Cyproterone products with daily doses of 10 mg or more should be restricted because of a risk of developing meningioma, says the safety committee of the European Medicines Agency.
Products containing cyproterone 10 mg daily or more should be used only in cases where other medicines, including lower dose, have failed for the treatment of androgen-dependent conditions such as hirsutism, alopecia, acne, and seborrhea. In addition, these products should be used for the reduction of sex-drive in sexual deviations in men only when other treatment options have failed.
Once higher doses have started working, the dose of cyproterone should be gradually reduced to the lowest effective dose, the committee notes.
The new guidance will be sent out directly to healthcare professionals across the European Union soon.
There are hundreds of such products on the market in various European countries. They are also marketed in many other developed countries, but not in the United States or Japan.
As part of ongoing surveillance, companies marketing products containing cyproterone 10 mg or more will be required to carry out a study to assess doctors' awareness of the risk of meningioma and how to avoid it.
The new guidance strengthens warnings that were already in place. The association with meningioma — noncancerous tumors that originate in the membranes that surround the brain and spinal cord — was first added in 2009 to the product information for products with cyproterone daily doses of 10 mg or more, as well as a contraindication for people with a history of meningioma.
The risk of meningioma is very low, notes the committee. It may affect between 1 and 10 in 10,000 people, depending on the dose and duration of treatment. Most cases have been reported after prolonged exposure (several years) to high doses of cyproterone (25 mg a day and above).
There is no change in the use of these products in the treatment of prostate cancer, the committee notes. These medicines are used as antiandrogen treatment in inoperable prostate cancer, including for prevention of the initial flare-up in treatment with luteinizing hormone-releasing hormone (LHRH) agonists.
There is also no change for products containing low-dose cyproterone (1 or 2 mg) in combination with ethinylestradiol or estradiol valerate and used in the treatment of acne, hirsutism, contraception, or hormone replacement therapy.
However, as a precaution, these products should not be used in people who have, or previously had, a meningioma, the committee notes.
Review of Safety Requested by France
The new guidance comes after a review carried out by the EMA's Pharmacovigilance Risk Assessment Committee (PRAC), which is responsible for the evaluation of safety issues for human medicines.
The review, which began last July, was requested by France and was prompted by a recent French study that found the risk of meningioma with long-term use of these products is higher than was first thought.
PRAC says that its review included this French study, which showed a cumulative dose-dependent association between cyproterone acetate and meningioma (Weill et al). It also included an analysis by the French medicines agency ANSM of cases of meningioma with cyproterone use in France, as well as recent published literature and analysis of the EU database of adverse events, EudraVigilance.
Cite this: EU Restricts High-Dose Cyproterone Because of Meningioma Risk - Medscape - Feb 14, 2020.