Piracetam-zdorovya

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT PIRACETAM-ZDOROV'YA

Composition:

Active substance: 1 ml of solution contains 200 mg of piracetam;

Excipients: sodium acetate trihydrate; acetic acid, diluted; water for injections.

Pharmaceutical form. Injection solution.

Main physico-chemical properties: clear, slightly colored solution.

Pharmacotherapeutic group. Psychostimulants and nootropics. ATC code N06B X03.

Pharmacological Properties.

Pharmacodynamics. Piracetam is a nootropic agent, i.e. a psychotropic drug that directly enhances the efficiency of cognitive functions. The drug likely exerts several mechanisms of action on the central nervous system: altering the rate of excitation propagation in the brain; enhancing metabolic processes in nerve cells; improving microcirculation by affecting blood rheological properties, without exerting vasodilatory effects.

Repeated or single administration of piracetam to patients with cerebral dysfunction causes significant changes in electroencephalogram (EEG), demonstrating increased alertness and improved cognitive function (increased α- and β-activity and decreased δ-activity).

Piracetam inhibits hyperaggregation of activated platelets. In cases of pathological erythrocyte rigidity, piracetam improves their filterability and elasticity. Piracetam exerts protective and restorative effects on impaired brain functions caused by hypoxia, intoxication, and electroconvulsive therapy.

Piracetam is used either as a monotherapy or as part of combination therapy for cortical myoclonus to reduce the impact of triggering factors—vestibular neuronitis.

Pharmacokinetics.

Absorption. After a single 2 g dose, maximum plasma concentration (Cmax) is achieved within 30 minutes, while in cerebrospinal fluid it is reached within 2–8 hours and amounts to 40–60 μg/mL.

Distribution. Piracetam does not bind to plasma proteins, and its apparent volume of distribution is approximately 0.6 L/kg. Piracetam distributes throughout all tissues and penetrates the blood-brain barrier, placental barrier, and membranes used during hemodialysis. Piracetam accumulates in cerebral cortex tissues, predominantly in the frontal, parietal, and occipital regions, as well as in the cerebellum and basal ganglia.

Biotransformation. Piracetam is active in its unchanged form and is not metabolized in animals.

Elimination. The elimination half-life of the drug from blood is 4–5 hours and from cerebrospinal fluid is 6–8 hours. This period may be prolonged in renal insufficiency. Piracetam is excreted unchanged by the kidneys. It is almost completely eliminated in urine (over 95%) within 30 hours. Renal clearance of piracetam in healthy volunteers is 86 mL/min.

Clinical characteristics.

Indications.

Adults:

• symptomatic treatment of pathological conditions associated with impaired memory and cognitive disorders, excluding diagnosed dementia;
• treatment of cortical myoclonus – as monotherapy or as part of combination therapy. To assess sensitivity to piracetam, a trial course of treatment may be conducted for a limited period of time.

Contraindications. Hypersensitivity to piracetam or pyrrolidone derivatives, as well as to other components of the medicinal product. Acute cerebral circulation disorders (hemorrhagic stroke). Terminal stage of renal failure. Huntington's chorea.

Interaction with other medicinal products and other forms of interactions.

Thyroid hormones. When used concomitantly with thyroid hormones, increased irritability, disorientation, and sleep disturbances may occur.

Acenocoumarol. In clinical studies in patients with severe recurrent thrombosis, administration of piracetam at a dose of 9.6 g/day did not require adjustment of acenocoumarol dosage to achieve an international normalized ratio of 2.5–3.5. However, when used concomitantly, a significant reduction was observed in platelet aggregation, β-thromboglobulin release, levels of fibrinogen, von Willebrand factor (coagulation activity (VIII:C), ristocetin cofactor activity (VIII:vW:Rco), and von Willebrand factor antigen in plasma (VIII:vW:Ag)), as well as whole blood and plasma viscosity.

Pharmacokinetic interactions. The likelihood of changes in piracetam pharmacokinetics due to other medicinal products is low, as approximately 90% of the drug is excreted unchanged in urine.

In vitro, piracetam does not inhibit the major human cytochrome P450 isoforms 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 value for inhibition of these two CYP isoforms is sufficient only when exceeding 1422 µg/mL. Therefore, metabolic interactions with drugs metabolized by these enzymes are unlikely.

Antiepileptic medicinal products. Administration of piracetam at a dose of 20 g daily for 4 weeks or longer did not alter the concentration-time profile or Cmax of antiepileptic drugs in blood serum (carbamazepine, phenytoin, phenobarbital, sodium valproate) in patients with epilepsy receiving stable doses.

Alcohol. Concurrent intake with alcohol did not affect the plasma concentration of piracetam, and alcohol concentration was not altered when 1.6 g of piracetam was administered.

Special precautions for use.

Effect on platelet aggregation. Since piracetam reduces platelet aggregation (see section "Pharmacological properties"), the drug should be prescribed with caution to patients with impaired hemostasis, conditions that may be associated with bleeding (e.g. peptic ulcer of the gastrointestinal tract), during major surgical procedures (including dental interventions), in patients with signs of severe hemorrhage, or in patients with a history of hemorrhagic stroke, as well as in patients receiving anticoagulants, platelet antiaggregants, including low-dose acetylsalicylic acid.

Renal impairment. The drug is excreted by the kidneys; therefore, special attention should be paid to patients with renal insufficiency (see section "Dosage and administration").

Elderly patients. During long-term therapy in elderly patients, regular monitoring of renal function parameters is recommended; the dose should be adjusted as necessary according to creatinine clearance test results (see section "Dosage and administration").

Discontinuation of the drug. In the treatment of patients with cortical myoclonus, abrupt discontinuation of therapy should be avoided due to the risk of generalized myoclonus or seizure occurrence.

Precautions related to excipients. The medicinal product contains less than 1 mmol (or 23 mg) of sodium per 24 g piracetam dose, thus being practically sodium-free.

Use during pregnancy or breastfeeding. The drug should not be used during pregnancy or breastfeeding.

Ability to affect reaction rate when driving or operating machinery. Due to adverse reactions observed with the use of this medicinal product, an effect on the ability to drive or operate machinery is possible and should be taken into account.

Method of administration and dosage.

The medicinal product in the form of an injectable solution is used when oral forms of piracetam cannot be administered. The medicinal product is administered by intravenous injection (given slowly over several minutes) or by infusion (administered continuously over 24 hours).

The medicinal product is intended for use in adults.

Treatment of conditions associated with memory impairment and cognitive disorders. The recommended daily dose is 2.4 g to 4.8 g, divided into 2 or 3 doses.

Treatment of cortical myoclonus. The initial daily dose is 7.2 g, which is increased by 4.8 g every three or four days up to a maximum dose of 24 g, divided into two or three doses. Treatment with other antimyoclonic medicinal products should be continued at the same doses. Depending on the therapeutic effect achieved, and if possible, the dose of other antimyoclonic medicinal products should be reduced.

Piracetam treatment should be continued until symptoms of the underlying brain disorder disappear. In patients with acute disease course, spontaneous improvement may occur over time; therefore, every 6 months an attempt should be made to reduce the dose or discontinue the medicinal product. For this purpose, the piracetam dose should be reduced by 1.2 g every two days (every three or four days in patients with Lanza-Adams syndrome, to prevent sudden relapse or occurrence of seizures associated with withdrawal of the medicinal product).

Special patient groups.

Elderly patients. Dose adjustment is recommended in elderly patients with diagnosed or suspected renal impairment (see section "Patients with renal impairment"). During treatment, creatinine clearance should be monitored to ensure appropriate dose adjustment in these patients, if necessary.

Patients with renal impairment. Since the medicinal product is eliminated by the kidneys, caution should be exercised when treating patients with renal insufficiency; renal function should be monitored in such patients.

Prolongation of elimination half-life is directly related to impaired renal function and creatinine clearance. This also applies to elderly patients, in whom creatinine clearance is age-dependent. The dosing interval should be adjusted based on renal function.

The dose should be calculated according to creatinine clearance using the following formula:

Treatment for such patients is prescribed depending on the degree of renal impairment, following these recommendations:

Patients with hepatic impairment. Dose adjustment is not required in patients with hepatic impairment alone. In cases of diagnosed or suspected hepatic and renal impairment, dose adjustment should be performed as indicated in the section «Patients with renal impairment».

Children. Not applicable.

Overdose. Symptoms: intensification of the drug's adverse effects. Overdose symptoms were observed following oral administration of the drug at a dose of 75 g.

Treatment: symptomatic. There is no specific antidote; hemodialysis may be used (eliminates 50–60% of piracetam).

Adverse reactions. Adverse reactions observed during clinical trials and post-marketing surveillance are listed by organ system classes and frequency.

Frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), frequency not known (cannot be estimated from available data).

Post-marketing data are insufficient to calculate the frequency of adverse reactions in the treated population.

Blood and lymphatic system disorders.

Frequency not known: hemorrhagic disorders.

Immune system disorders.

Frequency not known: hypersensitivity, anaphylactoid reactions.

Psychiatric disorders.

Common: nervousness.

Uncommon: depression.

Frequency not known: increased excitability, anxiety, confusion, hallucinations.

Nervous system disorders.

Common: hyperactivity.

Uncommon: somnolence.

Frequency not known: ataxia, loss of balance, increased frequency of epileptic seizures, headache, insomnia, tremor.

Ear and labyrinth disorders.

Frequency not known: dizziness.

Gastrointestinal disorders.

Frequency not known: abdominal pain, upper abdominal pain, diarrhea, nausea, vomiting.

Skin and subcutaneous tissue disorders.

Frequency not known: angioneurotic edema, dermatitis, urticaria, pruritus.

Reproductive system and breast disorders.

Frequency not known: increased sexual activity.

Vascular disorders.

Rare: hypotension, thrombophlebitis.

General disorders and administration site conditions.

Uncommon: asthenia.

Rare: pain at injection site, chills.

Investigations.

Common: weight gain.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, patients, or their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 4 years.

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

Keep out of reach and sight of children.

Incompatibilities. Not studied. The drug should not be mixed with other medicinal products.

Packaging. 5 ml in vials, pack of 10 in a box; 5×2 in blisters in a box; 10 ml in vials, pack of 5, pack of 10 in a box.

Prescription category. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY «CORPORATION «ZDOROV’YA».

Manufacturer's address and location of operations. 22, Shevchenka Street, Kharkiv, Kharkiv Oblast, 61013, Ukraine.