Lutéran, Lutényl and meningioma: 185 batches withdrawn from the market

[Mise à jour le 2 février 2022 à 17h08] The medications based on nomegestrol acetate (Lutenyl® and generics) and chlormadinone acetate (Luteran® and generics) are associated with a demonstrated increased risk of meningioma and recognized by the French health authorities. Their indications have been restricted and their deliverances in pharmacy require the presentation of an annual information certificate co-signed by the patient and her doctor. Due to the modification of notices medications and terms of prescription and dispensing (CPD), the Medicines Agency (ANSM) announces on February 1 the recall of 185 batches of Lutényl and Lutéran. Other batches are on the market and are not not affected by the recall because they already mention the new CPDs (in particular the delivery conditional on the co-signed information certificate for any treatment prior to more than 1 year). initiations of treatment and January 1, 2022 for renewals. associated with these drugs.

Lutéran® and Lutényl® are women-only progestins. A progestogen is a hormone naturally secreted in the middle of a woman’s menstrual cycle. It promotes the implantation of the egg in the uterus, therefore pregnancy. But taken during the cycle, it has the opposite effect. It thickens the uterine walls, which can no longer accommodate the egg. This is why this substance is used in the manufacture of progestin-only pills or hormonal IUDs. Used alone or coupled with estrogen, it acts like a contraceptive. Lutéran® and Lutényl® can be indicated during irregularities of the menstrual cycle, disorders preceding the rules and painful periods, of breast pain, of artificial cycle in association with an estrogen, ofendometriosis, of bleeding in connection with fibroids.

> See the Luteran drug sheet

> See the Lutenyl drug sheet

After an initial warning in February 2019, the Medicines Agency again alerted to the meningioma risk associated with the use of these treatments, and their generics in June 2020. It was the EPI-PHARE study, set up by the ANSM and the Cnam, which confirmed the increased risk of meningioma in women exposed to these macroprogestogen drugs, and demonstrated a significant increase in risk with the dose used, the duration of treatment and the age of the patient. The meningioma is a tumor, most often benign, which develops from the membranes that envelop the brain and the spinal cord (brains).

→ Women treated for more than 6 months by nomegestrol or chlormadinone acetate are exposed to a risk multiplied by 3.3 and 3.4 respectively compared to the baseline risk, then by 12.5 from a cumulative dose corresponding to 5 years of treatment for nomegestrol acetate and by 7 from a cumulative dose corresponding to 3.5 years of use of chlormadinone acetate.

→ The risk of meningioma leading to intracranial surgery increases sharply with age : it is 3 times higher for women aged 35 to 44 than for those aged 25 to 34.

As of January 12, 2021, for Lutéran® and generics: In women of childbearing age, in the following situations, when therapeutic alternatives have failed or are contraindicated:

• Endometriosis
• Functional bleeding
• Preoperative menorrhagia related to fibroids
• Severe mastopathy.

> The risk benefit of the treatment will be reassessed at least every years. The treatment should be as short as possible.

For Lutényl® and generics: In women of childbearing age, in the following situations, when therapeutic alternatives have failed or are contraindicated:

• Functional bleeding
• Preoperative menorrhagia related to fibroids
• Severe mastopathy.

> The risk benefit of the treatment will be reassessed at least every year. The treatment should be as short as possible”

Regardless of the duration of the treatment, it must be reassessed at each gynecological consultation and at least once a year.

When the treatment is continued beyond one year, any dispensing of these drugs in pharmacies requires presenting a annual information certificate co-signed by the patient and her doctor. This measure is mandatory from July 1, 2021 for treatment initiations and from January 1, 2022 for renewals.

For a woman starting treatment with Lutényl, Lutéran or one of their generics OR a woman treated for less than a year :

• The doctor must give the patient the information document and mention on the prescription “treatment less than one year” from July 1, 2021.
• The information certificate is not essential during the first year of treatment.
• The patient will be able to obtain her medication at the pharmacy uniquely if this mention appears on his prescription.

For a woman taking Lutényl, Lutéran or one of their generics for more than a year :

• On the occasion of the next gynecological consultation, the benefit of continuing the treatment should be reassessed, taking into account the individual benefit/risk ratio.
• No later than January 1, 2022, the doctor must give the patient the information document and a copy of the co-signed information certificate (the original is kept in the patient’s medical file). The certificate must be presented to obtain the drug from a pharmacy.

Warning : whatever the duration of the treatment, it must be reassessed at each gynecological consultation and at least once a year. If your treatment ensured your contraception, in the event of stopping, even punctually, you must remember to use an effective method of contraception.

As of January 12, 2021, the use of these two progestins should be prohibited due to a benefit/risk considered to be unfavorable and therapeutic alternatives available in the following cases:

• Menopause, artificial cycle in association with an estrogen
• Cycle irregularities
• Premenstrual syndrome (essential dysmenorrhea)
• Non-severe mastodynia
• Contraception (without associated cardiovascular risk factor).

Be attentive to the symptoms suggestive of a meningioma: frequent headaches, vision, language or hearing disorders, dizziness, memory problems, etc.

Magnetic resonance imaging (MRI) is the only examination capable of detecting small meningiomas. It must be performed regardless of the age of the patient:

• at any time during or after treatment in the event of signs suggestive of meningioma;
• after 1 year of treatment when the treatment needs to be continued, then 5 years after the first MRI, then every 2 years as long as the treatment is continued;
• at the initiation of treatment in the event of identified risk factors for meningioma (history of brain radiotherapy in childhood or neurofibromatosis type 2).

If you are or have been treated with Lutényl® or Lutéran® or their generics, the ANSM recommends :

• discuss your care with your doctor during a future gynecological consultation: in view of the new recommendations for use and follow-up, you may be required together to change your treatment and/or to set up follow-up by brain imaging depending on your situation;
• Symptoms. be attentive to the symptoms suggestive of a meningioma (frequent headaches, vision, language or hearing disorders, dizziness, memory problems, etc.) and consult your doctor as soon as possible in case of symptoms.
• If your treatment ensured your contraception, in the event of stopping, even punctually, you must remember to use an effective method of contraception.

Sources:

Specialties based on nomegestrol acetate or chlormadinone acetate – Laboratoires Arrow Génériques, Biogaran, EG Labo, Mylan SAS (Viatris), Sandoz, Teva and Theramex. ANSM. February 1st

Lutényl / Lutéran: documents to guarantee women’s information on the increased risk of meningioma. ANSM. 02/07/2021

Nomegestrol acetate (Lutenyl and generics)/chlormadinone acetate (Luteran and generics), and risk of meningioma: recommendations for use and patient follow-up. information point of January 12, 2021. ANSM.

ANSM press release, Lutényl/Lutéran and the risk of meningioma: call for participation with a view to a public consultation – Information point, September 10, 2020.

ANSM press release, Lutényl/Lutéran and generics: preliminary recommendations following confirmation of the increased risk of meningioma – Information Point, June 17, 2020