Brand name: Norvasc
Active ingredient (generic name): Amlodipine
Manufacturer: Pfizer
Importer: Behestan Darou
Pharmacotherapeutic group: Calcium channel blocker or calcium ion antagonist
Pharmaceutical form: 5mg tablets
Norvasc is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle.
The mechanism of the antihypertensive action of Norvasc is due to a direct relaxant effect on vascular smooth muscle. The precise mechanism by which Norvasc relieves angina has not been fully determined but Norvasc reduces total ischaemic burden by the following two actions.
1) Norvasc dilates peripheral arterioles and thus, reduces the total peripheral resistance (afterload) against which the heart works. Since the heart rate remains stable, this unloading of the heart reduces myocardial energy consumption and oxygen requirements.
2) The mechanism of action of Norvasc also probably involves dilatation of the main coronary arteries and coronary arterioles, both in normal and ischaemic regions. This dilatation increases myocardial oxygen delivery in patients with coronary artery spasm (Prinzmetal's or variant angina).
Pharmacokinetic:
After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels between 6-12 hours post dose.Absolute bioavailability has been estimated to be between 64 and 90%.
Amlodipine is extensively metabolized by the liver to inactive metabolites with 10% of the parent compound and 60% of metabolites excreted in the urine.The terminal plasma elimination half life is about 35-50 hours and is consistent with once daily dosing.
Therapeutic indication:
Hypertension.
Prophylaxis of chronic stable angina pectoris.
Prinzmetal's (variant) angina when diagnosed by a cardiologist.
In hypertensive patients, Norvasc has been used in combination with a thiazide diuretic, alpha blocker, beta-adrenoceptor blocking agent, or an angiotensin converting enzyme inhibitor. For angina, Norvasc may be used as monotherapy or in combination with other antianginal drugs in patients with angina that is refractory to nitrates and/or adequate doses of beta blockers.
Norvasc is well tolerated in patients with heart failure and a history of hypertension or ischaemic heart disease.
Dosage and administration:
For both hypertension and angina the usual initial dose is 5mg Norvasc once daily which may be increased to a maximum dose of 10mg depending on the individual patient's response.
Use in children: Children with hypertension from 6 years to 17 years of age. The recommended antihypertensive oral dose in paediatric patients ages 6-17 years is 2.5 mg once daily as a starting dose, up-titrated to 5 mg once daily if blood pressure goal is not achieved after 4 weeks. Doses in excess of 5 mg daily have not been studied in paediatric patients .The effect of amlodipine on blood pressure in patients less than 6 years of age is not known.
Adverse reaction:
Amlodipine is well tolerated . In Placebo controlled clinical trials involving patients with hypertention or angina, the most commonly observed side effects were headache and edema.
Contraindication:
Norvasc is contra-indicated in patients with a known sensitivity to dihydropyridines, amlodipine or any of the excipients.
Istin should not be used in cardiogenic shock, clinically significant aortic stenosis, unstable angina (excluding Prinzmetal's angina).
Pharmacokinetic interactions:
Norvasc has been safely administered with thiazide diuretics, alpha blockers, beta blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual glyceryl trinitrate, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycaemic drugs.
In vitro data from studies with human plasma, indicate that amlodipine has no effect on protein binding of digoxin, phenytoin, warfarin or indometacin.
Consumption of grapefruit/grapefruit juice should be avoided while taking Norvasc. The intake of grapefruit juice may result in increased plasma amlodipine concentrations, which may enhance the blood pressure lowering effects of amlodipine. This interaction has been observed with other dihydropyridine calcium antagonists and represents a class effect.
Special warnings:
Use in patients with Heart Failure: In a long-term, placebo controlled study (PRAISE-2) of Norvasc in patients with NYHA III and IV heart failure of nonischaemic aetiology, amlodipine was associated with increased reports of pulmonary oedema despite no significant difference in the incidence of worsening heart failure as compared to placebo. See section 5.1 “Pharmacodynamic Properties”.
Use in patients with impaired hepatic function: As with all calcium antagonists, amlodipine's half-life is prolonged in patients with impaired liver function and dosage recommendations have not been established. The drug should therefore be administered with caution in these patients.
There are no data to support the use of Norvasc alone, during or within one month of a myocardial infarction.
Pregnancy and lactation:
Although some dihydropyridine compounds have been found to be teratogenic in animals, data in the rat and rabbit for amlodipine provide no evidence for a teratogenic effect. There is, however, no clinical experience with the preparation in pregnancy or lactation. Accordingly, Norvasc should not be administered during pregnancy, or lactation, or to women of childbearing potential unless effective contraception is used.
Storage temperature:
Do not store above 25oC
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