VISANNE

Treatment of endometriosis .

Pregnancy

Data on the use of diénogest in pregnant women are limited.

Studies conducted in animals have shown no direct or indirect toxicity on reproductive functions (see section 5.3).

ENDOVELA must not be administered to pregnant women because it is not necessary to treat endometriosis during pregnancy.

Breastfeeding

ENDOVELA is not recommended during breastfeeding.

It is unknown if diénogest is excreted in breast milk. Data in animals have shown excretion of diénogest in the milk of rats.

The decision to discontinue breastfeeding or to abstain from treatment with ENDOVELA should be made by taking into account the benefit of breastfeeding for the child versus the benefit of the treatment for the patient.

Fertility

According to available data, ovulation is inhibited in the majority of patients during treatment with diénogest. ENDOVELA is, however, not a contraceptive.

If contraception is necessary, a non-hormonal method should be used (see section 4.2).

According to available data, the menstrual cycle returns to normal within 2 months following the discontinuation of treatment with ENDOVELA.

No effect on the ability to drive vehicles and use machines has been observed in users of products containing dienogest.

The presentation of adverse effects is based on the MedDRA dictionary.

The most appropriate MedDRA term is used to describe a certain reaction as well as its synonyms and associated conditions.

Adverse effects are more frequent during the first months of treatment with ENDOVELA and subside with continued treatment. Menstrual cycle disturbances such as spotting, irregular bleeding or amenorrhoea may be observed. The following adverse effects have been reported in users of dienogest 2 mg tablets.

The most frequently reported adverse effects during treatment with dienogest 2 mg are headache (9.0%), breast discomfort (5.4%), depressed mood (5.1%) and acne (5.1%).

Furthermore, the majority of patients treated with dienogest experienced disturbances in their menstrual cycle. Bleeding profiles were evaluated systematically using patient diaries and were analyzed based on 90-day reference periods (WHO method). During the first 90 days of treatment with dienogest 2 mg, the following bleeding profiles were observed (n = 290; 100 %): amenorrhea (1.7 %), infrequent bleeding (27.2 %), frequent bleeding (13.4 %), irregular bleeding (35.2 %), prolonged menstruation (38.3 %), normal menstruation, i.e. none of the previous categories (19.7 %). During the fourth reference period, the following bleeding profiles were observed (n = 149; 100 %): amenorrhea (28.2 %), infrequent bleeding (24.2 %), frequent bleeding (2.7 %), irregular bleeding (21.5 %), prolonged menstruation (4.0 %), normal menstruation, i.e. none of the previous categories (22.8 %). Menstrual cycle disturbances were only occasionally reported as adverse events by patients (see the adverse effects table).

The table below describes by frequency the adverse effects (AEs) reported with dienogest 2 mg according to the MedDRA system organ classification. Within each frequency group, adverse effects are presented in decreasing order of frequency. Frequencies are defined as follows: common (³ 1/100 to < 1/10) and uncommon (³ 1/1 000 to < 1/100). The frequencies indicated are based on pooled data from four clinical trials involving a total of 332 patients (100 %).

Table 1: Adverse effects, phase III clinical trials, n = 332

Decrease in Bone Mineral Density

In an uncontrolled clinical trial in 111 adolescents (aged 12 to <18 years) treated with dienogest, BMD was measured in 103 of them. Approximately 72% of the study participants experienced a decrease in BMD of the lumbar spine (L2-L4) after 12 months of treatment (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals report any suspected adverse reaction via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr/.