Codeine is one of the most commonly prescribed opioids and frequently is chosen because it is available at most pharmacies and is perceived to have a high margin of safety. Over the last decade, however, serious concerns have been raised regarding its safety, especially for pediatric patients. Many pediatric institutions and practitioners now discourage its use.

Codeine is used for both its analgesic and anti-tussive properties. It is available in the United States as a pill and liquid and as a stand-alone product or a combination product with acetaminophen.

In order to have analgesic efficacy, codeine must be converted in the liver by the drug metabolizing enzyme cytochrome P450 2D6 (CYP2D6) to its active metabolite, morphine. In patients who are “normal” metabolizers (termed extensive metabolizers) of codeine, approximately 10% of codeine is converted to morphine, hence the 60 milligram (mg) codeine to 6 mg morphine dosing equivalence.

Unfortunately, 6%-10% of...

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