Phezam^® (Capsules) Instructions for Use

Marketing Authorization Holder

Balkanpharma-Dupnitsa, AD (Bulgaria)

Manufactured By

FHI Zdravlje, A.D. (Serbia)

Or

Balkanpharma-Dupnitsa, AD (Bulgaria)

Contact Information

TEVA (Israel)

ATC Code

N06BX (Other psychostimulants and nootropic drugs)

Active Substances

Piracetam (Rec.INN registered by WHO)

Cinnarizine (Rec.INN registered by WHO)

Dosage Form

Phezam®

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

Dosage Form, Packaging, and Composition

Capsules hard gelatin, size No. 0, cylindrical, white; the capsule contents are a powdered mixture from white to almost white, the presence of conglomerates is allowed, which, when pressed with a glass rod, easily turn into powder.

Excipients: lactose monohydrate – 55 mg, colloidal silicon dioxide – 15 mg, magnesium stearate – 5 mg.

Capsule shell composition titanium dioxide – 2%, gelatin – 98%.

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

Clinical-Pharmacological Group

A drug that improves cerebral circulation and metabolism

Pharmacotherapeutic Group

Psychoanaleptics; psychostimulants, agents used in attention deficit hyperactivity disorder, and nootropic agents; other psychostimulants and nootropic agents

Pharmacological Action

A combined drug with a pronounced antihypoxic, nootropic and vasodilating effect. The components mutually potentiate the reduction of cerebral vascular resistance and contribute to increased blood flow in them.

Piracetam activates metabolic processes in the brain by enhancing energy and protein metabolism, accelerating glucose utilization by cells and increasing their resistance to hypoxia; improves interneuronal transmission in the central nervous system, improves regional blood flow in the ischemic zone.

Cinnarizine is a selective blocker of slow calcium channels and an antagonist of histamine H₁ receptors. It has been established that Cinnarizine inhibits the entry of calcium ions into cells and reduces their content in the plasmalemma depot, reduces the tone of arteriole smooth muscles, and reduces their response to biogenic vasoconstrictor substances (catecholamines, angiotensin and vasopressin). It has a vasodilating effect (especially concerning the vessels of the brain, enhancing the antihypoxic effect of piracetam), without significantly affecting blood pressure. It exhibits moderate antihistamine activity, reduces the excitability of the vestibular apparatus, and lowers the tone of the sympathetic nervous system. It increases the elasticity of erythrocyte membranes, their ability to deform, and reduces blood viscosity.

Pharmacokinetics

Piracetam

Absorption

Rapidly and completely absorbed from the gastrointestinal tract. C_max of piracetam in plasma is reached in 2-6 hours, the maximum concentration in cerebrospinal fluid is reached in 2-8 hours. Bioavailability is 100%.

Distribution

Does not bind to plasma proteins. The apparent V_d of piracetam is about 0.6 l/kg. Distributed in all organs and tissues, freely penetrates the blood-brain barrier. Selectively accumulates in the cerebral cortex, mainly in the frontal, parietal and occipital lobes, cerebellum and basal ganglia.

Penetrates the placental barrier.

Metabolism and excretion

Not metabolized.

T_1/2 from blood plasma is 4-5 hours, from cerebrospinal fluid – 8.5 hours. 80-100% of piracetam is excreted by the kidneys unchanged by renal filtration. The renal clearance of piracetam in healthy volunteers is 86 ml/min.

Pharmacokinetics in special patient groups

T_1/2 is prolonged in renal failure. Penetrates through the filtering membranes of hemodialysis apparatus.

The pharmacokinetics of piracetam does not change in patients with hepatic insufficiency.

Cinnarizine

Absorption and distribution

After oral administration, absorption is slow. C_max of cinnarizine in plasma is reached in 1-4 hours. Binds to plasma proteins by 91%.

Metabolism and excretion

Actively and completely metabolized by liver isoenzymes CYP2D6 via dealkylation.

T_1/2 is 4 hours. 1/3 of metabolites are excreted by the kidneys, 2/3 through the intestines.

Indications

• Cerebral circulation insufficiency (cerebral vascular atherosclerosis, recovery period of ischemic and hemorrhagic strokes, traumatic brain injuries, encephalopathy of various origins);
• Intoxications;
• Diseases of the central nervous system accompanied by a decrease in intellectual and mnestic functions (memory impairment, attention, mood);
• Conditions after a traumatic brain injury;
• Psycho-organic syndrome with a predominance of signs of asthenia and adynamia;
• Asthenic syndrome of psychogenic origin;
• Labyrinthopathies (dizziness, tinnitus, nausea, vomiting, nystagmus);
• Ménière’s syndrome;
• Prevention of migraine and motion sickness;
• As part of complex therapy for low learning ability in children with psycho-organic syndrome.

ICD codes

Dosage Regimen

Administer the drug orally.

For adult patients, the standard dose is 1-2 capsules taken three times daily.

Continue treatment for a duration of 1 to 3 months, depending on the severity of the underlying condition.

Repeat the treatment course 2-3 times per year as medically indicated.

For pediatric patients over 5 years of age, prescribe 1-2 capsules taken one to two times daily.

The treatment course for children should last from 1.5 to 3 months.

Adjust the dosage and frequency based on individual patient tolerance and clinical response.

Do not administer to children under 5 years of age.

Adverse Reactions

Allergic reactions in very rare cases – hypersensitivity reactions in the form of skin rash, dermatitis, itching, swelling, photosensitivity.

From the digestive system in some cases, increased salivation, nausea, vomiting, diarrhea, abdominal pain are possible.

From the nervous system hyperkinesia, nervousness, drowsiness, depression; in isolated cases – dizziness, headaches, ataxia, imbalance, insomnia, confusion, agitation, anxiety, hallucinations.

Other increased sexual activity.

With long-term therapy in elderly patients, tremor may appear.

Contraindications

• Severe renal failure (creatinine clearance <20 ml/min);
• Severe hepatic failure;
• Hemorrhagic stroke;
• Psychomotor agitation at the time of prescribing the drug;
• Huntington’s chorea;
• Children under 5 years of age;
• Pregnancy;
• Lactation period;
• Rare hereditary diseases (galactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose monohydrate));
• Hypersensitivity to piracetam, cinnarizine or to any of the excipients included in the drug.

With caution Parkinson’s disease; conditions associated with increased intraocular pressure; impaired liver and/or kidney function, impaired hemostasis, severe bleeding.

Use in Pregnancy and Lactation

Despite the absence of data on the teratogenic effect of piracetam and cinnarizine, the use of the drug during pregnancy is not recommended. Prescription of the drug Phezam^® to pregnant women is indicated only if the intended benefit to the mother outweighs the potential risk to the fetus.

Piracetam is excreted in breast milk, so it is recommended to stop breastfeeding during its use.

Use in Hepatic Impairment

Contraindicated in severe hepatic failure.

The drug should be prescribed with caution in case of impaired liver function.

Use in Renal Impairment

Contraindicated in severe renal failure (creatinine clearance <20 ml/min).

The drug should be prescribed with caution in case of impaired renal function.

Pediatric Use

Contraindicated in children under 5 years of age.

Special Precautions

The drug should be prescribed with caution to persons with liver and/or kidney diseases. In cases of mild and moderate renal failure (especially if creatinine clearance is less than 60 ml/min), the therapeutic dose should be reduced or the intervals between doses should be increased. In persons with impaired liver function, monitoring of liver enzyme levels is necessary.

Alcohol consumption should be avoided during treatment.

The drug may cause a false-positive reaction when testing for doping agents in athletes.

The drug enhances the activity of thyroid hormones and may cause tremor and anxiety.

Effect on the ability to drive vehicles and machinery

Caution should be exercised when driving vehicles and working with machinery and equipment during treatment, since at the beginning of treatment Cinnarizine may cause drowsiness.

Overdose

Phezam^® is very well tolerated by patients; in case of overdose, no serious side effects requiring drug withdrawal are observed.

In case of overdose in children, symptoms of excitation dominate: insomnia, restlessness, euphoria, irritability, tremor and in rare cases nightmares, hallucinations and convulsions.

Treatment symptomatic therapy, which may include hemodialysis. Gastric lavage should be performed, vomiting should be induced. There is no specific antidote.

Drug Interactions

When taken simultaneously with drugs that depress the central nervous system, tricyclic antidepressants and alcohol, the sedative effect is enhanced.

The drug potentiates the effect of nootropic and antihypertensive agents.

Vasodilators enhance the effect of the drug.

Improves the tolerability of antipsychotic drugs and tricyclic antidepressants.

Enhancement of the effect of oral anticoagulants is possible.

Storage Conditions

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

Shelf Life

The shelf life is 3 years. Do not use after the expiration date printed on the package.

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.