24.11.2020 - Notice within the graduated plan procedure (“Stufenplanverfahren”)

The Federal Institute for Drugs and Medical Devices (BfArM) implements the decision of the European Commission C(2022) 7954 (final) of 28.10.2022 with a notice in the national graduated plan procedure, dated 22 November 2022. The variations of the marketing authorizations will conclude the European risk assessment procedure under Article 31 of Directive 2001/83/EC on medicinal products containing chlormadinone and nomegestrol.

(available in German only)

11.11.2022 - European Commission final decision

With the decision of the European Commission, the risk assessment procedure according to Article 31 of Directive 2001/83/EC concerning chlormadinone- and nomegestrol-containing medicinal products has been completed.

02.09.2022 - CHMP opinion

EMA’s human medicines committee (CHMP) has endorsed the recommendation of the Pharmacovigilance Risk Assessment Committee (PRAC), which concluded that the benefits of medicines containing nomegestrol or chlormadinone outweigh the risks, provided new measures are taken to minimise the risk of meningioma.

08.07.2022 - PRAC recommendation

EMA’s safety committee (PRAC) has recommended new measures to minimise the risk of meningioma with medicines containing nomegestrol or chlormadinone, which are used for gynaecological and menstrual disorders, hormone replacement therapy and, at lower doses, as hormonal contraceptives (birth control). Meningioma is a tumour of the membranes covering the brain and spinal cord. It is usually benign and is not considered to be a cancer, but due to their location in and around the brain and spinal cord, meningiomas can in rare cases cause serious problems.

The PRAC has recommended that medicines containing high-dose chlormadinone (5 – 10 mg) or high-dose nomegestrol (3.75 – 5 mg) should be used at the lowest effective dose and for the shortest duration possible, and only when other interventions are not appropriate. In addition, low- and high-dose nomegestrol or chlormadinone medicines must not be used by patients who have, or have had, meningioma.

As well as restricting the use of the high-dose medicines, the PRAC has recommended that patients should be monitored for symptoms of meningioma, which can include change in vision, hearing loss or ringing in the ears, loss of smell, headaches, memory loss, seizures and weakness in arms or legs. If a patient is diagnosed with meningioma, treatment with these medicines must be permanently stopped.

The product information for the high-dose medicines will also be updated to include meningioma as a rare side effect.

The recommendations follow a review of available data, including post-marketing safety data and results from two recent epidemiological studies. ’ These data showed that the risk of meningioma increases with increasing dose and duration of treatment.

The PRAC recommendations will now be sent to the Committee for Medicinal Products for Human Use (CHMP) for the adoption of EMA’s final opinion. Further details will be published at the time of the CHMP opinion.

01.10.2021 - Procedure started

EMA has started a review of medicines containing the active substance nomegestrol or chlormadinone. These medicines can be used, alone or in combination with other active substances, to treat gynaecological disorders such as amenorrhea (absence of menstrual periods) and other menstrual disorders, uterine bleeding, endometriosis (a condition in which tissue similar to the lining of the womb grows elsewhere in the body), breast tenderness, and as hormone replacement therapy or contraceptives (birth control). EMA has started a review of medicines containing the active substance nomegestrol or chlormadinone. These medicines can be used, alone or in combination with other active substances, to treat gynaecological disorders such as amenorrhea (absence of menstrual periods) and other menstrual disorders, uterine bleeding, endometriosis (a condition in which tissue similar to the lining of the womb grows elsewhere in the body), breast tenderness, and as hormone replacement therapy or contraceptives (birth control).

The review was requested by the French medicines agency (ANSM) following new data from two epidemiological studies carried out in France in women taking these medicines to investigate the risk of meningioma, a tumour of the membranes covering the brain and spinal cord. This tumour is usually non-malignant and is not considered to be a cancer, but due to their location in and around the brain and spinal cord, meningiomas can in rare cases cause serious problems.

Cases of meningioma have been reported in women taking medicines containing nomegestrol or chlormadinone, and warnings are already included in the prescribing information for some of the medicines. However, the information for prescribers and patients may differ across EU Member States.

Data from the two studies suggest that the risk of meningioma increases with dose and duration of treatment and may be greater in women taking nomegestrol or chlormadinone for several years. The studies also showed that after women had stopped taking nomegestrol or chlormadinone for one year or more, the risk of developing these tumours was reduced and comparable to the risk in people who never used these medicines.

In light of these new data, EMA's safety committee (PRAC) will now examine the available evidence and make recommendations as to whether the marketing authorisations for nomegestrol- and chlormadinone-containing medicines should be amended across the EU.

More about the medicines

Medicines containing nomegestrol acetate or chlormadinone acetate are available as tablets to be taken by mouth. They are available on their own or in combination with oestrogens to treat gynaecological disorders such as amenorrhoea (absence of menstrual periods) and other menstrual disorders, uterine bleeding, endometriosis (a condition in which tissue similar to the lining of the womb grows elsewhere in the body), breast tenderness, and as hormone replacement therapy or contraceptives (birth control).

The medicines are marketed under several trade names including Belara, Lutenyl, Luteran, Naemis and Zoely and as generic medicines. With the exception of Zoely (nomegestrol acetate/estradiol), which is centrally authorised, all other medicines reviewed during this procedure have been authorised via national procedures. Warnings about the risk of meningioma are already included in the product information for some of them, although the wording may differ across EU Member States. The PRAC’s recommendation will lead to alignment of the product information for these medicines across the EU.

More about the procedure

The review of products containing nomegestrol or chlormadinone was initiated at the request of France, under Article 31 of Directive 2001/83/EC.

The review has been carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which has made a set of recommendations.

The PRAC recommendations will now be sent to the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which will adopt the Agency’s opinion. The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU Member States.

More information

Details of the procedure can be found on the Website of the European Medicines Agency (EMA):