Piracetam

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

Composition:

Active substance: piracetam;

1 tablet contains piracetam 200 mg or 400 mg;

Excipients: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, magnesium stearate, colloidal anhydrous silicon dioxide, talc.

Pharmaceutical form. Tablets.

Main physico-chemical properties: tablets of white with creamy shade color, flat cylindrical shape with beveled edges and a score line; marbling on the surface of the tablets is permissible.

Pharmacotherapeutic group. Psychostimulants and nootropic agents.

ATC code N06BX03.

Pharmacological Properties.

Pharmacodynamics.

Piracetam is a nootropic agent that acts on the brain, improving cognitive processes such as learning ability, memory, attention, and mental performance. Piracetam affects the central nervous system through multiple mechanisms: it alters the rate of excitation spread in the brain; improves metabolic processes in nerve cells; enhances microcirculation by influencing blood rheological properties without causing vasodilatory effects.

It improves interhemispheric connections and synaptic conductivity in cortical structures. Piracetam inhibits platelet aggregation and restores erythrocyte membrane elasticity, reducing erythrocyte adhesion. Piracetam exerts protective and restorative effects on impaired brain function due to hypoxia and intoxication. Piracetam reduces the intensity and duration of vestibular nystagmus.

Pharmacokinetics.

After oral administration, piracetam is rapidly and almost completely absorbed; peak plasma concentration is reached within 1 hour after intake. Bioavailability is nearly 100% after a single 2 g dose. The volume of distribution of piracetam is approximately 0.6 L/kg.

The elimination half-life of the drug from blood plasma is 4–5 hours and 6–8 hours from cerebrospinal fluid, with prolongation observed 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 impairment. Piracetam crosses the blood-brain barrier, placental barrier, and membranes used during hemodialysis. In animal studies, piracetam selectively accumulated in cerebral cortex tissues, predominantly in the frontal, parietal, and occipital lobes, as well as in the cerebellum and basal ganglia.

Clinical characteristics.

Indications.

For use in adults:

• For symptomatic treatment of pathological conditions accompanied by memory impairment and cognitive disorders, excluding diagnosed dementia;
• For treatment of cortical myoclonus: as monotherapy or as part of combination therapy.

Contraindications.

• Individual hypersensitivity to piracetam or pyrrolidone derivatives, as well as to other components of the medicinal product.
• Acute impairment of cerebral circulation (hemorrhagic stroke).
• Terminal stage of renal failure (with creatinine clearance less than 20 ml/min).
• Huntington's chorea.

Interaction with other medicinal products and other types of interactions.

Pharmacokinetic interactions.

The potential for 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 value for these two CYP isoenzymes is sufficient when exceeding the level of 1422 µg/ml. Therefore, metabolic interaction with drugs undergoing biotransformation by these enzymes is unlikely.

Thyroid hormones.

When used concomitantly with thyroid hormones (T3+T4), increased irritability, disorientation, and sleep disturbances may occur.

Acenocoumarol.

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

Antiepileptic medicinal products.

Administration of piracetam at a dose of 20 mg daily for 4 weeks did not alter the concentration-time curve or peak concentration of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, sodium valproate) in patients with epilepsy.

Alcohol.

Concomitant intake with alcohol does not affect the concentration of piracetam in blood serum, and the serum alcohol concentration is not altered following a single 1.6 g dose of piracetam.

In elderly individuals, piracetam enhances the effect of antianginal agents and increases the efficacy of antidepressants.

Special precautions for use.

Effect on platelet aggregation.

Since piracetam reduces platelet aggregation, the drug should be prescribed with caution to patients with impaired hemostasis, conditions that may be associated with bleeding (e.g., gastrointestinal ulcer), during major surgical procedures (including dental surgery), in patients with symptoms of severe hemorrhage; in patients with a history of hemorrhagic stroke; and in patients receiving anticoagulants, platelet antiaggregants, including low-dose acetylsalicylic acid.

Renal impairment.

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

Elderly patients.

For elderly patients undergoing long-term therapy, regular monitoring of renal function parameters is recommended. Dose adjustment may be necessary based on creatinine clearance test results.

Discontinuation of treatment.

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

The drug penetrates through the filtering membranes of hemodialysis equipment.

Important information on excipients.

The preparation contains lactose. Therefore, the drug should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Do not use the drug during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

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

Dosage and Administration.

The medicinal product should be administered orally, before or during meals. Tablets should be taken with liquid (water or juice). The duration of treatment and selection of individual dosage depend on the severity of the patient's condition and the rate of positive clinical response.

Administration to adults.

Treatment of conditions associated with impaired memory and cognitive disorders.

The initial daily dose is 4.8 g during the first week of treatment. This dose should be divided into 2–3 doses. The maintenance dose is 2.4 g per day (divided into 2–3 doses). Subsequently, a gradual reduction of the dose by 1.2 g per day may be possible.

Treatment of cortical myoclonus.

The initial dose is 24 g/day for 3 days. If the desired therapeutic effect is not achieved within this period, the medicinal product should be continued at the same dosage (24 g/day) up to 7 days. If the desired therapeutic effect is not achieved by day 7, treatment with piracetam should be discontinued. If a therapeutic effect is achieved, starting from the day when stable improvement occurs, the dose should be gradually reduced by 1.2 g every 2 days until symptoms of cortical myoclonus reappear. This approach allows determination of the average effective dose.

The daily dose should be divided into 2–3 doses. Concomitant therapy with other antimyoclonic agents should be maintained at previously prescribed dosages. Treatment should be continued until disappearance of disease symptoms. To prevent worsening of the patient's condition, abrupt discontinuation of the medicinal product is not allowed. The dose should be gradually reduced by 1–2 g every 2–3 days. Repeated treatment courses should be prescribed every 6 months, adjusting the dose according to the patient's condition, until symptoms disappear or decrease.

Administration to elderly patients.

Dosage adjustment is recommended for elderly patients with diagnosed or suspected renal function disorders. In long-term treatment, creatinine clearance should be monitored in these patients when necessary, to ensure appropriate dosage adjustment.

Dosage in patients with impaired renal function.

Since the medicinal product is eliminated via the kidneys, caution should be exercised when treating patients with renal insufficiency.

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 according to renal function parameters.

The dose should be calculated based on the patient's creatinine clearance estimated using the following formula:

Prescribe treatment depending on the degree of renal impairment, following these recommendations:

Patients with impaired liver function do not require dose adjustment.

In cases of diagnosed or suspected liver and kidney dysfunction, dose 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: dyspeptic symptoms such as diarrhea with blood and abdominal pain were reported.

Treatment: symptomatic. Following significant oral overdose, gastric lavage or induction of emesis should be performed immediately. There is no specific antidote; hemodialysis may be used (eliminates 50–60% of piracetam).

Adverse Reactions

Adverse reactions, particularly reported during post-marketing surveillance, are listed below by system organ class and frequency of occurrence.

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), not specified (frequency cannot be estimated based on available data).

Vestibular system

Not specified: vertigo.

Gastrointestinal system

Not specified: anorexia, abdominal pain, upper abdominal pain, nausea, diarrhea, vomiting, constipation.

Metabolism and nutritional disorders

Common: weight gain.

Nervous system

Common: hyperactivity.

Uncommon: somnolence.

Not specified: extrapyramidal disorders, ataxia, tremor, loss of balance, dizziness, headache, excitement, irritability, sleep disturbances, insomnia, increased frequency of epileptic seizures, convulsions.

Psychiatric disorders

Common: nervousness.

Uncommon: depression.

Not specified: increased excitability, confusion, anxiety, disorientation, hallucinations.

Cardiac disorders

Not specified: worsening of angina pectoris, arterial hypertension.

Blood and lymphatic system disorders

Not specified: thrombophlebitis, haemorrhagic disorders.

Immune system disorders

Not specified: hypersensitivity reactions, including anaphylaxis.

Skin and subcutaneous tissue disorders

Not specified: angioneurotic edema, dermatitis, pruritus, rash, urticaria.

Reproductive system disorders

Not specified: increased sexual activity.

General disorders

Not specified: hyperthermia, asthenia.

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and 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. 2 years.

Do not use 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 of children.

Packaging.

10 tablets in a blister pack, 6 blisters in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

JSC "CHEMICAL PHARMACEUTICAL PLANT "CHERVONA ZIRKA".

Manufacturer's address and place of business.

Ukraine, 61010, Kharkiv region, Kharkiv city, Gordienkivska Street, 1.