There are growing concerns regarding the safety of third- and fourth-generation combined oral contraceptives following media reports on blood clots (venous thromboembolism) associated with the use of more recently-introduced contraceptive products containing newer progestins such as drospirenone, gestodene and desogestrel. France has requested that the European Medicines Agency (EMA) review this class of drugs to determine if their use should be restricted. This is the first time that a member state has requested the EMA to give an EU-wide recommendation for these medicines under the framework of the new pharmacovigilance legislation.
The French government announced at the beginning of this year that it will stop reimbursing prescription costs for third- and fourth-generation oral contraceptives and initiatives were made to reduce their use in favour of second-generation oral contraceptives. The advice issued in France was that third- and fourth-generation oral contraceptives should only be prescribed to women who cannot use other forms of contraception. The move was apparently prompted by the case where a woman sued Bayer after a stroke attack, caused by a blood clot attributed to the use of Meliane (gestodene/ethinylestradiol).
Earlier this week, French regulators from the Agence Nationale de Securite du Medicament et des Produits de Sante (ANSM) launched an investigation into Bayer’s acne treatment Diane 35 (cyproterone/ethinylestradiol) and its generics following several deaths due to thrombosis. The drug, marketed under the trade name Dianette, is used as a contraceptive in some countries but not in France. The French newspaper Le Figaro reported that according to the country’s pharmacovigilance database, seven women had died in circumstances linked to Diane 35 since its launch in 1987. However, only four of these deaths are thought to be caused by the drug, with three women dying because of embolisms and one due to cerebral thrombosis. The ANSM is now conducting an analysis of the risk-to-benefit profile of Diane 35 and data on its safety profile will be presented next week.
Combined contraceptives are known to carry a very small risk of venous thromboembolism, “between 20 and 40 cases per 100,000 women in one year of use,” according to the EMA but the risk is not the same between the different generations of combined contraceptives. According to a report issued by the agency earlier this month, there was no new evidence of any safety risk from third- and fourth-generation combined contraceptives.
The EMA’s pharmacovigilance risk assessment committee (PRAC) will, however, review whether currently available product information for third- and fourth-generation combined oral contraceptives may need changing to enable doctors and patients to make appropriate healthcare decisions. More information about the review will be available after PRAC’s next meeting on 4 to 7 February 2013.