PRILACE

What it is

Prilace contains ramipril. Prilace tablets are available in four strengths containing 1.25 mg, 2.5 mg, 5 mg and 10 mg of ramipril, and Prilace capsules contain 10 mg of ramipril. Ramipril is a prodrug which, after absorption from the gastrointestinal tract, is hydrolysed in the liver to form the active moiety, ramiprilat. Ramipril and ramiprilat inhibit angiotensin-converting enzyme (ACE) which is identical to kininase II.

Approved indications

— Treatment of hypertension. — Post-myocardial infarction heart failure. — Prevention of progressive renal failure in patients with persistent proteinuria in excess of 1 g/day. — Reducing the risk of myocardial infarction, stroke, cardiovascular death or the need for revascularisation procedures in patients 55 years of age or more who have clinical evidence of coronary artery disease, stroke or peripheral vascular disease. — Reducing the risk of myocardial infarction, stroke, cardiovascular death or revascularisation procedures in diabetic patients 55 years or more with one or more of the following risk factors: systolic blood pressure >160 mmHg or diastolic blood pressure > 90 mmHg (or on antihypertensive treatment); total cholesterol >5.2 mmol/L or HDL cholesterol <0.9 mmol/L; current smoker; known microalbuminuria; any evidence of previous vascular disease.

Dosing overview

For hypertension, the recommended initial dosage for patients not receiving a diuretic is Prilace 2.5 mg once a day, which may then be increased at intervals of two to three weeks, first to 5 mg and then to a maximum of 10 mg once daily. For post-myocardial infarction heart failure, the recommended initial dose is Prilace 5 mg daily, divided into two doses of 2.5 mg each; if the patient does not tolerate this, 1.25 mg may be given twice daily for two days; the dose may then be doubled at intervals of one to three days, with a maximum permitted daily dose of ramipril 10 mg to be given in divided doses. For progressive renal failure in patients with persistent proteinuria in excess of 1 g/day, the recommended initial dose is Prilace 1.25 mg once daily, which should be doubled at intervals of two to three weeks, depending on how the drug is tolerated. For patients at increased cardiovascular risk, the recommended initial dose is Prilace 2.5 mg once daily; depending on tolerability, the dose should be doubled after one week of treatment and, after three weeks, should be increased to 10 mg, which is the usual maintenance dose.

Key safety warnings

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with ACE inhibitors; if angioedema occurs, the product should be promptly discontinued and the patient carefully observed until the swelling disappears. Laryngeal oedema can be fatal, and where there is angioedema involving swelling of the tongue, glottis or larynx likely to cause airway obstruction, subcutaneous adrenaline solution 1:1,000 (0.3 to 0.5 mL) should be promptly administered. Hypotension may occur in patients commencing treatment with ACE inhibitors; excessive hypotension is rarely seen in uncomplicated hypertensive patients but is a possible consequence of use in severely salt/volume depleted persons, such as patients with renovascular hypertension, those treated vigorously with diuretics, after severe diarrhoea or patients undergoing dialysis. Because ACE inhibitors decrease the formation of angiotensin II, which results in decreased production of aldosterone, increase in serum potassium levels (> 5.5 mEq/L) is not unexpected with this class of drugs; hyperkalaemia is more likely in patients with some degree of renal impairment, those treated with potassium-sparing diuretics or potassium supplements and/or consuming potassium-containing salt substitutes. A persistent dry (non-productive) irritating cough has been reported with most ACE inhibitors in use; the frequency of reports has been increasing since cough was first recognised as a side effect of ACE inhibition, and in various studies, the incidence of cough varies between 2% and 15% depending upon the drug, dosage and duration of use.

Contraindications

Prilace is contraindicated in patients with hypersensitivity to ramipril, or to any other ACE inhibitor, or to any of the excipients; history of hereditary and/or idiopathic angioedema or angioedema associated with previous treatment with an ACE inhibitor; and haemodynamically relevant renal artery stenosis either bilateral or unilateral in the single kidney. ACE inhibitors should not be used in patients with haemodynamically relevant left ventricular inflow or outflow impediment, such as stenosis of aortic or mitral valve. Prilace is contraindicated in hypotensive or haemodynamically unstable patients; pregnancy; lactation; and renal failure. Extracorporeal treatments leading to contact of blood with negatively charged surfaces must be avoided, such as dialysis or haemofiltration with high-flux dialyser membranes; life-threatening anaphylactoid hypersensitivity reactions, sometimes progressing to shock, have been described in the course of dialysis with high-flux membranes during ACE inhibitor therapy. Ramipril must not be used with aliskiren-containing medicines in patients with diabetes or with moderate to severe renal impairment (creatinine clearance <60mL/min). Ramipril must not be used with angiotensin II receptor antagonists (AIIRAs) in patients with diabetic nephropathy. Ramipril must not be used concomitantly with sacubitril/valsartan therapy.

Regulatory history

Prilace was first listed on the ARTG on 6 March 2007 in six formulations: ramipril 1.25 mg tablets, 2.5 mg tablets, 5 mg tablets, 10 mg tablets, and 10 mg capsules in both blister pack and bottle presentations.