Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Odrik (Roussel Uclaf Australia)
0.5 mg, 1 mg and 2 mg capsules
Trandolapril is a new entrant into the important market of antihypertensive drugs. (In 1992-3, public expenditure on antihypertensive drugs, excluding beta blockers, exceeded $250 million.) It is unclear whether any of trandolapril's characteristics, e.g. a long duration of action, are significant advantages over the competition.
Trandolapril is rapidly absorbed and converted into trandolaprilat, an active metabolite. Trandolaprilat is highly lipophilic and is a potent inhibitor of angiotensin converting enzyme (ACE). One day after a single 2 mg dose, 80%of ACE activity will remain inhibited. A steady state is reached after 4 days of single daily dosing. Elimination has a slow terminal phase, excretion of radiocarbon-labelled drug takes 7 days, but over 80% is eliminated within 2days. Although trandolaprilat and its metabolites are mainly excreted in the faeces, dose reductions are required for patients with renal insufficiency as well as for those with liver disease.
The usual starting dose is 1 mg daily for patients with mild to moderate essential hypertension. A lower dose is used if the patient has been taking a diuretic. Trandolapril lowers blood pressure, probably as effectively as other ACE inhibitors, with a maximum response after 2-4 weeks. If no response occurs, another drug may be added or the dose can be increased.
Trandolapril can cause the same adverse effects as other ACE inhibitors e.g. first dose hypotension, angioedema, hyperkalaemia. Cough occurred in approximately5% of patients involved in long-term studies.