Sibelium

Sibelium

flunarizine

Manufacturer:

Janssen

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Flunarizine hydrochloride.
Description
Each tablet contains flunarizine hydrochloride equivalent to 5mg flunarizine base.
Excipients/Inactive Ingredients: Colloidal anhydrous silica, Lactose monohydrate, Magnesium stearate, Maize starch, Crosarmellose sodium, Purified Water, Hypromellose 2910 15mPa.s, Polysorbate 20, Microcrystalline Cellulose.
Action
Pharmacotherapeutic Group: antivertigo preparations. ATC Code: N07CA03.
Pharmacology: Pharmacodynamics: Pharmacodynamic Effects: 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: Absorption: The drug is well absorbed reaching peak plasma concentrations within 2 - 4 hours and reaching steady state at 5 - 6 weeks.
Flunarizine is well absorbed (>80%) from the gastrointestinal tract, reaching peak plasma concentrations within 2 to 4 hours after oral dosing. Under conditions of reduced gastric acidity (higher gastric pH), bioavailability may be moderately lower.
Plasma concentrations of flunarizine reach steady-state after approximately 8 weeks of once-daily multiple dosing and are about 3-fold higher than those observed after a single dose. Steady-state flunarizine concentrations are proportional over a dose range of 5 mg to 30 mg.
Distribution: Flunarizine is >99% bound to plasma proteins. It has a large volume of distribution of approximately 78 L/kg in healthy subjects and approximately 207 L/kg in epileptic patients indicating extensive distribution into extravascular tissue. The drug quickly crosses the blood brain barrier; concentrations in the brain are approximately 10 times higher than those in plasma.
Metabolism: Flunarizine is metabolized in the liver into at least 15 metabolites. The primary metabolic pathway is CYP2D6.
Elimination: Flunarizine is primarily eliminated as parent drug and metabolites through the feces via bile. Within 24 to 48 hours after administration, approximately 3% to 5% of the administered dose of flunarizine is eliminated in the feces as parent drug and metabolites and less <1% is excreted as unchanged drug in urine. Its terminal elimination half-life is highly variable, ranging from 5 to 15 hours in most individual subjects after a single dose. Some subjects show measurable plasma concentrations of flunarizine (>0.5 ng/mL) for a prolonged time period (up to 30 days), possibly due to redistribution of the drug from other tissues.
Toxicology: Non-clinical Information: Preclinical effects of a CNS nature (e.g., sedation, salivation, ataxia) were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
Indications/Uses
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.
Dosage/Direction for Use
Adults and elderly (18 years of age and older): Migraine prophylaxis: Starting dose: Treatment is started at 10 mg daily (at night) for adult patients aged 18 to 64 years and at 5 mg daily for elderly patients aged 65 years and older. If, during this treatment, depressive, extrapyramidal or other unacceptable adverse experiences occur, administration should be discontinued (see Precautions and Adverse Reactions). If, after 2 months of this initial treatment, no significant improvement is observed, the patient should be considered a non-responder and administration should be discontinued.
Maintenance treatment: If the patient responds satisfactorily and if a maintenance treatment is needed, the dosage schedule should be changed so that each week the patient receives 5 days of 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.
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 2 months.
If, however, no significant improvement is observed after 1 month for chronic vertigo or after 2 months for paroxysmal vertigo, the patient should be considered a non-responder and administration should be discontinued.
Overdosage
Symptoms and signs: 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. Activated charcoal may be given if considered appropriate.
Contraindications
SIBELIUM is contraindicated in patients with a history of depressive illness, or with pre-existing symptoms of Parkinson's disease or other extrapyramidal disorders (see Precautions and Adverse Reactions).
Hypersensitivity to flunarizine or to any of the excipients.
Special Precautions
Treatment with SIBELIUM 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 SIBELIUM 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 (see Dosage & Administration).
Effects on Ability to Drive and Use Machines: Since somnolence may occur, especially at the start of the treatment, caution should be exercised during activities such as driving or operating dangerous machinery.
Use In Pregnancy & Lactation
Pregnancy: The safety of SIBELIUM 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.
Breast-feeding: Breast-feeding should be discouraged in women taking SIBELIUM. 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.
Adverse Reactions
Throughout this section, adverse reactions are presented. Adverse reactions are adverse events that were considered to be reasonably associated with the use of flunarizine hydrochloride based on the comprehensive assessment of the available adverse event information. A causal relationship with flunarizine hydrochloride cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinical Trial Data: Placebo-Controlled Double-Blind Data - Adverse Reactions Reported at ≥1% Incidence: The safety of SIBELIUM (5 to 10 mg/day) was evaluated in 500 subjects (of which 247 were treated with SIBELIUM, 253 were given placebo) who participated in two placebo-controlled, double-blind parallel clinical trials, one in the treatment of migraine and the other in the treatment of vertigo.
Adverse reactions reported by ≥1% of SIBELIUM-treated subjects in these trials are shown in Table 1. (See Table 1.)

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Active Comparator-Controlled Data - Adverse Reactions Reported at ≥1% Incidence: Two double-blind active comparator-controlled trials were selected to determine the incidence of adverse reactions. In these two studies, 476 subjects were treated with 10 mg/day SIBELIUM, one in the treatment of migraine and the other in the treatment of vertigo or migraine.
Adverse reactions reported by ≥1% of SIBELIUM-treated subjects noted in the active-comparator controlled clinical trials and not listed in Table 1 are shown in Table 2. (See Table 2.)

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Placebo- and Active Comparator-Controlled Data - Adverse Reactions Reported at <1% Incidence: Additional adverse reactions that occurred in <1% of SIBELIUM-treated subjects in either of the previously mentioned two clinical datasets are listed in Table 3. (See Table 3.)

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Postmarketing Data: Adverse events first identified as adverse reactions during postmarketing experience with SIBELIUM are included in Table 4. The frequencies are provided according to the following convention: Very common ≥1/10, Common ≥1/100 to <1/10, Uncommon ≥1/1,000 to <1/100, Rare ≥1/10,000 to <1/1,000, Very rare <1/10,000, including isolated reports, Not known the frequency cannot be estimated from the available data.
In Table 4, adverse reactions are presented by frequency category based on spontaneous reporting rates, and are also presented by frequency category based on incidence in clinical trials, when known. (See Table 4.)

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Drug Interactions
Excessive sedation can occur when alcohol, hypnotics or tranquillisers are taken simultaneously with SIBELIUM.
SIBELIUM is not contraindicated in patients who use beta blocking agents.
The pharmacokinetics of flunarizine were unaffected by topiramate. During co-administration of SIBELIUM with topiramate 50 mg every 12 hours, a 16% increase in the systemic exposure to flunarizine in migraine patients was observed comparable to a 14% increase in patients treated with flunarizine only. 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.
Caution For Usage
Instructions for Use and Handling: Not applicable.
Incompatibilities: None known.
Storage
Do not store above 25°C.
ATC Classification
N07CA03 - flunarizine ; Belongs to the class of antivertigo preparations.
Presentation/Packing
Tab 5 mg (white, oblong with the inscription "J-C" on one side and "FL5" on the other side) x 200's.
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