COMPOSITION: ALMADIN (amlodipine besylate) is a dihydropyridine derivative, and has the following chemical name: 3-ethyl 5-methyl 2-(2-aminoethoxy-methyl)-4-(2-chlorophenyl)-1, 4-dihydro-6-methyl-3,5-pyridine-dicarboxylate benzenesulphonate.
Each ALMADIN 5 mg tablet contains amlodipine besylate equivalent to 5 mg active amlodipinebase.
Each ALMADIN 10 mg tablet contains amlodipine besylate equivalent to 10 mg active amlodipine base.
PHARMACOLOGICAL CLASSIFICATION: A 7.1 VasodiIators, hypotensive medicines.
PHARMACOLOGICAL ACTION: Amlodipine is a dihydropyridine calcium channel blocker. It inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle without affecting serum calcium concentrations. Direct relaxation of vascular smooth muscle forms the basis of the antihypertensive action. In angina pectoris, amlodipine acts as a peripheral arteriolar vasodilator resulting in a reduction in total peripheral resistance (afterload). Myocardial energy and oxygen requirements are reduced. Amlodipine exerts its activity by binding to the dihydropyridine binding sites. It exerts minimal action on cardiac conduction, contraction and heart rate. Pharmacokinetics:
Complete absorption of amlodipine is slow following oral administration, with peak plasma levels being attained after 6 to 12 hours. Amlodipine has a bioavailability of about 64% and a plasma elimination half-Iife of 35 to 50 hours, allowing for once-daily oral dosing. Steady state plasma concentrations are achieved after 7 to 8 days of consecutive dosing. The volume of distribution is about 20L/kg. Metabolism is via the liver and is extensive, with less than 10% of amlodipine appearing unchanged in the urine. Metabolites are inactive and primarily (up to 60%) excreted via the kidney.
INDICATIONS: ALMADIN is indicated for the:
Treatment of angina pectoris.
Treatment of mild to moderate hypertension, alone or in combination with other antihypertensives.
CONTRA-INDICATIONS: Hypersensitivity to any of the ingredients.
Hypersensitivity to dihydropyridines.
WARNINGS: Use in the Elderly:
Amlodipine clearance is decreased (40 - 60%) in the elderly, which results in increases of amlodipine area under the concentration-time curve (AUC) and elimination half-life. Therefore, elderly patients should start ALMADIN therapy at a lower dose.
Use in Renal Failure:
Although ALMADIN is excreted primarily via the kidney, mild renal impairment does not appear to have an effect on plasma concentrations. Severe renal impairment may however require a dosage reduction. Amlodipine is not dialysable.
Use in Impaired Hepatic Function:
The half-life of ALMADIN is significantly prolonged in patients with impaired hepatic function. ALMADIN should therefore be administered at lower doses in these patients.
Use in Children:
Safety and efficacy has not been established.
Use in Heart Failure:
An increased incidence of pulmonary oedema has been reported.
ALMADIN may have a negative inotropic effect. AUC of ALMADIN may increase in patients with heart failure.
Safety has not been established.
INTERACTIONS: Concurrent administration of sublingual nitroglycerin, long-acting nitrates, beta-blockers or other antianginal agents with amlodipine may produce additive antihypertensive and antianginal effects. Sublingual nitroglycerin may be used as needed to abort acute angina attacks during amlodipine therapy. Nitrate medication may be used during amlodipine therapy for angina prophylaxis. Amlodipine will not protect against the consequences of abrupt beta-blocker withdrawal; gradual beta-blocker dose reduction is recommended.
Although no rebound effecthas been reported upon discontinuation of amlodipine, a gradual decrease of dosage, with medical practitioner supervision, is recommended.
PREGNANCY AND LACTATION: Safety in pregnancy and lactation has not been established (see CONTRA-INDICATIONS).
DOSAGE AND DIRECTIONS FOR USE:
Hypertension and Angina Pectoris: Adults: An initial dose of 5 mg ALMADIN once daily is recommended which may be increased to 10 mg once a day after 10 - 14 days of therapy if there is no improvement.
No dose reduction is required when adding ALMADIN to thiazide diuretics, beta-blockers, or angiotensin-converting enzyme inhibitors.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS: Side-effects: Blood and lymphatic system disorders: Less Frequent: Purpura, thrombocytopenia, leucopenia. Metabolism and nutrition disorders: Less frequent: Hyperglycaemia. Nervous system/Psychiatric disorders: Frequent: Dizziness, headache, somnolence. Less Frequent: Hypertonia, hypoaesthesia/paraesthesia, peripheral neuropathy, tremor, insomnia, mood changes. Autonomic nervous system disorders: Frequent: Flushing. Less Frequent: Dry mouth, increased sweating. Eye disorders: Less Frequent: Visual disturbances. Ear and other special senses disorders: Less Frequent: Taste perversion, tinnitus. Cardiovascular disorders: Frequent: Peripheral oedema, palpitations. Less Frequent: Hypotension (including orthostatic hypotension), syncope, vasculitis, myocardial infarction, arrhythmia (including ventricular tachycardia and atrial fibrillation), chest pain. Respiratory disorders: Less frequent: Coughing, dyspnoea. Gastrointestinal disorders: Frequent: Nausea, abdominal pain. Less Frequent: Altered bowel habits, vomiting, dyspepsia, gingival hyperplasia, pancreatitis. Hepatobilliary disorders: Less Frequent: Hepatitis, jaundice, raised liver enzymes (mostly consistent with cholestasis). Skin and subcutaneous tissue disorders: Less Frequent: Alopecia. Musculoskeletal disorders: Less Frequent: Arthralgia, asthenia, back pain, muscle cramps, myalgia. Renal and urinary disorders: Less Frequent: Increased urinary frequency. Reproductive system and breast disorders: Less frequent: Impotence, gynaecomastia. General disorders: Frequent: Fatigue. Less Frequent: Pain, weight increase/decrease. Hypersensitivity reactions: Less Frequent: Allergic reactions with pruritus, rash, angioedema, and erythema
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: There is no documented experience with ALMADIN overdosage. Gastric lavage may be of benefit. Gross overdosage could result in excessive peripheral vasodilation, resulting in marked and probably prolonged systemic hypotension. Clinically significant hypotension due to ALMADIN overdosage requires active cardiovascular support.
Intravenous calcium gluconate may be of benefit in reversing the effects of calcium channel blockade. Since amlodipine is highly protein-bound, dialysis is not likely to be of benefit.
TREATMENT IS SYMPTOMATIC AND SUPPORTIVE.
IDENTIFICATION: ALMADIN 5 mg Tablets: White, circular, flat, bevelled, uncoated tablet with 5embossed on one face and central breakline on the other.
ALMADIN 10 mg Tablets: White, circular, flat, bevelled, uncoated tablet with 10embossed on one face and central breakline on the other.
PRESENTATION: ALMADIN 5 mg and ALMADIN 10 mg are both available in aluminium blister strips of 10 tablets packed in blister packs, each containing 30 tablets.
STORAGE INSTRUCTIONS: Store below 25°C. Protect from light.
KEEP OUT OF REACH OF CHILDREN.