RAMIPRIL-WGR

What it is

RAMIPRIL-WGR contains the active ingredient ramipril. RAMIPRIL-WGR tablets are available in three strengths containing 1.25 mg, 2.5 mg and 5 mg of ramipril, and 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), 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. — For 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. — For 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 RAMIPRIL-WGR 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 RAMIPRIL-WGR 5 mg daily, divided into two doses of 2.5 mg each, 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 RAMIPRIL-WGR 1.25 mg once daily, which should be doubled at intervals of two to three weeks, with no efficacy data regarding doses above 5 mg/day in patients with nephropathy. For patients at increased cardiovascular risk, the recommended initial dose is RAMIPRIL-WGR 2.5 mg once daily, which should be doubled after one week of treatment and increased to 10 mg after three weeks, with the usual maintenance dose being RAMIPRIL-WGR 10 mg daily.

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, and where there is angioedema involving swelling of the tongue, glottis or larynx likely to cause airway obstruction, appropriate therapy such as 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, and excessive hypotension 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. If RAMIPRIL-WGR is to be used in patients with severe congestive heart failure for treatment of hypertension, therapy should be started under very close supervision, and such patients should be followed closely for the first two weeks of treatment and whenever the dosage, with or without a diuretic, is increased. A persistent dry (non-productive) irritating cough has been reported with most ACE inhibitors, with incidence varying between 2% to 15% depending upon the drug, dosage and duration of use. Because ACE inhibitors decrease the formation of angiotensin II, which results in decreased production of aldosterone, increase in serum potassium levels are not unexpected with this class of drugs, and hyperkalaemia is more likely in patients with some degree of renal impairment, those treated with potassium sparing diuretics or potassium supplements.

Contraindications

RAMIPRIL-WGR is contraindicated in patients with hypersensitivity to ramipril, or to any other ACE inhibitor, or to 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. RAMIPRIL-WGR is contraindicated in hypotensive or haemodynamically unstable patients. Pregnancy and lactation are contraindications to use. 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

RAMIPRIL-WGR was first listed on the ARTG on 12 October 2020, with five registered variants comprising 10 mg capsules in bottle and blister pack, 5 mg tablets in blister pack, 2.5 mg tablets in blister pack, and 1.25 mg tablets in blister pack.