Esodip2.5 mg

Esodip is indicated for the treatment of hypertension (high blood pressure), to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.

• Established use: Hypertension in adults, used alone or in combination with other classes of antihypertensive agents (e.g., ACE inhibitors, angiotensin receptor blockers, diuretics, beta-blockers).
• Established use (pediatric): Hypertension in children and adolescents 6 to 17 years of age.

Esodip contains the pharmacologically active S-enantiomer of amlodipine, allowing effective blood pressure control at approximately half the milligram dose of racemic amlodipine.

Each tablet of Levamlodipine Maleate contains Levamlodipine Maleate equivalent to 2.5 mg or 5 mg of levamlodipine (the active S-isomer of amlodipine). Other commonly used strengths in the region include 1.25 mg. Inactive ingredients typically include microcrystalline cellulose, pregelatinized starch, silicon dioxide, and magnesium stearate.

Esodip is the maleate salt of levamlodipine, the pharmacologically active S-enantiomer of the racemic dihydropyridine calcium channel blocker amlodipine. Because most of the antihypertensive activity of amlodipine resides in the S-isomer, Esodip produces comparable blood-pressure-lowering effects to amlodipine at roughly half the dose, which some clinicians consider may translate to a reduced burden of dose-related adverse effects such as peripheral edema, although this has not been definitively established in large comparative trials.

Esodip is administered orally, once daily, and is used long-term for chronic blood pressure control.

Esodip belongs to the dihydropyridine calcium channel blocker (CCB) class of antihypertensive agents. It is the single active enantiomer of amlodipine.

Mechanism of Action

Levamlodipine Maleate inhibits the transmembrane influx of calcium ions into vascular smooth muscle and, to a lesser extent, cardiac muscle. This selectively relaxes vascular smooth muscle, causing peripheral arterial vasodilation and a reduction in peripheral vascular resistance, which lowers blood pressure. Levamlodipine Maleate is the pharmacologically active, antihypertensive isomer of amlodipine; the R-enantiomer contributes minimally to the antihypertensive effect.

Pharmacokinetics

• Absorption: Well absorbed orally; peak plasma concentrations occur 6–12 hours after dosing. Bioavailability is not significantly affected by food.
• Distribution: Approximately 93% bound to plasma proteins.
• Metabolism: Extensively metabolized in the liver (~90%) to inactive metabolites.
• Elimination: Biphasic elimination with a terminal half-life of approximately 30–50 hours; steady state is reached after 7–8 days of once-daily dosing. Half-life is prolonged in patients with hepatic impairment.

Esodip is administered orally, once daily, with or without food, at approximately the same time each day. Tablets may be swallowed whole; do not stop taking Esodip abruptly without medical advice, particularly in patients with underlying coronary artery disease, as abrupt discontinuation may be associated with worsening symptoms.

The following interactions with Esodip are clinically significant and well documented:

• Strong/moderate CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir): may increase levamlodipine plasma concentrations, increasing the risk of hypotension and edema; monitor for adverse effects and consider dose reduction.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort): may reduce plasma concentrations of Esodip and its antihypertensive effect; monitor blood pressure closely.
• Simvastatin: Co-administration increases simvastatin exposure and risk of myopathy/rhabdomyolysis; limit simvastatin to 20 mg daily in patients also taking Esodip.
• Cyclosporine and tacrolimus: Concomitant use may increase serum concentrations of these immunosuppressants; monitor drug levels and adjust dose as needed.
• Sildenafil and other PDE5 inhibitors: Each agent may independently lower blood pressure; additive hypotensive effect is possible with concomitant use.
• Other antihypertensive agents (diuretics, beta-blockers, ACE inhibitors, ARBs): Additive blood-pressure-lowering effect, which is often used therapeutically but requires monitoring for symptomatic hypotension.

Adverse effects of Esodip are generally dose-related.

Common (≥1%)

• Peripheral edema (dose-dependent; more common in females)
• Flushing
• Palpitations
• Dizziness
• Headache
• Fatigue
• Nausea and abdominal discomfort
• Somnolence

Less Common / Postmarketing

• Jaundice and hepatic enzyme elevations
• Gynecomastia
• Extrapyramidal disorder (rare)
• Worsening angina or myocardial infarction, particularly on initiation or dose increase in patients with severe obstructive coronary artery disease (see Precautions and Warnings)

Pregnancy

Data on the use of Esodip in pregnant women are limited and insufficient to establish a drug-associated risk of major birth defects or miscarriage. Animal reproduction studies with amlodipine showed no evidence of teratogenicity at doses many times the maximum recommended human dose, though decreased litter size and increased intrauterine deaths were observed at very high doses. Esodip should be used during pregnancy only if clearly needed and the potential benefit justifies the potential risk to the fetus; consult a physician before use.

Lactation

Amlodipine (and therefore levamlodipine) is present in human milk at low levels, with no reported adverse effects on breastfed infants in available data. Because information is limited, Esodip should be used during breastfeeding only after consultation with a physician, weighing the benefits of treatment against any potential risk to the infant, with monitoring of the infant for any adverse effects.

• Symptomatic hypotension: As with other calcium channel blockers, symptomatic hypotension is possible, particularly in patients with severe aortic stenosis; use Esodip with caution in this population.
• Worsening angina/myocardial infarction: Rarely, patients, particularly those with severe obstructive coronary artery disease, may develop increased frequency, duration, or severity of angina, or acute myocardial infarction, on starting Esodip therapy or at the time of dose increase.
• Hepatic impairment: Esodip is extensively metabolized by the liver; elimination half-life is prolonged in hepatic impairment. Initiate at the lowest dose and titrate slowly with close monitoring in patients with severe hepatic impairment.
• Heart failure: Use with caution in patients with heart failure, particularly in decompensated states; calcium channel blockers have been associated with increased risk of cardiovascular events in some heart failure populations.
• Abrupt discontinuation: The onset of antihypertensive effect with Esodip is gradual. Avoid abrupt discontinuation without medical guidance, particularly in patients with coronary artery disease.
• Peripheral edema: Dose-dependent peripheral edema is the most common reason for discontinuation; report significant swelling of the ankles or feet to your physician.

Overdose of Esodip may cause excessive peripheral vasodilation, marked and potentially prolonged systemic hypotension, and reflex tachycardia. In case of a known or suspected overdose, seek immediate medical attention or contact emergency services / a poison control center right away. Management is supportive and may include cardiovascular monitoring, elevation of the extremities, careful monitoring of fluid status, and vasopressor support if clinically indicated; because Esodip is highly protein-bound, hemodialysis is unlikely to be of benefit. Do not attempt to manage a suspected overdose at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric Use

Safety and effectiveness of Esodip for hypertension have been established in pediatric patients 6 to 17 years of age; doses above 2.5 mg daily have not been studied in this group. Safety and efficacy in children under 6 years of age have not been established.

Geriatric Use

Elderly patients may have reduced clearance of Esodip, with increased systemic exposure. Dose selection for an elderly patient should be cautious, usually starting at the lower end of the dosing range (e.g., 1.25 mg once daily), reflecting the greater frequency of decreased hepatic, renal, or cardiac function and concomitant disease or other drug therapy in this population.

Hepatic Impairment

Use the lowest starting dose (1.25 mg once daily) with slow titration and close monitoring (see Precautions and Warnings).

Renal Impairment

No dose adjustment is required.

Esodip is generally used as a long-term, chronic therapy for the management of hypertension. Duration of treatment is determined by the prescribing physician based on ongoing blood pressure control and cardiovascular risk, and treatment is typically continued indefinitely unless a change in therapy is medically indicated. Do not stop Esodip abruptly without consulting your physician.

Dihydropyridine Calcium Channel Blocker (CCB); Antihypertensive

Levamlodipine Maleate works by inhibiting the influx of calcium ions through L-type calcium channels in vascular smooth muscle cell membranes. This reduces intracellular calcium, leading to relaxation of vascular smooth muscle (particularly arterial/arteriolar smooth muscle), decreased peripheral vascular resistance, and a resulting reduction in blood pressure. As the pharmacologically active S-enantiomer of amlodipine, Levamlodipine Maleate achieves this effect at approximately half the milligram dose of the racemic mixture.

Esodip is approved for the treatment of hypertension in pediatric patients 6 to 17 years of age, at an initial dose of 1.25–2.5 mg once daily; doses greater than 2.5 mg daily have not been studied in this age group. Safety and efficacy in children younger than 6 years of age have not been established, and Esodip is not recommended for use in this younger population outside specialist guidance.