Amlodipine Tablets 5 mg and 10 mg
QUALITATIVE AND QUANTITATIVE COMPOSITION
Active Ingredient: amlodipine.
The tablets contains: Amlodipine Besilate (equivalent to amlodipine 5 mg and 10 mg).
Tablet for oral administration.
5 mg tablets
10 mg tablets
Prophylaxis of chronic stable angina pectoris.
Prinzmetal’s (variant) angina when diagnosed by a cardiologist.
In hypertensive patients, Amedin has been used in combination with thiazide diuretic, alpha blocker, β-adrenoceptor blocking agent, or an angiotensin converting enzyme inhibitor. For angina, Amedin may be used as monotherapy or in combination with other antiangina drugs in patients with angina that is refractory to nitrates and/or adequate doses of β-blockers.
Amedin is well tolerated in patients with heart failure and a history of hypertension or ischaemic heart disease.
POSOLOGY AND METHOD OF ADMINISTRATION
In adults: For both hypertension and angina the usual initial dose is 5 mg Amedin once daily which may be increased to a maximum dose of 10 mg depending on the individual patient’s response.
No dose adjustment of Amedin is required upon concomitant administration of thiazide diuretics, beta blockers, and angiotensin-converting enzyme inhibitors.
Use in children: Not recommended.
Use in the elderly: Amedin, used at similar doses in elderly or younger patients, is equally well tolerated. Therefore normal dosage regimens are recommended.
Patients with hepatic impairment: See below.
Patients with renal impairment: Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment, therefore the normal dosage is recommended. Amlodipine is not dialysable.
Amedin is contr-indicated in patients with a known sensitivity to dihydropyridines.
Amedin should not be used in cardiogenic shock, clinically significant aortic stenosis, unstable angina (excluding Prinzmetal’s angina).
As with all calcium antagonists, amlodpine’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 Amedin alone, during or within one month of a myocardial infarction. The safety and efficacy of Amedin in hypertensive crisis has not been established.
Interactions with other medicinal products and other forms of interaction: Amedin has been safely administered with thiazide diuretics, alpha blockers, β blockers, angiotensin converting enzyme inhibitors, long-acting nitrates, sublingual glyceryl trinitrate, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycaemic drugs.
Pharmacokinetic studies with cyclosporin have demonstrated that amlodipine does not significantly alter the pharmacokinetics of cyclosporin. Special studies have indicated that the co-administration of Amedin with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers, and that co-administration of cimetidine did not alter the pharmacokinetics of amlodipine. In healthy male volunteers, the co-administration of Amedin does not significantly alter the effect of warfarin on prothrombin response time.
In vitro data from studies with human plasma, indicate that amlodipine has no effect on protein binding of digoxin, phenytoin, warfarin or indomethacin.
Grapefruit juice may interact with Amedin to increase the plasma concentration. However this increase is too small to significantly alter blood pressure or heart rate.
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, Amedin should not be administered during pregnancy or lactation, or to women of childbearing potential unless effective contraception is used.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Clinical experience with Amedin indicate that therapy is unlikely to impair a patient’s ability to drive or use machinery.
The most commonly reported side-effects of Amedin are headache, oedema, rash, fatigue, nausea, flushing and dizziness. Gingival hyperplasia has been reported after Amedin. The following adverse reactions have been reported rarely: alopecia, pruritus, angiooedema, palpitations, dyspnoea, abdominal pain, back pain, dyspepsia, muscle cramps, asthenia, somnolence, altered bowel habit, myalgia, arthralgia, peripheral neuropathy, pancreatitis, mood changes, dry mouth, increased urinary frequency, hyperglycaemia, impotence, increased sweating, syncope, thrombocytopenia, vasculitis and visual disturbances. In many instances, causal association is uncertain. The following adverse reactions have been reported very rarely: abnormal liver function tests, hepatitis, jaundice, erythema multiforme and gynaecomastia.
As with other calcium channel blockers the following adverse events have been rarely reported and cannot be distinguished from the natural history of the underlying disease: myocardial infarction, arrhythmia (including ventricular tachycardia and atrial fibrillation) and chest pain.
In humans, experience with intentional overdose is limited. Gastric lavage may be worthwhile in some cases. Available data suggest that gross overdosage could result in excessive peripheral vasodilatation with subsequent marked and probably prolonged systemic hypotension. Clinically significant hypotension due to Amedin 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. Since Amedin is highly protein-bound, dialysis is not likely to be of benefit.
Amedin 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 Amedin is due to a direct relaxant effect on vascular smooth muscle. The precise mechanism by which Amedin relieves angina has not been fully determined but Amedin reduces total ischaemic burden by the following two actions. Amedin 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 Amedin 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). In patients with hypertension, once daily dosing provides clinically significant reductions of blood pressure in both the supine and standing positions throughout the 24 hour interval. Due to the slow onset of action, acute hypotension is not a feature of Amedin administration. In patients with angina, once daily administration of Amedin increases total exercise time, time to angina onset, and time to 1 mm ST segment depression, and decreases both angina attack frequency and glyceryl trinitrate tablet consumption. Amedin has not been associated with any adverse metabolic effects or changes in plasma lipids and is suitable for use in patients with asthma, diabetes, and gout. Haemodynamic studies and exercise based controlled clinical trials in NYHA Class II- IV heart failure patients have shown that Amedin did not lead to clinical deterioration as measured by exercise tolerance, left ventricular ejection fraction and clinical symptomatology. A placebo controlled study (PRAISE) designed to evaluate patients in NYHA Class III-IV heart failure receiving digoxin, diuretics and ACE inhibitors has shown that Amedin did not lead to an increase in risk of mortality or combined mortality and morbidity with heart failure.
Absorption, distribution, plasma protein binding.
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.
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
Use in the elderly: The time to reach peak plasma concentrations of amlodipine is similar in elderly and younger subjects. Amlodipine clearance tends to be decreased with resulting increases in AUC and elimination half-life in elderly patients. Increases in AUC and elimination half-life in patients with congestive heart failure were as expected for the patient age group studied.
The expiry date is indicated on the packaging.
Special precautions for storage
Store in a dry place below 25 °C and protect from light.
Nature and contents of container
Amedin is available in blister packs.
Instruction for use/handling
No special requirements.
Further information is available upon request.
Not all presentations are available in every country.
PLEASE KEEP OUT OF THE REACH AND SIGHT CHILDREN.
Package insert leaflet revised April 2009.
© MEDREICH plc 2007
Amedin is a trademark of
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