APO-ENALAPRIL

What it is

APO-ENALAPRIL contains enalapril maleate as the active ingredient, available in tablet strengths of 5 mg, 10 mg and 20 mg. Enalapril maleate is a pro-drug which when administered orally is hydrolysed to release the active converting enzyme inhibitor enalaprilat, with the liver appearing to be the main site for this conversion.

Approved indications

APO-ENALAPRIL is indicated in the treatment of hypertension (all grades of essential hypertension and renovascular hypertension). — Congestive heart failure (all degrees of symptomatic heart failure). — Left ventricular dysfunction (all degrees of left ventricular dysfunction where the left ventricular ejection fraction is less than 35%, irrespective of the presence or severity of obvious symptoms of heart failure).

Dosing overview

The recommended initial dose in patients not on diuretics is 5 mg once a day. The usual dosage range is 10 to 40 mg per day administered in a single dose or two divided doses. For elderly patients over 65 years, the starting dose should be 2.5 mg. In renovascular hypertension, therapy should be initiated with a lower starting dose (e.g., 5 mg or less), with dosage then adjusted according to patient needs, and most patients may be expected to respond to 20 mg taken once daily. In congestive heart failure, the initial dose should be lower (2.5 mg or less), administered under close medical supervision, with the dose gradually increased to the usual maintenance dose of 10–20 mg given in a single or divided dose.

Key safety warnings

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with APO-ENALAPRIL, which may occur at any time during treatment, and in such cases APO-ENALAPRIL should be promptly discontinued and the patient carefully observed until the swelling disappears. Very rarely, fatalities have been reported due to angioedema associated with laryngeal oedema or tongue oedema, and patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Excessive hypotension is a possible consequence of APO-ENALAPRIL use in severely salt/volume depleted persons, and in patients with heart failure with or without associated renal insufficiency, excessive hypotension has been observed and may be associated with oliguria and/or progressive azotaemia, and rarely with acute renal failure and/or death. Elevated serum potassium (greater than 5.7 mmol/L) was observed in approximately one percent of hypertensive patients in clinical trials, and in most cases these were isolated values which resolved despite continued therapy, with hyperkalaemia being a cause of discontinuation of therapy in 0.28 percent of hypertensive patients. Hyperkalaemia can cause serious, sometimes fatal, arrhythmias. A persistent non-productive, ticklish cough has been reported in some patients undergoing treatment with APO-ENALAPRIL and other ACE inhibiting drugs, the cough is often worse when lying down, and the cough is more common in women (who account for about two thirds of reported cases).

Contraindications

APO-ENALAPRIL is contraindicated in patients with a history of previous hypersensitivity to enalapril or to any component of the formulation, and in patients with a history of angioneurotic oedema relating to previous treatment with an angiotensin-converting enzyme inhibitor, and in patients with hereditary or idiopathic angioedema. APO-ENALAPRIL is contraindicated in pregnancy. APO-ENALAPRIL should not be administered with aliskiren in patients with diabetes. APO-ENALAPRIL is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril).

PBS listing

APO-ENALAPRIL tablets containing enalapril maleate 5 mg, 10 mg and 20 mg are listed on the PBS with both unrestricted and restricted items. The ex-manufacturer price for the 5 mg strength is A$2.50, for the 10 mg strength is A$3.37, and for the 20 mg strength is A$3.65.

Regulatory history

APO-ENALAPRIL was first listed on the ARTG on 28 May 2013, with registrations for 5 mg (ARTG 196472), 10 mg (ARTG 196466) and 20 mg (ARTG 196504) tablet strengths.