MILDRONATE

APPROVED

by Order of the Ministry of Health

of Ukraine

as of 06.08.10 No. 655

Registration Certificate

No. UA/3419/01/01

 

INSTRUCTION

For medical application of drug

MILDRONATE®

 

 

Drug Formulation:

active substance: Meldonium;

1 ml of solution contains meldonium 0.1 g;

5 ml of solution (1 ampule) contain meldonium 0.5 g;

adjuvants: water for injections.

Dosage Form.

Solution for injections.

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; abstinence syndrome in case of chronic alcoholism (in combination with specific alcoholism therapy).

Contraindications.

Hypersensitivity to meldonium, 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.

Ways of introduction – intravenously, and parabulbarly.

Cardiovascular diseases.

As part of combined therapy: 0.5-1.0 g per day (5-10 ml of solution for injection 0.5g/5ml), applying the whole dose at a time or having divided it for 2 times. Course of treatment is 4-6 weeks.

Disturbed cerebral circulation.

Acute phase – 0.5 g once a day intravenously during 10 days, then the drug is applied internally. General course of treatment is 4-6 weeks.

Chronic disorders – the oral form of the drug is applied.

Recurrent courses (usually 2-3 times a year) may be taken after consulting a doctor.

Vascular pathology and dystrophic diseases of retina.

0.5 ml of solution for injections 0.5 g/ 5 ml is applied parabulbarly during 10 days.

Intellectual and physical overstress.

0.5 g intravenously once a day. Course of treatment is 10-14 days. If necessary, the treatment is repeated in 2-3 weeks.

Chronic alcoholism.

0.5 g intravenously twice 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.

General disorders and reaction at points of introduction: hyperaemia, pain at point of introduction.

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

 

Overdosage.

There have been no reports of cases of Mildronate® overdosage. The drug is low-toxic, and does not cause any side effects which may threaten the life of patients.

In case of decreased arterial pressure, headaches, dizziness, tachycardia, and general weakness are possible. The treatment is symptomatic.

In case of severe overdosage, it is necessary to control liver and kidneys function.

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.

The long-term experience of treatment of acute myocardial infarction and unstable stenocardia in cardiology departments shows that Mildronate® is not the first-row drug in case of acute coronary syndrome.

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.

Mildronate® may potentiate the action of nitroglycerin, nifediphine, β-adrenoceptor blockers, antihypertensive agents, and peripheral vasodilators.

 

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.

Its bioavailability is 100%. Maximum concentration in blood plasma is reached immediately after having been introduced. Period of half-excretion is 3-6 hours.

 

Pharmaceutical Characteristics.

Main Physicochemical Properties: transparent colourless liquid.

 

Incompatibility.

Unknown. Mildronate® solution shall not be mixed with other drugs in one syringe.

 

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.

5 ml in ampule of colourless glass, I hydrolytic class with fracture line of fracture point.

5 ampules in strip cellular packaging (pallet) of PVC film.

Two strip cellular packages (pallets) in carton.

Category of Selling.

On prescription.

Registration Certificate Holder.

JSС «Grindeks», Latvia.

 

Location.

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

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

E-mail: grindeks@grindeks.lv

 

Manufacturer.

HBM Pharma s.r.o., Slovakia.

 

Location.

30 Sklabynska St., Martin, 036 80 Slovakia.

 

Date of Last Revision.

Stamp: Agreed with the materials of registration file and reliable data concerning application of the drug.