Public health advisories from the U.S. Food and Drug Administration (FDA) and Health Canada were associated with significant reductions in the rate of dispensing of codeine to postpartum women, according to a study in the May 12 issue of JAMA.
Some patients are ultra-rapid metabolizers of codeine, with prevalence ranging from 2 percent to 40 percent. Nursing mothers who take codeine may be putting their infant at risk if they carry the gene variants for elevated activity of an enzyme that metabolizes codeine to morphine. High levels of morphine in breast milk may lead to infant death from a drug-induced respiratory problem. The U.S. FDA released a public health advisory in August 2007 warning about the potentially life-threatening adverse effects in infants of breast-feeding mothers taking codeine. Health Canada published a similar advisory in October 2008, according to background information in the article.
Kate Smolina, Ph.D., of the University of British Columbia, Vancouver, Canada, and colleagues examined postpartum codeine use among all women with live births between January 2002 and December 2011 in British Columbia to evaluate the rate of codeine dispensations before and after the two regulatory advisories. Information about prescription dispensations came from BC PharmaNet, a comprehensive database of every prescription filled outside of acute care hospitals, regardless of patient age or insurance status.
During the study period, there were 320,351 live births to 225,532 women. Of these, new mothers filled at least 1 codeine prescription during 47,095 postpartum periods. Before the FDA advisory, the monthly average for the proportion of postpartum mothers filling at least 1 codeine prescription was 17 percent, which declined to a monthly average of 9 percent from September-December 2011, a 45 percent relative reduction over 4 years.
The authors write that the reduction may reflect the adoption of the recommendations by clinicians. "Some of the reduction could also reflect changes in patient behavior, including not filling written prescriptions, not asking for codeine, or both. The speed and the magnitude of the response suggests that regulatory warnings regarding postpartum drug safety can have a strong influence on prescribing patterns."
(doi:10.1001/jama.2015.3642; Available pre-embargo to the media at http://media.
Editor's Note: This study was supported by a Canadian Institutes for Health Research (CIHR) grant. Dr. Smolina is funded in part by a CIHR Banting postdoctoral fellowship. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.