The benefits of Diane 35 and its generics outweigh the risks in certain patient groups

23.05.2013

The European Medicines Agency’s Pharmacovigilance Risk Assessment Committee (PRAC), concluded that the benefits of Diane 35 (cyproterone acetate 2 mg / ethinylestradiol 35 micrograms) and its generics outweigh the risks, provided that several measures are taken to minimise the risk of thromboembolism (VTE and ATE - the formation of blood clots in the veins and arteries). These medicines should be used solely for the treatment of moderate to severe acne related to androgen sensitivity or hirsutism (excessive unwanted growth of facial hair) in women of reproductive age, as is already stated in the Summary of Product Characteristics and the Package Leaflet approved in the Republic of Croatia for these medicines.
Furthermore, Diane 35 should only be used for the treatment of acne when alternative treatments, such as topical therapy and antibiotic treatment, have failed. PRAC concluded that in the treatment of alopecia, the benefits of Diane 35 and its generics do not outweigh the risks. Furthermore, since Diane 35 and its generics act as contraceptives, they should not be used in combination with other hormonal contraceptives. The concomitant use of Diane 35 and its generics with another hormonal contraceptive will expose women to a higher dose of oestrogen and increase the risk of thromboembolism.

PRAC's recommendation will be sent to the The Co-ordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh), which will adopt final position for the EU member states, about which professionals and the general public will be notified.

The risk of venous thromboembolism (VTE) with these medicines is low but well known, and warnings are included in their Summary of Product Characteristics and the Package Leaflet to alert patients and prescribers to the risks related to their use.

Risk management activities

PRAC recommended adding new contraindications and warnings for patients and healthcare professional that are not very different from the contraindications and warnings stated in the Summary of Product Characteristics and the Package Leaflet approved in the Republic of Croatia for Diane 35 and its generics.
According to PRAC's recommendation, it is necessary to contribute to raising awareness about the risks, signs and symptoms of thromboembolism in order to promptly diagnose and start treatment. This includes providing educational materials to doctors and patients that emphasize the risks of thromboembolism.
PRAC also recommended further pharmacovigilance activities, such as studies on the use of Diane 35 and its generics pursuant to the abovementioned changes in the medicinal product information, as well as studies on the efficiency of the recommended risk minimization measures.

Additional information on the safety review

These medicinal products have been authorized through the national procedure for granting marketing authorization in individual Member States and have been widely used across Europe for many years. However, their authorized uses differ between Member States. In the process of the safety review, PRAC assessed all the available information on the risk of thromboembolism from Diane 35 and its generics based on postmarketing data in Europe and other published literature.

The European Medicines Agency invited stakeholders, including health care professionals, patients’ organisations and the general public, to submit data relevant to the procedure. Eight stakeholders submitted data that was included in the review. For the purposes of the safety review, an advisory group of experts, including a patients’ representative, was formed.

The use of these medicinal products in Croatia

The new recommendations by PRAC are not very different to the information that has already been approved for Diane 35 and its generics in Croatia. Based on the consumption data, HALMED estimates that these medicines have been consistently prescribed for the approved indications and no off-label use has been noted. The annual Diane 35 consumption is 30,000 packages per year, with one package being sufficient for a one month of therapy, which can be seen in a graph here. So far, HALMED has not received any reports of adverse drug reactions with fatal effects related to the use of Diane 35 and its generics.

Earlier information from the safety review of Diane 35 and its generics are available on the following links: