MILDRONATE (capsule)

APPROVED

by Order of the Ministry of Health

of Ukraine

as of 06.08.10 No. 655

Registration Certificate

No. UA/3419/02/01

 

INSTRUCTION

For medical application of drug

MILDRONATE®

 

Drug Formulation:

active substance: Meldonium;

1 capsule contains 250 mg of meldonium;

adjuvants: potato starch, silicon dioxide, calcium stearate;

capsule (shell and cap): titanium dioxide (E 171), gelatine.

Dosage Form.

Hard capsules.

Pharmacotherapeutic Group.

Cardiologic drugs. ATC Code C01E B.

Clinical Characteristics.

Indications.

For combined therapy of ischemic heart disease (stenocardia, myocardial infarction, chronic cardiac decompensation, and dyshormonal cardiomyopathy); acute and chronic disturbances of brain blood supply (cerebral strokes, and chronic cerebral circulatory insufficiency); haemophtalm and haemorrhages in retina of various aetiology, thrombosis of retina central vein and its branches, retinopathy of various aetiology (diabetic, hypertensive); decreased working efficiency, physical overstress, including in sportsmen; abstinence syndrome in case of chronic alcoholism (in combination with specific alcoholism therapy).

 

Contraindications.

Hypersensitivity to meldonium or any components of the drug, increased intracranial pressure (in case of impaired venous drainage, intracranial tumours), organic lesion of central nervous system (CNS). Children’s age.

 

Method of Application and Dosage.

Applied internally in adults.

Cardiovascular diseases or disturbed cerebral circulation.

As part of combined therapy: 0.5-1.0 g per day taken at a time (or divide the daily dose for 2 times). Course of treatment is 4-6 weeks.

Cardialgia against the background of dyshormonal myocardiodystrophy – 0.5 g per day taken at a time (or divided for 2 takings). Course of treatment is 12 days.

Acute phase of disturbed cerebral circulation – drug injections are applied within 10 days; afterwards the drug is applied internally in the dose of 0.5-1.0 g per day taken at a time (or divided for 2 takings). Course of treatment is 4-6 weeks.

Chronic disorders of cerebral circulation – 0.5 g per day taken internally at a time (or divided for two takings). Course of treatment is 4-6 weeks. Recurrent courses (usually 2-3 times a year) may be taken after consulting a doctor.

Vascular pathology and dystrophic diseases of retina.

The drug is applied in form of injections.

Intellectual and physical stress, including in sportsmen.

0.25 g four times a day. Course of treatment is 10-14 days. If necessary, the treatment is repeated in 2-3 weeks.

Sportsmen should take 0.5-1.0 g internally twice a day before training. Duration of treatment during preparatory period is 14-21 days, during the period of competition – 10-14 days.

Chronic alcoholism.

0.5 g 4 times a day. Course of treatment is 7-10 days.

 

Side effects.

On cardiovascular system: rarely – tachycardia, arrhythmia, changes of arterial pressure.

On blood formation system: eosinophilia.

On central nervous system: rarely – headache, dizziness, psychomotor disorders, paresthesia, tremor, excitement.

On gastrointestinal tract: rarely – diarrhoea, nausea, vomiting, abdominal pain, dyspepsia, metallic taste in mouth, dry mouth or hypersalivation.

Allergic reactions: rarely – redness of skin and itching, urticaria, rash, angioneurotic oedema, very rarely – anaphylactic shock.

On respiratory system: dyspnoea, dry cough.

Other: shiver, chest pain, weakness, hyperthermia, hyperhidrosis.

 

Overdosage.

Sharp changes of arterial pressure are possible. Treatment is symptomatic.

 

Application during Pregnancy and Breast-Feeding Periods.

Safety of Mildronate® application during the pregnancy period has not been proved. In order to avoid possible negative effect of the drug on foetus, it should not be applied during pregnancy.

It is unknown whether the drug is secreted into breast milk. If mother requires treatment with Mildronate®, breast-feeding shall be stopped.

 

Children.

Experience of drug application in children is absent.

 

Peculiarities of Application.

The drug should be carefully applied in case of chronic liver and renal diseases.

Due to possible development of stimulating effect it is recommended to take Mildronate® before noon.

 

Ability to Affect the Rate of Reactions when Driving or Operating Other
Mechanisms

There is no data about Mildronate® negative effect on rate of reactions.

 

Interaction with Other Drugs and Other Types of Interaction.

The drug may be combined with antianginal agents, anticoagulants and antiaggregants, antiarrhythmic drugs, cardiac glycosides, diuretics, bronchial spasmolytics, and other drugs.

 

Pharmacological Properties.

Pharmacodynamics.

Mildronate® (meldonium) is a structural analogue of gamma-butyrobetaine, a substance which is a carnitine precursor. Inhibiting the activity of γ-butyrobetaine hydroxylase, the drug decreases biosynthesis of carnitine and transportation of long-chain fatty acids trough cellular membranes, prevents accumulation of activated forms of unoxidized fatty acids – derivatives of acylcarnitine A in cells, thus, preventing their adverse effect.

Mildronate® restores balance between processes of oxygen supply and consumption in cells; prevents disturbance of ATP transportation, and at the same time activates glycolysis which is performed without additional oxygen consumption.

Decrease in carnitine concentration results in intensification of synthesis of γ-butyrobetaine which possesses vasorelaxant properties.

Mildronate® mechanism of action determines the wide range of its pharmacological effects. It increases working efficiency, and reduces symptoms of mental and physical overstress.

The drug possesses strong cardioprotective action. In case of impaired cardiac function, it improves contractive ability of myocardium, increases tolerance to physical stress. In case of stable II or III functional class stenocardia, it increases physical efficiency of patients, and reduces frequency of stenocardia attacks.

In case of acute and chronic ischemic disturbances of cerebral circulation, Mildronate® improves blood circulation in ischemia focus, influencing the redistribution of cerebral blood flow for the benefit of ischemic area.

Mildronate also possesses tonic effect on CNS, it eliminates functional disturbances of somatic and vegetative nervous system, including in case of abstinence syndrome in patients with chronic alcoholism. The drug also demonstrates positive effect on dystrophically changed retina vessels and cellular immunity.

Pharmacokinetics.

After having been taken orally, the drug is rapidly absorbed from gastrointestinal tract. Its bioavailability is 78%. Maximum concentration in blood plasma is reached in 1-2 hours after taking. Period of half-excretion is 3-6 hours.

 

Pharmaceutical Characteristics.

Main Physicochemical Properties:

Hard gelatine capsules of white colour. Capsules content – white crystalline powder with light odour. Powder is hygroscopic.

 

Effective Period.

4 years.

Do not apply the drug after the expiration date indicated on the packaging.

 

Storage Conditions.

Store in dry place under the temperature below 25°C.

Store in place out of reach of children.

 

Packaging.

10 capsules in blister; 4 blisters in carton.

Category of Selling.

On prescription.

Manufacturer Name and Address.

JSС «Grindeks», Latvia.

Location.

Latvia, Riga, LV-1057, 53 Krustpils St.

Tel./Fax: +371 67083205 / + 371 67083505

E-mail: grindeks@grindeks.lv

Date of Last Revision.