Provasc

White bi-convex round tablet with 'ACME' on one face and a breakline on the other face.
Each tablet contains: Amlodipine (as besilate) BP 5 mg or 10 mg.

Pharmacology: Pharmacodynamics: Amlodipine 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 amlodipine is due to a direct relaxant effect on vascular smooth muscle. The precise mechanism by which amlodipine relieves angina has not been fully determined but amlodipine reduces total ischaemic burden by the following two actions: Amlodipine 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.
The mechanism of action of amlodipine 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).
Pharmacokinetics: Absorption: 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 80%. The bioavailability of amlodipine is not affected by food intake.
Distribution: The volume of distribution is approximately 21 L/kg. In vitro studies have shown that approximately 97.5% of circulating amlodipine is bound to plasma proteins.
Biotransformation/elimination: The terminal plasma elimination half-life is about 35-50 hours and is consistent with once daily dosing. Amlodipine is extensively metabolised by the liver to inactive metabolites with 10% of the parent compound and 60% of metabolites excreted in the urine.

Amlodipine is used to treat hypertension (high blood pressure) and for prophylaxis of angina. As calcium channel blockers, it blocks calcium thus causing the blood vessels to relax and widen so blood can flow more easily. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems.

The usual initial antihypertensive oral dose of Amlodipine is 5 mg once daily with a maximum dose of 10 mg once daily. Small, fragile, or elderly individuals, or patients with hepatic insufficiency may be started on 2.5 mg once daily and this dose may be used when adding to other antihypertensive therapy. Dosage should be adjusted according to each patient's need.

Amlodipine overdose could result to excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported.
Management: Clinically significant hypotension due to amlodipine overdose calls for active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. Gastric lavage may be worthwhile in some cases. In healthy volunteers the use of charcoal up to 2 hours after administration of amlodipine 10 mg has been shown to reduce the absorption rate of amlodipine. Since amlodipine is highly protein-bound, dialysis is not likely to be of benefit.

Amlodipine is contraindicated in patients with hypersensitivity to dihydropyridine derivatives, severe hypotension, shock (including cardiogenic shock), obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis), haemodynamically unstable heart failure after acute myocardial infarction.

Before taking amlodipine, tell the doctor or pharmacist if the patient is allergic to it; or if the patient has any other allergies. May be used cautiously in patients who have a medical history especially of heart disease and liver disease. Limit intake of alcohol while taking this drug.

The safety of amlodipine in human pregnancy has not been established. Use in pregnancy is only recommended when there is no safer alternative and when the disease itself carries greater risk for the mother and fetus. Amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has been estimated with an interquartile range of 3-7%, with a maximum of 15%. The effect of amlodipine on infants is unknown. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with amlodipine should be made taking into account the benefit of breast-feeding to the child and the benefit of amlodipine therapy to the mother.

The most common side effects of Amlodipine are fatigue or tiredness; headache; insomnia; vivid or abnormal dreams; flushing; abdominal pain; nausea, diarrhea or constipation; increased or difficult in urination.
Tell the doctor immediately if any of these highly unlikely but very serious side effects occur: worsening chest pain (attacks are more frequent, more severe, or last longer), jaundice or yellowing of the eyes or skin, dark urine, severe dizziness or fainting, swelling of the legs or ankles, psychosis.

The blood pressure lowering effects of amlodipine adds to the blood pressure-lowering effects of other medicinal products with antihypertensive properties. In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin or warfarin. Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily. There is a risk of increased tacrolimus blood levels when co administered with amlodipine. In order to avoid toxicity of tacrolimus, administration of amlodipine in a patient treated with tacrolimus requires monitoring of tacrolimus blood levels and dose adjustment of tacrolimus when appropriate. No drug interaction studies have been conducted with ciclosporin and amlodipine in healthy volunteers or other populations with the exception of renal transplant patients, where variable trough concentration increases (average 0%-40%) of ciclosporin were observed. Consideration should be given for monitoring ciclosporin levels in renal transplant patients on amlodipine, and ciclosporin dose reductions should be made as necessary.
Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients resulting in increased blood pressure lowering effects. Due to risk of hyperkalaemia, it is recommended that the co-administration of calcium channel blockers such as amlodipine be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.

Special Precautions for Handling and Disposal: Any unused medicine should be disposed properly. Consult a pharmacist or local waste management center for more details about how to safely discard expired or unused medicines.

Store at a temperature not exceeding 30°C. Protect from light.

Calcium Antagonists / Anti-Anginal Drugs

C08CA01 - amlodipine ; Belongs to the class of dihydropyridine derivative selective calcium-channel blockers with mainly vascular effects. Used in the treatment of cardiovascular diseases.

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