SIBELIUM Tablet Ref.[7536] Active ingredients: Flunarizine

Flunarizine may give rise to extrapyramidal and depressive symptoms and reveal Parkinsonism, especially in elderly patients. Therefore, it should be used with caution in such patients.

The recommended dose should not be exceeded. Patients should be seen at regular intervals, especially during maintenance treatment, so that extrapyramidal or depressive symptoms may be detected early and if so, treatment discontinued.

Female patients with a history of depressive illness may be at particular risk of depression during chronic treatment with this medicine.

Accumulation may occur if given at dose levels higher than recommended, with an increased incidence of side effects.

In rare cases fatigue may increase progressively during flunarizine therapy. In this event, the therapy should be discontinued and possibly initiated again at a lower dosage.

Lactose

Flunarizine tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Each tablet contains less than 1 mmol sodium (23 mg), and is essentially sodium-free.

When used in conjunction with anti-hypertensive drugs, dosage of the latter may need adjustment.

Galactorrhoea has been reported in some female patients on oral contraceptives within the first two months of flunarizine treatment.

Excessive sedation can occur when alcohol, hypnotics or tranquillisers are taken simultaneously with flunarizine.

The pharmacokinetics of flunarizine were unaffected by topiramate. After repeated dosing in migraine patients, systemic exposure to flunarizine increased by 14%. When flunarizine was co-administered with topiramate 50 mg every 12 hours, repeated dosing resulted in a 16% increase in systemic exposure to flunarizine. The steady-state pharmacokinetics of topiramate were unaffected by flunarizine. Chronic administration of flunarizine did not affect the disposition of phenytoin, carbamazepine, valproate or phenobarbital. Plasma concentrations of flunarizine were generally lower in patients with epilepsy taking these anti-epileptic drugs (AEDs) compared to healthy subjects given similar doses. The plasma protein binding of carbamazepine, valproate, and phenytoin is not affected by co-administration with flunarizine.

Pregnancy

There are no data from the use of flunarizine in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. As a precautionary measure, it is preferable to avoid the use of flunarizine during pregnancy.

Lactation

It is unknown whether flunarizine is excreted in human milk. Animal studies have shown excretion of flunarizine in breast milk. A decision on whether to discontinue breast-feeding or to continue/discontinue therapy with flunarizine should be made taking into account the benefit of breast-feeding to the child and the benefit of therapy to the woman.

Since somnolence may occur, especially at the start of the treatment, caution should be exercised during activities such as driving or operating dangerous machinery.

The safety of Sibelium (5 to 10mg/day) was evaluated in 247 flunarizine-treated subjects who participated in two placebo-controlled clinical trials in the treatment of vertigo and migraine, and in 476 flunarizine-treated subjects who participated in two comparator-controlled clinical trials in the treatment of vertigo and/or migraine. Based on pooled safety data from these clinical trials, the most commonly reported (≥4% incidence) adverse reactions were: Weight Increased (11%), Somnolence (9%), Depression (5%), Increased Appetite (4%); and Rhinitis (4%).

Including the above-mentioned adverse reactions, the following table displays adverse reactions that have been reported with the use of Sibelium from both clinical trial and post-marketing experiences. The displayed frequency categories use the following convention: Very common (≥1/10); common (≥1/100 to 1/10); uncommon (≥1/1,00 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

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 are asked to report any suspected adverse reactions via: HPRA Pharmacovigilance, Website: www.hpra.ie.

Not applicable.