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 nootropic agents.

ATC code N06B X03.

Pharmacological Properties.

Pharmacodynamics.

Piracetam is a nootropic agent, i.e., a psychotropic drug acting on the brain and improving cognitive functions. The drug likely affects the central nervous system through several mechanisms: 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.

Repeated or single administration of piracetam to patients with cerebral dysfunction results in 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 pathologically increased erythrocyte rigidity, piracetam enhances their filterability and elasticity. Piracetam exerts protective and restorative effects on impaired brain function due to hypoxia, intoxication, and electroconvulsive therapy.

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

Pharmacokinetics.

Absorption

After a single 2 g dose, 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.

Distribution

Piracetam does not bind to plasma proteins. The volume of distribution of piracetam 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 the tissues of the cerebral cortex, 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.

Excretion

The elimination half-life of the drug from plasma is 4–5 hours and, correspondingly, 6–8 hours from cerebrospinal fluid. This half-life may be prolonged in renal impairment. 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 treatment course may be administered 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 types of interactions.

Thyroid hormones.

Concomitant use with thyroid hormones may lead to increased irritability, disorientation, and sleep disturbances.

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 (INR) of 2.5–3.5. However, when used concomitantly, a significant reduction was observed in platelet aggregation, fibrinogen levels, von Willebrand factor levels [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 the pharmacodynamics of piracetam 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 µg/mL.

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

Alcohol.

Concomitant intake with alcohol did not affect the serum concentration levels of piracetam, and serum alcohol concentrations were not altered following administration of 1.6 g of piracetam.

Special precautions for use.

Effect on platelet aggregation.

Since piracetam reduces platelet aggregation (see section "Pharmacodynamic properties"), caution is required when prescribing the drug 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 patients with a history of hemorrhagic stroke; and 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; dose adjustment according to creatinine clearance may be necessary (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.

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 rate when driving or operating machinery.

Due to the adverse reactions observed with this medicinal product, a possible effect on the ability to drive vehicles or operate machinery should be considered.

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 may 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 recommended daily dose is 2.4 g to 4.8 g, divided into 2 or 3 administrations.

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 administrations.

Concomitant treatment with other antimyoclonic agents should be maintained at previously prescribed doses. Depending on the therapeutic response achieved, and if possible, the dosage of other antimyoclonic drugs should be reduced. Treatment should continue until symptoms of the underlying brain disorder have resolved. In patients with acute disease progression, spontaneous improvement may occur over time; therefore, every 6 months an attempt should be made to reduce the dose or discontinue the drug. For this purpose, the dose of piracetam should be reduced by 1.2 g every two days (every three or four days in cases of Landau–Adams syndrome, to prevent sudden relapse or withdrawal-related seizures).

Elderly patients.

Dosage 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 elimination half-life is directly related to worsening renal function and reduced creatinine clearance. This also applies to elderly patients, in whom creatinine clearance is 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)

Treat such patients according to the degree of renal impairment, following these recommendations:

Patients with impaired liver function

Dose adjustment is not required in patients with impaired liver function. In cases of diagnosed or suspected disorders of both liver and kidney function, dose adjustment should be performed as indicated in the section "Patients with impaired kidney function."

Children. Not to be used.

Overdose.

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

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

Adverse Reactions

Adverse reactions observed during clinical trials and post-marketing surveillance are listed below 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 available data).

Post-marketing data are insufficient to determine 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 breastfeeding disorders

Frequency not known: increased sexual activity

Vascular disorders

Rare: hypotension, thrombophlebitis

General disorders and administration site conditions

Uncommon: asthenia
Rare: injection site pain, chills

Investigations

Common: weight increase

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after drug registration is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, as well as patients or their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life

5 years.

Do not use the medicinal product 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 and sight of children.

Incompatibilities

No studies have been conducted. The medicinal product should not be mixed with other medicinal products.

Packaging

5 ml, 10 ml, or 20 ml in a vial. 10 vials per pack.

5 ml, 10 ml, or 20 ml in a vial. 5 vials per blister. 2 blisters per pack.

Prescription category

Prescription only.

Manufacturer

JSC "Farmak"

Manufacturer's address

74, Kyrylivska Street, Kyiv, 04080, Ukraine