Levamlodipine Maleate

Approved Indications:

• Hypertension:
  Indicated for the treatment of mild to moderate hypertension in adults and children aged ≥6 years. It may be used as monotherapy or in combination with other antihypertensive agents.
• Chronic Stable Angina:
  Used to reduce the frequency of anginal attacks and improve exercise tolerance in patients with chronic stable angina.
• Vasospastic (Prinzmetal’s) Angina:
  Effective in preventing coronary artery spasms and relieving chest pain associated with vasospastic angina.

Clinically Accepted (Off-label) Uses:

• Hypertension in the elderly: Preferred due to its gradual onset of action and lower incidence of peripheral edema compared to racemic amlodipine.
• Hypertension in patients with diabetes: Used to manage blood pressure with renal protection benefits.
• Raynaud’s phenomenon: Occasionally used off-label for its vasodilatory effects.

Route of Administration: Oral
Available Strengths: 2.5 mg and 5 mg tablets

Adults:

• Initial dose: 2.5–5 mg once daily.
• Maintenance dose: 2.5 to 5 mg once daily depending on blood pressure response.
• Maximum dose: 5 mg once daily.

Elderly:

• Initial dose: 2.5 mg once daily.
• Dose titration should be cautious due to increased sensitivity to antihypertensive effects.

Pediatric Patients (≥6 years):

• Usual dose: 1.25–2.5 mg once daily.
• Safety and efficacy in children under 6 years of age have not been established.

Renal Impairment:

• No dose adjustment necessary; however, patients should be monitored closely.

Hepatic Impairment:

• Start at the lowest dose (2.5 mg once daily) and adjust cautiously due to prolonged drug half-life in hepatic dysfunction.

Co-administration:

• May be used in combination with diuretics, ACE inhibitors, ARBs, or beta-blockers.

Levamlodipine, the S-enantiomer of amlodipine, selectively inhibits L-type calcium channels in vascular smooth muscle and cardiac muscle. It reduces intracellular calcium influx during depolarization, resulting in relaxation of vascular smooth muscle, vasodilation, and reduction in peripheral vascular resistance, leading to decreased blood pressure. In angina, the coronary artery dilation improves myocardial oxygen supply, thereby alleviating ischemic pain. Levamlodipine is approximately twice as potent as racemic amlodipine, with a lower incidence of side effects like peripheral edema.

• Absorption: Rapid and well absorbed; not significantly affected by food.
• Bioavailability: Approximately 60–65%.
• Time to Peak Concentration: 6–12 hours after oral administration.
• Distribution: Widely distributed; plasma protein binding ~93–98%.
• Metabolism: Extensively metabolized in the liver via CYP3A4 to inactive metabolites.
• Elimination Half-life: Approximately 30–50 hours.
• Excretion: Primarily excreted in urine (~60%) as metabolites; <10% excreted unchanged.
• Steady-State: Achieved after 7–8 days of consistent dosing.

• Pregnancy: Category C. Animal studies have shown adverse effects on the fetus. There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk.
• Lactation: Unknown whether Levamlodipine is excreted in human milk. Due to its long half-life, caution is advised. Consider the potential risk to the infant or choose an alternative therapy.
• Recommendation: Use during pregnancy or breastfeeding only when clearly needed and under medical supervision.

• Primary Class: Antihypertensive
• Subclass: Dihydropyridine Calcium Channel Blocker (CCB)
• Generation: Third-generation dihydropyridine (S-enantiomer of amlodipine)

• Known hypersensitivity to Levamlodipine, amlodipine, or any component of the formulation
• Severe hypotension (systolic blood pressure <90 mmHg)
• Cardiogenic shock
• Advanced aortic stenosis
• Acute myocardial infarction (within the first few days)

• Hypotension: May cause symptomatic hypotension, especially in volume-depleted or sodium-depleted patients.
• Hepatic impairment: Use with caution; reduced metabolism may lead to higher plasma concentrations.
• Heart failure: Although generally safe, use cautiously in patients with severe heart failure due to the risk of worsening symptoms.
• Peripheral edema: Common with dihydropyridines; incidence may be lower with Levamlodipine than with racemic amlodipine.
• Elderly: Greater sensitivity observed; initiate therapy with lower doses.
• Drug withdrawal: Gradual dose reduction is advised if discontinuing therapy.

Common:

• Cardiovascular: Peripheral edema, palpitations, flushing
• CNS: Headache, dizziness, fatigue
• Gastrointestinal: Nausea, abdominal pain

Less Common:

• Hypotension
• Somnolence
• Dry mouth
• Constipation

Serious Adverse Effects:

• Exacerbation of angina or myocardial infarction in patients with severe coronary artery disease
• Hepatotoxicity (rare)
• Severe hypotension or syncope

Timing & Severity:

• Most common adverse effects occur within the first 1–2 weeks of therapy and are dose-dependent. Serious reactions are rare but require immediate discontinuation and medical attention.

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): May increase plasma levels and effects of Levamlodipine.
• CYP3A4 inducers (e.g., rifampicin, carbamazepine): May reduce the efficacy of Levamlodipine.
• Simvastatin: Co-administration may increase the risk of myopathy. Limit simvastatin to ≤20 mg/day.
• Beta-blockers: Additive hypotensive effect; monitor for bradycardia or excessive blood pressure drop.
• Alcohol: May enhance the hypotensive effect; avoid or use cautiously.
• Grapefruit juice: Minimal interaction, but caution is advised.

• Hypertension Guidelines (AHA/ESC 2023–2024): Levamlodipine is listed among preferred calcium channel blockers for first-line management of hypertension, especially in patients prone to edema or those requiring lower-dose therapy.
• Pediatric Hypertension: Recognized for use in children aged ≥6 years based on recent clinical guidance.
• Fixed-Dose Combinations: Increasing use in combination products with ACE inhibitors or ARBs to improve adherence and therapeutic efficacy.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Humidity: Store in a dry environment.
• Light Protection: Keep in the original blister pack to protect from light.
• Handling Precautions: Keep out of reach of children. Do not use if the packaging is torn or tablets are discolored.
• Reconstitution: Not applicable; tablet formulation only.