Graduated Residency Do I Need to Register for Ipledge Again

The Usa has ramped upwardly efforts to mitigate the risk of birth defects associated with isotretinoin (Accutane) by requiring physicians and patients to register before they can prescribe or have the drug. The response in Canada has been markedly less stringent, despite recommendations last year from a federal authorities expert informational committee.

Isotretinoin, used to care for recalcitrant nodular acne, is known to have serious side furnishings, including nascency defects, astringent depression and, potentially, vascular incidents.

Figure. This epitome appears on the Roche Pharmaceuticals patient information for Accutane. Photo by: Roche Pharmaceuticals

On Mar. 1, the US Food and Drug Administration (FDA) made iPLEDGE, its risk management program aimed at preventing use of the drug during pregnancy, compulsory (www.ipledgeprogam.com). To obtain the drug, patients must annals with iPLEDGE, complete an informed consent form and obtain counseling nigh the risks. Women of childbearing age must take 2 pregnancy tests and exist on 2 forms of nativity command or abstain from sexual activity. Physicians must also register with iPLEDGE prior to prescribing isotretinoin.

The FDA made the changes post-obit recommendations from ii of its advisory commission in 2000 and again in 2004. "Fetal exposures continued to occur, and the take a chance [of pregnancy] had non been adequately mitigated," says Dr. Jill Lindstrom, acting deputy director, Sectionalization of Dermatologic and Dental Products Centre for Drug Evaluation and Enquiry of the FDA.

Between 1982, when the drug first came on the Usa marketplace, and 2000, its manufacturer Roche Pharmaceuticals reported 1995 pregnancy exposures and 383 alive births. Of those births, 162 infants had birth defects. Between 2001 and 2003, there were 325 known pregnancy exposures. The FDA estimates that 100 000 prescriptions are written for the drug each calendar month in the United states.

In Canada, an estimated 224 600 prescriptions for isotretinoin were filled in the past year, according to IMS Health (retail value of $32 meg). The manufacturer reports an average of 3.vi pregnancy exposures per year between 1996 and 2003. Between Jan 1983 and December 2004, Health Canada identified only 3 "fetal disorders" as "peradventure due to Accutane exposure."

Health Canada recently stated that although FDA information suggests a "signficant rate" of pregnancy exposures "Health Canada'due south pharmacovigilance program... has shown no testify of a comparable situation in Canada." (CMAJ 2005;172:15).

Withal, the Motherisk Program at the Toronto Hospital for Sick Children receives an average of ten to xx pregnancy exposure reports annually.

Non all cases are reported, says Motherisk Director Dr. Gideon Koren, because Health Canada doesn't have a comprehensive monitoring arrangement. Wellness Canada discontinued the development of Mothernet, which would have captured such cases, several years ago.

"Unfortunately pregnant women are not a priority for Health Canada," says Koren.

Health Canada requires that women taking isotretinoin requite written informed consent, receive teaching about the teratogenicity of the drug, and concur to utilise two contraceptive methods while on the drug. Like measures in the US were ruled by the FDA to be insufficient to protect fetuses.

Rather than an iPLEDGE-type registry, Motherisk suggests a mandatory Spider web-based training program and certification of physicians equally a condition for prescribing isotretinoin. A similar program exists for methadone.

In May 2005, Health Canada's Scientific Advisory Panel on isotretinoin unanimously rejecting the idea of an i-PLEDGE type registry for Canada, simply otherwise its recommendations were strikingly similar to those measures being taken in the US, including introducing an expanded physicians' checklist, a consent form, a toll-free information number, a Web site, an education plan for family unit doctors and pharmacists, and pregnancy testing.

Dr. Jack Toole, chair of the panel says "There is absolutely no question that pregnancy exposure on isotretinoin must be prevented and that we must practise all that we perhaps can to do that."

The console'southward recommendations have not been acted on. Health Canada spokesperson, Christopher Williams, says the government expects to convene a working grouping by September to "analyze the best way of putting them into effect. Nonetheless, it is unlikely that any implementation will take place in 2006."

In April, Wellness Canada released another advisory near the drug, asking doctors to report whatever cases of myocardial infarction, cerebrovascular and thromboembolic disorders suspected of being associated with isotretinoin (CMAJ 2006;174:1211). Since 1983 at that place have been 29 reported incidents of vascular disorders. Williams said that "no causal link betwixt this type of side consequence and the drug has been established."

The drug ranks in the superlative 10 of the The states FDA'due south database of drugs associated with reports of depression and suicide attempts. In Canada, 25% of adverse responses reported since isotretinoin was introduced relate to psychiatric events. A warning of the possible link was issued in 2001.

Although it is intended equally a drug of last resort for extreme cases of acne, isotretinoin is increasingly beingness used for milder cases, as well as for psoriasis rosacea and other weather.

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Source: https://www.cmaj.ca/content/174/12/1701