Lercanidipine

Generic Name: Lercanidipine hydrochloride
Therapeutic Class: Antihypertensive
Pharmacological Class: Calcium channel blocker (CCB), dihydropyridine class
ATC Code: C08CA13
Common Brand Names: Zanidip, Lercan, Lercadip, Lercaprel (combination with enalapril), Zanextra
Legal Status: Prescription-only medication (Rx)
Available Formulations: Oral tablets (10 mg and 20 mg)

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Chemical and Pharmacological Properties

• Chemical Class: Dihydropyridine derivative

• Molecular Formula: C36H41ClN2O6

• Molecular Weight: 634.2 g/mol (hydrochloride salt)

• Lipid Solubility: Highly lipophilic, providing a prolonged duration of action

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Mechanism of Action

Lercanidipine is a selective L-type calcium channel blocker, primarily acting on vascular smooth muscle. Its mechanism involves:

• Inhibition of calcium influx through L-type calcium channels

• Vasodilation of arteriolar smooth muscle, leading to reduced peripheral vascular resistance

• Lowering of systemic blood pressure without significantly affecting cardiac conduction or heart rate

It has high vascular selectivity, gradual onset of action, and minimal reflex tachycardia, distinguishing it from older dihydropyridines like nifedipine.

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Therapeutic Indications

Approved for use in:

1. Essential hypertension (mild to moderate):

   • As monotherapy or in combination with other antihypertensives

2. Combination therapy (e.g., with ACE inhibitors):

   • For patients not adequately controlled on monotherapy

Lercanidipine is not indicated for angina or arrhythmias.

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Dosage and Administration

Standard Dosage:

• Initial dose: 10 mg orally once daily

• Titration: May be increased to 20 mg once daily after 2 weeks based on clinical response

• Maximum dose: 20 mg/day

Administration Instructions:

• Take at least 15 minutes before a meal, preferably before breakfast

• Swallow whole with water

• High-fat meals significantly increase plasma levels – avoid taking with food

Special Populations:

• Elderly: Start with 10 mg/day; titrate cautiously

• Renal impairment (mild to moderate): 10 mg/day; avoid in severe impairment

• Hepatic impairment: Start at 10 mg/day with caution; not recommended in severe hepatic dysfunction

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Pharmacokinetics

• Absorption: Rapid but variable; low bioavailability due to first-pass metabolism (10% at 10 mg dose)

• Peak Plasma Concentration: ~1.5–3 hours post-dose

• Protein Binding: >98%

• Metabolism: Extensive hepatic metabolism via CYP3A4

• Elimination Half-Life: Terminal half-life is 8–10 hours, though pharmacodynamic effects last ~24 hours

• Excretion: Mainly feces (50%), minor renal excretion (10%)

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Contraindications

• Known hypersensitivity to lercanidipine or other dihydropyridines

• Severe hepatic impairment

• Severe renal impairment (creatinine clearance <30 mL/min)

• Unstable angina or recent myocardial infarction (within 1 month)

• Left ventricular outflow obstruction (e.g., aortic stenosis)

• Pregnancy and breastfeeding

• Co-administration with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir)

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Warnings and Precautions

1. Cardiac Effects:

   • Use with caution in patients with left ventricular dysfunction, heart failure (especially NYHA III-IV)

   • Not appropriate for treating angina; may exacerbate anginal symptoms

2. Liver Function:

   • Hepatic metabolism via CYP3A4 increases drug levels significantly in liver impairment

   • Avoid in severe hepatic dysfunction

3. Kidney Function:

   • Increased exposure in renal impairment; dose adjustment may be required

4. CYP3A4 Interactions:

   • Grapefruit juice and CYP3A4 inhibitors markedly increase plasma concentrations

   • Avoid concurrent use with potent inhibitors or inducers of CYP3A4

5. Alcohol Use:

   • May enhance vasodilatory and hypotensive effects

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Adverse Effects

Common (>1%):

• Headache

• Dizziness

• Flushing

• Tachycardia

• Palpitations

• Edema (especially ankle swelling)

• Fatigue

Uncommon (0.1–1%):

• Gastrointestinal disturbances (nausea, dyspepsia)

• Myalgia

• Rash

• Increased urination

Rare (<0.1%):

• Hypotension

• Syncope

• Elevated liver enzymes

• Angina exacerbation

• Gingival hyperplasia (rare)

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Drug Interactions

CYP3A4 Substrate:

Lercanidipine is extensively metabolized by CYP3A4. Several interactions may occur:

Contraindicated Co-administration:

• Strong CYP3A4 inhibitors:

  • Ketoconazole, itraconazole

  • Ritonavir, indinavir

  • Clarithromycin

  • Grapefruit juice

Use With Caution:

• Moderate CYP3A4 inhibitors: Erythromycin, diltiazem

• CYP3A4 inducers: Rifampin, carbamazepine, phenytoin, phenobarbital (may reduce effectiveness)

Other interactions:

• Ciclosporin: Increases lercanidipine levels; risk of nephrotoxicity

• Simvastatin: Lercanidipine increases simvastatin levels; separate administration by at least 12 hours

• Beta-blockers and other antihypertensives: Additive hypotensive effect

• Alcohol: Increases vasodilation and lowers blood pressure further

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Use in Pregnancy and Lactation

Pregnancy:

• Category D (contraindicated)

• Animal studies show fetal toxicity

• Not to be used in pregnant women or women planning pregnancy

Lactation:

• Unknown if excreted in breast milk

• Use contraindicated during breastfeeding

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Overdose and Toxicity

Symptoms:

• Excessive vasodilation

• Hypotension

• Reflex tachycardia

• Syncope

• Myocardial ischemia in extreme cases

Management:

• Supportive care (supine positioning, IV fluids)

• Vasopressors if needed

• No specific antidote

• Hemodialysis likely ineffective due to high protein binding

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Comparison with Other Calcium Channel Blockers

Feature	Lercanidipine	Amlodipine	Nifedipine
Class	3rd gen dihydropyridine	2nd gen dihydropyridine	1st gen dihydropyridine
Onset of Action	Slow	Gradual	Rapid
Duration	~24 hours	24–36 hours	Short/intermediate
Reflex Tachycardia	Minimal	Minimal	More common
Lipophilicity	Very high	Moderate	Moderate
Vascular Selectivity	High	High	Moderate
Preferred For	Mild/moderate hypertension	Hypertension, angina	Acute BP control

Monitoring Parameters

• Blood pressure and heart rate regularly during dose titration

• Signs of peripheral edema or dizziness

• Renal function tests in patients with pre-existing renal disease

• Hepatic function if underlying liver disease suspected

• Monitor for CYP3A4 interaction symptoms (e.g., hypotension, palpitations)

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Patient Counseling Information

• Take once daily on an empty stomach, 15 minutes before a meal

• Do not take with grapefruit juice

• Do not stop abruptly unless instructed

• Avoid alcohol and CYP3A4 inhibitors while on this medication

• May cause dizziness or fatigue, especially at therapy initiation

• Report swelling of the legs, palpitations, or chest pain

• Store in a dry place at room temperature

• Regular BP monitoring is essential during therapy