Piracetam

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

Composition:

Active substance: piracetam;

One tablet contains 200 mg of piracetam;

Excipients: potato starch, povidone, heavy magnesium carbonate, calcium stearate;

Coating composition: refined sugar, silicon dioxide, povidone, heavy magnesium carbonate, titanium dioxide (E 171), tartrazine (E 102), beeswax, sunflower oil.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: film-coated tablets of yellow color, biconvex. Two layers are visible in cross-section.

Pharmacotherapeutic group.

Psychostimulants and nootropic agents. Piracetam. ATC code N06BX03.

Pharmacological Properties

Pharmacodynamics

The active component of the drug is piracetam, a cyclic derivative of γ-aminobutyric acid.

Piracetam is a nootropic agent acting on the brain, improving cognitive functions such as learning ability, memory, attention, and mental performance. The drug likely exerts multiple 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 causing vasodilatory effects. It enhances interhemispheric connections and synaptic conductivity in neocortical structures, inhibits platelet aggregation, restores erythrocyte membrane elasticity, and reduces erythrocyte adhesion. Piracetam provides protective and restorative effects on impaired brain function due to hypoxia, intoxication, or electroconvulsive therapy. Piracetam reduces the intensity and duration of vestibular nystagmus.

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

Pharmacokinetics

After oral administration, piracetam is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is nearly 100%. Peak plasma concentration (C_max) following a 2 g dose is reached within 30 minutes, while peak concentration in cerebrospinal fluid is achieved within 2–8 hours and amounts to 40–60 µg/mL. The volume of distribution of piracetam is approximately 0.6 L/kg. The elimination half-life from plasma is 4–5 hours and 6–8 hours from cerebrospinal fluid. This half-life may be prolonged in renal impairment. Piracetam does not bind to plasma proteins and is not metabolized in the body. 80–100% of piracetam is excreted unchanged by the kidneys via glomerular filtration.

Renal clearance of piracetam in healthy volunteers is 86 mL/min. The pharmacokinetics of piracetam are not altered in patients with hepatic insufficiency. Piracetam crosses the blood-brain barrier, placental barrier, and membranes used during hemodialysis. Animal studies have shown that piracetam selectively accumulates in cerebral cortical tissues, predominantly in the frontal, parietal, and occipital regions, as well as in the cerebellum and basal ganglia.

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.

Contraindications.

• Hypersensitivity to piracetam or to pyrrolidone derivatives, as well as to any other components of the medicinal product;
• Acute cerebrovascular accident (hemorrhagic stroke);
• Terminal stage of renal failure;
• Huntington's chorea.

Interaction with other medicinal products and other types of interactions.

Thyroid hormones.

Concomitant use with thyroid hormones (T3+T4) may result in increased irritability, disorientation, and sleep disturbances.

Acenocoumarol.

Clinical studies have shown that in patients with severe recurrent thrombosis, administration of piracetam at doses of 9.6 g/day did not lead to the need for dose adjustment of acenocoumarol to achieve an international normalized ratio (INR) of 2.5–3.5. However, when used concomitantly, a significant reduction in platelet aggregation, β-thromboglobulin release, fibrinogen levels, von Willebrand factors (VIII:C; VIII:vW:Ag; VIII:vW:Rco), whole blood and plasma viscosity was observed.

Pharmacokinetic interactions.

The likelihood of changes in the pharmacokinetics of piracetam 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 liver 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 at concentrations exceeding 1422 µg/mL. Therefore, metabolic interaction with drugs undergoing biotransformation by these enzymes is unlikely.

Antiepileptic medicinal products.

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

Alcohol.

Concomitant 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, the drug should be prescribed with caution to patients with coagulation disorders, 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 in patients with a history of hemorrhagic stroke; also in patients receiving anticoagulants, platelet antiaggregants, including low-dose acetylsalicylic acid.

Renal function impairment.

The drug is eliminated by the kidneys; therefore, special attention should be given to patients with renal insufficiency.

Discontinuation of treatment.

In the treatment of patients with cortical myoclonus, abrupt discontinuation of therapy should be avoided due to the risk of generalization of myoclonus or occurrence of seizures.

Elderly patients.

During long-term therapy in elderly patients, regular monitoring of renal function is recommended; dose adjustment may be necessary based on creatinine clearance test results.

Precautions related to excipients.

Due to the presence of refined sugar in the drug coating, patients with known sugar intolerance should consult their physician before taking this medicinal product.

The medicinal product contains the azo dye tartrazine (E 102), which may cause allergic reactions.

Use during pregnancy or breastfeeding.

Piracetam should not be used during pregnancy or breastfeeding.

Ability to influence reaction rate when driving or operating machinery.

Due to adverse reactions observed with this medicinal product, an effect on the ability to drive vehicles or operate machinery is possible and should be taken into account.

Method of Administration and Dosage

The drug is administered orally, taken with a small amount of water.

Adults.

Treatment of conditions associated with memory impairment and cognitive disorders.

The initial daily dose is 4.8 g during the first week of treatment. The dose is usually divided into 2–3 doses. The maintenance dose is 2.4 mg per day, divided into 2–3 doses. Subsequently, the dose may be gradually reduced by 1.2 g per day.

Treatment of cortical myoclonus.

The initial daily dose is 24 g for 3 days. If the desired therapeutic effect is not achieved within this period, the drug is continued at the same dosage (24 g/day) for up to 7 days. If no therapeutic effect is observed by day 7, treatment should be discontinued. If a therapeutic effect is achieved, starting from the day when stable improvement is observed, the dose should be gradually reduced by 1.2 g every 2 days until symptoms of cortical myoclonus reappear. This will allow determination of the average effective dose.

The daily dose should be divided into 2–3 administrations. Treatment with other antimyoclonic agents should be maintained at previously prescribed doses. Treatment should continue until symptoms of the disease disappear. To prevent worsening of the patient's condition, the drug must not be discontinued abruptly. The dose should be gradually reduced by 1.2 g every 2–3 days. Repeated courses of treatment with the drug should be prescribed every 6 months, adjusting the dose according to the patient's condition, until symptoms disappear or decrease.

Use in elderly patients.

Dose adjustment is recommended for elderly patients with diagnosed or suspected renal impairment (see section "Dosage in patients with renal impairment"). During long-term treatment, if necessary, such patients should have creatinine clearance monitored to ensure appropriate dose adjustment.

Dosage in patients with renal impairment.

Since the drug is eliminated from the body via the kidneys, caution should be exercised when treating patients with renal insufficiency.

Prolongation of elimination half-life is directly related to worsening 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.

Dose calculation should be based on estimation of creatinine clearance using the following formula:

[140 – age (years)] * m (kg)
Ccr = —————————————— × 0.85 (for women)
72 * plasma creatinine (mg/dL)

Treatment in such patients should be prescribed according to the severity of renal insufficiency, following these recommendations:

Dosage in patients with hepatic impairment.

Dose adjustment is not required solely for patients with hepatic impairment. In case of diagnosed or suspected hepatic and renal dysfunction, dosage adjustment should be performed as indicated in the section «Dosage in patients with renal impairment».

Children.

Not applicable.

Overdose.

Symptoms: intensification of adverse drug reactions. Symptoms of overdose were observed following oral administration of the drug at a dose of 75 g.

Treatment: symptomatic; gastric lavage, induction of emesis. There is no specific antidote; hemodialysis can be used (eliminates 50–60% of piracetam).

Adverse Reactions

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

Frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be estimated from the available data).
Post-marketing data are insufficient to determine the frequency of adverse reactions in the treated population.

Nervous system disorders

Common: hyperactivity
Uncommon: somnolence
Frequency not known: ataxia, balance disorder, increased frequency of epileptic seizures, headache, insomnia, tremor

Psychiatric disorders

Common: nervousness
Uncommon: depression
Frequency not known: increased excitability, anxiety, confusion, hallucinations

Blood and lymphatic system disorders

Frequency not known: haemorrhagic disorders

Immune system disorders

Frequency not known: hypersensitivity, anaphylactoid reactions

Ear and labyrinth disorders

Frequency not known: dizziness

Gastrointestinal disorders

Frequency not known: abdominal pain, upper abdominal pain, diarrhoea, nausea, vomiting

Skin and subcutaneous tissue disorders

Frequency not known: angioneurotic oedema, dermatitis, urticaria, pruritus

Reproductive system and breast disorders

Frequency not known: increased sexual drive

General disorders

Uncommon: asthenia

Investigations

Common: weight increased

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions in accordance with applicable regulatory requirements.

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of the reach of children.

Packaging. 10 tablets per blister; 3 or 6 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Halychpharm"

Manufacturer's name and address of the place of business.
6/8 Opryshkivska Street, Lviv, 79024, Ukraine