Janssen Products

Flunarizine

Sibelium^TM

Formulation: Each capsule contains flunarizine hydrochloride equivalent to 5 mg flunarizine.

Description
Flunarizine (Sibelium^TM) is a selective calcium antagonist available in red and grey capsules.

The inactive ingredients are lactose, maize starch, talc, magnesium stearate and colloidal anhydrous silica.

The capsule itself contains erythrosine sodium, yellow ferric oxide, titanium dioxide, black ferrous oxide and red ferric oxide, gelatin.

Properties
Pharmacodynamics
Flunarizine is a selective calcium antagonist. It prevents cellular calcium overload by reducing excessive transmembrane calcium influx. Flunarizine has no effect on contractility or conduction of the heart.

Pharmacokinetics
The drug is well absorbed from the gut, reaching peak plasma levels within 2-4 hours and reaching steady state at 5-6 weeks. After extensive hepatic metabolism, the drug and its metabolites are excreted through the feces via the bile. The mean terminal elimination half-life is about 18 days.
Plasma protein binding is 90%.

Indications
Prophylaxis of classic (with aura) or common (without aura) migraine. Symptomatic treatment of vestibular vertigo, due to a diagnosed functional disorder of the vestibular system.

Contraindications
Flunarizine (Sibelium^TM) is contraindicated in patients with a history of depressive illness, or with pre-existing symptoms of Parkinson's disease or other extrapyramidal disorders (see Adverse reactions).

Warnings and precautions
This treatment may give rise to extrapyramidal and depressive symptoms and reveal Parkinsonism, especially in predisposed patients, such as the elderly. Therefore, it should be used with caution in such patients.

In rare cases fatigue may increase progressively during flunarizine (Sibelium^TM) therapy: in this event, the therapy should be discontinued.

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. If, during maintenance treatment, the therapeutic effects wane, treatment should also be discontinued (for duration of treatment see also Dosage and Administration).

Interactions
Excessive sedation can occur when alcohol, hypnotics or tranquillizers are taken simultaneously with flunarizine (Sibelium^TM).
Flunarizine (Sibelium^TM) is not contraindicated in patients who use betablocking agents.

Pregnancy and lactation
The safety of flunarizine (Sibelium^TM) for use in human pregnancy has not been established. An evaluation of animal studies does not indicate direct or indirect harmful effects with respect to reproduction, development of the embryo or fetus, the course of gestation or peri- and postnatal development.
Studies in lactating dogs have shown that flunarizine is excreted in the milk and that the concentration in the milk is greater than in the plasma. No data are available on the excretion in human breast milk. Nursing should therefore be discouraged in women taking flunarizine (Sibelium^TM).

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

Dosage and administration
(See also Warnings and Precautions).

1. Migraine prophylaxis

   • Starting dose:
     Treatment is started at 10 mg daily (at night) for patients younger than 65 years of age and at 5 mg daily for patients older than 65 years. If, during this treatment, depressive, extrapyramidal or other unacceptable adverse experiences occur, administration should be discontinued. If, after 2 months of this initial treatment, no significant improvement is observed, the patient should be considered a non-responder and administration should also be discontinued.

   • Maintenance treatment:
     If the patient responds satisfactorily and if a maintenance treatment is needed, the dose should be decreased so that each week he/she has 5 days treatment at the same daily dose and 2 successive drug-free days.

     Even if the prophylactic maintenance treatment is successful and well tolerated, it should be interrupted after 6 months and re-initiated only if the patient relapses.

2. Vertigo
   The same daily doses should be used as for migraine, but the starting treatment should not be given longer than needed for symptom control, which generally takes less than two months.

   If, however, no significant improvement is observed after one month for chronic vertigo or after two months for paroxysmal vertigo, the patient should be considered a non-responder and administration should be discontinued.

Adverse reactions
The most frequent adverse experiences are drowsiness and/or fatigue (20%), which are generally transient, and also weight gain (and/or increased appetite) (11%).

The following serious adverse experiences my occur during chronic treatment:

• depression, of which female patients with a history of depressive illness may particularly be at risk.

• extrapyramidal symptoms (such as bradykinesia, rigidity, akathisia, orofacial dyskinesia, tremor), of which elderly patients seem particularly at risk.

Infrequently reported adverse experiences are:

• gastrointestinal: heartburn, nausea, gastralgia

• central nervous system: insomnia, anxiety

• others: galactorrhea, dry mouth, muscle ache, skin rash.

Overdosage
Symptoms
On the basis of the pharmacological properties of the drug, sedation and asthenia may be expected to occur. A few cases of acute overdosage (up to 600 mg in one intake) have been reported and the observed symptoms were sedation, agitation and tachycardia.

Treatment
There is no specific antidote. Within the first hour after ingestion, gastric lavage may be performed.

Activated charcoal may be given if considered appropriate.

How supplied
Capsules containing 5 mg flunarizine in boxes of 100's and 200's. Storage conditions
Store between 15ºC and 30ºC.
Keep out of reach of children.

CAUTION:
Food, Drugs, Devices and Cosmetics Act prohibits dispensing without prescription.

Manufactured by:
Interphil Laboratories, Inc.
Canlubang Industrial Estate
Bo. Pittland, Cabuyao, Laguna
for: Johnson & Johnson (Philippines), Inc.
Edison Road, Bo. Ibayo
Parañaque, Metro Manila
Under license from:
JANSSEN PHARMACEUTICA
Beerse, Belgium
Exclusively distributed by:
ZUELLIG PHARMA CORPORATION
Sen. Gil Puyat Avenue
Makati City