4.6 Pregnancy and lactation

 Women of childbearing potential / Contraception in females

Before initiation of Gilenya treatment, women of childbearing potential should be counselled regarding the potential for serious risk to the foetus and the need for effective contraception during treatment with Gilenya. Since it takes approximately two months to eliminate fingolimod from the body on stopping treatment (see section 4.4), the potential risk to the foetus may persist and contraception should be continued during that period.

Pregnancy

Before initiation of treatment in women of childbearing potential a negative pregnancy test result needs to be available. While on treatment, women should not become pregnant and active contraception is recommended. If a woman becomes pregnant while taking Gilenya, discontinuation of Gilenya is recommended.

Animal studies have shown reproductive toxicity including foetal loss and organ defects, notably persistent truncus arteriosus and ventricular septal defect (see section 5.3). Furthermore, the receptor affected by fingolimod (sphingosine 1-phosphate receptor) is known to be involved in vascular formation during embryogenesis. There are very limited data from the use of fingolimod in pregnant women.

There are no data on the effects of fingolimod on labour and delivery.

Breast-feeding

Fingolimod is excreted in milk of treated animals during lactation at concentrations 2-3-fold higher than that found in maternal plasma (see section 5.3). Due to the potential for serious adverse reactions to fingolimod in nursing infants, women receiving Gilenya should not breastfeed.

Fertility

Data from preclinical studies do not suggest that fingolimod would be associated with an increased risk of reduced fertility (see section 5.3).

4.7 Effects on ability to drive and use machines

 Gilenya has no or negligible influence on the ability to drive and use machines.

However, dizziness or drowsiness may occasionally occur when initiating therapy with Gilenya. On initiation of Gilenya treatment it is recommended that patients be observed for a period of 6 hours (see section 4.4, Bradyarrhythmia).

4.8 Undesirable effects

 Summary of the safety profile

A total of 1,703 patients on Gilenya (0.5 or 1.25 mg) constituted the safety population in the two Phase III studies in patients with relapsing-remitting multiple sclerosis (see section 5.1). Study D2301 (FREEDOMS) was a 2-year placebo-controlled clinical study in 854 patients treated with fingolimod (placebo: 418). In this study the most serious adverse reactions on Gilenya 0.5 mg were infections, macular oedema and transient atrioventricular block at treatment initiation. The most frequent adverse reactions (incidence 10%) on Gilenya 0.5 mg were headache, influenza, diarrhoea, back pain, liver enzyme elevations and cough. The most frequent adverse reaction reported for Gilenya 0.5 mg leading to treatment interruption was serum transaminase elevations (3.8%). The adverse reactions in Study D2302 (TRANSFORMS), a 1-year study in 849 patients treated with fingolimod which used interferon beta-1a as comparator, were generally similar to Study D2301, taking into account the differences in study duration.

Adverse reactions reported with Gilenya 0.5 mg in Studies D2301 (FREEDOMS) and D2302 (TRANSFORMS) are shown below. Frequencies were defined using the following conve