Codeine

Codeine sulfate is an opioid agonist relatively selective for the mu-opioid receptor, but with a much weaker affinity than morphine. The analgesic properties of codeine have been speculated to come from its conversion to morphine, although the exact mechanism of analgesic action remains unknown.

• Codeine Sulfate Tablets are indicated for the management of mild to moderate pain, where treatment with an opioid is appropriate and for which alternative treatments are inadequate. Limitations of Use: • Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see Warnings and Precautions ( 5.1 )] , reserve opioid analgesics, including Codeine Sulfate Tablets, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

• Codeine Sulfate Tablets are contraindicated for: • All children younger than 12 years of age [see Warnings and Precautions ( 5.6 )] . • Post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Warnings and Precautions ( 5.6 )] .contraindicated

• Codeine Sulfate Tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. ( 2.1 ) • Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of Codeine Sulfate Tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. ( 2.1 , 5 ) • Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. ( 2.1 ) • Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. ( 2.1 , 5.1 ) • Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Codeine Sulfate Tablets. Consider this risk when selecting an initial dose and when making dose adjustments.

• Opioid-Induced Hyperalgesia and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation. ( 5.8 ) • Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients : Regularly evaluate closely, particularly during initiation and titration. ( 5.9 ) • Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.11 ) • Severe Hypotension : Regularly evaluate during dosage initiation and titration. Avoid use of Codeine Sulfate Tablets in patients with circulatory shock. ( 5.12 ) • Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness : Monitor for sedation and respiratory depression. Avoid use of Codeine Sulfate Tablets in patients with impaired consciousness or coma. ( 5.13 ) 5.1 Addiction, Abuse, and Misuse Codeine Sulfate Tablets contain codeine, a Schedule II controlled substance. As an opioid, Codeine Sulfate Tablets exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence ( 9 )]. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Codeine Sulfate Tablets. Addiction can occur at recommended dosages and if the drug is misused or abused.

The following serious adverse reactions are described, or described in greater detail, in other sections: • Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] • Life-Threatening Respiratory Depression [see Warnings and Precautions ( 5.2 )] • Interactions with Benzodiazepines and Other CNS Depressants [see Warnings and Precautions ( 5.3 )] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.4 )] • Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children [see Warnings and Precautions ( 5.6 )] • Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.8 )] • Adrenal Insufficiency [see Warnings and Precautions ( 5.11 )] • Severe Hypotension [see Warnings and Precautions ( 5.12 )] • Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.14 )] • Seizures [see Warnings and Precautions ( 5.15 )] • Withdrawal [see Warnings and Precautions ( 5.16 )] The following adverse reactions associated with the use of codeine were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Serious adverse reactions associated with codeine were respiratory depression and, to a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest.

• Pregnancy : May cause fetal harm. ( 8.1 ) • Lactation : Breastfeeding not recommended. ( 8.2 ) 8.1 Pregnancy Risk Summary: Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.4 )] . Available data with Codeine Sulfate Tablets are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, codeine administration during organogenesis has been shown to produce delayed ossification in the offspring of mice at 1.4 times maximum recommended human dose (MRHD) of 360 mg/day, embryolethal and fetotoxic effects in the offspring of rats and hamsters at approximately 2 to 3 times the MRHD, and cranial malformations/cranioschisis in the offspring of hamsters between 2 and 8 times the MRHD [ see Data ]. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Metabolism

Absorption: Codeine is absorbed from the gastrointestinal tract with maximum plasma concentration occurring 60 minutes post administration. Administration of 15 mg of codeine sulfate every four hours for 5 days resulted in steady-state concentrations of codeine, morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) within 48 hours.

Clinical Presentation: Acute overdose with codeine can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology ( 12.2 )] . Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication. Treatment of Overdose: In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures.

• Aug 21, 1981ANDAANDA087508Genus Lifesciences
• Sep 30, 1988ANDAANDA089805Strides Pharma Intl
• Sep 30, 1988ANDAANDA089828Strides Pharma Intl
• Sep 30, 1988ANDAANDA089990Strides Pharma Intl
• Jul 30, 1992NDANDA020232Actavis Labs Ut Inc
• Aug 31, 1998ANDAANDA074951Stevens J
• Jul 16, 2009NDANDA022402Hikma
• Jun 22, 2015NDANDA206323Mainpointe

1. 1Dependence6,57232%
2. 2Pain2,53512%
3. 3Overdose2,53212%
4. 4Drug Ineffective2,35011%
5. 5Fatigue2,32711%
6. 6Arthralgia2,27011%
7. 7Rash1,9329.4%
8. 8Dyspnoea1,8829.2%
9. 9Off Label Use1,8639.1%
10. 10Drug Hypersensitivity1,8439.0%
11. 11Rheumatoid Arthritis1,8148.9%
12. 12Nausea1,7908.7%
13. 13Joint Swelling1,6998.3%
14. 14Headache1,6858.2%
15. 15Confusional State1,6538.1%

Recent PubMed references pinned to Codeine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Assessment of the acceptability of effervescent oxycodone/paracetamol in the management of moderate-to-severe pain: the FirAlgos study.
  European review for medical and pharmacological sciences · 2026 · Vellucci R, Tur E, Lepri A, et al.
  PMID 42237960DOI 10.26355/eurrev_202605_37822
• Oxycodone versus Sufentanil for Postoperative Analgesia and Early Recovery After Radical Gastrectomy: A Propensity Score-Matched Study.
  Drug design, development and therapy · 2026 · Wang Y, Hu L, Chen Z, et al.
  PMID 42232092DOI 10.2147/DDDT.S606394
• Effects of oxycodone and sufentanil on the quality of recovery after laparoscopic total hysterectomy: A randomized controlled trial.
  Medicine · 2026 · Liu Z, Guo S
  PMID 42216335DOI 10.1097/MD.0000000000048778
• Tegileridine, a Biased μ-Opioid Receptor Agonist, versus Oxycodone for Postoperative Analgesia and Postoperative Nausea and Vomiting After Total Laparoscopic Hysterectomy: A Randomized, Double-Blind, Single-Center, Controlled Trial.
  Drug design, development and therapy · 2026 · Fu Y, Chen X, Gao FP, et al.
  PMID 42199806DOI 10.2147/DDDT.S598457
• Diagnosis of acetaminophen and codeine poisoning in a dog using earwax analysis by headspace gas chromatography-mass spectrometry (HS/GC-MS).
  Veterinary research communications · 2026 · de Vicente MC, Barros ACM, de Souza GS, et al.
  PMID 42176063DOI 10.1007/s11259-026-11280-7
• Postnatal environment differentially modulates neurodevelopmental outcomes following voluntary prenatal oxycodone exposure in rats.
  Neurotoxicology and teratology · 2026 · Gildawie KR, Budge KE, Isgate SB, et al.
  PMID 42031343DOI 10.1016/j.ntt.2026.107603
• Comparative risk of psychiatric comorbidities associated with codeine and tramadol in patients with hip osteoarthritis: a nationwide population-based cohort study.
  Journal of global health · 2026 · Kim Y, Choo E, Shin S, et al.
  PMID 42024864DOI 10.7189/jogh.16.04121
• Pharmacological Mechanisms and Clinical Applications of Oxycodone in Cancer Pain Management: A Narrative Review.
  Drug design, development and therapy · 2026 · Xia Y, Huang G
  PMID 42007393DOI 10.2147/DDDT.S594973

The 10 most recently updated of 552 ClinicalTrials.gov registrations naming Codeine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Evaluating a Potential Pharmacokinetic Kratom-oxycodone Interaction Concurrent With Clinical Endpoints
  Recruiting · Early phase 1 · Interventional · 16 enrolled · Washington State University
  NCT05846451updated 2026-06-03
• Opioid Use After Laparoscopic Salpingectomy
  Recruiting · Phase 4 · Interventional · 38 enrolled · Johns Hopkins University
  NCT06434233updated 2026-06-03
• Nonopioid Pain Control Regimen After Arthroscopic Hip Procedures
  Completed · Phase 4 · Interventional · 86 enrolled · Mayo Clinic
  NCT05076110updated 2026-06-03
• Suzetrigine for Opioid-Sparing Postoperative Analgesia Following Transvaginal Pelvic Reconstructive Surgery
  Not yet recruiting · Phase 4 · Interventional · 120 enrolled · University of California, Los Angeles
  NCT07600697updated 2026-06-02
• Biased Opioid Agonists for Treatment of Opioid Withdrawal in OUD
  Terminated · Phase 2 · Interventional · 5 enrolled · National Institute on Drug Abuse (NIDA)
  NCT04316559updated 2026-06-02
• Opioid-Free Pain Control Regimen Following Robotic Radical Prostatectomy
  Terminated · Phase 2 · Phase 3 · Interventional · 58 enrolled · Wake Forest University Health Sciences
  NCT05597878updated 2026-06-01
• Examining Analgesic Synergy and Efficacy in Trauma Care
  Not yet recruiting · Phase 4 · Interventional · 282 enrolled · Wake Forest University Health Sciences
  NCT07435077updated 2026-05-26
• 5x-Multiplier vs 3-Tier Model for Discharge Opioid Prescriptions After Intra-abdominal Cancer Surgery: A Randomized Clinical Trial
  Active not recruiting · Phase 2 · Interventional · 170 enrolled · M.D. Anderson Cancer Center
  NCT06232577updated 2026-05-14
• Opioid Drug Interaction Study
  Recruiting · Phase 1 · Phase 2 · Interventional · 25 enrolled · Shanna Babalonis, PhD
  NCT06757140updated 2026-05-14
• Effect of CYP2D6*10 Gene Mutation on Perioperative Precision Analgesia of Oxycodone in Elderly Patients
  Completed · Observational · 100 enrolled · Henan Provincial People's Hospital
  NCT07484867updated 2026-05-12

CPIC-curated drug–gene pairs for Codeine. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• COMTCPIC C
  CYP2D6, OPRM1, COMT, and Opioids
• CYP2D6CPIC AClinPGx 1AFDA label: Actionable PGx
  CYP2D6, OPRM1, COMT, and Opioids
• OPRM1CPIC CClinPGx 3
  CYP2D6, OPRM1, COMT, and Opioids

Ranked by 2D fingerprint (Tanimoto) similarity over PubChem structures. Structural proximity only — not a claim of therapeutic equivalence.

• MorphineOpioid Agonist99%
• BuprenorphinePartial Opioid Agonist92%
• HydrocodoneOpioid Agonist87%
• HydromorphoneOpioid Agonist87%
• OxycodoneOpioid Agonist84%
• OxymorphoneOpioid Agonist84%
• NaloxoneOpioid Antagonist82%
• NaltrexoneOpioid Antagonist82%

Frequently asked questions

How does Codeine work?

Codeine sulfate is an opioid agonist relatively selective for the mu-opioid receptor, but with a much weaker affinity than morphine. The analgesic properties of codeine have been speculated to come from its conversion to morphine, although the exact mechanism of analgesic action remains unknown.

What is Codeine used for?

According to FDA labeling, Codeine carries indications including: Codeine Sulfate Tablets are indicated for the management of mild to moderate pain, where treatment with an opioid is appropriate and for which alternative treatments are inadequate. Limitations of Use: • Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see Warnings and Precautions ( 5.1 )] , reserve opioid analgesics, including Codeine Sulfate Tablets, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Codeine?

Codeine is classified as Opium alkaloids and derivatives, Full Opioid Agonists, Monoamine Oxidase Inhibitors, Analgesia, Decreased Medullary Respiratory Drive, Decreased Organized Electrical Activity.

What are the brand names for Codeine?

Codeine is marketed under brand names including Ambifed CD, Ambifed-G CD, Ascomp, Biotussin, Brontex, BroveX CB, Brovex PBC, Cheratussin.

What are the contraindications for Codeine?

Codeine labeling lists contraindications including: Codeine Sulfate Tablets are contraindicated for: • All children younger than 12 years of age [see Warnings and Precautions ( 5.6 )] . • Post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Warnings and Precautions ( 5.6 )] .. Always consult the full prescribing information and a clinician.