Description of Amlodipine
Table of Contents
Amlodipine Besilate is a calcium channel blocker used in the treatment of high blood pressure otherwise known as hypertension. It can be used alone or in combination with other antihypertensive drugs for a better result. The dosage forms of Amlodipine are tablet and oral suspension. It comes in different strength of 2.5 mg, 5 mg and 10 mg.
Uses and Indications of Amlodipine
- Chronic stable angina pectoris
- Vasospastic (Prinzmetal’s) angina
- Angiographically documented Coronary Artery Disease in patients without heart failure or EF <40%
Posology and Method of Administration
For both hypertension and angina, the usual initial dose is 5 mg once daily which may be increased to a maximum dose of 10 mg depending on the individual patient’s response. In hypertensive patients, it has been used in combination with a thiazide diuretic, alpha blocker, beta blocker, or an angiotensin converting enzyme inhibitor.
For angina, it may be used as monotherapy or in combination with other antianginal medicinal products in patients with angina that is refractory to nitrates and/or to adequate doses of beta blockers.
No dose adjustment of amlodipine is required upon concomitant administration of thiazide diuretics, beta blockers, and angiotensin-converting enzyme inhibitors.
Method of administration
Contraindications of Amlodipine
It 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
Special Warnings and Precautions for Amlodipine use
Its safety and efficacy in hypertensive crisis has not been established.
Patients with cardiac failure:
Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.
Use in patients with impaired hepatic function
The half life of amlodipine is prolonged and AUC values are higher in patients with impaired liver function. It should therefore be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose.
Use in elderly patients:
In the elderly increase of the dosage should take place with care
Use in renal failure:
It may be used in such patients at normal doses. Its changes in plasma concentrations are not correlated with degree of renal impairment. It is not dialysable.
Amlodipine and Drugs Interactions
Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to significant increase in amlodipine exposure.
The concomitant use of CYP3A4 inducers (i.e. rifampicin, hypericum perforatum) may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.
In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with hyperkalaemia after administration of verapamil and intravenous dantrolene. Due to risk of hyperkalacmin, 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.
Its Effects on other medicinal products:
The blood pressure lowering effects of this product 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, warfarin or cyclosporin.
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 amlodipineto 20 mg daily.
Amlodipine in Pregnancy and lactation
The safety of this product in human pregnancy has not been established. In animal studies, reproductive toxicity was observed at high doses. Use in pregnancy is only recommended when there is no safer alternative and when the disease itself carries greater risk for the mother and foetus.
It is not known whether amlodipine is excreted in breast milk. 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.
Side Effects of Amlodipine
The most commonly reported adverse reactions during treatment are:
- Abdominal pain
- Ankle swelling
Overdose of Amlodipine
Overdosage of Amlodipine could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension including shock with fatal outcome have been reported.
- Clinically significant hypotension due to amlodipine overdosage 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 its absorption.
- Since amlodipine is highly protein-bound, dialysis is not likely to be of benefit.
Pharmacological Properties of Amlodipine
Pharmacotherapeutic group: Calcium channel blockers, selective calcium channel blockers with mainly vascular effects. 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 it relieves angina has not been fully determined but it reduces total ischaemic burden by the following two actions:
- It dilates peripheral arterioles and thus, reduces the total peripheral resistance (after load) against which the heart works. Since the heart rate remains stable, this unloading of the heart reduces myocardial energy consumption and oxygen requirements.
It’s mechanism of action 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).
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 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. Its bioavailability is not affected by food intake.
It is extensively metabolised 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.
Special precaution for storage
Store below 30°C. Protect from light, heat & moisture. Keep out of the reach of children.