Codeine Is so Last Week

An editorial published in the Canadian Medical Association Journal discusses whether or not the pain reliever codeine should be phased out due to its significant risks and lack of analgesic effectiveness.

Codeine has been used for pain relief for more than 200 years, but it has never been subjected to the rigorous regulatory and safety requirements applied to all new drugs and its pharmacokinetics are unpredictable, write the editorial’s authors, Noni MacDonald MD MSc and Stuart M. MacLeod MD PhD.

MacDonald MD is the Canadian Medical Association Journal’s section editor, Public Health, and MacLeod, is a professor of Pediatrics at the University of British Columbia,

Vancouver, BC.

The genetic variations present in patients can result in very different responses to codeine, some with serious consequences.

Among the highlighted genetic variations that affect the individual outcomes for patients treated with morphine are the “polymorphisms that occur in the cytochrome P450 isoenzyme CYP2D6,” the authors write. These polymorphisms “enhance codeine metabolism to morphine.”

“Additional polymorphisms affecting morphine metabolism, blood—brain barrier

transition or opioid and opiate receptor kinetics, or combinations of these polymorphisms, may also substantially augment effects from codeine.”

Infants and children are particularly vulnerable, and there have been several deaths due to different genetic responses. Serious, life-threatening effects have also been reported in adults. “Pharmaco-genetic variants have been implicated in the death of a breastfed

neonate whose mother had been given codeine postpartum, and in the death and anoxic brain injury of two young children prescribed codeine for postoperative pain following tonsillectomy for sleep apnea,” they write.

“Because the need for oral pain control is so pervasive, the potential risk associated with codeine must be mitigated,” write pediatricians Drs. Noni MacDonald, section editor, Public Health, CMAJ and Dr. Stuart MacLeod, University of British Columbia.

While limiting use of codeine, with minimum ages for codeine-based treatment, is one option, it is not ideal, the editorial reads. Genetic testing prior to codeine use is expensive and impractical.

“Perhaps a more direct approach is now needed: to stop using the prodrug codeine altogether and instead use its active metabolite, morphine. Not only is the metabolism of morphine more predictable than that of codeine, but also it is cheaper,” they write. They call for a warning to physicians and modifications to existing guidelines for codeine use and research to define safety parameters.