Lecarnidipine

Lercanidipine is an Antihypertensive agent belonging to Calcium Channel blockers.

Lercanidipine is a calcium channel blocker for the treatment of Hypertension, the management of angina pectoris, and Raynaud's syndrome.

Lercanidipine is rapidly and completely absorbed from the gastrointestinal tract with a bioavailability of approx 10%. It is quickly and widely distributed to tissues and organs. The volume of distribution is about 2 to 2.5 L/kg with plasma protein binding: >98%. It is extensively metabolized by CYP3A4 into inactive metabolites, undergoes extensive first-pass metabolism, and gets excreted via urine (approx 50% as metabolites). Elimination half-life: 8-10 hours.

The common side effects are dizziness, drowsiness, headache, weakness, Nausea, strong irregular heartbeat, swelling, and dizziness upon standing.

Lercanidipine is available in the form of dosage forms, such as tablets.

Lercanidipine is available in South Korea, Europe, Australia, the UK, and India.

Lercanidipine is a dihydropyridine calcium antagonist which selectively inhibits the transmembrane influx of Ca into cardiac and vascular smooth muscle (greater effect on vascular than on cardiac, smooth muscle) during depolarisation. It reduces peripheral vascular resistance, which leads to lower arterial blood pressure by directly relaxing the vascular smooth muscle.

Lercanidipine is available in the form of a dosage forms, such as tablets.

Lercanidipine tablet is taken by mouth. It is usually taken once or twice a day with or without food.

Lercanidipine is a calcium channel blocker for the treatment of Hypertension, management of angina pectoris and Raynaud’s syndrome.

Lercanidipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes, possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum.

Lercanidipine is approved for its use in the following clinical indications:

• Hypertension

Adult: Initially, 10 mg once daily, may increase to 20 mg once daily after at least 2 weeks according to patient’s response.

The dosage and the duration of treatment should be as per the clinical judgment of the treating physician.

Lercanidipine is available in various dosage strengths:10 mg and 20 mg

Lercanidipine is available in the form of dosage forms such as tablets.

• Dose Adjustment in Kidney Patients:

Although the pharmacokinetics of lercanidipine in patients with mild to moderate renal impairment are similar to those observed in the general population, special care should be exercised when commencing treatment in such patients. The usual recommended dose of 10 mg daily may be tolerated; however, an increase to 20 mg daily should be approached with caution.

• Dose Adjustment in Hepatic Impairment Patient

No dosage adjustment is necessary.

• Dose Adjustment in Pediatric Patients.

Safety and efficacy have not been established.

Lercanidipine is approved for the treatment of Hypertension.

Hypertension: It has been observed that the low-salt Dietary Approach to Stop Hypertension (DASH) diet lowers blood pressure. Sometimes after a few weeks, its effects on blood pressure become noticeable.

Lercanidipine may be contraindicated in the following.

• Known hypersensitivity to lercanidipine, any dihydropyridine or any other ingredient in APO-Lercanidipine tablets ;
• Severe hepatic impairment;
• Severe renal impairment (creatinine clearance <12 mL/min);
• Concomitant treatment of APO-Lercanidipine tablets with cyclosporin should be avoided.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

Ischaemic Heart Disease

It has been suggested that some short-acting dihydropyridines may be associated with increased cardiovascular risk in patients with ischaemic heart disease. Although lercanidipine is long-acting, caution should be required in such patients.

Outflow Obstruction (Aortic Stenosis)

Lercanidipine should be administered with caution in patients with left ventricular outflow obstruction (aortic stenosis).

Congestive Heart Failure

In general, calcium channel blockers should be used with caution in patients with heart failure. Although animal data and acute haemodynamic evaluation in patients with preserved left ventricular function have not demonstrated that lercanidipine exerts a direct negative inotropic effect, safety in patients with congestive heart failure has not been established. Therefore, as for other calcium channel blockers, lercanidipine should be used with caution in such patients, especially if untreated.

Unstable Angina Pectoris or within one month of a Myocardial Infarction

Rarely patients have developed documented increased frequency, duration and/or severity of angina on starting calcium channel blocker therapy or at the time of dosage increase (particularly those with severe obstructive coronary artery disease). The mechanism of this effect has not been elucidated; however, the possibility of an exacerbation of angina and/or cardiac ischaemia exists. It is therefore suggested that the use of calcium channel blockers is not advisable in patients with unstable angina pectoris or recent myocardial infarction.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence for genotoxic activity was observed with lercanidipine in in vitro assays of gene mutation (reverse mutation in S. Typhimurium, forward mutation in Chinese Hamster V79 fibroblasts), gene conversion (in Saccharomyces cerevisiae D4) or chromosomal damage (CHO cytogenetic assay). Negative findings were also obtained with lercanidipine in an in vivo assay of chromosomal damage (mouse micronucleus test).

Avoid taking alcohol with Lercanidipine as it may result in side effects like headache, dizziness and faintness.

Use in Pregnancy (Category C)

Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations.

These effects may be reversible. Accompanying texts should be consulted for further details.There is no clinical experience with lercanidipine in pregnancy, but other dihydropyridine compounds have been found to cause irreversible malformations in animals. Therefore, lercanidipine should not be administered during pregnancy or to women with childbearing potential unless effective contraception is used.

In animal studies, pregnant rats given lercanidipine orally at doses ≥ 2.5 mg/kg/day, beginning prior to mating, or 12 mg/kg/day, beginning from early gestation, showed signs of dystocia and had an increased incidence of still births and a lower neonatal survival index. The no-effect dose for effects on parturition and neonatal survival was 0.5 mg/kg/day (associated with lercanidipine concentration (AUC) about 50% of the expected human AUC) when dosing started before pregnancy or 2.5 mg/kg/day (about 3 times the human AUC) when dosing started during early gestation. Administration with lercanidipine at doses of 2.5 mg/kg/day during gestation also caused a higher incidence of foetal visceral abnormalities (mono/bilateral renal pelvic and/or ureteric dilatation) and skeletal abnormalities (mainly delayed ossification) at all dose levels. A no-effect dose was not established. The effects of lercanidipine during pregnancy have not been investigated adequately in a non-rodent species.

Salt Substitutes: Those who are taking Lercanidipine should avoid sodium, calcium and magnesium-rich foods. The salts may reduce the blood-pressure lowering effect of Lercanidipine.

The adverse reactions related to molecule Lercanidipine can be categorized as

• Common Adverse effect: Dizziness, vertigo, Palpitations/tachycardia, Flushing, asthenia (including fatigue and muscle weakness).
• Less Common Adverse effects: Hypotension, orthostatic hypotension, periorbital edema, anginal pain, myocardial infarction, cardiac failure, Dyspnea.
• Rare Common Adverse effects: Myalgia, Polyuria, urinary frequency, impotence.

The clinically relevant drug interactions of Lercanidipine is briefly summarized here.

Reduced antihypertensive effect with CYP3A4 inducers (e.g., phenytoin, rifampicin). Increased absorption with midazolam. Decreased serum concentration with metoprolol.

Potentially Fatal: Increased serum concentration with ciclosporin and strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, erythromycin).

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Symptoms:

Peripheral vasodilation, hypotension, tachycardia, bradycardia and negative inotropic effect (at very high doses), dizziness, headache and palpitations.

Management:

Supportive treatment. Monitor cardiac and respiratory function, circulating fluid volume, and urine output.

Pharmacodynamics:

Lercanidipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat Hypertension, chronic stable angina pectoris, and Prinzmetal’s variant angina. Lercanidipine is similar to other peripheral vasodilators. Lercanidipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes, possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

Pharmacokinetics:

• Absorption:

Rapidly and completely absorbed from the gastrointestinal tract. Bioavailability: Approx 10%. Time to peak plasma concentration: Approx 1.5-3 hours.

• Distribution:

Rapidly and widely distributed to tissues and organs. Volume of distribution: 2 to 2.5 L/kg. Plasma protein binding: >98%.

• Metabolism:

Extensively metabolized by CYP3A4 into inactive metabolites; undergoes extensive first-pass metabolism.

• Excretion:

Via urine (approx 50% as metabolites). Elimination half-life: 8-10 hours.

1. https://www.mims.com/india/drug/info/Lercanidipine ?type=full&mtype=generic

2. https://www.uptodate.com/contents/Lercanidipine-drug-information?search=Lercanidipine-drug-in&usage_type=panel&kp_tab=drug_general&source=search_result&selectedTitle=1~37&display_rank=1#F162889

3. https://go.drugbank.com/drugs/DB00590

4. https://www.rxlist.com/consumer_Lercanidipine _cardura/drugs-condition.htm

5. https://reference.medscape.com/drug/cardura-xl-Lercanidipine -342343