Anapril Tablet

Enalapril, after hydrolysis to enalaprilate, inhibits Angiotensin Converting Enzyme (ACE). ACE is a peptidyl dipeptidase that catalyses the conversion of angiotensin I to the vasoconstrictor substance angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. The beneficial effects of enalapril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin aldosterone system.

The maximum daily dose is 40 mg. The absorption of Enalapril is not affected by food. Essential and renovascular hypertension: Treatment should be initiated with 5 mg once a day. Where concomitant therapy is a diuretic, the recommended initial dose of Enalapril 2.5 mg. The dose should be titrated to give optimum control of blood pressure.The usual maintenance dose is 10-20 mg given once daily. In severe hypertension, the dosage may be increased incrementally to a maximum of 40 mg once daily. The dosage of other antihypertensive agents being used together with Enalapril may need to be adjusted. Where Enalapril replaces a beta-blocking drug in the therapeutic regimen, the beta-blocking agent should not be discontinued abruptly; the dosage should be titrated down after commencing therapy with Enalapril.

With concomitant diuretic therapy: The recommended initial dose of Enalapril is 2.5 mg. Symptomatic hypotension can occur following the initial dose of Enalapril; this is more likely when Enalapril is added to previous diuretic therapy. Caution is recommended, therefore, since these patients may be volume or salt depleted. If possible,the diuretic therapy should be discontinued for 2-3 days prior to initiation of therapy with Enalapril. Enalapril minimises the development of thiazide-induced hypokalaemia and hyperuricaemia.

Use in the elderly (over 65 years): The starting dose should be 2.5 mg. Enalapril is effective in the treatment of hypertension in the elderly. Some elderly patients may be more responsive to Enalapril than younger patients. The dose should be titrated according to need for the control of blood pressure.

Heart failure: Enalapril can be used as an adjunctive therapy with non-potassium-sparing diuretics and /or digitalis. Enalapril should be introduced for the treatment of heart failure following stabilisation of the patient on diuretic therapy. Therapy with Enalapril should be initiated under close medical supervision (in hospital for severe heart failure) with a recommended starting dose of 2.5 mg once daily.The dose of Enalapril should be gradually increased depending upon tolerability to the recommended maintenance dose (10-20 mg) given as a single or twice daily dose. This dosage schedule has been shown to improve survival. In order to decrease the possibility of symptomatic hypotension, patients on previous high dose diuretics should have the diuretic dose reduced before introducing Enalapril, The appearance of hypotension after the initial dose of Enalapril dose not preclude subsequent careful dose titration with the drug, following effective treatment of the hypotension.

Use in impaired renal function: Enalapril is excreted by kidney. It should be used with caution in patients with renal impairment. The recommended starting dose is 2.5 mg. The dose should be titrated against the response, and should be kept as low as possible to maintain adequate control of blood pressure or heart failure. Enalapril is dialysable. Dialysis patients may be given the usual dose of Enalaprilon dialysis. On the days when patients are not on dialysis the dosage should be tailored to the blood pressure response.

Children: The paediatric use of Enalapril has not been studied.

Combination with other antihypertensive agents such as beta-blockers, methyldopa, calcium antagonists, and diuretics may increase the antihypertensive efficacy. Adrenergic - blocking drugs should only be combined with Anapril under careful supervision, Concomitant propranolol may reduce the bioavailability of Anapril, but this does not appear to be of any clinical significance. Plasma potassium usually remains within normal limits, although cases of hyperkalaemia have been reported. If Anapril is given with potassium losing diuretic, the likelihood of diuretic-induced hypokalaemia may be lessened. Anapril may elevate plasma potassium levels in patients with renal failure. Potassium supplements, potassium-containing saft substitutes are not recommended, particularly in patients with impaired renal function, since they may lead to significant increases in plasma potassium.

Hypersensitivity to the product or any of its components, and in patients with a history of angioneurotic oedema relating to previous treatment with an ACE inhibitor.

Severe hypotension and renal failure have occurred in association with therapy with Anapril. These appear to occur in certain specific sub-groups. Other adverse reactions include dizziness, headache, fatigue, asthenia, orthostatic hypotension, syncope, nausea, diarrhoea, muscle cramps, rash, cough. Less frequently renal dysfunction, renal failure, and oliguria have been reported.

Less common side effects include: Myocardial infarction, chest pain, palpitations, rhythm disturbances, angina pectoris, pancreatitis, hepatitis-either hepatocellular or cholestatic, jaundice, abdominal pain, vomiting, dyspepsia, constipation, anorexia, stomatitis, depression, confusion, somnolence, insomnia, nervousness, paraesthesiae, vertigo, bronchospasm, asthma, dyspnoea, rhinorrhoea, sore throat and hoarseness, diaphoresis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pruritus, urticaria, alopecia, impotence, flushing, taste alteration, tinnitus, glossitis, blurred vision, etc. Angioneurotic oedema of the face, extremities, lips, tongue, glottis, and /or larynx has been reported rarely.

Enalapril has been shown to be fetotoxic in rabbits during middle and late pregnancy. Because of these findings Enalapril is contra-indicated in pregnancy. Enalapril and enalaprilat are excreted in human milk; caution should be exercised if Enalapril is given to lactating mothers.

Pretreatment assessment of renal function: Assessment of renal function prior to initiation of therapy, and during treatment where appropriate. Symptomatic hypotension was seen rarely in uncomplicated hypertensive patients. It has been reported mainly in patients with severe heart failure and who have been volume-depleted by diuretic therapy. By initiating therapy with a small dose (2.5 mg Anapril) the duration of any hypotensive effect may be lessened.

Similar considerations in terms of initiating therapy with a small dose may apply also to patients with ischaemic heart or cerebrovascular disease in whom severe hypotension could result in a myocardial infarct or cerebrovascular accident. Severe hypotension has been reported, mainly in patients with severe heart failure with or without associated renal insufficiency. This is most likely in those patients on high doses of loop diuretics, or with hyponatraemia or functional renal impairment. The appearance of hypotension after the initial dose of Anapril does not preclude subsequent careful dose titration with the drug after effective management of the hypotention.

Impaired renal function: Anapril should be used with caution in patients with renal insufficiency as they may require reduced or less frequent doses. As with all antihypertensive agents, renal function should be assessed in patients with hypertension or congestive heart failure before initiating therapy. Angioneurotic oedema has been reported with angiotensin-converting enzyme inhibitors, including Anapril. In such cases, Anapril should be discontinued immediately and appropriate monitoring should be instituted to ensure complete resolution of symptoms prior to dismissing the patient.

Haemodialysis patients: A high incidence of anaphylactoid reactions have been reported in patients dialyzed with high flux membranes (e.g., AN 69) and treated concomitantly with an ACE inhibitor. Anapril should therefore be avoided.

Cough: Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy.

Surgery/Anaesthesia: In patients undergoing major surgery or during anaesthesia with agents that produce hypotension. Anapril blocks angiotensin II formation secondary to compensatory renin release. This may lead to hypotension which can be corrected by volume expansion. Anapril should not be used in patients with aortic stenosis or outflow obstruction.

Limited data are available for overdosage in humans. The most prominent features of overdosage reported to date are marked hypotension, beginning some six hours after ingestion of tablets, concomitant with blockage of the renin - angiotensin system, and stupor. The recommended treatment of overdosage is intravenous infusion of normal saline solution. If ingestion is recent, induce emesis. Anapril can be removed from the general circulation by haemodialysis

Angiotensin-converting enzyme (ACE) inhibitors

Do not store above 25°C. Keep away from light and wet place. Keep out of reach of children.