Hepatobiliary disorders

Hepatic transaminases increased

Change to section 4.3 - Contraindications

Use in patients with current depressive illness or with a history of recurrent depression (see Sections 4.4 and 4.8).

Use in patients with pre-existing symptoms of Parkinson’s Disease or other extrapyramidal disorders (see Sections 4.4 and 4.8).

Change to section 4.4 - Special warnings and precautions for use

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.

Lactose

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

Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

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. 

Change to section 4.6 - Pregnancy and lactation

4.6.1          Use during 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.

4.6.2          Use during 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..

Change to section 4.7 - Effects on ability to drive and use machines

4.6.1          Use during 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.

4.6.2          Use during 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..

Change to section 4.8 - Undesirable effects

Addition of hypotension

Change to section 4.9 - Overdose

On the basis of the pharmacological properties of the drug, sedation and asthenia may be expected to occur. Cases of acute overdosage (up to 600 mg in one intake)

Change to section 10 - Date of revision of the text

March 2011