Esmya, a drug indicated for the preoperative or sequential treatment of uterine fibroids (benign tumors located in the lining of the uterus) and which has been taken by 700,000 women around the world, worries the European health authorities and French.

He is suspected to be at the origin of 5 cases of severe liver injury accompanied by liver failure requiring liver transplantation in four women, including two French, one Portuguese and two German since marketing. Among them, the German patient died of sepsis after transplantation in October 2017. Finally, about twenty cases, much less serious, were also reported.

All these patients could be identified thanks to a report made on September 22, 2017 (which coincided with the systematic annual review of the drug in question) with the National Agency for Drug Safety (ANSM). The latter then alerted the European Medicines Agency (EMA), which resulted in a pharmacovigilance survey throughout Europe from which resulted a European arbitration was launched in November 2017 to review the benefit / risk of the drug.

Caregivers and patients are advised to take special precautions

"There have been enough cases in France to decide to ask our European colleagues to be interested," explains Dr. Pierre Demolis, head of the European Strategy Steering Center at ANSM . had suspicions about Esmya, but there was little evidence to confirm or deny his responsibility.It was likely that French patients had liver disease before taking Esmya, which would have triggered hepatitis, or that Esmya had The two cases were not very clear, but for the German patient who died, so the case was reported to us only last week, we retrieved the information and are think about it, and for the moment, it seems quite likely that Esmya is responsible. "

In order to guarantee patient safety, ANSM and EMA decided, as of February 9, 2018, to take certain preventive measures.

Thus, they specify that "for patients in the course of treatment, the choice of the continuation of the treatment must be re-evaluated on a case-by-case basis with the prescribing physician taking into account the individual risk benefit". However, health agencies recommend not starting new cycles of treatment (3 months) in previously treated patients "as a precautionary measure," says the head of the European Strategy Steering Center at ANSM. An information sheet will have to be given by the doctors and pharmacists at the time of a possible monthly renewal.

Patients who would have the approval of their doctor to continue their treatment under this specialty should also perform a liver test (blood test) at least once a month (and then 2 to 4 weeks after stopping) and monitor the appearance of symptoms indicating a possible liver problem (lack of severe appetite, weight loss, nausea and vomiting, unexplained fatigue, muscle weakness, pain in the upper right of the abdomen, yellowing of the skin or whites of the eyes, dark urine). If they have these signs, or if their liver function has transaminase levels higher than twice normal, then they should, always in agreement with a doctor, stop this treatment and be placed under surveillance.

In addition, agencies are recommending that health professionals not prescribe Esmya for the first time. "The measures put in place are temporary and only serve to 'block' the problem for a while, the aim being to prevent new patients from having serious liver problems, but this is a sufficiently disturbing event that we will not be able to put no more new patients under Esmya in Europe "

Conclusions expected in the second quarter of 2018

A possible interaction is notably one of the tracks carved out by the health authorities "Esmya We already advise against taking in women with hepatic impairment Generally, we are already doing around the issue of interaction before the setting. on the market for a drug, but that's one of the things we have to look at, these women may have eaten herbal tea or used a household product ... It's not necessarily an interaction with another drug that This is because we can do hepatitis for a lot of reasons and that's what we try to understand, "says our expert.

According to him, the conclusions of this investigation will be made public by the second quarter of the year 2018. "If all goes well and that we worried for nothing, Esmya will be prescribed as before. it may be decided to withdraw it from the market, except perhaps for patients for whom it is vital. "

How can a medicine cause hepatitis?

"All drugs are metabolized, filtered and evacuated by the kidney or liver, says Dr. Pierre Demolis.Some times, he does not have the" weapons "to get rid of it, either because of a too much or because they trigger an allergy, for example, and get intoxicated.In less severe cases, some liver cells may burst and transaminases increase slightly.

On the other hand, one has to worry when transaminases (enzymes that reflect the activity of the liver) increase in a massive way, that is, 15, 20 or 30 times normal, as this indicates that many cells Hepatica are bursting, the transaminases pass into the blood instead of remaining locked in the liver, and there is a risk of acute hepatitis: the liver derails, the patient's condition worsens progressively, the organ no longer works and one can die of it. "

Esmya, a treatment put on the market in 2012

Marketed by the Hungarian laboratory Gedeon Richter, Esmya benefits from two indications: one granted in 2012, as part of a pre-operative treatment of uterine fibroids for a period of three months; the other obtained in May 2015 for the sequential treatment of fibroids, and which advocates cycles of a duration of three months.

Its active substance is ulipristal acetate, a selective modulator of progesterone (hormone) receptors. It works by blocking the progesterone receptor, which is involved in controlling the growth of the lining of the uterus. In some women, progesterone can promote the growth of fibroids, which can lead to excessive uterine bleeding (uterine bleeding during or after menses), anemia (low blood counts due to bleeding), and abdominal pain ( such as period pain or pain in the belly area). When progesterone activity is blocked, the fibroids cease to divide and eventually die, reducing the size of the fibroids and reducing the symptoms caused by them.

If in doubt, consult your doctor.
You can report any adverse reaction suspected to be due to Esmya at www.signalement-sante.gouv.fr.