Fezam

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Phezam®

Composition:

Active substances: 1 capsule contains piracetam 400 mg, cinnarizine 25 mg;

Excipients: lactose monohydrate, colloidal silicon dioxide anhydrous, magnesium stearate, hard gelatin capsules: gelatin, titanium dioxide (E 171).

Pharmaceutical form. Hard capsules.

Main physicochemical properties: hard, cylindrical gelatin capsules of white color, filled with a white or pale cream-colored powder-like mixture; agglomerates may be present.

Pharmacotherapeutic group. Psychostimulants and nootropics.

ATC code: N06BX.

Pharmacological Properties

Pharmacodynamics

Fezam® is a combined medication. The active components of the drug are piracetam, a cyclic derivative of γ-aminobutyric acid, and cinnarizine, a selective calcium channel blocker.

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 are likely multiple: altering the rate of excitation propagation in the brain; enhancing metabolic processes in nerve cells; improving microcirculation by influencing blood rheological properties, without causing vasodilatory effects. It improves interhemispheric connections and synaptic conduction in neocortical structures. After prolonged use in patients with impaired brain functions, improvement in cognitive functions and attention is observed.

Cinnarizine inhibits contractions of vascular smooth 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 is tissue-dependent, resulting in antivasoconstrictive effects without affecting arterial pressure or heart rate. Cinnarizine may further improve impaired microcirculation by increasing erythrocyte membrane elasticity and reducing blood viscosity. Cellular resistance to hypoxia is enhanced. 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 is 91% bound to 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 condition.
• Post-traumatic cerebrasthenia.
• Encephalopathy of various etiologies.
• Psycho-organic syndrome with predominant memory and other cognitive function impairments.
• Labyrinthopathies – vertigo, tinnitus, nausea, vomiting, nystagmus.
• Ménière's syndrome.
• Prophylaxis 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 excitation.

Pregnancy or breastfeeding period.

Interaction with other medicinal products and other types of interactions.

Concomitant use of alcohol and drugs that depress the central nervous system (CNS), as well as tricyclic antidepressants, enhances their sedative effect.

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

Phenotropil® 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 reactivity responses during skin testing; therefore, its use should be discontinued 4 days prior to the test.

Antiepileptic medicinal products. No interaction has been reported 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 was observed in platelet aggregation, fibrinogen levels, von Willebrand factor [coagulation activity (VIII:C); ristocetin cofactor (VIII:vW:Rco); and plasma protein (VIII:vW:Ag)], as well as blood and plasma viscosity.

Pharmacokinetic interactions

The likelihood of changes in piracetam's pharmacodynamics under the influence of other medicinal products is low, since 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 isoenzymes 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 drug should be administered with caution in patients with kidney disorders. In cases of mild or moderate renal insufficiency, it is recommended to reduce the therapeutic dose or increase the dosing interval, especially when creatinine clearance is <60 mL/min.

Hepatic impairment. The drug should be administered with caution in patients with hepatic insufficiency. Liver enzyme levels should be monitored in patients with impaired liver function.

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

The drug passes through the filtering membranes of hemodialysis equipment.

The use of the drug should be avoided in porphyria.

Effect on laboratory tests. The drug may produce false-positive results in doping control tests in athletes, as well as in tests for radioactive iodine, due to the presence of iodine-containing dyes in the capsule coating.

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

Like other antihistamine medicinal products, Fezam® may cause irritation in the epigastric area; taking the drug after meals 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 types of interactions").

Excipients. The medicinal product contains lactose. Therefore, patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

Use during pregnancy or breastfeeding.

The medicinal product 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 the potential occurrence of adverse reactions affecting the central nervous system.

Dosage and Administration

Administer Fezam® capsules orally after meals, without chewing, with water.

Adults

1–2 capsules three times daily.

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 administered.

Children: Not recommended.

Overdose

Symptoms: Exaggerated manifestations of 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 have been observed. In children, excitatory reactions predominate in overdose—insomnia, restlessness, euphoria, irritability, tremor, and rarely nightmares, hallucinations, and seizures.

Treatment: Gastric lavage (preferably within the first hour after ingestion) and administration of activated charcoal. Provide symptomatic therapy. Hemodialysis may be considered.

Adverse reactions.

Central and peripheral nervous system disorders: hyperkinesia, ataxia, headache, sleep disturbances, 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, skin reactions.

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

Skin and subcutaneous tissue disorders: angioneurotic edema, dermatitis, pruritus, rash, urticaria, photosensitivity, hyperhidrosis, lichenoid keratosis, erythematous lupus, and lichen planus.

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

Musculoskeletal and connective tissue disorders: muscle rigidity.

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

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

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

10 capsules in a blister; 2 or 6 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Balkanpharma-Dupnitsa AD.

Manufacturer's address and place of business.

3 Samokovsko Shose Str., Dupnitsa, 2600, Bulgaria.