PRAC July 2022 – New measures for medicinal products containing nomegestrol or chlormadinone and start of assessment of neurodevelopmental disorders when using topiramate

date: 13/07/2022

During its July 2022 meeting, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA)  recommends new measures to minimise the risk of meningioma with medicines containing nomegestrol or chlormadinone. The PRAC also starts the review on the risk of neurodevelopmental disorders with topiramate.

Medicines containing nomegestrol or chlormadinone: PRAC recommends new measures to minimise risk of meningioma
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. If a patient is diagnosed with meningioma, treatment with these medicines must be permanently stopped. 

More information is available in EMA’s public health communication.

The following nomegestrol-containing medicines are authorised and marketed in Belgium: LUTENYL 5 mg, NOGEST 5 mg, NOMEGESTROL STRAGEN 5 mg and ZOELY 2.5-1.5 mg

The following chlormadinone-containing medicines are authorised and marketed in Belgium: BELLINA 0.03 mg-2 mg and HELEN 0.03 mg-2 mg

New safety information for healthcare professionals
As part of its advice on safety-related aspects to other EMA committees, the PRAC discussed a direct healthcare professional communication (DHPC) containing important information for medicines containing chlormadinone- or nomegestrol.

This DHPC aims to inform healthcare professionals that medicines containing high doses of chlormadinone or nomegestrol should only be indicated when other interventions are considered inappropriate. Furthermore, all medicines containing nomegestrol or chlormadinone must not be used by patients who have, or have had, meningioma.

The DHPC will be forwarded to EMA’s human medicines committee (CHMP). Following the CHMP decision, the DHPC will be disseminated to healthcare professionals by the marketing authorisation holder, according to an agreed communication plan, and published on the Direct healthcare professional communications page and in national registers in EU Member States.

PRAC starts review on risk of neurodevelopmental disorders with topiramate 
PRAC has started a review of topiramate to assess new data on a potential risk of neurodevelopmental disorders in children who have been exposed  to the medicine during pregnancy.

Topiramate is indicated for the treatment of epilepsy, either used alone (monotherapy) or in conjunction with other medicines (combination therapy), as well as for the prevention of migraine. The use of topiramate by pregnant women is already known to increase the risk of birth defects. For that reason, women with epilepsy are advised to avoid becoming pregnant whilst being treated with topiramate, and to consult their doctor for advice in case they wish to become pregnant. Pregnant women, or women of childbearing potential not using highly effective birth control, must not be treated for prevention of migraine.

Recently, a study investigating the risk of neurodevelopmental disorders, including autism spectrum disorder and intellectual disability, associated with several anti-epileptic drugs, including topiramate has been published. The study is based on Nordic registry data and includes more than 24,000 children exposed in utero to at least one anti-epileptic drug, including 471 who were exposed to topiramate. 

The study conclusions suggest a possible increase in the risk of autism spectrum disorders, intellectual disability and child neurodevelopmental disorders with the exposure to topiramate during pregnancy. 

In light of the importance of this new information, the PRAC decided to start a review to further assess data from the study, as well as its potential impact on the use of topiramate.

Data from the study is being assessed as a ’safety signal’ - information on new or changes in known adverse events that may potentially be associated with a medicine and that warrants further investigation.

EMA will communicate further as soon as more information becomes available.

The following topiramate-containing medicines are authorised and marketed in Belgium: TOPAMAX and TOPIRAMATE EG.

More information is available on the EMA website.
 

Last updated on 13/07/2022