1 / In which cases are Nomestrol (Lotényl) and Chlormadinone (Lutéran) acetate used?
Nomestrol acetate and chlormadinone acetate are progesterone derivatives indicated in particular in the management of menopause, menstrual disorders (painful rules, cycle irregularities), uterine fibroids and endometriosis. Use outside the approved indications have also been reported: Lotényl and Lotéran have been able to be prescribed as a contraceptive pill or as an acne treatment.2 / What is a meningioma?
Meningioma is a tumor that develops from meninges (envelopes around the brain). These tumors are most often non -cancerous but can cause serious disorders that may require heavy and at risk surgery.In the general population, around 9 to 10 new cases of meningioma per 100,000 patients are observed each year.
3 / What are the symptoms of meningioma?
The signs can be very different depending on the size and location of the tumor.The most often encountered symptoms are: frequent headaches, dizziness, vision disorders, weakness in arms or legs, paralysis, language or hearing disturbances, smell disorders, convulsions, memory disorders.
If you are or have been treated by Lotényl, Lotéran or their generics and you have one or more of these symptoms, consult your doctor who will prescribe a brain control MRI.
If in doubt do not hesitate to contact your doctor.
4 / Since Lotényl, Lotéran and their generics increase the risk of meningioma, why are they not withdrawn from the market?
Lotényl, Lutéran and their generics are useful for taking care of certain pathologies that may have a impact on the quality of life of patients (especially for women suffering from endometriosis, uterine fibroids and certain menstrual disorders). Given the therapeutic interest in these drugs, their marketing in France is not called into question.However, appropriate conditions for using these drugs must be established in terms of the risk of meningioma and the needs of women for which these treatments are justified. These measures will be implemented after a public consultation organized on Monday, November 2, 2020 with representatives of health professionals and patients concerned.
5 / I am currently treated by Lotényl, Lotéran or their generics, what should I do? Do I have to stop my treatment?
If you are currently being treated by Lutényl Lotéran, or their generics we invite you to consult your doctor (attending or gynecologist) to discuss with him your care. It is indeed the best able to judge the relevance of your treatment taking into account your personal medical situation as a whole (= individual benefit-risk). It is on this occasion that the stop or pursuit of your treatment will be decided. If you want to stop your treatment it is better to talk to your doctor before making your decision.Pending the measures to be determined following the public consultation held on November 2nd, preliminary recommendations were developed in June 2020 to ensure the safety of women's care. These preliminary recommendations stipulate that a brain MRI is recommended in the following situations :
- If you are over 35 years old and have been treated with nomegestrol acetate (Lutényl and generics) or chlormadinone acetate (Lutéran and generics) for more than 5 years: your doctor may suggest that you undergo brain imaging (MRI) even if you do not have symptoms;
- If you are, or have been, treated with nomegestrol acetate (Lutényl and generics) or chlormadinone acetate (Lutéran and generics) and you have symptoms suggestive of a meningioma (frequent headaches, dizziness, vision problems, weakness in the arms or legs, paralysis, speech or hearing problems, smell problems, seizures, memory problems, etc.), consult your doctor who will prescribe a brain imaging (MRI).
In girls and young women treated for short periods , there is no need to offer a brain MRI. Indeed, it is accepted that the risk of meningioma increases with age and the doses of nomegestrol acetate (Lutényl and generics) or chlormadinone acetate (Lutéran and generics) received.
If meningioma is diagnosed with you, you should stop your treatment.
6 / What are the risks to stop my treatment myself?
A priori, there is no risk to put an end to your treatment yourself. However, for certain uses such as endometriosis or uterine fibroids, stopping treatment may be associated with a reappearance of certain symptoms (including bleeding and pain).These drugs with a contraceptive effect, if you decide to stop your treatment, your contraception will no longer be ensured and you will need to consider a new contraceptive method.
7 / I was treated by Lotényl, Lotéran or their generics, what should I do?
If you have been treated by Lotényl, Lotéran or their generics and you have symptoms evocative of meningioma (frequent headache, dizziness, vision disorders, weakness in arms or legs, paralysis, language or hearing disturbances, smell disorders, convulsions, memory disorders, etc.) (MRI).However, in the absence of clinical signs, brain imaging is not necessary.
In the event of specific questions or clinical signs, do not hesitate to contact your doctor, he will assess the need or not to prescribe an MRI.
8 / If my doctor prescribes an MRI, should I go urgently?
If your doctor has prescribed a brain MRI following signs evocative of meningioma (frequent headache, dizziness, vision disorders, weakness in arms or legs, paralysis, language or hearing disorders, smell disorders, convulsions, memory disorders, etc.), we invite you to make this MRI make.In the absence of a neurological symptom, if your doctor has prescribed a control MRI as part of a treatment for more than 5 years, it can be carried out without an emergency.
9 / I am where I was under Lotényl, Lotéran or their generics and a meningioma was detected to me. Will I have to have an operation?
If a meningioma is detected while you are being treated with Lutényl, Lutéran or their generics, your doctor will ask you to stop your treatment and you should never take these medications again, nor even cyproterone acetate (Androcur and generics); these medications are said to be contraindicated in cases of meningiomas or a history of meningioma.Your doctor will also have to orient you towards a neurosurgery consultation in order to assess whether surgical intervention is necessary or not.
10 / What are the progestin drugs concerned by the risk of meningioma? (Androcur, Lotényl, Lotéran and their generics)
A first pharmaco-epidemiology study conducted in 2018 by the Scientific Interest Group Epi-Phare on Cyproterone Acetate (Androcur and Generics) highlighted the risk of meningioma linked to the use of this drug.Another study was then conducted by Epi-Phare on two other progestin treatments which had also been the subject of reports of meningioma cases. These two progestins are nomestrol (lutenyl and generic) acetate and chlormadinone (luteran and generic) acetate.
This study confirms the over-risk of developing a meningioma linked to the use of lutenyl and luteran (and their generics).
| Numegestrol (lutenyl and generic) acetate) | Chlormadinone acetate (Ltéran and Generics) | Cyproterone acetate 50 mg
(Androcur and generics) |
|
| Multiplication of the risk of meningiom compared to the basic risk | x 3.3 beyond
6 months of use |
x 3.4 beyond
6 months of use |
x 7 Beyond 6 months of treatment |
| x 12.5 from a cumulative dose corresponding to
5 years of treatment (5 mg /20 days per month) |
X 7 from a cumulative dose corresponding to 3.5 years of use
(10 mg /20 days per month) |
x 20 from 5 years of treatment |
In addition, the ANSM closely monitors all the reported cases of meningiomas under progestin. In this regard, the second part of the current pharmacovigilance survey since October 2018 will be presented at the end of 2020 during a permanent scientific committee (CSP) Surveillance and pharmacovigilance.
11 / Is the risk of meningioma linked to these drugs a known risk?
In February 2019, following reports of meningioma cases, a letter was sent to healthcare professionals to inform them of the potential risk of meningioma associated with nomegestrol acetate (Lutényl and generics) or chlormadinone acetate (Lutéran and generics) – the letter can be viewed HERE . This information is already available in the patient information leaflets for these medications (Package Leaflet and Summary of Product Characteristics (SmPC)).The results of a large recent epidemiological study (June 2020) make it possible for the first time to quantify this risk: it increases with the duration of treatment, the dose used and the age of the patient.
Thus the risk of developing meningioma is multiplied by more than 3 beyond 6 months of use of Lotényl or Lotéran. From 5 years of treatment by Lotényl this risk is multiplied by 12.5. It is multiplied by 7 after 3.5 years of treatment with Lotéran.
| Nomestrol acetate (Lotényl and Generics) | Chlormadinone acetate (Ltéran and Generics) | |
| Multiplication of the risk of meningiom compared to the basic risk | x 3.3 beyond 6 months of use | x 3.4 beyond 6 months of use |
| x 12.5 from a cumulative dose corresponding to 5 years of treatment
(5 mg /20 days per month) |
X 7 from a cumulative dose corresponding to 3.5 years of use
(10 mg /20 days per month) |
In addition, the risk of meningioma leading to surgery at the skull level (= intracranial surgery) increased sharply with age: it is, for example, 3 times higher for women aged 35 to 44 than for those aged 25 to 34.
12 / Have health professionals been informed? What recommendations have been given to them?
An information letter was sent in February 2019 to all endocrinologists, gynecologists, neurosurgeons, neurologists, general practitioners, community pharmacists and hospital pharmacists to remind them that- Nomestrol acetate and chlormadinone acetate are contraindicated in the event of meningiomas or a history of meningioma;
- Any identification of meningioma in use of one of these drugs must lead to interrupt the treatment.
This letter also alerted health professionals about the possible link between meningioma and numegestrol / chlormadinone acetate and guided them as to the driving to be taken. They were notably asked to:
- Inform patients of the existence of the risk of meningioma,
- (Re)-Evaluate the benefit/risk balance for each patient, taking into account the risk of meningioma,
- Check with patients the absence of a history of meningioma or well -known meningioma,
- Prescribe in compliance with the indications authorized by the AMM,
- Prescribe the lowest possible doses and over a shortest possible duration.
In addition, preliminary recommendations on this subject were issued by the ANSM in June 2020. We therefore urge you to follow these recommendations and inform your patients of the risk of meningioma:
- Revalle the relevance of a nomigestrol acetate treatment or chlormadinone acetate taking into account the individual benefit-risk; limit the duration of use of these drugs as well as their dosage with effective minimum doses (cumulative dose effect);
- Do not substitute macroprogestatives between them (nomestrol acetate, chlormadinone acetate and cyproterone acetate) in the event of meningioma or a history of meningioma;
- Have a brain MRI made in case of symptoms evocative of a meningioma: frequent headache, vision disorders, language or hearing, dizziness, memory disorders ...
- In the event of prolonged treatment (from 5 years old), offer your patients over 35 years old, brain imaging by MRI.
Besides, we recall that:
- Nomestrol acetate, chlormadinone acetate and cyproterone acetate (Androcur and generics) are contraindicated in the event of meningiomas or a history of meningioma;
- Any identification of meningioma in use of one of these drugs must lead to interrupt the treatment. None of these 3 substances can be resumed in the event of meningioma;
These recommendations will be discussed on November 2, 2020, during a public consultation bringing together representatives of health professionals and patients concerned.
13 / I am a health professional and I treat women with Lotényl, Lotéran or their generics, what should I do?
Lotényl, Lutéran and their generics have a therapeutic interest in the management of certain pathologies such as endometriosis or fibroids in which the drug therapeutic options are limited. However, appropriate measures of their use must be established in the light of the risk of meningioma and the needs of women for which these treatments are justified. These measures will be implemented after a public consultation organized on Monday, November 2, 2020 with representatives of health professionals and patients concerned.Pending the dissemination of appropriate guidelines for the use of Lutényl and Lutéran, preliminary recommendations were developed in June 2020 to ensure the safety of women's care. We therefore urge you to follow these preliminary recommendations and inform your patients of the risk of meningioma:
- Revalle the relevance of a nomigestrol acetate treatment or chlormadinone acetate taking into account the individual benefit-risk; limit the duration of use of these drugs as well as their dosage with effective minimum doses (cumulative dose effect);
- Do not substitute macroprogestatives between them (nomestrol acetate, chlormadinone acetate and cyproterone acetate) in the event of meningioma or a history of meningioma;
- Have a brain MRI made in case of symptoms evocative of a meningioma: frequent headache, vision disorders, language or hearing, dizziness, memory disorders ...
- In the event of prolonged treatment (from 5 years old), offer your patients over 35 years old, brain imaging by MRI.
Besides, we recall that:
- Nomestrol acetate, chlormadinone acetate and cyproterone acetate (Androcur and generics) are contraindicated in the event of meningiomas or a history of meningioma;
- Any identification of meningioma in use of one of these drugs must lead to interrupt the treatment. None of these 3 substances can be resumed in case of meningioma.
14 / How can I declare an adverse effect linked to my treatment by Lotényl, Lotéran or their generics?
If you think you have developed an adverse effect related to your treatment, we encourage you to report it directly on the adverse event reporting portal: signalement-sante.gouv.fr The report can be declared in a few clicks directly by a patient, by his doctor or any other healthcare professional or by an association of patients or users.
Declaring adverse effects is always useful, this contributes to better taking into account the risks associated with drugs
