Flunarizine hydrochloride.
Each capsule contains: Flunarizine hydrochloride eq. to Flunarizine 5 mg.
Pharmacology: 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 atrioventicular (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 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 it is not recommended for treatment of acute attacks.
Usual adult dose: 10 mg once a day in the evening.
Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.
Caution required in patients with history of mental depression or with Parkinsonian syndrome or other extrapyramidal disorders.
Carcinogenicity/Mutagenicity: A 24-month study in 4 groups of 50 male and 50 female Wistar rats at doses 0, 5, 10 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.
Use in Children: 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.
Use in Elderly: Elderly patients are more likely to have age-related renal function impairment, which may require in patients receiving calcium channel blocking agents.
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.
Differences in frequencies are due to differences in pharmacological effects. Also cause parkinsonian extrapyramidal effects (less common), galactorrhea (rare), mental depression (less common), drowsiness (more common), dryness of mouth (less common), increased appetite and/or weight gain (more common).
Store at temperature not more than 30°C.
N07CA03 - flunarizine ; Belongs to the class of antivertigo preparations.
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