Piracetam

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

Composition:

Active substance: piracetam;

1 ml of solution contains 200 mg of piracetam;

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

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless liquid.

Pharmacotherapeutic group.

Psychostimulants and nootropics.

ATC code N06B X03.

Pharmacological Properties

Pharmacodynamics

The active component of the medicinal product is piracetam, a cyclic derivative of gamma-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 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 influencing blood rheological properties without vasodilatory effects. It enhances interhemispheric connections and synaptic conduction in neocortical structures. Piracetam inhibits platelet aggregation, restores erythrocyte membrane elasticity, and reduces erythrocyte adhesion. Piracetam exerts protective and restorative effects on impaired brain function due to hypoxia, intoxication, and electroconvulsive therapy. Piracetam reduces the intensity and duration of vestibular nystagmus.

Piracetam is used as a monotherapy or as part of combination therapy for cortical myoclonus, as an agent to reduce the severity of triggering factors—such as vestibular neuronitis.

Pharmacokinetics

After administration of 2 g of the drug, maximum plasma concentration is reached within 30 minutes, while in cerebrospinal fluid it is achieved within 2–8 hours and amounts to 40–60 mcg/mL. The volume of distribution of piracetam is approximately 0.6 L/kg. The elimination half-life from plasma is 4–5 hours and correspondingly 6–8 hours from cerebrospinal fluid. This half-life may be prolonged in renal insufficiency. 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 penetrates the blood-brain barrier, placental barrier, and membranes used during hemodialysis. Animal studies have shown that piracetam selectively accumulates in cerebral cortex 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 part of monotherapy or combination therapy.

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.

Clinical studies have shown that in patients with severe recurrent thrombosis, administration of high-dose piracetam (9.6 g/day) did not affect the required dosage of acenocoumarol to achieve a prothrombin time ratio (INR) 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:vW:Ag)], as well as in blood and plasma viscosity.

Pharmacokinetic interactions.

The likelihood of changes in piracetam's pharmacodynamics due to other medicinal products is low, as 90% of the drug 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 mcg/mL.

At a concentration of 1422 mcg/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 mcg/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 serum concentration-time curves or maximum concentrations (Cmax) of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, sodium valproate) in patients with epilepsy.

Alcohol.

Concomitant use with alcohol did not affect the serum concentration of piracetam, and serum alcohol concentration remained unchanged when 1.6 g of piracetam was administered.

Special precautions for use.

Effect on platelet aggregation.

Since piracetam reduces platelet aggregation (see section "Pharmacodynamic properties"), 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 interventions), patients with signs of severe hemorrhage, or patients with a history of hemorrhagic stroke; and to patients receiving anticoagulants, platelet antiaggregants, including low-dose acetylsalicylic acid. The drug is eliminated by the kidneys; therefore, special attention should be paid to patients with renal impairment.

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

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

This medicinal product contains less than 1 mmol (23 mg) of sodium per 24 g of piracetam, i.e. it is practically sodium-free.

Use during pregnancy or breastfeeding.

The medicinal product should not be used during pregnancy or breastfeeding.

Ability to influence reaction speed when driving or operating machinery.

In clinical studies, hyperkinesia, somnolence, nervousness, and depression were observed more frequently in patients receiving piracetam than in the placebo group when doses ranged from 1.6 to 15 g per day. There are no data available regarding the ability to drive or operate machinery when doses of 15 to 20 grams per day are administered.

Caution should be exercised when driving or operating machinery.

Method of Administration and Dosage

The drug in the form of an injectable solution should be used in acute cases or when oral forms of piracetam cannot be administered. The drug can be administered either intravenously (given slowly over several minutes) or by infusion (administered continuously over 24 hours).

The drug is intended for use in adult patients.

Treatment of conditions associated with impaired memory 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 administrations. The maintenance dose is 2.4 g per day. Subsequently, the dose may be gradually reduced by 1.2 g per day.

Treatment of cortical myoclonus.

The initial daily dose is 24 g, administered over 3 days. If the desired therapeutic effect is not achieved within this period, continue administration at the same dosage (24 g/day) for up to 7 days. If the desired therapeutic effect has not been achieved by day 7, treatment should be discontinued. If a therapeutic effect has been achieved, starting from the day stable improvement is observed, the dose of piracetam should be gradually reduced by 1.2 g every 2 days until symptoms of cortical myoclonus reappear. This allows determination of the average effective dose.

Concomitant treatment with other antimyoclonic agents should be continued at previously prescribed doses. Treatment should continue until symptoms of the disease disappear. To prevent worsening of the patient's condition, the drug should not be discontinued abruptly. The dose should be gradually reduced by 1.2 g of piracetam 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.

Elderly patients.

Dose adjustment is recommended for 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.

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 the elimination half-life is directly related to impaired renal function and reduced creatinine clearance. This also applies to elderly patients, in whom creatinine elimination levels are age-dependent. The dosing interval should be adjusted according to the degree of renal function impairment.

Dosage calculation should be based on assessment of the patient's creatinine clearance. Creatinine clearance should be calculated using the following formula:

Creatinine clearance = [140 - age (years)]×body weight (kg) (×0.85 for women)

72×plasma creatinine concentration (mg/dl)