Combitropil^® (Capsules) Instructions for Use

Marketing Authorization Holder

Sintez PJSC (Russia)

Contact Information

Sintez OJSC Kurgan Joint Stock Company of Medical Preparations and Products (Russia)

ATC Code

N06BX (Other psychostimulants and nootropic drugs)

Active Substances

Piracetam (Rec.INN)

Cinnarizine (Rec.INN)

Dosage Form

Combitropil®

Capsules 400 mg+25 mg: 30 or 60 pcs.

Dosage Form, Packaging, and Composition

Capsules gelatin, size No. 0, white; the contents of the capsules are a white or almost white powder.

Excipients: microcrystalline cellulose M102, lactose monohydrate, magnesium stearate, talc.

Composition of the gelatin capsule: titanium dioxide, gelatin.

10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (6) – cardboard packs.

Clinical-Pharmacological Group

A drug that improves cerebral circulation and metabolism

Pharmacotherapeutic Group

Nootropic agent

Pharmacological Action

A combined drug with a pronounced antihypoxic, nootropic and vasodilating effect.

Both components mutually potentiate their own antihypoxic action and have a vasodilating effect. The combined drug also contributes to a significant increase in blood flow in the brain. The toxicity of the combination does not exceed the toxicity of the individual components of the drug.

Piracetam is a nootropic agent. It has a positive effect on the metabolic processes of the brain: it increases the concentration of ATP in the brain tissue, enhances the synthesis of RNA and phospholipids, stimulates glycolytic processes, and enhances glucose utilization.

It improves the integrative activity of the brain, promotes memory consolidation, and facilitates the learning process.

It changes the rate of propagation of excitation in the brain, improves microcirculation, without having a vasodilating effect, and suppresses the aggregation of activated platelets.

It has a protective effect in brain damage caused by hypoxia, intoxication, electric shock; enhances α- and β-activity, reduces δ-activity on the EEG, and reduces the severity of vestibular nystagmus.

It improves interneuronal transmission and synaptic conduction in neocortical structures, increases mental performance, and improves cerebral blood flow.

The effect develops gradually. It has practically no sedative or psychostimulating effect.

The therapeutic effect of piracetam appears after 1-6 hours.

Cinnarizine is a selective blocker of slow calcium channels, reduces the entry of calcium ions into cells and reduces its content in the plasmalemma depot, reduces the tone of arteriole smooth muscles, and reduces their response to biogenic vasoconstrictor substances (including epinephrine, norepinephrine, dopamine, angiotensin, vasopressin, serotonin).

It has a vasodilating effect (especially in relation to the vessels of the brain, enhancing the antihypoxic effect of piracetam), without having a significant effect on blood pressure.

It exhibits moderate antihistamine activity, reduces the excitability of the vestibular apparatus, and lowers the tone of the sympathetic nervous system.

In patients with impaired peripheral circulation, it improves the blood supply to organs and tissues (including the myocardium) and enhances post-ischemic vasodilation.

It increases the elasticity of erythrocyte membranes, their ability to deform, and reduces blood viscosity.

Pharmacokinetics

The drug is rapidly and completely absorbed from the gastrointestinal tract.

Piracetam

Absorption

The bioavailability of piracetam is 95%. C_max of piracetam is reached in 2-6 hours.

Distribution

Piracetam penetrates the blood-brain barrier, the placental barrier. It accumulates in the brain tissue 1-4 hours after oral administration. It is eliminated from the cerebrospinal fluid much more slowly than from other tissues.

Metabolism and excretion

Piracetam is practically not metabolized. T_1/2 of piracetam from blood plasma is 4.5 hours, T_1/2 from the brain is on average 7.7 hours. It is excreted mainly by the kidneys (2/3 unchanged within 30 hours).

Cinnarizine

Absorption

C_max of cinnarizine is reached in 1-4 hours.

Distribution

C_max of cinnarizine after 1-4 hours is noted not only in the blood but also in the liver, kidneys, heart, lungs, spleen, and brain. Plasma protein binding is 91%.

Metabolism and excretion

Cinnarizine is completely metabolized in the liver (by dealkylation).

60% of cinnarizine is excreted unchanged in the feces, the rest is excreted in the urine as metabolites in about 5 hours.

Indications

• Cerebrovascular accidents (in cerebral atherosclerosis, ischemic stroke, convalescent period after hemorrhagic stroke, after traumatic brain injuries);
• Encephalopathies of various origins;
• Comatose and subcomatose states after intoxications and brain injuries;
• CNS diseases accompanied by a decrease in intellectual and mnestic functions;
• Labyrinthopathies of various origins (accompanied by dizziness, tinnitus, nystagmus, nausea and vomiting), Ménière’s syndrome;
• Depression;
• Psycho-organic syndrome with a predominance of signs of asthenia and adynamia;
• Asthenia of psychogenic origin;
• Prevention of migraine and motion sickness;
• Memory impairment, thinking function and concentration;
• Intellectual developmental delay in children.

ICD codes

Dosage Regimen

The drug should be taken orally.

Adults – 1-2 capsules 3 times/day for 1-3 months depending on the severity of the disease.

Children from 5 years old – 1-2 capsules 1-2 times/day for 1-3 months.

Treatment courses are conducted 2-3 times a year.

In chronic renal failure (CrCl<60 ml/min), a dose reduction or an increase in the interval between doses of the drug is necessary.

Adverse Reactions

From the nervous system: irritability, sleep disturbance, headache, tremor of the extremities.

From the digestive system: dyspepsia, epigastric pain, dry mouth.

Allergic reactions: skin rash.

Contraindications

• Severe hepatic failure;
• Severe renal failure;
• Parkinsonism;
• Pregnancy;
• Lactation period;
• Children under 5 years of age;
• Hypersensitivity to the components of the drug.

With caution, the drug should be used in Parkinson’s disease, renal or hepatic insufficiency.

Use in Pregnancy and Lactation

The use of the drug is contraindicated during pregnancy and breastfeeding.

Use in Hepatic Impairment

The use of the drug is contraindicated in severe hepatic failure.

Use in Renal Impairment

The use of the drug is contraindicated in severe renal failure.

Pediatric Use

Contraindication: children’s age (under 5 years). Children over 5 years of age 1-2 capsules 1-2 times/day for 1-3 months.

Special Precautions

Liver function should be monitored during treatment.

At the beginning of treatment, the patient should refrain from drinking alcohol.

Due to the cinnarizine content, the drug may cause a positive reaction in athletes during a doping test.

The drug should be used with caution in increased intraocular pressure.

Effect on ability to drive vehicles and mechanisms

During treatment, caution must be exercised when driving a car and engaging in activities that require increased concentration and speed of psychomotor reactions.

Overdose

There are no data on drug overdose.

Drug Interactions

Combitropil^® enhances the effects of drugs that depress the central nervous system, ethanol, as well as nootropic and hypotensive agents.

It improves the tolerability of antipsychotic drugs (neuroleptics) and tricyclic antidepressants.

Vasodilating drugs enhance the action of Combitropil^®.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F) in the original packaging (cardboard pack).

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.