Each capsule contains: Flunarizine hydrochloride, BP eq. to Flunarizine 5 mg.
Pharmacology: Mechanism of Action: These agents are calcium-ion influx inhibitors (slow-channel blocking agents). Although their mechanism is not completely understood, they are thought to inhibit calcium ion entry through select voltage-sensitive areas termed "slow channels" across cell membranes. By reducing intracellular calcium concentration in cardiac and vascular smooth muscle cells, they dilate coronary arteries and peripheral arteries and arterioles, and may reduce heart rate, decrease myocardial contractility (negative inotropic effect), and slow atrioventricular (AV) nodal conduction.
By inhibiting the vasoconstriction that occurs in the prodromal phase, calcium channel blockade may relieve or prevent reactive vasodilation.
Pharmacokinetics: Absorption: Well absorbed.
Protein binding: Very high (99%).
Half-life: 19 days.
Time to peak concentration: 2 to 4 hours.
Time to peak effect: Multiple doses: Several weeks.
Elimination: Drug and its metabolites: very slow and prolonged.
Biliary/fecal: Less than 6% in the first 48 hours.
Renal: Less than 0.2% in the first 48 hours.
Flunarizine is indicated for reducing frequency and severity of vascular headaches, but is not recommended for treatment of acute attacks.
Oral: Usual adult dose: 10 mg once a day in the evening.
Or as prescribed by a physician.
Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.
Risk-benefit should be considered when the following medical problems exist: Mental depression, history of (Flunarizine may precipitate mental depression).
Parkinsonian syndrome or Extrapyramidal disorders, other (Flunarizine may produce parkinsonian extrapyramidal symptoms not responsive to antiparkinsonian medications).
Carcinogenicity/Mutagenicity: A 24-month study in 4 groups of 50 male and 50 female Wistar rats at doses of 0, 5, 20, or 40 mg/kg per day (the 40 mg/kg group received 80 mg/kg for the first 2 months) did not produce an effect on tumor rate or type; however, the validity of the study is questionable because of an extremely high mortality rate (more than 90% in the males and 80% in the females), Mutagenicity studies (Ames test, sister chromatid exchange test in human lymphocytes, sex-linked recessive lethal test in Drosophila melanogaster, micronucleus test in male rats, dominant lethal test in male and female mice) were negative.
Pediatrics: Although appropriate studies on the relationship of age to the effects of calcium channel blocking agents have not been performed in the pediatric population, pediatrics-specific problems that would limit the usefulness of calcium channel blocking agents in children are not expected.
Geriatrics: Elderly patients are more likely to have age-related renal function impairment, which may require caution in patients receiving calcium channel blocking agents.
Pregnancy/Reproduction: Fertility: In studies in male and female Wistar rats at doses of 0 and approximately 10, 40, and 160 mg/kg given for 60 days pre-mating in the males or 14 days pre-mating and 21 days of gestation in the females, treated animals were mated with non-treated animals. In treated females at the highest dose, there were no pregnancies and a large number of deaths; at the 40 mg/kg dose, there was decreased weight gain during pregnancy, decreased rate of pregnancy, increase in the number of resorbed fetuses, decreased litter size, and decreased weight of pups at birth. In non-treated females mated with treated males, a slight increase in resorption was seen only at the highest dose.
Pregnancy: Studies in humans have not been done.
There was a slight increase in resorptions and decrease in number of live fetuses in female Wistar rats given 40 mg/kg, with no effects seen at doses of 0, 10, or 20 mg/kg; there was no evidence of teratogenicity. There was a dose-related increase in the number of resorptions in New Zealand rabbits given doses of 0, 2.5, or 10 mg/kg from day 6 to day 18 of pregnancy, with a corresponding decrease in number of live births; there was no evidence of teratogenicity.
Breast-feeding: It is not known whether Flunarizine is distributed into breast milk in humans; however, it is distributed into the milk of dogs, at concentrations much higher than in plasma.
Those indicating need for medical attention: Incidence less frequent: Extrapyramidal effects, parkinsonian (loss of balance control, mask-like face, shuffling walk, stiffness of arms or legs, trembling and shaking of hands and fingers, trouble in speaking or swallowing); Mental depression.
Incidence rare: Allergic reaction (skin rash); Galactorrhea (unusual secretion of milk).
Note: Symptoms are not responsive to antiparkinsonian medications, but are reversible on withdrawal of Flunarizine.
Medical attention needed only if continuing or bothersome: Incidence more frequent: Drowsiness.
Incidence less frequent: Dizziness or lightheadedness; Dryness of mouth; Increased appetite and/or weight gain; Nausea; Unusual tiredness or weakness.
Note: Combination containing any of the following medications, depending on the amount present, may also interact with this medication.
Anesthetics, hydrocarbon inhalation (concurrent use with calcium channel blocking agents may produce additive hypotension; although calcium channel blocking agents may be useful to prevent supraventricular tachycardias, hypertension, or coronary Spasm during surgery, caution is recommended during use).
Non-Steroidal Anti-inflammatory drugs (NSAIDs), especially Indomethacin (Indomethacin, and possibly other NSAIDs, may antagonize the antihypertensive effect of calcium channel blocking agents by inhibiting renal prostaglandin synthesis and/or by causing sodium and fluid retention; the patient should be carefully monitored to confirm that the desired effect is being obtained.
Beta-adrenergic blocking agents, systemic or ophthalmic; Calcium supplements; Carbamazepine; Cyclosporine; Quinidine or Theophylline or Valproate; Cimetidine; Ranitidine and Famotidine do not appear to significantly affect calcium channel blocking agent metabolism; Digitalis; Disopyramide or Flecainide; Erythromycin; Estrogens; Grapefruit juice; Highly protein-bound medications, such as: anticoagulants, Coumarin- and Indandione-derivative anticonvulsants, Hydantoin, anti-inflammatory drugs, nonsteroidal; Quinine; Salicylates Sulfinpyrazone; Hypokalemia-producing medications, such as: parenteral Amphotericin B; Carbonic anhydrase inhibitors; Corticosteroids, glucocorticoid, especially those with significant mineralocorticoid activity; Corticosteroids, mineralocorticoid; Corticotropin (ACTH) Diuretics, potassium-depleting (such as Bumetanide, Ethacrynic acid, Furosemide, Indapamide. Mannitol. or thiazides) Sodium phosphates; Hypotension-producing medications; Lithium; Neuromuscular blocking agents; Phenobarbital; Prazosin, and possibly other alpha-adrenergic blocking agents, Procainamide or Quinidine or Other medications causing Q-T interval prolongation; Rifampin, and possibly other hepatic enzyme inducers; Sympathomimetics; Tacrolimus.
Store at temperatures not exceeding 30°C.
N07CA03 - flunarizine ; Belongs to the class of antivertigo preparations.