Nomegestrol and chlormadinone

• Meningiomas have been reported with the use of nomegestrol- or chlormadinone-containing medicines. 
• This risk, which is very low, is increased when the medicines are used at high doses (3.75 - 5 mg for nomegestrol and 5 - 10 mg for chlormadinone) and for prolonged periods of time. 
• EMA is therefore recommending that these medicines should only be used at the lowest effective dose and for the shortest duration possible. Higher doses (3.75 – 5 mg nomegestrol and 5 - 10 mg chlormadinone) should only be considered if other interventions are not possible.
• You should not use or be prescribed nomegestrol- or chlormadinone-containing medicines if you have a meningioma or have had one in the past.
• Contact your doctor immediately if you experience a change in vision (seeing double or blurriness), hearing loss or ringing in the ears, loss of smell, headaches that worsen with time, memory loss, seizures and weakness in your arms or legs.
• If you are diagnosed with a meningioma while using a nomegestrol- or chlormadinone-containing medicine, your doctor will stop your treatment with the medicine.
• The risk of meningioma may decrease after you stop treatment with a nomegestrol- or chlormadinone-containing medicine.

• Meningiomas (single and multiple) have been reported with the use of nomegestrol- or chlormadinone-containing medicines, particularly at high doses and for prolonged time. The risk increases with increasing cumulative doses.
• The use of these medicines at high doses should be restricted to situations where other interventions are considered inappropriate, and they should be used at the lowest effective dose and for the shortest duration.
• Nomegestrol- or chlormadinone-containing medicines are contraindicated in patients with meningioma or a history of meningioma.
• Patients should be monitored for signs and symptoms of meningiomas in line with clinical practice. If a patient is diagnosed with meningioma, treatment with these medicines should be permanently stopped.
• Available evidence suggests that the risk of meningioma decreases after treatment discontinuation of the nomegestrol- or chlormadinone-containing medicine.

A direct healthcare professional communication (DHPC) has been sent to healthcare professionals prescribing, dispensing or administering the medicine. The DHPC has also been published on a dedicated page on the EMA website.

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 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 CHMP recommendation will lead to alignment of the product information for these medicines across the EU.

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 was first carried out by the PRAC, the Committee responsible for the evaluation of safety issues for human medicines, which made a set of recommendations.

The PRAC recommendations were sent to the CHMP, responsible for questions concerning medicines for human use, which adopted the Agency’s opinion. The CHMP’s opinion was forwarded to the European Commission, which issued final legally binding decisions applicable in all EU Member States between 28 October and 28 November 2022.