APO-PERINDOPRIL

What it is

APO-PERINDOPRIL contains perindopril erbumine as the active ingredient. APO-Perindopril Tablets are available in strengths of 2 mg, 4 mg or 8 mg perindopril erbumine. APO-Perindopril Tablets are intended for oral administration.

Approved indications

— Treatment of hypertension. — Treatment of heart failure, with recommendations that perindopril be given with a diuretic and/or digoxin under close medical supervision. — In patients with established coronary artery disease who are stable on concomitant therapy and have no heart failure, to reduce the risk of nonfatal myocardial infarction or cardiac arrest.

Dosing overview

For hypertension, the usual starting dose of perindopril is 4 mg once daily, taken in the morning, with optimum control of blood pressure achieved by increasing the dose to a maximum of 8 mg once daily. Elderly patients with hypertension should start treatment with 2 mg daily, with titration to 4 mg if necessary. For congestive heart failure, the usual starting dose of perindopril is 2 mg once daily, which should be given with a diuretic and/or digitalis, and is increased to 4 mg daily for maintenance. In patients with stable coronary artery disease, Perindopril should be introduced at a dose of one 4 mg tablet once daily for two weeks, and then increased to one 8 mg tablet once daily, depending on tolerance and renal function. In patients with renal failure, treatment should begin with 2 mg daily, with dosage adjusted according to creatinine clearance: one 2 mg tablet daily for creatinine clearance between 30 and 60 mL/min, one 2 mg tablet every 2 days for creatinine clearance between 15 and 30 mL/min, and one 2 mg tablet on day of dialysis for creatinine clearance below 15 mL/min.

Key safety warnings

ACE inhibitors reduce angiotensin II formation, which can result in increased serum potassium, though this effect is usually not significant in patients with normal renal function. Serum electrolytes should be measured regularly when ACE inhibitors are given, especially when diuretics are also prescribed, as hyperkalaemia can cause serious, sometimes fatal, arrhythmias. Life threatening angioedema has been reported with most ACE inhibitors, with an overall incidence of approximately 0.1 to 0.2 per cent. Angioedema of the face, extremities, lips, tongue, mucous membranes, glottis and/or larynx has been reported uncommonly with perindopril. If angioedema occurs, perindopril should be promptly discontinued and the patient carefully observed until the swelling disappears. Hypotension has been reported in patients commencing treatment with ACE inhibitors. Symptomatic hypotension is rarely seen in uncomplicated hypertension but is a potential consequence of perindopril use in patients with salt or volume depletion, those vigorously treated with diuretics, patients on dialysis, those with impaired renal function, following severe diarrhoea or vomiting, or those with severe renin-dependent hypertension. A persistent dry irritating cough has been reported with most ACE inhibitors, with incidence varying between 2 per cent and 15 per cent depending upon the medicine, dosage and duration of use.

Contraindications

Perindopril is contraindicated in patients with history of previous hypersensitivity to perindopril, ACE inhibitors or to any component of the formulation. Perindopril is contraindicated during pregnancy and for lactating women. Bilateral or unilateral renal artery stenosis is a contraindication. Perindopril is contraindicated in patients with a history of hereditary and/or idiopathic angioedema, or angioedema associated with previous treatment with an ACE inhibitor. Combined use with aliskiren-containing products is contraindicated in patients with diabetes or renal impairment (GFR less than 60 mL/min/1.73 m²). Combined use with sacubitril/valsartan fixed dose combinations is contraindicated, with perindopril not to be initiated earlier than 36 hours after the last dose of sacubitril/valsartan.

Regulatory history

APO-PERINDOPRIL perindopril erbumine tablets in strengths of 2 mg, 4 mg and 8 mg were first listed on the ARTG on 19 September 2008.