Codeine

Administration

• Type: Opioid analgesic, antitussive
• Dosage Forms: Tablet: 15, 30, 60 Oral Solution: 30mg/5 mL
• Routes of Administration: Oral

Blackbox Warning

• Death related to ultra-rapid metabolism: respiratory depression and death have occurred in children who received codeine post-tonsillectomy and/or adenoidectomy and were ultra-rapid CYP2D6 metabolizers

Adult Dosing

• Mild to moderate pain: 15-60mg PO q4-6h PRN
  • Max: 360mg/day
  • Give with food
  • Doses >60mg are rarely more effective in opioid-naive patients

• Cough: 15-30mg PO q4-6h PRN
  • Max: 120mg/day

• Diarrhea: 45-270mg/day PO divided q4-6h PRN
  • Start: 30-60mg/day PO divided QD-bid, then increase by 30-60mg/day PRN
  • Max: 60mg/dose up to 270mg/day

Pediatric Dosing

• Pain, mild-moderate
  • 3-6 yo: 0.5-1mg/kg PO q4-6h PRN
  • 7-12 yo: 15-30mg PO q4-6h PRN
  • 13-17 yo: 15-60mg PO q4-6h PRN
  • Max: 60mg/dose up to 360mg/day
• Cough
  • 2-5 yo: 1-1.5mg/kg/day PO divided q4-6h PRN; Max: 30mg/day
  • 6-11 yo: 1-1.5mg/kg/day PO divided q4-6h PRN; Max: 60mg/day

Special Populations

• Pregnancy risk factor: C

Renal Dosing

• CrCl 10-50: decrease dose 25%; CrCl <10: decrease dose 50%; HD/PD: no supplement

Contraindications

• hypersensitivity to codeine
• respiratory depression
• paralytic ileus
• post-tonsillectomy or adenoidectomy (peds)

Adverse Reactions

Serious

• respiratory depression
• CNS depression
• hypotension
• bradycardia
• syncope
• anaphylactoid reaction

Common

• lightheadedness
• dizziness
• sedation
• nausea/vomiting

Pharmacology

• Half-life: 2.5-4 hours
• Metabolism: Liver
• Excretion: Urine

Mechanism of Action

• Opioid agonist

See Also

• Opioids
• Opioid toxicity

References

• Micromedex
• Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]
• American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. Practice bulletin no. 177: obstetric analgesia and anesthesia. Obstet Gynecol. 2017 129(4):e73-e89. [PubMed 28333819]
• American Pain Society. Principles of Analgesic. 7th ed, Glenview, IL: American Pain Society, 2016.
• Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007, p 18, 135.
• Aurora RN, Kristo DA, Bista SR, et al. The treatment of restless legs syndrome and periodic limb movement disorder in adults—an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine clinical practice guideline. Sleep. 2012;35(8):1039-1062. [PubMed 22851801]
• Berna C, Kulich RJ, Rathmell JP. Tapering long-term opioid therapy in chronic noncancer pain: evidence and recommendations for everyday practice. Mayo Clin Proc. 2015;90(6):828-842. doi: 10.1016/j.mayocp.2015.04.003. [PubMed 26046416]
• Bolser DC, “Cough Suppressant and Pharmacologic Protussive Therapy: ACCP Evidence-Based Clinical Practice Guidelines,” Chest, 2006, 129(1 Suppl):238-48. [PubMed 16428717]
• Brennan MJ. The effect of opioid therapy on endocrine function. Am J Med. 2013;126(3)(suppl 1):S12-S18. doi: 10.1016/j.amjmed.2012.12.001. [PubMed 23414717]
• Broussard CS, Rasmussen SA, Reefhuis J, et al, "National Birth Defects Prevention Study: Maternal Treatment With Opioid Analgesics and Risk for Birth Defects," Am J Obstet Gynecol, 2011, 204(4):314. [PubMed 21345403]
• Cardan E, “Fatal Case of Codeine Poisoning,” Lancet, 1981, 1(8233):1313.
• Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm.