Meldonium is a cardioprotective and anti-ischemic agent belonging to the class of medicines that modulate cellular metabolism. Its primary mechanism of action involves the inhibition of gamma-butyrobetaine hydroxylase, an enzyme crucial for the synthesis of L-carnitine. By reducing L-carnitine availability, meldonium limits the transport of long-chain fatty acids into the mitochondria, shifting energy production during ischemia and high workload towards the more oxygen-efficient glucose oxidation pathway. This results in enhanced cellular tolerance to ischemia, reduced lactate accumulation, and improved recovery of mechanical function. It is indicated for use in various cardiovascular and neurological conditions where compromised blood flow and energy deficit are central to the pathology.

Features

• Pharmacological Class: Cardiovascular agent, metabolic modulator
• Active Ingredient: Meldonium dihydrate
• Standard Dosage Forms: Oral capsules (250 mg, 500 mg), Injectable solution (100 mg/mL)
• Mechanism of Action: Selective inhibition of gamma-butyrobetaine hydroxylase
• Primary Pharmacological Effects: Anti-ischemic, cardioprotective, antianginal, neuromodulatory
• Bioavailability: Approximately 78% following oral administration
• Time to Peak Plasma Concentration (Tmax): 1-2 hours post oral dose
• Plasma Protein Binding: Low
• Elimination Half-life: 3-6 hours
• Route of Elimination: Primarily renal (as unchanged drug and metabolites)

Benefits

• Enhances myocardial tolerance to ischemia by optimizing cellular energy metabolism, reducing the risk of damage during low-oxygen states.
• Improves physical capacity and functional performance in patients with chronic heart failure and stable angina pectoris.
• Supports neurological recovery and function in cases of acute and chronic cerebrovascular insufficiency.
• Reduces the frequency of angina attacks and the need for sublingual nitroglycerin use.
• Promotes faster recuperation following periods of intense physical and psychological strain.
• Contributes to the normalization of compromised microcirculation and hemodynamics in various vascular beds.

Common use

Meldonium is clinically employed in a range of conditions characterized by compromised energy metabolism and reduced oxygen supply. Its primary use is within cardiology for the treatment of stable angina pectoris (Functional Class II-III) and chronic heart failure (NYHA Class I-III), where it improves exercise tolerance and reduces symptoms. In neurology, it is used as part of a comprehensive treatment plan for patients recovering from ischemic stroke, transient ischemic attacks (TIAs), and to address functional impairments associated with chronic cerebrovascular disease. Furthermore, it is utilized in ophthalmology for certain retinal vascular pathologies and, in some regions, is prescribed off-label to aid recovery from excessive physical and mental overload in otherwise healthy individuals.

Dosage and direction

Dosage is highly individualized based on the specific medical condition, its severity, and the formulation used. Always adhere to the prescribing physician’s instructions.

Oral Administration (Capsules):

• General Adult Dosage: Typically 500 mg - 1000 mg (1-2 capsules of 500 mg) per day, administered once or divided into two doses (morning and afternoon).
• Course of Treatment: Usually spans 4-6 weeks. Courses may be repeated 2-3 times per year, as determined by a physician.
• Administration: Capsules should be swallowed whole with a sufficient amount of water, with or without food.

Intravenous Administration (Solution):

• General Adult Dosage: 500 mg - 1000 mg (5-10 mL of 100 mg/mL solution) per day, administered via slow intravenous injection or infusion.
• Administration: The parenteral form is often used in acute settings or at the beginning of a treatment course, potentially transitioning to oral therapy for maintenance.

The maximum daily dose should not exceed 2000 mg. Treatment should not be initiated after 3 PM to avoid potential central nervous system activation that could interfere with sleep.

Precautions

• Renal Impairment: Use with caution in patients with severe renal impairment due to the primary renal route of elimination. Dose adjustment may be necessary.
• Hepatic Impairment: Caution is advised in patients with severe liver disease, although meldonium is not extensively metabolized hepatically.
• Pregnancy and Lactation: The safety of meldonium during pregnancy and breastfeeding has not been conclusively established. Use is only permissible if the potential benefit to the mother justifies the potential risk to the fetus or infant. A thorough risk-benefit analysis by a healthcare provider is mandatory.
• Driving and Operating Machinery: While meldonium is not typically a sedative, individual responses can vary. Patients should exercise caution until they are certain the medication does not adversely affect their reaction speed and concentration.
• Pediatric Use: Safety and efficacy in children and adolescents under 18 years of age have not been established.

Contraindications

Meldonium is contraindicated in patients with:

• Known hypersensitivity to meldonium or any of the excipients in the formulation.
• Severely elevated intracranial pressure (e.g., due to intracranial hemorrhage, acute cerebral circulation disorders with raised ICP).
• Severe hepatic or renal failure (definitive thresholds should be determined by a physician based on individual patient assessment).

Possible side effect

Meldonium is generally well-tolerated. Side effects are typically mild and transient. The frequency categories below are defined as: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000).

• Immune System Disorders: Uncommon: Allergic reactions (skin rash, pruritus, erythema, angioedema).
• Nervous System Disorders: Common: Headache; Uncommon: psychomotor agitation, emotional lability, sleep disturbances (insomnia or drowsiness).
• Cardiac Disorders: Uncommon: Palpitations, tachycardia, blood pressure fluctuations (hypotension or hypertension).
• Gastrointestinal Disorders: Common: Dyspepsia; Uncommon: nausea, vomiting, diarrhea, feeling of heaviness in the epigastrium.
• General Disorders: Common: Asthenia; Uncommon: general weakness.

Drug interaction

Formal interaction studies are limited. Theoretical and observed interactions include:

• Other Cardiovascular Agents: Meldonium may potentiate the effects of antianginal drugs (e.g., nitrates, beta-blockers, calcium channel blockers), coronary dilators, and some antihypertensive medications. Concurrent use requires monitoring for additive effects, particularly hypotension and bradycardia.
• Anticoagulants and Antiplatelets: A synergistic effect is possible, potentially increasing the risk of bleeding. Close monitoring of coagulation parameters is advised when used with warfarin, dabigatran, clopidogrel, or aspirin.
• Substrates of OCTN2 Transporter: As a substrate for this transporter, meldonium could potentially compete with other drugs (e.g., levocarnitine, certain beta-lactam antibiotics), though the clinical significance is likely low.
• Alcohol: Concomitant use with alcohol is not recommended, as it may exacerbate certain side effects like dizziness and blood pressure changes.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. Do not take a double dose to make up for a missed one. Consistently missing doses may reduce the overall efficacy of the treatment.

Overdose

Cases of overdose are rare. Symptoms are likely to be an exaggeration of known side effects and may include pronounced weakness, dizziness, headache, tachycardia, hypotension, and nausea. There is no specific antidote. Treatment is symptomatic and supportive. Gastric lavage may be considered if the overdose was recent and the oral formulation was ingested. Hemodialysis may be effective due to the drug’s low molecular weight and plasma protein binding. In case of suspected overdose, immediate medical attention should be sought.

Storage

• Store in the original packaging to protect from light and moisture.
• Keep at a temperature not exceeding 25°C (77°F).
• Keep out of the sight and reach of children.
• Do not use the medicine after the expiration date printed on the packaging.
• Do not dispose of medication via wastewater or household waste. Consult a pharmacist on the proper disposal method in accordance with local regulations.

Disclaimer

This information is intended for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The information provided is based on general product characteristics and may not reflect the specific approved labeling in your country.

Reviews

• “As a cardiologist, I have incorporated meldonium into the management plans for select patients with stable angina and CHF. The observed improvements in exercise tolerance and reduction in subjective complaints of breathlessness are notable. It serves as a useful adjunct to first-line therapies.” – Medical Professional, Cardiology
• “Following a minor ischemic event, my neurologist prescribed a course of meldonium. I noticed a significant improvement in my concentration and a reduction in the dizzy spells I was experiencing. The treatment was well-tolerated with no side effects.” – Patient, Neurological Recovery
• “From a clinical pharmacology perspective, the mechanism of meldonium is fascinating. Its action on substrate utilization offers a distinct approach to managing ischemic conditions. More robust, large-scale clinical data would be welcome to further solidify its place in treatment guidelines.” – Clinical Researcher
• “I used it during a period of intense professional burnout on my doctor’s recommendation. While not a miracle cure, I felt it aided my recovery by improving my energy levels and mental clarity, helping me get through the day more effectively.” – Patient, Off-label Use for Overexertion