Amlevo5 mg

Amlevo is a dihydropyridine calcium channel blocker used for the following indications:

Established/Approved Uses

• Hypertension: Amlevo is indicated for the treatment of high blood pressure, either alone or in combination with other classes of antihypertensive agents, to lower blood pressure and reduce the risk of cardiovascular events such as stroke and myocardial infarction.
• Chronic Stable Angina: Amlevo is indicated for symptomatic management of chronic stable angina pectoris, alone or in combination with other antianginal agents.
• Vasospastic (Prinzmetal's) Angina: Amlevo is indicated for the treatment of confirmed or suspected vasospastic angina.

Adjunct/Combination Use

• In patients with hypertension or angina not adequately controlled on a single agent, Amlevo may be added to an existing antihypertensive or antianginal regimen under physician supervision.

Amlevo should only be used for indications confirmed by a qualified physician after clinical evaluation.

Each tablet contains S- Amlodipine Besilate INN, equivalent to Levamlodipine 2.5 mg or 5 mg, formulated as the besilate (besylate) salt of the pharmacologically active S-enantiomer of amlodipine.

Amlevo is a long-acting dihydropyridine calcium channel blocker containing only the pharmacologically active S-enantiomer (levo-isomer) of amlodipine, rather than the racemic (R+S) mixture found in conventional amlodipine besylate products. Because the R-enantiomer contributes minimally to the calcium-channel-blocking effect, Amlevo is formulated to allow a lower effective milligram dose (typically half that of racemic amlodipine) while providing comparable blood-pressure-lowering and antianginal efficacy, with the aim of a potentially improved tolerability profile.

Amlevo works by relaxing vascular smooth muscle, reducing peripheral vascular resistance, and improving coronary blood flow, thereby lowering blood pressure and relieving anginal symptoms.

Calcium Channel Blocker (Dihydropyridine derivative) – Antihypertensive and Antianginal agent

S- Amlodipine Besilate is the S-enantiomer of amlodipine, a dihydropyridine calcium channel blocker. It inhibits the transmembrane influx of calcium ions into vascular smooth muscle, and to a lesser extent cardiac muscle, by binding to L-type calcium channels.

Mechanism of Action

• Relaxes vascular smooth muscle, causing peripheral arterial vasodilation and a reduction in total peripheral resistance, which lowers blood pressure.
• Dilates coronary arteries and arterioles, both in normal and ischemic regions, increasing myocardial oxygen delivery in patients with vasospastic angina.
• Reduces cardiac afterload and myocardial oxygen demand in patients with chronic stable angina.

Pharmacokinetics

S- Amlodipine Besilate is slowly and almost completely absorbed after oral administration, with peak plasma concentrations reached in 6–12 hours. It has a long elimination half-life (approximately 30–50 hours), allowing effective once-daily dosing, and is extensively metabolized in the liver with metabolites excreted mainly in urine.

Take Amlevo orally, once daily, with or without food, at the same time each day. Swallow the tablet whole with water. Do not stop taking Amlevo abruptly without consulting a physician.

The following are well-established, clinically significant interactions with Amlevo:

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir): may increase plasma concentrations of Amlevo, increasing the risk of hypotension and edema; dose adjustment or closer monitoring may be needed.
• Strong CYP3A4 inducers (e.g., rifampin): may decrease plasma concentrations of Amlevo, reducing antihypertensive/antianginal efficacy.
• Simvastatin: Coadministration with Amlevo increases simvastatin exposure; the simvastatin dose should be limited to 20 mg daily in patients also taking Amlevo.
• Other antihypertensive agents and diuretics: Additive blood-pressure-lowering effect when combined with Amlevo; risk of symptomatic hypotension, especially with initiation or dose increases.
• Tacrolimus: Amlevo may increase tacrolimus blood levels; monitoring of tacrolimus levels is advised.
• PDE5 inhibitors (e.g., sildenafil): Each may exert an independent hypotensive effect when combined with Amlevo; use together with caution.

Common and less common side effects reported with Amlevo include:

Peripheral edema with Amlevo is dose-dependent and is a common reason for treatment adjustment; it is not usually associated with fluid retention or weight gain.

Pregnancy

Safety data on Amlevo use during pregnancy are limited. Amlevo should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus. Calcium channel blockers, including Amlevo, may be used cautiously for pregnancy-related hypertensive disorders under close obstetric supervision. A physician must be consulted before use of Amlevo in pregnancy.

Lactation

It is not known with certainty whether Amlevo is excreted in human breast milk in clinically significant amounts; amlodipine (the racemic parent compound) is excreted in breast milk in small quantities. A decision should be made whether to discontinue breastfeeding or discontinue Amlevo, taking into account the benefit of breastfeeding and the mother's clinical need for therapy, in consultation with a physician.

• Significant aortic stenosis: Use Amlevo with caution, as with all peripheral vasodilators, in patients with severe aortic stenosis due to a theoretical risk of reduced coronary perfusion.
• Symptomatic hypotension: More likely in patients with severe aortic stenosis or when Amlevo is combined with other antihypertensives; monitor blood pressure, especially after starting therapy or increasing the dose.
• Worsening angina/acute MI: 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 Amlevo or at dose increase.
• Hepatic impairment: Amlevo is extensively metabolized by the liver; patients with hepatic impairment may have prolonged elimination — start at the lowest dose (1.25 mg once daily) and titrate slowly (see Use in Special Populations).
• Elderly patients: Clearance of Amlevo may be reduced; use a lower starting dose and titrate cautiously.
• Peripheral edema: Dose-related with Amlevo; see Side Effects.
• Congestive heart failure: Use Amlevo with caution; long-term use in patients with severe heart failure should be individualized under specialist supervision.

Amlevo is not an antibiotic; no antimicrobial stewardship precautions apply.

Overdose of Amlevo can cause excessive peripheral vasodilation with marked and potentially prolonged systemic hypotension, and reflex tachycardia. Significant hypotension leading to shock has been reported with amlodipine overdose.

If overdose of Amlevo is suspected, seek immediate medical attention or contact a poison control center/emergency services without delay. Management is supportive and may include active cardiac and respiratory monitoring, elevation of the extremities, careful monitoring of fluid status and urine output, and vasopressor support as directed by a physician. Because Amlevo is highly protein-bound, hemodialysis is unlikely to be of significant benefit. Do not attempt to manage a suspected Amlevo overdose at home.

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

• Pediatric use: Safety and efficacy of Amlevo specifically in children have not been established; see Pediatric Uses.
• Elderly: Clearance of Amlevo is decreased with increased area-under-curve (AUC); an initial dose of 1.25 mg once daily is recommended, with slow titration and close monitoring.
• Hepatic impairment: Amlevo should be started at the lowest available dose (1.25 mg once daily) and titrated slowly, as elimination half-life is prolonged in hepatic impairment.
• Renal impairment: Changes in plasma concentration of Amlevo are not closely correlated with degree of renal impairment; usual doses can generally be used, with individualized monitoring. Amlevo is not effectively removed by hemodialysis.
• Pregnancy and lactation: See Pregnancy and Lactation section.

Amlevo is generally prescribed for long-term, ongoing management of hypertension or chronic angina rather than short-term use. Duration of treatment with Amlevo should be determined by the prescribing physician based on blood pressure control, symptom response, and periodic clinical review; treatment should not be stopped or altered without medical advice.

Calcium Channel Blockers – Dihydropyridine derivatives

S- Amlodipine Besilate selectively inhibits calcium ion influx across the cell membrane of vascular smooth muscle by binding L-type calcium channels, producing vasodilation of peripheral and coronary arteries. This reduces peripheral vascular resistance and blood pressure, and improves myocardial oxygen supply, without significant direct negative inotropic or chronotropic effects at therapeutic doses.

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The safety and efficacy of Amlevo specifically in pediatric patients have not been established, and it is not generally recommended for use in children. Racemic amlodipine (the parent compound) has established pediatric hypertension dosing in some regulatory labels for children aged 6–17 years, but corresponding pediatric data specific to Amlevo are lacking. If a physician determines that use of Amlevo in a child is necessary, dosing must be individualized and closely supervised, as the evidence base for Amlevo in children is limited.