Women who receive the potent teratogen isotretinoin for acne control have inadequate adherence to pregnancy prevention, according to a study published online April 25 in the Canadian Medical Association Journal.
"The current isotretinoin pregnancy prevention program in Canada is not effective in preventing pregnancies during treatment," author Brandace Winquist, PhD, from the University of British Columbia, Vancouver, and the Saskatchewan Health Quality Council, told Medscape Medical News.
The study, a collaborative effort of the Canadian Network for Observational Drug Effect Studies, estimated that one or two children in Canada are born each year with birth defects related to isotretinoin use.
The authors also found that contraceptive use while receiving isotretinoin is only 50% to 70% effective in Canada. The pregnancy prevention program for isotretinoin users in Canada requires informed consent, two negative pregnancy tests before starting treatment, and two reliable birth control methods during treatment.
"Patients should be counseled on all contraceptive methods and their associated failure rates," Dr Winquist stressed.
Patients with severe cystic acne often receive isotretinoin, but it has a major drawback: it can cause spontaneous abortions and significant birth defects. Women who use isotretinoin are often in their twenties and are advised to avoid pregnancy during and 1 month after use.
Use of the drug has recently increased, along with expanded usage among people with milder forms of acne. Online ordering and the rise of generic isotretinoin, whose manufacturers may not provide adequate educational messaging about its use, may contribute to nonadherence to pregnancy prevention, according to background information in the article.
In the study, researchers used administrative databases to identify 59,271 women aged 12 to 48 years who used isotretinoin between 1996 and 2011. The databases drew from four Canadian provinces: British Columbia, Saskatchewan, Manitoba, and Ontario, with a combined population of 20.7 million individuals.
Over the course of 15 years, 1473 pregnancies and 118 (8.0%) live births occurred among women receiving isotretinoin, out of which 11 (9.3%) infants had birth defects.
Because of the limitations of administrative data, the study used two different definitions of pregnancy (a high-specificity definition and a high-sensitivity definition). That gave an estimated pregnancy rate between 4 and 6 per 1000 female users receiving a 3-month course of isotretinoin. Because risk continues for at least 1 month after the end of treatment, pregnancy rates were even higher for an analysis that included a longer time frame.
Between 24.3% and 32.9% of women filled oral contraceptive prescriptions while receiving isotretinoin, rates that were pretty much unchanged from 12 months before starting the drug (range, 28.3% - 35.9%).
About 90% of pregnancies ended spontaneously or by medical intervention, and 70.7% were terminated electively, which raises ethical issues according to Dr Winquist. Because of the potential for such severe birth defects, women who become pregnant while receiving isotretinoin may feel abortion is their only option, although the situation is completely preventable with compliance to pregnancy prevention.
"Awareness of the problem is certainly a first step. However, if we cannot reduce and ideally eliminate fetal exposure to isotretinoin, other more restrictive measures may need to be imposed in Canada," she noted.
Clear areas for improvement include compliance with contraception guidelines and limiting the medication only to patients with severe acne who do not respond to standard therapy. Ongoing surveillance and monitoring are also needed, she added. Also, pharmacists can play an important role in reinforcing the message about the importance of pregnancy prevention during isotretinoin use.
"Given that pregnancy rates are considerably higher in marginalized populations, physicians must take care to provide counseling to patients who may face barriers to access in contraception or have lower literacy levels," Dr Winquist emphasized.
Although rates of fetal exposure resulting from maternal isotretinoin use vary across countries, the problem is "fairly universal," Dr Winquist said, even though a worldwide Pregnancy Prevention Program has been in existence since 1988.
Although direct comparisons are difficult because of difference in study design, studies in the United States suggest that Canada's rates are higher than those in the United States, which has a stricter risk management program.
In 2006, the United States launched the mandatory iPLEDGE program, which requires patient registration, informed consent, and counseling about the risks for isotretinoin. It also requires women of childbearing age who use isotretinoin to comply with pregnancy testing. In addition, only registered prescribers and pharmacists can prescribe or dispense the drug.
Even so, a recent study has shown only a slight, nonsignificant improvement in compliance compared with the previous risk management program. That unsatisfying result may have prompted the US Food and Drug Administration to implement a policy in 2012 of issuing warnings to providers who do not comply and permanently deactivating those who continue not to comply.
This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reports salary support from the Fonds de recherche du Québec–Santé, as well as personal or consulting fees from Pfizer, Amgen, AbbVie, and Novartis. The other authors have disclosed no relevant financial relationships.