Mildronate 500

Mildronate GX 500 mg Tablets №60 (6x10)

Composition:
Active ingredient: meldonium phosphate;
Each tablet contains 500 mg of meldonium phosphate (calculated as meldonium).
Excipients: mannitol (E 421), povidone, potato starch, silicon dioxide, microcrystalline cellulose, magnesium stearate.

Dosage Form:
Tablets.

Physical Characteristics:
White, biconvex, oval tablets with “GX” engraved on one side and “500” on the other.

Pharmacotherapeutic Group:
Cardiac therapy. Other cardiac preparations.
ATC Code: C01EB22.

Pharmacological Properties

Pharmacodynamics:
Meldonium, a precursor of carnitine, structurally resembles gamma-butyrobetaine (GBB) with a nitrogen substitution for one carbon atom. Its effects can be explained in two primary mechanisms:

1. Impact on Carnitine Biosynthesis:

   • Meldonium reversibly inhibits gamma-butyrobetaine hydroxylase, reducing carnitine synthesis and restricting long-chain fatty acid transport into cells. This prevents the accumulation of activated non-oxidized fatty acids, which could damage cell membranes.
   • Under ischemic conditions, meldonium optimizes oxygen utilization, stimulates glucose oxidation, and enhances ATP transport from mitochondria to cytosol. This improves cell nutrition and oxygen use.
   • Increased GBB synthesis activates NO synthase, improving blood flow properties and reducing vascular resistance.

2. Mediator Role in the Hypothetical GBBergic System:

   • Meldonium acts as a mediator in the GBBergic system, potentially replacing GBB ester and mimicking its role. This substitution increases metabolic activity across various systems, including the central nervous system (CNS).

Cardiovascular Effects:

• Meldonium enhances myocardial contractility, protects against catecholamine- or alcohol-induced myocardial damage, prevents arrhythmias, and reduces myocardial infarction zones.

CNS Effects:

• Meldonium boosts motor activity, physical endurance, and resilience under stress. It optimizes cerebral blood flow and fortifies neurons against hypoxia.

Pharmacokinetics:

• Absorption: Peak plasma concentration occurs 1–6 hours post-administration, with oral bioavailability at 78%.
• Distribution: Meldonium distributes quickly in tissues, with a volume of distribution between 84.1–88.73 L.
• Metabolism: Primarily metabolized in the liver.
• Excretion: Meldonium is eliminated via renal excretion, with a terminal half-life of 44.7–50.2 hours.

Indications:
Part of combination therapy for:

• Cardiovascular conditions (e.g., stable angina, chronic heart failure, cardiomyopathy).
• Ischemic cerebrovascular disorders.
• Physical and emotional strain-induced fatigue.
• Recovery from strokes, head injuries, or encephalitis.

Contraindications:

• Hypersensitivity to meldonium or any excipients.
• Severe hepatic or renal impairment.
• Intracranial hypertension.

Interactions:
Meldonium is compatible with nitrates, beta-blockers, cardiac glycosides, anticoagulants, and antiplatelet drugs. However, it may amplify the effects of antihypertensive or vasodilatory medications.

Special Precautions:

• Use with caution in elderly patients or those with mild to moderate hepatic or renal impairment.
• Not recommended for children or adolescents due to insufficient safety data.