Codeine

Aka: Codeine, Tylenol #3, Acetaminophen with Codeine, Tylenol with codeine

1. Indications
   1. Analgesic (low efficacy and potential for adverse effects)
   2. Cough Suppressant (other agents are preferred)
2. Contraindications
   1. Breastfeeding women
   2. All children under age 12 years old
   3. Children ages 12 to 18 years old with additional risks
      1. Tonsillectomy or adenoidectomy
      2. Obesity
      3. Sleep Apnea
   4. References
      1. FDA Drug Safety Communication (4-20-2017)
         1. https://www.fda.gov/Drugs/DrugSafety/ucm549679.htm
3. Preparations: Codeine 30 with Acetaminophen 300 tablets
   1. Dose: 1-2 tablets orally every 4-6 hours
   2. Avoid due to low efficacy and increased toxicity risk
4. Preparations: Acetaminophen with Codeine Elixir (not recommended)
   1. Risk of Opioid induced respiratory depression and other Overdose adverse effects (especially in children)
      1. Deaths in children have occurred with codeine Analgesics following Tonsillectomy and adenoidectomy
      2. Resulted in FDA black box warning in 2013
      3. (2013) Presc Lett 20(4): 21
      4. FDA Drug Safety Communication
         1. http://www.fda.gov/Drugs/DrugSafety/ucm339112.htm
   2. Components
      1. Acetaminophen (120 mg/5ml Elixir)
      2. Codeine (12 mg/5ml Elixir)
   3. Dosing
      1. Age 3 to 6 years: 5 ml/dose every 4 hours prn
      2. Age 7 to 12 years: 10 ml/dose every 4 hours prn
5. Efficacy
   1. Acetaminophen is a safe and effective Analgesic
   2. Codeine is no more effective than standard NSAIDs
      1. Naprosyn is as effective in post-operative pain
      2. Ouellette (1986) Curr Ther Res 39(5):839 [PubMed]
      3. Busquets (1988) Curr Ther Res 43(2):311 [PubMed]
   3. Codeine offers no significant benefit to Tylenol
      1. Zhang (1996) J Clin Pharm Ther 21(4):261 [PubMed]
   4. Adding Codeine to Tylenol increases adverse effects
      1. Jochimsem (1978) J Am Geriatr Soc 26(11):521 [PubMed]
   5. Codeine 60 mg equivalent to Aspirin 650 mg
6. Precautions
   1. Weak Analgesic, with abuse potential and risk of death in ultrarapid CYP2D6 metabolizers
      1. Other agents are preferred: NSAIDs, Acetaminophen, short acting Morphine, Hydrocodone, Oxycodone
   2. Non-responders to Codeine: 10% of patients
      1. Lack endogenous enzyme to convert to Morphine
   3. Risk of Opioid induced respiratory depression and other Overdose adverse effects (especially in children)
      1. Associated with CYP2D6 ultrarapid metabolization (fast metabolizers) found in 5-30% (depending on ethnicity)
      2. Deaths in children have occurred with codeine Analgesics following Tonsillectomy and adenoidectomy
      3. Deaths likely related to ultrarapid metabolizers with underlying airway disorders (e.g. Sleep Apnea)
      4. Resulted in FDA black box warning in 2013
      5. AAP recommends no use of Codeine products under age 18 years old
      6. FDA Drug Safety Communication
         1. http://www.fda.gov/Drugs/DrugSafety/ucm339112.htm