APX-RAMIPRIL

What it is

APX-RAMIPRIL contains ramipril. The medicine is available in tablet strengths of 1.25 mg, 2.5 mg and 5 mg, and in a 10 mg capsule formulation. 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), a peptidyl dipeptidase that catalyses the conversion of angiotensin I to the vasoconstrictor substance, angiotensin 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 is 2.5 mg once a day, which may 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 5 mg daily in divided doses of 2.5 mg each (morning and evening); if not tolerated, 1.25 mg may be given twice daily for two days, then increased by doubling at intervals of one to three days, with a maximum of 10 mg daily in divided doses. For patients at increased cardiovascular risk, the recommended initial dose is 2.5 mg once daily, doubled after one week and increased to 10 mg after three weeks, with usual maintenance at 10 mg daily. For progressive renal failure with persistent proteinuria >1 g/day, the initial dose is 1.25 mg once daily, doubled at intervals of two to three weeks; there are no efficacy data for doses above 5 mg/day in patients with nephropathy. In elderly patients, the recommended starting dose is 1.25 mg once daily, which can then be increased according to individual blood pressure response.

Key safety warnings

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with ACE inhibitors, and if angioedema occurs, the product should be promptly discontinued and the patient carefully observed until the swelling disappears. Laryngeal oedema can be fatal; where angioedema involves 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, and hospitalisation with observation for at least 12 to 24 hours is advisable. The onset of angioedema associated with ACE inhibitor use may be delayed for weeks or months, and patients may have multiple episodes with long symptom-free periods. Hypotension may occur in patients commencing treatment with ACE inhibitors, with excessive hypotension rarely seen in uncomplicated hypertensive patients but possible in severely salt or volume depleted persons, those treated vigorously with diuretics, after severe diarrhoea, or patients undergoing dialysis. In patients with severe congestive heart failure with or without associated renal insufficiency, excessive hypotension has been observed with ACE inhibitors, which may be associated with syncope, neurological deficit, oliguria and progressive azotaemia, but rarely with acute renal failure or death. A persistent dry, non-productive irritating cough has been reported with most ACE inhibitors, with incidence varying between 2% to 15% depending on the drug, dosage and duration of use. Because ACE inhibitors decrease the formation of angiotensin II, which results in decreased aldosterone production, increases in serum potassium levels (>5.5 mEq/L) are not unexpected, and hyperkalaemia is more likely in patients with renal impairment, those treated with potassium-sparing diuretics or potassium supplements, or consuming potassium-containing salt substitutes.

Contraindications

APX-RAMIPRIL is contraindicated in patients with hypersensitivity to ramipril, any other ACE inhibitor, or any of the excipients, and in those with a history of hereditary and/or idiopathic angioedema or angioedema associated with previous treatment with an ACE inhibitor. Haemodynamically relevant renal artery stenosis either bilateral or unilateral in the single kidney is a contraindication. 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. APX-RAMIPRIL is contraindicated in hypotensive or haemodynamically unstable patients. Pregnancy and lactation are contraindications. Extracorporeal treatments leading to contact of blood with negatively charged surfaces must be avoided, such as dialysis or haemofiltration with high-flux dialyser membranes, due to the risk of life-threatening anaphylactoid hypersensitivity reactions; this includes polyacrylonitrile membranes such as AN69. Ramipril must not be used with aliskiren-containing medicines in patients with diabetes or with moderate to severe renal impairment (creatinine clearance <60 mL/min). Ramipril must not be used with angiotensin II receptor antagonists in patients with diabetic nephropathy. Ramipril must not be used concomitantly with sacubitril/valsartan therapy.

Regulatory history

APX-RAMIPRIL was first listed on the ARTG on 2020-10-12, with registrations covering 1.25 mg, 2.5 mg and 5 mg tablet formulations and 10 mg capsule formulations in both blister pack and bottle presentations.