Lercanidipine

Lercanidipine is a medicine that lowers blood pressure (antihypertensive). Lercanidipine is a calcium channel blocker from the class of dihydropyridines. Lercanidipine is used primarily for the treatment of essential hypertension, but also for angina pectoris symptoms and Raynaud's syndrome, and is particularly indicated in patients with additional renal dysfunction. Lercanidipine is used in the form of the hydrochloride and is taken orally.

It was patented in 1984 and approved for medical use in 1997.

Pharmacodynamics

Like other calcium channel blockers of the dihydropyridine class, lercanidipine blocks L-type calcium channels in the smooth muscle cells of blood vessels. This relaxes them and allows better blood flow, which lowers blood pressure. Unlike the non-dihydropyridine calcium channel blockers verapamil and diltiazem, lercanidipine has no significant effect on calcium channels in the heart at usual therapeutic doses and therefore does not lower heart rate.

Pharmacokinetics

Lercanidipine is slowly but completely absorbed from the intestine. Bioavailability is only 10% due to an extensive first-pass effect, but can be as high as 40% when taken after a high-fat meal. Peak blood plasma levels are reached after 1.5 to 3 hours. Lercandipine is almost completely (>98%) bound to plasma proteins but in unbound form can be readily deposited in adipose tissue, resulting in a mild depot effect. It is completely metabolized in the liver, mainly via the enzyme CYP3A4. The elimination half-life is 8 to 10 hours. Due to the depot effect, the antihypertensive effect lasts for at least 24 hours. Lercandipine is excreted in the urine.

Interactions

The substance is metabolized by the liver enzyme CYP3A4. This also metabolizes a number of other drugs. This results in a number of possible interactions.

CYP3A4-inhibiting drugs may increase the plasma level of lercandipine and thus enhance the effect and promote undesirable side effects. These include, for example, the agents ketoconazole and itraconazole, ciclosporin, erythromycin, and grapefruit juice. Conversely, CYP3A4 inducers such as carbamazepine, rifampicin, and St. John's wort likely lower plasma levels and thus reduce the efficacy of lercanidipine. Lercanidipine may increase plasma levels of ciclosporin and digoxin.

Side effects

Lercanidipine is generally well tolerated. No adverse effect was observed in more than 1% of treated patients.

Typical side effects include:

• Headache
• Dizziness
• Tachycardia (rapid heartbeat)
• Palpitations
• Flushing
• Edema

Edema occurs much less frequently with lercanidipine compared with first-generation dihydropyridines such as nifedipine.

Contraindications

• Like other dihydropyridines, lercanidipine is contraindicated in unstable angina, uncontrolled heart failure, soon after myocardial infarction, and in patients with left ventricular outflow tract obstruction.
• It is also contraindicated during pregnancy and in women who may become pregnant, as there are no data on safety to the unborn child, and in patients with severe hepatic and renal dysfunction.
• The drug must not be combined with strong inhibitors of the liver enzyme CYP3A4 or with the immunosuppressant ciclosporin.