TRITACE

What it is

Tritace is available as tablets containing 1.25 mg, 2.5 mg, 5.0 mg and 10 mg ramipril and a capsule containing 10 mg ramipril. Ramipril is a 2-aza-bicyclo [3.3.0]-octane-3-carboxylic acid derivative. Ramipril is an ACE inhibitor with ATC code C09AA05.

Approved indications

— Treatment of hypertension. — Post MI 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; 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 2.5 mg ramipril once a day. Depending upon the patient's response, the dosage may then be increased at intervals of 2–3 weeks, first to 5 mg and then to a maximum of 10 mg once daily. For post-MI heart failure, the recommended initial dose is 5 mg ramipril daily, divided into two doses of 2.5 mg each. The maximum permitted daily dose is 10 mg ramipril to be given in divided doses. For patients at increased cardiovascular risk, the recommended initial dose is 2.5 mg ramipril once daily. Depending on the tolerability, the dose should be doubled after one week of treatment and, after three weeks, should be increased to 10 mg. The usual maintenance dose is ramipril 10 mg daily. For progressive renal failure in patients with persistent proteinuria in excess of 1 g/day, the recommended initial dose is 1.25 mg ramipril once daily. This should be doubled at intervals of 2–3 weeks, depending on how the drug is tolerated.

Key safety warnings

Ramipril is contraindicated in patients with a history of angioedema. Angioedema can occur immediately after starting treatment with an ACE inhibitor, however severe angioedema may also occur at any time during long-term treatment. 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 must be promptly discontinued and the patient carefully observed until the swelling disappears. 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. Blood pressure should be measured repeatedly after the first dose of ramipril, after a dosage increase of ramipril and after the first dose of an additional diuretic plus any dosage increase of the diuretic. This should be done until blood pressure has satisfactorily stabilised. If hypotension occurs the patient should be placed in a supine position and, if necessary, receive an intravenous infusion of normal saline. 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. In various studies, the incidence of cough varies 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, increases in serum potassium levels are 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, or in patients taking other medicines associated with increases in serum potassium.

Contraindications

Hypersensitivity to ramipril, or to any other ACE inhibitor, or to any of the excipients of Tritace. History of hereditary and/or idiopathic angioedema or angioedema associated with previous treatment with an ACE inhibitor. Haemodynamically relevant renal artery stenosis, bilateral or unilateral in the single kidney. ACE inhibitors should not be used in patients with haemodynamically relevant left ventricular inflow or outflow impediment (e.g. stenosis of aortic or mitral valve). Hypotensive or haemodynamically unstable patients. Pregnancy. Lactation.

PBS listing

Tritace is listed on the PBS in tablet strengths of 1.25 mg, 2.5 mg and 5 mg, and a 10 mg capsule. The 1.25 mg tablet has 2 PBS items with unrestricted and restricted listings. The 2.5 mg tablet has 2 PBS items with unrestricted and restricted listings. The 5 mg tablet has 2 PBS items with restricted and unrestricted listings. The 10 mg capsule has 2 PBS items with restricted and unrestricted listings. The ex-manufacturer price is A$2.50 for tablets and A$3.50 for the capsule.

Regulatory history

Tritace was first registered on the ARTG on 20 December 1995 as a 1.25 mg tablet (ARTG 34515). The 2.5 mg tablet (ARTG 56537) and 5.0 mg tablet (ARTG 56538) were registered on 13 August 1996. The 10 mg capsule (ARTG 75202) was registered on 18 July 2000, and the 10 mg tablet (ARTG 79253) was registered on 30 July 2001.