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-life 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 20 L/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: PHARMA DYNAMICS AMLODIPINE BESYLATE 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 concentration in the area under the concentration-time curve (AUC) and elimination half-life. Therefore, elderly patients should start PHARMA DYNAMICS AMLODIPINE BESYLATE therapy at a lower dose. Use in Renal Failure: Although PHARMA DYNAMICS AMLODIPINE BESYLATE is excreted primarily via the kidney, mild renal impairment does not appear to have an effect on the plasma concentrations. Severe renal impairment may however require a dosage reduction. Amlodipine is not dialysable. Use in Impaired Hepatic Function: The half-life of PHARMA DYNAMICS AMLODIPINE BESYLATE is significantly prolonged in patients with impaired hepatic function. PHARMA DYNAMICS AMLODIPINE BESYLATE 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. PHARMA DYNAMICS AMLODIPINE BESYLATE may have a negative inotropic effect. AUC of PHARMA DYNAMICS AMLODIPINE BESYLATE may increase in patients with heart failure. Porphyria: 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 effect has 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 PHARMA DYNAMICS AMLODIPINE BESYLATE 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 PHARMA DYNAMICS AMLODIPINE BESYLATE to thiazide diuretics, beta-blockers, or angiotensin-converting enzyme inhibitors.
SIDE EFFECTS AND SPECIAL PRECAUTIONS: Side effects:
Cardiac: Frequent: Palpitations. Less Frequent: Myocardial infarction; arrhythmia (including ventricular tachycardia and atrial fibrillation); chest pain. Vascular: Frequent: Peripheral oedema. Less Frequent: Hypotension (including orthostatic hypotension); syncope; vasculitis. Neurological: Frequent: Dizziness; headache; somnolence. Less Frequent: Hypertonia; hypoesthesia/paresthesia; peripheral neuropathy; tremor; insomnia; mood changes; dry mouth; increase sweating. Gastro-intestinal: Frequent: Nausea; abdominal pain. Less Frequent: Altered bowel habits; vomiting; dyspepsia; gingival hyperplasia. Musculoskeletal: Less Frequent: Arthralgia; asthenia; back pain; muscle cramps; myalgia; pain. Hepato-billiary: Less Frequent: Hepatitis; jaundice; raised liver enzymes (mostly consistent with cholestasis). Blood: Less Frequent: Purpura; thrombocytopenia; leucopoenia. Renal and urinary: Less Frequent: Increased urinary frequency. Reproductive system and breast: Less Frequent: Impotence; gynaecomastia. Endocrine: Less frequent: Hyperglycemia; pancreatitis. Skin: Less frequent: Alopecia. Respiratory: Less frequent: Coughing; dyspnoea. Eye: Less Frequent: Visual disturbances. Ear: Less Frequent: Tinnitus. Metabolism and nutritional: Less Frequent: Weight increase/decrease. Immune system: Less Frequent: Allergic reactions with pruritus, rash, angioedema and erythema multiforme. General: Frequent: Fatigue; flushing. Less Frequent: Taste perversion.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: There is no documented experience with PHARMA DYNAMICS AMLODIPINE BESYLATE overdosage. Gastric lavage may be of benefit. Gross overdosage could result in excessive peripheral vasodilatation, resulting in marked and probably prolonged systemic hypotension. Clinically significant hypotension due to PHARMA DYNAMICS AMLODIPINE BESYLATE 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.
PHARMA DYNAMICS AMLODIPINE BESYLATE 5 mg: White, round (diameter 8,0 mm), slightly biconvex, tablet scored on one side. PHARMA DYNAMICS AMLODIPINE BESYLATE 10 mg: White, round (diameter 10,5 mm), slightly biconvex, tablet scored on one side.
PRESENTATION: Blister packs consisting of cold formed OPA/AL/PVC film and heat sealing aluminium foil; the pack size is 30 tablets.
STORAGE INSTRUCTIONS: Store below 25ºC. Protect from light. Do not remove blisters from outer carton until required for use.
KEEP OUT OF REACH OF CHILDREN.