Diane-35 was approved by Health Canada for sale on the Canadian market in 1998 and has since been prescribed to teenage women and women of menopausal age for long periods of time, as a lifestyle drug, despite repeated warnings by Health Canada that warn both physicians and Diane-35 users has been associated with an increased risk of blood clots (warning 1, warning 2, warning 3), as compared with other, more safe, oral contraceptives. A 2013 review of the safety of Diane-35 by Health Canada found that "...the drug's benefits continue to outweigh the risks, when used as authorized." A central problem is that Diane-35 is often prescribed inappropriately and when other, safer medicine alternatives are available. While Diane-35 does prevent pregnancy, a U.S. study also found it increases the risk of blood clots by up to four times more than standard birth control pills.
A 2003 CBC investigation found that more than 800,000 prescriptions for Diane-35 were written for Canadian women in 2002. The majority of these women were taking Diane-35 as an oral contraceptive. Barbara Mintzes says that "Diane-35 was one of the first medications to be marketed to the public in Canada aggressively and illegally." After the revealing CBC documentary in 2003, prescriptions of Diane-35 continued to increase. This is especially problematic because Diane-35 has never been tested on the population for which it is approved - individuals suffering from severe acne.
The widely known off-label and promoted prescription of Diane-35 is reflected in a warning issued by Health Canada, but written by Berlex Canada Inc., the Canadian maker of Diane-35. This warning states that:
"Based on an analysis, commissioned by Berlex, of recently published information, users of Diane®-35 appear to have an elevated risk of venous thromboembolic events compared to users taking low-dose combination oral contraceptives in some studies. [...] Diane®-35 should not be taken for the purpose of contraception alone. During treatment with Diane®-35, other oral contraceptives should not be used. Anyone taking Diane®-35 should discuss this safety information with their physician." [emphasis added.]
Diane-35 is not approved for use as an oral contraceptive.
The United States Food and Drug Administration (US FDA) had never approved Diane-35, possibly because of the drug's potential connection between its one of its active components, cyproterone acetate, and liver cancer. It is unlikely that liver cancer would be linked or attributed to Diane-35 use because it develops over a long period of time and liver cancer is not widely known to be a side effect associated with cyproterone acetate. The data on which federal health agency approval and rejection decisions are made are kept confidential and are considered to be proprietary to the submitting company. We, therefore, do not know how many times drug applications are rejected and resubmitted by companies seeking approval, among other transparency issues.
Health Canada initiated its most recent review of Diane-35 in February 2013, after the Agence Nationale de Sécurité du Médicament (ANSM) decided to suspend the marketing authorization in France for the drug. Diane-35 was approved in France, but in January 2013, after being associated with deadly blood clots, it was reviewed and recalled from the French market. A similar situation in 2009 surrounded the ANSM, which underwent an overhaul after Mediator, a diabetes drug marketed off-label for weight loss, caused up to 2,000 deaths. Louis Servier, the founder of Servier, which manufactured and marketed Mediator, faced trial for charges of involuntary manslaughter in 2013.
In July 2013, Brussels in the European Commission, ordered that France lift the ban on marketing and selling Diane-35 in France. This decision has faced skepticism because just prior, the ANSM warned doctors not to prescribe Diane-35 and other third/fourth generation contraceptive pills as a first line treatments. This decision was informed by research that linked these widely prescribed pills off-label as oral contraceptives to 2,500 cases of potentially fatal blood clots.
On January 13, 2014, after being suspended for 12 months, the ANSM released a statement that France would be re-introducing Diane-35 to the French market. This decision comes after French drug safety authority revealed that "...125 women had suffered "undesirable" and possibly life-threatening side-effects linked to Diane-35 or its generics." Furthermore, French newspaper Le Figaro uncovered confidential internal documents that stated "...37 of the women had not fully recovered after taking the pills [Diane-35] made by Bayer, the German pharmaceutical company." Approximately 4-5 million boxes of Diane-35 are sold in France each year. The average age of women who are affected by Diane-35 are 25 years old.
According to the European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC), Diane-35 and its generic bioequivalents should be prescribed for only the treatment of severe acne related to androgen sensitivity or excessive and unwanted growth of hair in women of reproductive age, when other treatments have failed. The ANSM letter to healthcare professionals and EMA press release fails to acknowledge that Diane-35 should be used only in the short-term.
The decision to re-introduce Diane-35 to the French market is controversial, especially since dozens of lawsuits concerning Diane-35 and its generic bioequivalents have been launched in France by women who have suffered adverse events including blood clots and strokes. Since these lawsuits, the French government has advised that doctors limit their prescription of some contraceptive pills. This statement further reflects the widespread and accepted nature of Diane-35 as an oral contraceptive.
Geraldine Matus, founder of Justisse Healthworks for Women in Edmonton, argues that "...all hormonal contraceptives are prescribed off-label whether it is to "regulate" periods or prevent PMS." Matus states that regardless of available data, hormone-based Diane-35 and other hormonal birth controls should not be prescribed to women suffering with acne. She maintains that:
"[She] is appalled that for something like acne, we give young women such a powerful endocrine disrupter. It's like repairing a Swiss watch with a jackhammer. It is total overkill. The birth control pill in any form never cures anything. It only alters symptoms[...] The cause of acne can be hormonal imbalance, but Diane-35, and any hormonal contraceptive, only suppresses and replaces the natural hormone cycle with a constant stream of synthetic hormones whilst suppressing the entire endocrine system. The pills do not rectify the imbalance. [...] The birth control pill suppresses immunological function and so can in fact aggravate acne by worsening underlying issues like poor gut health." (see the statement here.)
Health Canada Warns About Acne Drug Diane-35
Brussels Orders France to Lift Ban on Drug Accused of Blood Clot Risk
Medicine by Media: Did a Critical Television Documentary Affect the Prescribing of Cyproterone Estradiol (Diane-35)?
Cyproterone Acetate: A Genotoxic Carcinogen?France confirms Diane-35 drug deaths: Secret report reveals 125 women suffered possibly life-threatening side-effects linked to Diane-35 or its generics
La pilule Diane 35 remise sur le marché en France
Google search: "cyproterone acetate and carcinogen"
Health Canada search: "Diane-35" (quotes in search)
Diane-35: Reconsidering the Risks
Diane-35: Family whose daughter died after taking drug sues Shoppers Drug Mart
Health Canada's review of Diane-35 supports current labelling and use
Health Canada to review safety of drug Diane-35
Archive – Health Canada Advises Consumers of New Warning for DIANE-35
Archived - Important Safety Information about DIANE®-35 and the risk of venous thromboembolism - Berlex Canada Inc. - Health Professional Advisory
Health Canada's review of Diane-35 supports current labeling and use
RxISK.org: Diane-35 reported side effectsDiane 35 et ses génériques : remise sur le marché en France avec restriction de l’indication, modification des contre-indications et renforcement des mises en garde - Lettre aux professionnels de santé
Benefits of Diane 35 and generics outweigh risks in specific patient group
Mediator Scandal: France Replaces Pharmaceutical Regulatory Agency
France Launches New Drug Regulatory Agency
French Drug Exec Charged with Manslaughter Over Drug Safety
France Investigates its Own Drug Regulator for Involuntary Manslaughter
Mediator Scandal Rocks French Medical Community