Evrizam

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT Evrizam (Evrizam)

Composition:

Active substances: piracetam, cinnarizine;

1 capsule contains: piracetam – 400 mg, cinnarizine calculated as 100% dry substance – 25 mg;

Excipients: lactose monohydrate, colloidal anhydrous silicon dioxide, magnesium stearate;

Capsule composition: gelatin, iron oxide yellow (E 172), iron oxide red (E 172), titanium dioxide (E 171).

Pharmaceutical form. Capsules.

Main physicochemical properties: hard gelatin capsules size № 0. The body of the capsule is white and the cap is beige. The capsule contents – a crystalline powder mixture white or almost white in color.

Pharmacotherapeutic group. Psychostimulants and nootropic agents.

ATC code: N06BX.

Pharmacological Properties

Pharmacodynamics

Eurisam is a combination drug. The active components of the medicinal product are piracetam, a cyclic derivative of γ-aminobutyric acid, and cinnarizine, a selective calcium channel antagonist.

Piracetam is a nootropic agent acting on the brain, improving cognitive functions such as learning ability, memory, attention, and mental performance. The mechanisms of the drug's action on the central nervous system (CNS) are likely multiple: modification of the rate of excitation propagation in the brain; enhancement of metabolic processes in nerve cells; improvement of microcirculation by influencing the rheological properties of blood, without vasodilatory effects. Eurisam improves interhemispheric connections and synaptic conduction in neocortical structures. After prolonged use in patients with impaired brain functions, cognitive functions and attention improve.

Cinnarizine inhibits the contraction of smooth vascular muscle cells by blocking calcium channels. In addition to direct calcium antagonism, cinnarizine reduces the contractile effects of vasoactive substances such as norepinephrine and serotonin by blocking their receptor-mediated calcium channels. The blockade of calcium influx into cells depends on the tissue type, resulting in antivasoconstrictive effects without affecting arterial blood pressure or heart rate. Cinnarizine may further improve impaired microcirculation by increasing erythrocyte membrane elasticity and reducing blood viscosity. Cellular resistance to hypoxia is increased. Cinnarizine suppresses stimulation of the vestibular system, thereby inhibiting nystagmus and other autonomic disturbances. Cinnarizine prevents the occurrence of acute vertigo attacks.

Pharmacokinetics

The drug is rapidly and completely absorbed in the gastrointestinal tract. Cinnarizine reaches peak plasma concentrations within one hour after oral administration. It is completely metabolized. It binds to 91% with plasma proteins. 60% is excreted unchanged in feces, and the remainder is excreted in urine as metabolites.

Maximum plasma concentration of piracetam is reached within 2–6 hours. Piracetam freely penetrates the blood-brain barrier and is excreted unchanged in urine.

Clinical characteristics.

Indications.

• Chronic and latent cerebral circulation insufficiency in atherosclerosis and arterial hypertension; angiodystonic ischemic stroke and post-stroke state.
• Post-traumatic cerebрастhenia.
• Encephalopathy of various origins.
• Psychorganic syndrome with predominant memory and other cognitive function disorders.
• Labyrinthopathies – dizziness, tinnitus, nausea, vomiting, nystagmus.
• Ménière’s syndrome.
• Prevention of kinetoses.

Contraindications.

Hypersensitivity to piracetam, cinnarizine, or any excipient of the medicinal product; individual sensitivity to pyrrolidone derivatives.

Severe renal insufficiency, acute disturbance of cerebral circulation (hemorrhagic stroke), Huntington's chorea, parkinsonism, increased intraocular pressure, psychomotor agitation.

Pregnancy or lactation period.

Interaction with other medicinal products and other types of interactions.

Concomitant use of alcohol and drugs that suppress the CNS, as well as tricyclic antidepressants, may enhance their sedative effect.

The drug potentiates the action of nootropics, antihypertensives, and vasodilators. Concurrent use with vasodilating agents enhances its effect, while the presence of cinnarizine reduces the activity of hypertensive agents.

Eurizam enhances the activity of thyroid hormones and may cause tremor and restlessness.

Diagnostic intervention: due to its antihistaminic effect, cinnarizine contained in the drug may mask positive skin reactions when performing skin tests; therefore, its use should be discontinued 4 days prior to testing.

Antiepileptic medicinal products: no interaction has been observed with carbamazepine, phenytoin, phenobarbital, or sodium valproate (information based on known data of piracetam use at a dose of 20 mg/day daily for 4 weeks).

May enhance the effect of oral anticoagulants.

Acenocoumarol.

In patients with severe recurrent thrombosis, administration of high-dose piracetam (9.6 g/day) did not affect the dosing of acenocoumarol required to achieve a prothrombin time (international normalized ratio) of 2.5–3.5. However, when used concomitantly, a significant reduction in platelet aggregation, fibrinogen levels, von Willebrand factors [coagulation activity (VIII:C); ristocetin cofactor (VIII:vW:Rco); and plasma protein (VIII:vW:Ag)], blood and plasma viscosity was observed.

Pharmacokinetic interactions.

The likelihood of changes in the pharmacodynamics of piracetam under the influence of other drugs is low, as 90% of piracetam is excreted unchanged in urine.

In vitro, piracetam does not inhibit cytochrome P450 isoenzymes CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 4A9/11 at concentrations of 142, 426, and 1422 µg/mL.

At a concentration of 1422 µg/mL, slight inhibition of CYP2A6 (21%) and 3A4/5 (11%) was observed. However, the Ki values for these two CYP isomers are sufficiently high to exceed 1422 µg/mL. Therefore, metabolic interaction with drugs undergoing biotransformation by these enzymes is unlikely.

Special precautions for use.

Renal impairment.

The medicinal product should be administered with caution in patients with kidney disease. In cases of mild or moderate renal impairment, it is recommended to reduce the therapeutic dose or increase the interval between doses, especially if creatinine clearance is < 60 ml/min.

Hepatic impairment.

The drug should be administered with caution in patients with liver disease. Patients with impaired liver function should have their liver enzyme levels monitored.

Elderly patients.

During long-term therapy in elderly patients, regular monitoring of kidney function parameters is recommended; dose adjustment should be considered based on creatinine clearance test results, if necessary.

The drug passes through the filtration membranes of hemodialysis equipment.

The use of the drug should be avoided in cases of porphyria.

Effect on laboratory tests.

The drug may produce false positive results in doping tests in athletes.

Effect on platelet aggregation.

Since piracetam reduces platelet aggregation, the drug should be administered with caution in patients with coagulation disorders, conditions associated with bleeding (e.g. gastrointestinal ulcer), during major surgical procedures (including dental interventions), in patients with symptoms of severe hemorrhage or with a history of hemorrhagic stroke, as well as in patients receiving anticoagulants, platelet antiaggregants, including low-dose acetylsalicylic acid.

Like other antihistamine medicinal products, Eurisam may cause irritation in the epigastric region; administration after food intake may reduce gastric irritation.

Concomitant use of alcohol or antidepressants should be avoided, as the drug may cause drowsiness, especially at the beginning of treatment (see section "Interaction with other medicinal products and other forms of interaction").

Content of excipients.

The drug contains lactose. Therefore, this medicinal product should not be used in patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

The drug should not be used during pregnancy or breastfeeding.

If treatment with the drug is necessary, breastfeeding should be discontinued.

Ability to influence reaction rate while driving or operating machinery.

Caution should be exercised when driving or operating machinery due to possible adverse reactions affecting the central nervous system.

Dosage and Administration

Eurizam capsules should be taken orally after meals, without chewing, with water.

Adults

1–2 capsules three times a day.

Treatment duration – 1–3 months depending on the severity of the disease.

Do not use for longer than 3 months without interruption! 2–3 courses per year may be conducted.

Children. Not to be used.

Overdose.

Symptoms: intensified adverse drug reactions. In individual cases of acute overdose, dyspeptic symptoms (diarrhea with blood, abdominal pain), altered consciousness ranging from drowsiness to stupor and coma, vomiting, extrapyramidal symptoms, and arterial hypotension may occur. In children, excitatory reactions predominate – insomnia, restlessness, euphoria, irritability, tremor, rarely nightmares, hallucinations, and seizures.

Treatment: gastric lavage (preferably within the first hour after ingestion), administration of activated charcoal. Provide symptomatic therapy. Hemodialysis may be used.

Adverse reactions.

Nervous system disorders: hyperkinesia, ataxia, headache, insomnia, vestibular disorders, dizziness, increased frequency of epileptic seizures, impaired balance, worsening of epilepsy, tremor, hypersomnia, lethargy, dyskinesia, parkinsonism, fatigue. Prolonged use in elderly patients may lead to the development of extrapyramidal symptoms.

Immune system disorders: hypersensitivity, including anaphylaxis.

Gastrointestinal disorders: dry mouth sensation, dyspepsia, abdominal pain, upper abdominal pain, gastric discomfort, diarrhea, cholestatic jaundice, increased salivation, nausea, vomiting.

Skin disorders: angioneurotic edema, dermatitis, pruritus, rash, urticaria, photosensitivity, hyperhidrosis, lichenoid keratosis, erythematous lupus, and discoid lupus erythematosus.

Psychiatric disorders: increased excitability, nervousness, confusion, somnolence, depression, anxiety, hallucinations.

Musculoskeletal system disorders: muscle rigidity.

Other: asthenia, increased sweating, sexual excitement, hemorrhagic disorders.

During prolonged treatment, weight gain may be observed in isolated cases.

Shelf life. 3 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

10 capsules in a blister. 2 or 6 blisters per carton.

Prescription category. Prescription only.

Manufacturer.

JSC "Farmak".

Manufacturer's name and address of the place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.