Larcadip

Approved Indications:

• Essential Hypertension:
  Indicated for the treatment of mild to moderate essential (primary) hypertension in adults.

Clinically Accepted Off-Label Use:

• Hypertension in the Elderly:
  May be used as monotherapy or part of combination therapy in elderly hypertensive patients, especially when metabolic neutrality and tolerability are desired.

Route of Administration: Oral (tablets swallowed whole), preferably taken at least 15 minutes before a meal.

Adults:

• Initial Dose: 10 mg once daily.
• Titration: May be increased to 20 mg once daily after 2 weeks if needed and well tolerated.

Elderly:

• No initial dose adjustment is required. Start with 10 mg daily and monitor blood pressure closely.

Renal Impairment:

• Mild to Moderate: Use with caution. Start at 10 mg once daily.
• Severe (creatinine clearance <30 mL/min): Not recommended.

Hepatic Impairment:

• Mild to Moderate: Start with caution at 10 mg once daily.
• Severe: Contraindicated.

Pediatric Use:

• Not recommended; safety and efficacy have not been established in children and adolescents under 18 years of age.

Lercanidipine is a third-generation dihydropyridine calcium channel blocker that selectively inhibits L-type calcium channels in vascular smooth muscle. This inhibition reduces the transmembrane influx of calcium ions, causing vasodilation of peripheral arterioles. The resulting decrease in peripheral vascular resistance leads to a lowering of blood pressure. Unlike some earlier calcium channel blockers, lercanidipine has a gradual onset and prolonged action with high lipophilicity, allowing sustained antihypertensive effect with improved tolerability.

• Absorption: Rapidly absorbed; peak plasma concentrations are reached in 1.5–3 hours.
• Bioavailability: Approximately 10% due to high first-pass metabolism.
• Protein Binding: >98% bound to plasma proteins.
• Distribution: Highly lipophilic; extensively distributed in tissues.
• Metabolism: Metabolized in the liver via CYP3A4 to inactive metabolites.
• Half-Life: Terminal half-life is 8–10 hours, with antihypertensive effect lasting 24 hours.
• Elimination: Primarily through biliary excretion (feces); less than 1% in urine as unchanged drug.
• Food Effect: High-fat meals significantly increase absorption; should be taken before meals to avoid exaggerated effects.

• Pregnancy:
  Lercanidipine is contraindicated in pregnancy due to its potential teratogenic effects and risk of fetal toxicity. Women of childbearing potential should use effective contraception during treatment.
• Lactation:
  It is unknown whether lercanidipine is excreted into human breast milk. Due to the risk of harm to the infant, breastfeeding is not recommended during treatment.

• Primary Class: Antihypertensive
• Subclass: Dihydropyridine Calcium Channel Blocker (3rd Generation)

• Hypersensitivity to lercanidipine or any dihydropyridine derivative
• Severe hepatic impairment
• Severe renal impairment (creatinine clearance <30 mL/min)
• Pregnancy and lactation
• Left ventricular outflow tract obstruction (e.g., severe aortic stenosis)
• Untreated congestive heart failure
• Recent myocardial infarction (within one month)
• Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir)

• Hepatic or Renal Impairment:
  Use with caution in patients with mild to moderate dysfunction; contraindicated in severe cases.
• Cardiovascular Conditions:
  Use cautiously in patients with ischemic heart disease or heart failure; may provoke angina or myocardial infarction, especially at dose initiation or titration.
• Hypotension:
  Symptomatic hypotension may occur, particularly in patients with volume depletion.
• CYP3A4 Drug Interactions:
  Avoid use with strong CYP3A4 inhibitors due to increased risk of hypotension.
• Driving or Machinery Use:
  May cause dizziness or fatigue; patients should be cautious.

Common (≥1%):

• Cardiovascular: Flushing, palpitations, peripheral edema
• Neurological: Headache, dizziness
• Gastrointestinal: Nausea, dyspepsia
• General: Fatigue, asthenia

Uncommon (<1%):

• Hypotension
• Muscle cramps
• Dry mouth
• Increased liver enzymes

Rare but Serious:

• Angina exacerbation
• Myocardial infarction (especially in patients with pre-existing coronary disease)
• Allergic skin reactions
• Hepatic dysfunction

• Strong CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir):
  Increase plasma concentrations of lercanidipine significantly; contraindicated.
• CYP3A4 Inducers (e.g., rifampicin, carbamazepine):
  May decrease effectiveness of lercanidipine.
• Cyclosporine:
  Increases levels of both drugs; concomitant use is contraindicated.
• Beta-blockers and Other Antihypertensives:
  Additive antihypertensive effects; monitor for hypotension.
• Grapefruit Juice:
  Inhibits CYP3A4 and may raise lercanidipine levels; should be avoided.
• Alcohol:
  May enhance vasodilatory effects; caution advised.

• European Society of Hypertension (ESH) and ESC Guidelines:
  Lercanidipine is listed as a preferred agent in the treatment of mild to moderate hypertension, particularly for elderly patients or those requiring metabolically neutral therapy.
• Recent Emphasis:
  Highlighted use of the 10 mg starting dose, with titration to 20 mg based on tolerability and blood pressure response.
• Safety Alerts:
  Ongoing caution advised with CYP3A4 inhibitors and in patients with ischemic heart disease due to risk of angina exacerbation.

• Temperature: Store below 30°C (86°F)
• Humidity: Protect from moisture
• Light: Store in the original package to protect from light
• Handling: Do not split, crush, or chew the tablets
• Refrigeration: Not required