Lercanidipine hydrochloride is a third-generation dihydropyridine calcium channel blocker approved for the treatment of mild to moderate essential hypertension. It was first approved in Europe in 1997 and is included in the European Medicines Agency (EMA) database. Lercanidipine is marketed in many countries under various brand names such as Zanidip, Lercan, and Lercadip.
In the United Kingdom, it is approved by the Medicines and Healthcare products Regulatory Agency (MHRA), and in Australia, it is approved by the Therapeutic Goods Administration (TGA). In India, it has been approved by the Central Drugs Standard Control Organization (CDSCO) and is widely available in generic formulations.
BRAND NAMES
Zanidip: Zanidip is used to treat mild to moderate hypertension. The usual dose is 10 mg once daily, taken 15 minutes before meals. If needed, it can be increased to 20 mg once daily. Dose adjustment may be required in elderly or patients with liver or kidney issues.
Lercan: Lercan is a brand of Lercanidipine hydrochloride used to treat mild to moderate essential hypertension. It helps lower blood pressure by relaxing blood vessels.
Lercadip: Lercadip treats mild to moderate high blood pressure. Take 10 mg once daily before meals; may increase to 20 mg if needed.
MECHANISMOF ACTION
Lercanidipine is a third-generation dihydropyridine calcium channel blocker that selectively inhibits L-type voltage-gated calcium channels located primarily in the vascular smooth muscle cells of peripheral arteries. Calcium ions play a critical role in muscle contraction by entering smooth muscle cells through these L-type channels. When calcium enters, it binds to calmodulin, which activates myosin light-chain kinase, leading to contraction of the smooth muscle and vasoconstriction. Lercanidipine binds to and blocks these L-type calcium channels, reducing calcium influx into the cells. This leads to relaxation of the vascular smooth muscle (vasodilation), particularly in the arterial walls, which decreases peripheral vascular resistance. The reduction in resistance lowers systolic and diastolic blood pressure without significantly affecting heart rate or myocardial contractility. Its high lipophilicity allows it to bind strongly to the membrane, resulting in a slow onset but prolonged duration of action, which supports once-daily dosing.
PHARMACOKINETICS
Absorption
Lercanidipine is rapidly absorbed after oral administration, but due to extensive first-pass metabolism in the liver, its oral bioavailability is low (around 10%). Peak plasma concentrations (Cmax) are typically reached within 1 to 3 hours after dosing.
Distribution:
It has a large volume of distribution. It is extensively bound to plasma proteins (>98%).
Metabolism:
Lercanidipine undergoes extensive metabolism primarily by the liver enzyme CYP3A4 via oxidative pathways. It is converted into several inactive metabolites.
Elimination:
The drug and its metabolites are mainly eliminated through the biliary route into the feces. Only a small fraction (<5%) is excreted unchanged in urine.The elimination half-life is approximately 8 to 10 hours, but due to its strong membrane binding and slow dissociation, its antihypertensive effect lasts about 24 hours, supporting once-daily.
PHARMACODYNAMICS
Lercanidipine works by selectively blocking L-type calcium channels in vascular smooth muscle, causing artery relaxation and lowering peripheral vascular resistance. This results in a decrease in both systolic and diastolic blood pressure. Unlike some other calcium channel blockers, it has minimal effect on heart rate or myocardial contractility. Because of its slow onset and prolonged binding to membranes, it provides a smooth and sustained antihypertensive effect with once-daily dosing, reducing the risk of reflex tachycardia and other cardiovascular side effects.
DOSAGE AND ADMINISTRATION
The recommended starting dose of Lercanidipine for adults with mild to moderate essential hypertension is 10 mg once daily, taken at least 15 minutes before meals to ensure optimal absorption. If the desired blood pressure reduction is not achieved after 2 to 4 weeks of treatment, the dose may be increased to a maximum of 20 mg once daily, depending on the patient’s response and tolerance.
DRUG INTERACTIONS
- Avoid with CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, grapefruit juice) – increases drug levels and risk of hypotension.
- Avoid with CYP3A4 inducers (e.g., rifampicin, phenytoin) – reduces effectiveness.
- Do not use with cyclosporine – increases toxicity risk.
- May enhance effects of other antihypertensives – risk of low blood pressure.
- Separate dosing from simvastatin – take lercanidipine in the morning and simvastatin in the evening.
CONTRAINDICATIONS
- Hypersensitivity to lercanidipine or any of its components
- Severe hepatic or renal impairment
- Unstable angina or recent myocardial infarction (within 1 month)
- Left ventricular outflow tract obstruction (e.g., aortic stenosis)
- Untreated congestive heart failure
- Use with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir)
- Co-administration with cyclosporine
- Grapefruit juice intake – increases drug levels and side effects
SIDE EFFECTS
- Flushing
- Headache
- Dizziness
- Swelling of ankles or feet (peripheral edema)
- Palpitations
- Tiredness
- Nausea
- Heartburn
TOXICITY
In cases of overdose, Lercanidipine may cause excessive vasodilation, leading to severe hypotension, dizziness, palpitations, and reflex tachycardia. In extreme cases, it can result in collapse or loss of consciousness. There is no specific antidote. Treatment is supportive and may include monitoring cardiovascular function, positioning the patient supine, and administering fluids or vasopressors if needed.
