Lacidipine

Approved Indications:

• Essential Hypertension (Mild to Moderate):
  Lacidipine is indicated for the treatment of mild to moderate essential hypertension in adults. It may be used as monotherapy or in combination with other antihypertensive agents.

Clinically Accepted Off-Label Uses:

• Isolated Systolic Hypertension in the Elderly:
  Due to its vascular selectivity and gradual onset, lacidipine is sometimes used in older patients for isolated systolic hypertension.
• Hypertension in Diabetic Patients:
  Used cautiously in diabetic patients due to minimal metabolic interference.

Adults:

• Initial Dose: 2 mg once daily
• Maintenance Dose: 2–4 mg once daily
• Maximum Dose: 6 mg once daily
• Doses should be adjusted at 3–4 week intervals depending on patient response.

Pediatric Use:

• Not recommended due to insufficient safety and efficacy data.

Elderly:

• Start at the lower end of the dosing range; monitor for hypotension.

Renal Impairment:

• No dose adjustment needed; lacidipine is not renally eliminated.

Hepatic Impairment:

• Use with caution. Start at lower doses as metabolism may be impaired.

Route of Administration:

• Oral. Taken once daily at the same time each day, with or without food.

Duration:

• Long-term; continued as necessary to maintain blood pressure control.

Lacidipine is a dihydropyridine calcium channel blocker (CCB) that selectively inhibits L-type calcium channels in vascular smooth muscle. This inhibits calcium ion influx, leading to arteriolar vasodilation and a reduction in peripheral vascular resistance. Lacidipine decreases blood pressure by relaxing vascular smooth muscle, without significantly affecting cardiac contractility or conduction. Its high lipid solubility allows for a prolonged duration of action and a gradual onset, reducing the likelihood of reflex tachycardia.

• Absorption: Rapidly absorbed after oral administration; peak plasma concentration within 0.5–2 hours
• Bioavailability: ~10–20% due to significant first-pass metabolism
• Distribution: Highly lipophilic, extensively distributed in vascular tissue
• Protein Binding: >95%
• Metabolism: Extensively metabolized in the liver, primarily via CYP3A4
• Active Metabolites: No known active metabolites
• Elimination: Mainly via feces (~70%); minimal renal excretion
• Half-life: 13–19 hours
• Steady State: Achieved within 4–5 days of once-daily dosing

• Pregnancy:
  Safety in human pregnancy has not been established. Animal studies have shown fetal toxicity at high doses. Should be used only if clearly needed and when benefits outweigh risks.
• Lactation:
  Unknown if lacidipine is excreted in human breast milk. Use with caution in breastfeeding women. Monitor infants for possible adverse effects.
• Recommendation:
  Avoid use during pregnancy and lactation unless no safer alternatives are available.

• Primary Class: Antihypertensive
• Subclass: Dihydropyridine Calcium Channel Blocker (DHP CCB)
• Generation: Third-generation DHP

• Hypersensitivity to lacidipine or any component of the formulation
• Severe aortic stenosis
• Unstable angina or recent myocardial infarction
• Untreated congestive heart failure
• Severe hypotension (systolic BP <90 mmHg)
• Pregnancy (unless absolutely necessary)

• Aortic Stenosis: Vasodilation may worsen perfusion; contraindicated in severe cases
• Heart Failure: Use with caution in stable heart failure; avoid in decompensated cases
• Hepatic Impairment: Reduced clearance may occur; dose adjustment may be necessary
• Peripheral Edema: Dose-dependent; common with dihydropyridine CCBs
• Titrate Gradually: Full antihypertensive effect may take 2–4 weeks to develop
• Driving or Operating Machinery: May cause dizziness; caution advised

Common Adverse Effects:

• Cardiovascular: Peripheral edema, flushing, hypotension, palpitations
• Neurological: Headache, dizziness, fatigue
• Gastrointestinal: Nausea, abdominal pain
• General: Asthenia, malaise

Serious or Rare Adverse Effects:

• Allergic reactions (rash, pruritus)
• Gingival hyperplasia (rare)
• Elevated liver enzymes
• Syncope
• Worsening of angina in patients with severe coronary artery disease (rare)

Onset & Severity:

• Most adverse effects are mild, transient, and occur within the first weeks of treatment. Peripheral edema is dose-dependent.

• CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): May increase lacidipine levels and risk of hypotension
• CYP3A4 Inducers (e.g., rifampicin, phenytoin): May reduce efficacy by increasing metabolism
• Beta-Blockers: Additive antihypertensive effects; monitor BP and heart rate
• Grapefruit Juice: May increase systemic drug exposure; avoid
• Alcohol: May enhance hypotensive effect; use cautiously

Enzyme System:

• Primarily metabolized by the CYP3A4 enzyme system

• ESH/ESC Guidelines:
  Dihydropyridine calcium channel blockers like lacidipine are recommended as first-line treatment for hypertension.
• No recent changes in dosage or major safety alerts have been issued by regulatory authorities such as FDA or EMA.

• Temperature: Store below 30°C (86°F)
• Humidity: Protect from moisture
• Light: Store in original packaging to protect from light
• Handling Precautions: No special handling required
• Reconstitution/Refrigeration: Not applicable