10 mg film-coated tablets
Approved indication: hypertension
Australian Medicines Handbook Section 6.4.6
Lercanidipine is a dihydropyridine calcium channel antagonist. Four other dihydropyridines are already available in Australia (see `Calcium channel antagonists' Aust Prescr 1997;20:5-8).
Like other dihydropyridines, lercanidipine relaxes vascular smooth muscle to lower peripheral resistance. This vasodilatation occurs slowly so patients are less likely to develop acute hypotension and reflex tachycardia.
Although lercanidipine is completely absorbed its bioavailability is reduced to 10% by first-pass metabolism. The tablets should be taken at least 30 minutes before a meal because food increases the bioavailability. As the enzymes involved in the first-pass metabolism can become saturated, doubling the dose causes the plasma concentrations to more than double.
Lercanidipine is eliminated by liver metabolism. It is completely metabolized with approximately half the metabolites being excreted in the urine. This metabolism involves cytochrome P450 3A4 so the plasma concentration of lercanidipine may be increased by drugs, such as erythromycin, fluoxetine and ketoconazole, which inhibit the enzyme. The plasma concentration may be reduced by drugs, such as phenytoin and carbamazepine, which induce CYP 3A4. Lercanidipine is contraindicated in patients with moderate or severe liver disease and in patients with severe renal impairment. Although the half-life of lercanidipine is relatively short, its antihypertensive effect is sustained for 24 hours.
Short-term studies show that lercanidipine reduces diastolic blood pressure by 5-7 mmHg more than a placebo. During comparative studies lasting 12-16 weeks no significant differences emerged between lercanidipine and slow-release nifedipine, atenolol, hydrochlorothiazide or captopril. In a double-blind crossover study of 16 patients, lercanidipine reduced diastolic blood pressure by 13 mmHg while amlodipine produced a 10 mmHg reduction.1
Many of the adverse effects of lercanidipine are caused by vasodilatation. Headache, flushing and palpitations are the commonest adverse reactions. As most studies have only lasted a few months, more information is needed on the long-term safety of lercanidipine. Given the concerns about the adverse effects of dihydropyridines2, it is unlikely that lercanidipine will have a prominent role in the treatment of hypertension.
Although it appears to be effective for mild to moderate hypertension it is not indicated for severe hypertension.
- De Giorgio LA, Orlandini F, Malasoma P, Zappa A. Double-blind, crossover study of lercanidipine versus amlodipine in the treatment of mild-to-moderate essential hypertension. Curr Ther Res Clin Exp 1999;60:511-20 .
- Calcium channel blockers: the continuing controversy. .
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.