Pro–con debate: is codeine a drug that still has a useful role in pediatric practice?

Background: The widespread use of codeine in children has been questioned in recent years because of concerns about unpredictable analgesia and side effects compared to other agents. Objective: To debate the advantages and disadvantages of the use of codeine as an analgesic for children. Design/Participants: 2 debaters (a pediatrician from the United Kingdom and a pharmacist from New Zealand) present arguments for and against the use of codeine. The pharmacist lays out his objections against codeine, which has been used for its analgesic, anti-tussive, and anti-diarrheal properties. Codeine's analgesic action is mediated through its metabolite, morphine. Clinicians have long noted variability and lack of analgesia in the response to codeine among certain patients, which is likely due to variations in a particular gene—CYP 2D6—that governs the metabolism of codeine to morphine. Metabolizers can be poor, intermediate, or extensive; 7% to 10% of whites are slow metabolizers, so codeine's conversion to morphine is limited, and this would partly explain the lack of efficacy. Only 2% of Asians are slow metabolizers. Neonates have enzymatic immaturity, and codeine is an impractical drug in this age group. Codeine has 1/10 the potency of morphine, so 60 mg of codeine has a morphine equivalence of 6 mg. The pharmacist makes a pitch for the use of oral morphine, compared to codeine, in hospital settings. This is not common in the United States, in part because of its taste as well as greater familiarity with intravenous use. The pediatrician argues that codeine has a long history of clinical usage with effective dose regimens and is available in liquid formulations for children. He concedes, however, that there are no large randomized trials involving codeine in discrete age-specific clinical situations. He argues that it should not be the drug of choice for acute severe pain in cases in which morphine, in particular, is a drug of choice. Until medications such as Tramadol, hydromorphone, or oxycodone are better studied in children, he believes codeine remains the main oral medication if acetaminophen and nonsteroidal anti-inflammatory medications are ineffective. Regarding safety, he notes that the use of codeine for many years and in many patients suggests a good safety record. Conclusions: Both discussants note that experience with codeine is extensive and that alternatives for moderate pain currently are limited. They agree that codeine is likely to remain a popular drug in pediatric medicine for the foreseeable future. Reviewer's Comments: The fact of slow versus fast metabolizers of codeine is likely under-appreciated by clinicians. It is something to consider if you have a patient on codeine who is not responding to standard dosing. Also, be sure to think about adding acetaminophen in some combination for the synergistic effects. (Reviewer-Mark F. Ditmar, MD).