk or severity of adverse effects can be increased when Codeine is combined with Ticrynafen.Withdrawn
TiletamineThe risk or severity of adverse effects can be increased when Codeine is combined with Tiletamine.Vet Approved
TilidineThe risk or severity of adverse effects can be increased when Codeine is combined with Tilidine.Experimental
TiotropiumThe risk or severity of adverse effects can be increased when Tiotropium is combined with Codeine.Approved
TipranavirThe therapeutic efficacy of Codeine can be decreased when used in combination with Tipranavir.Approved, Investigational
TizanidineThe risk or severity of adverse effects can be increased when Codeine is combined with Tizanidine.Approved
TocilizumabThe serum concentration of Codeine can be decreased when it is combined with Tocilizumab.Approved
TolcaponeThe risk or severity of adverse effects can be increased when Codeine is combined with Tolcapone.Approved, Withdrawn
ToloxatoneThe risk or severity of adverse effects can be increased when Codeine is combined with Toloxatone.Approved
TolterodineThe risk or severity of adverse effects can be increased when Tolterodine is combined with Codeine.Approved, Investigational
TolvaptanThe risk or severity of adverse effects can be increased when Codeine is combined with Tolvaptan.Approved
TopiramateThe risk or severity of adverse effects can be increased when Codeine is combined with Topiramate.Approved
TorasemideThe risk or severity of adverse effects can be increased when Codeine is combined with Torasemide.Approved
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Codeine.Approved, Investigational
Trans-2-PhenylcyclopropylamineThe risk or severity of adverse effects can be increased when Codeine is combined with Trans-2-Phenylcyclopropylamine.Experimental
TranylcypromineThe therapeutic efficacy of Codeine can be decreased when used in combination with Tranylcypromine.Approved
TrazodoneThe risk or severity of adverse effects can be increased when Codeine is combined with Trazodone.Approved, Investigational
TriamtereneThe risk or severity of adverse effects can be increased when Codeine is combined with Triamterene.Approved
TriazolamThe risk or severity of adverse effects can be increased when Codeine is combined with Triazolam.Approved
Tricaine methanesulfonateThe risk or severity of adverse effects can be increased when Codeine is combined with Tricaine methanesulfonate.Vet Approved
TrichlormethiazideThe risk or severity of adverse effects can be increased when Codeine is combined with Trichlormethiazide.Approved, Vet Approved
TrichloroethyleneThe risk or severity of adverse effects can be increased when Codeine is combined with Trichloroethylene.Experimental
TrifluoperazineThe risk or severity of adverse effects can be increased when Codeine is combined with Trifluoperazine.Approved
TrifluperidolThe risk or severity of adverse effects can be increased when Codeine is combined with Trifluperidol.Experimental
TriflupromazineThe risk or severity of adverse effects can be increased when Codeine is combined with Triflupromazine.Approved, Vet Approved
TrihexyphenidylThe risk or severity of adverse effects can be increased when Trihexyphenidyl is combined with Codeine.Approved
TrimethaphanThe risk or severity of adverse effects can be increased when Trimethaphan is combined with Codeine.Approved
TrimipramineThe risk or severity of adverse effects can be increased when Codeine is combined with Trimipramine.Approved
TriprolidineThe risk or severity of adverse effects can be increased when Codeine is combined with Triprolidine.Approved
TropatepineThe risk or severity of adverse effects can be increased when Tropatepine is combined with Codeine.Experimental
TropicamideThe risk or severity of adverse effects can be increased when Tropicamide is combined with Codeine.Approved
TrospiumThe risk or severity of adverse effects can be increased when Trospium is combined with Codeine.Approved
TubocurarineThe risk or severity of adverse effects can be increased when Tubocurarine is combined with Codeine.Approved
UlaritideThe risk or severity of adverse effects can be increased when Codeine is combined with Ularitide.Investigational
Valproic AcidThe risk or severity of adverse effects can be increased when Codeine is combined with Valproic Acid.Approved, Investigational
VapreotideThe metabolism of Codeine can be decreased when combined with Vapreotide.Approved, Investigational
VecuroniumThe risk or severity of adverse effects can be increased when Vecuronium is combined with Codeine.Approved
VenlafaxineThe therapeutic efficacy of Codeine can be decreased when used in combination with Venlafaxine.Approved
VeraliprideThe risk or severity of adverse effects can be increased when Codeine is combined with Veralipride.Experimental
VerapamilThe metabolism of Codeine can be decreased when combined with Verapamil.Approved
VigabatrinThe risk or severity of adverse effects can be increased when Codeine is combined with Vigabatrin.Approved
Vinyl etherThe risk or severity of adverse effects can be increased when Codeine is combined with Vinyl ether.Experimental
VoriconazoleThe metabolism of Codeine can be decreased when combined with Voriconazole.Approved, Investigational
VortioxetineThe risk or severity of adverse effects can be increased when Codeine is combined with Vortioxetine.Approved
XenonThe risk or severity of adverse effects can be increased when Codeine is combined with Xenon.Experimental
XipamideThe risk or severity of adverse effects can be increased when Codeine is combined with Xipamide.Experimental
XylazineThe risk or severity of adverse effects can be increased when Codeine is combined with Xylazine.Vet Approved
ZaleplonThe risk or severity of adverse effects can be increased when Codeine is combined with Zaleplon.Approved, Illicit, Investigational
ZiconotideThe risk or severity of adverse effects can be increased when Codeine is combined with Ziconotide.Approved
ZimelidineCodeine may increase the serotonergic activities of Zimelidine.Withdrawn
ZiprasidoneThe therapeutic efficacy of Codeine can be decreased when used in combination with Ziprasidone.Approved
ZolazepamThe risk or severity of adverse effects can be increased when Codeine is combined with Zolazepam.Vet Approved
ZolpidemCodeine may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.Approved
ZonisamideThe risk or severity of adverse effects can be increased when Codeine is combined with Zonisamide.Approved, Investigational
ZopicloneThe risk or severity of adverse effects can be increased when Codeine is combined with Zopiclone.Approved
ZotepineThe risk or severity of adverse effects can be increased when Codeine is combined with Zotepine.Approved
ZuclopenthixolThe risk or severity of adverse effects can be increased when Codeine is combined with Zuclopenthixol.Approved, Investigational
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]
External Links
Human Metabolome Database
HMDB04995
KEGG Drug
D03580
KEGG Compound
C06174
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
N02AA59 — Codeine, combinations excl. psycholepticsN02AA79 — Codeine, combinations with psycholepticsR05DA04 — Codeine
AHFS Codes
  • 48:08.00 — Antitussives
  • 28:08.08 — Opiate Agonists
MSDS
Download (52.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceDrug Biotransformation / Membrane Transport1
1CompletedBasic ScienceGenotype-related Drug Metabolism1
1CompletedTreatmentConstipation Drug Induced / Healthy Volunteers1
1CompletedTreatmentDiabetic Neuropathies / Fibromyalgia / Major Depressive Disorder (MDD) / Vasomotor Symptoms1
1CompletedTreatmentPain4
1Unknown StatusTreatmentMechanically Ventilated Neonates / Painful Procedures in Newborns1
1, 2CompletedTreatmentSickle Cell Disorders1
2CompletedTreatmentCervical Pain1
2Not Yet RecruitingTreatmentPainful musculoskeletal conditions1
2, 3CompletedTreatmentIdiopathic Intracranial Hypertension (IIH)1
3CompletedTreatmentMyopia1
3CompletedTreatmentPostoperative Dental Pain1
3TerminatedTreatmentPain1
4CompletedSupportive CarePain / Unspecified Adult Solid Tumor, Protocol Specific1
4CompletedTreatmentBack Pain / Synovitis of osteoarthritis1
4CompletedTreatmentGastric Motility Disorder1
4CompletedTreatmentImpacted Third Molar Tooth1
4CompletedTreatmentPain / Tonsillitis1
4CompletedTreatmentPostcraniotomy Pain1
4CompletedTreatmentPostoperative pain1
4CompletedTreatmentTraumas1
4Not Yet RecruitingTreatmentPain1
4RecruitingTreatmentCervical Preparation / Pain / Pregnancy Termination1
4RecruitingTreatmentPain1
4RecruitingTreatmentPostoperative pain1
4Unknown StatusTreatmentPostoperative Laminectomy Pain / Postoperative pain1
4WithdrawnBasic ScienceSickle Cell Disorders1
4WithdrawnTreatmentPain, Chronic1
Not AvailableCompletedPreventionHeadaches1
Not AvailableCompletedTreatmentPain2
Not AvailableCompletedTreatmentPeriapical Abscess1
Not AvailableRecruitingDiagnosticGastric Emptying / Healthy Volunteers / Motility Disorders1
Not AvailableRecruitingTreatmentLow Back Pain (LBP)1
Not AvailableUnknown StatusTreatmentFracture Bone / Pain1

Pharmacoeconomics

Manufacturers
  • Roxane laboratories inc
Packagers
Dosage forms
FormRouteStrength
SolutionOral
TabletOral
TabletOral300 mg/1
CapsuleOral
LiquidOral
Tablet, extended releaseOral
Tablet, extended releaseOral100 mg
Tablet, extended releaseOral150 mg
Tablet, extended releaseOral200 mg
Tablet, extended releaseOral50 mg
SolutionIntramuscular; Subcutaneous30 mg
SolutionIntramuscular; Subcutaneous60 mg
LiquidIntramuscular; Subcutaneous30 mg
SyrupOral25 mg
SyrupOral5 mg
TabletOral60 mg
SolutionOral15 mg/2.5mL
SolutionOral30 mg/5mL
TabletOral15 mg/1
TabletOral30 mg/1
TabletOral60 mg/1
SolutionOral10 mg
LiquidOral10 mg
SyrupOral
TabletOral15 mg
TabletOral30 mg
KitOral
Suspension, extended releaseOral
ElixirOral
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)
US8062667No2009-03-292029-03-29Us
US8790700No2007-03-152027-03-15Us
US9066942No2012-01-032032-01-03Us
US6383471No1999-04-062019-04-06Us
US6248363No1999-11-232019-11-23Us
US9107921No2012-01-032032-01-03Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)157.5 °CPhysProp
boiling point (°C)250 °C at 2.20E+01 mm HgPhysProp
water solubility9000 mg/L (at 20 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP1.19AVDEEF,A ET AL. (1996)
logS-1.52ADME Research, USCD
pKa8.21 (at 25 °C)LIDE,DR (1995)
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
Human
Pharmacological action
Yes
Actions
Partial 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. Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [PubMed:15509185]
  2. Takahama K, Shirasaki T: Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs. Cough. 2007 Jul 9;3:8. [PubMed:17620111]
  3. Freissmuth M, Beindl W, Kratzel M: Binding and structure-activity-relation of benzo[f]isoquinoline- and norcodeinone-derivatives at mu-opioid receptors in the rat cerebral cortex. Br J Pharmacol. 1993 Dec;110(4):1429-36. [PubMed:8306082]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Partial agonist
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Takahama K, Shirasaki T: Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs. Cough. 2007 Jul 9;3:8. [PubMed:17620111]
  4. 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]
Kind
Protein
Organism
Human
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. Ortiz MI, Castro-Olguin J, Pena-Samaniego N, Castaneda-Hernandez G: Probable activation of the opioid receptor-nitric oxide-cyclic GMP-K+ channels pathway by codeine. Pharmacol Biochem Behav. 2005 Dec;82(4):695-703. Epub 2006 Jan 4. [PubMed:16386786]
  2. 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]
  3. Loghin F, Popa DS, Socaciu C: Influence of glutethimide on rat brain mononucleotides by sub-chronic codeine treatment. J Cell Mol Med. 2001 Oct-Dec;5(4):409-16. [PubMed:12067475]
  4. Advenier C, Girard V, Naline E, Vilain P, Emonds-Alt X: Antitussive effect of SR 48968, a non-peptide tachykinin NK2 receptor antagonist. Eur J Pharmacol. 1993 Nov 30;250(1):169-71. [PubMed:8119316]
  5. Karlsson JA, Lanner AS, Persson CG: Airway opioid receptors mediate inhibition of cough and reflex bronchoconstriction in guinea pigs. J Pharmacol Exp Ther. 1990 Feb;252(2):863-8. [PubMed:2156065]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Details
1. Cytochrome P450 2D6
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. Duquette PH, Peterson FJ, Crankshaw DL, Lindemann NJ, Holtzman JL: Studies of the metabolic N- and O-demethylation of [6-3H]codeine. Drug Metab Dispos. 1983 Sep-Oct;11(5):477-80. [PubMed:6138234]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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. Duquette PH, Peterson FJ, Crankshaw DL, Lindemann NJ, Holtzman JL: Studies of the metabolic N- and O-demethylation of [6-3H]codeine. Drug Metab Dispos. 1983 Sep-Oct;11(5):477-80. [PubMed:6138234]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
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

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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]

Drug created on June 13, 2005 07:24 / Updated on October 23, 2017 14:13