Several organizations including the US Food and Drug Administration, European Medicines Agency, and the UK Medicines and Healthcare products Regulatory Agency have put out warnings or established restrictions on the use of codeine in pediatric patients. The Pediatric Pharmacy Advocacy Group (PPAG) supports the established warnings and restrictions and further suggests that codeine may no longer have a place in therapy for any pediatric patient.
Codeine is metabolized via CYP 2D6 to morphine. People with a certain CYP 2D6 polymorphism are ultra-rapid metabolizers of codeine and can receive a disproportionate amount of morphine. In addition, it is estimated that 5-10% of the population lacks the appropriate enzyme activity to metabolize codeine to morphine, rendering the medication ineffective. The following discussion points may be useful in stressing the importance of limiting the use of codeine in the pediatric population:
- Codeine has increasingly been reported to have unpredictable safety and efficacy and is dangerous in pediatric patients under the age of 12 years old. Specifically codeine has been linked to deaths in children with the ultra-rapid metabolizer polymorphism who had obstructive sleep apnea and were administered acetaminophen with codeine postoperatively following tonsillectomy and/or adenoidectomy.
- Codeine can be dangerous when given to lactating women. Deaths have been reported in neonates when they were exposed to codeine via breastmilk due to maternal and neonatal ultra-rapid metabolizer status.
- Limiting availability of codeine by removing from hospital formularies or electronic clinical decision support will ensure that pediatric patients under the age of 12 years are not inadvertently exposed either through inappropriate prescribing.
- Safety review update of codeine use in children; new Boxed Warning and Contraindication on use after tonsillectomy and/or adenoidectomy. http://www.fda.gov/Drugs/DrugSafety/ucm339112.htm, Accessed August 26, 2016.
- Andrzejowski P, Carroll W. Codeine in paediatrics: pharmacology, prescribing, and controversies. Arch Dis Child Educ Pract Ed 2016;l01:148-51.
- Berlin CM, Van den Anker. Safety during breastfeeding: drugs, foods, environmental chemicals, and maternal infections. Semin Fetal Neonatal Med 2013; 18: 13-8.
- Jerome J, Solodiuk JC, Sethna N, McHale J, Berde C. A single institution’s effort to translate codeine knowledge into specific clinical practice. J Pain Symptom Manage Jul 2014; 48(1): 119-26.
- Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical pharmacogenetics implementation consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther. 2012;91(2):321-6.