PIRACETAM

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

Composition:

Active ingredient: piracetam;

1 ml of solution contains 200 mg of piracetam;

Excipients: sodium acetate trihydrate E 262, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear colorless liquid.

Pharmacotherapeutic group. Psychostimulants and nootropics. Piracetam.

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 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, with no vasodilatory effect.

Prolonged or single-dose 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 rigidity of erythrocytes, piracetam enhances their filterability and elasticity. Piracetam exerts a protective and restorative effect in impaired brain function due to hypoxia, intoxication, and electroconvulsive therapy.

Piracetam is used either as a monotherapy or as part of complex treatment 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 reached within 30 minutes, while in cerebrospinal fluid it is achieved within 2–8 hours and amounts to 40–60 μg/mL.

Distribution

Piracetam does not bind to plasma proteins, and the 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 the 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.

Excretion

The elimination half-life of the drug from blood is 4–5 hours and 6–8 hours from cerebrospinal fluid. This period may be prolonged in renal insufficiency. Piracetam is excreted by the kidneys in unchanged form. 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.

For use in adults:

• for symptomatic treatment of pathological conditions associated with impaired memory and cognitive disorders, excluding diagnosed dementia;
• for treatment of cortical myoclonus, either as monotherapy or as part of combination therapy.

A trial treatment period over a limited duration may be conducted to assess sensitivity to piracetam.

Contraindications.

• Hypersensitivity to piracetam or to pyrrolidone derivatives, or to any of the excipients.
• Acute cerebral circulation disorders (hemorrhagic stroke).
• Terminal stage of renal failure.
• Huntington's chorea.

Interaction with other medicinal products and other forms of interaction.

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

Pharmacokinetic interactions.

The likelihood of altered pharmacokinetics 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 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 CYP3A4/5 (11%) was observed. However, the Ki value for inhibition of these two CYP isoforms is 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 profiles or maximum concentrations (Cmax) of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, sodium valproate) in patients with epilepsy receiving stable doses.

Alcohol.

Concomitant intake with alcohol did not affect plasma concentrations 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 "Pharmacodynamics"), the drug should be prescribed with caution to patients with disorders of hemostasis, conditions that may be associated with bleeding (e.g. peptic ulcer of the gastrointestinal tract), 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.

Renal impairment.

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

Elderly patients.

During long-term therapy in elderly patients, renal function parameters should be monitored regularly; dose adjustment should be performed as necessary based on 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 myoclonus generalization or seizure occurrence.

Precautions related to excipients.

The medicinal product contains 1 mmol (23 mg) of sodium per 24 g of piracetam. This should be taken into account if the patient is on a sodium-controlled diet.

Use during pregnancy or breastfeeding.

The drug should not be used during pregnancy or breastfeeding.

Ability to influence reaction speed when driving or operating machinery.

Due to 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 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 drug is intended for use in adults.

Treatment of conditions associated with memory impairment and cognitive disorders.

The recommended daily dose is from 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, 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, 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 occurrence of seizures associated with drug withdrawal).

Special patient groups.

Elderly patients.

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

Patients with impaired renal function.

Since the drug is eliminated from the body via 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 excretion levels are age-dependent. The dosing interval should be adjusted based on renal function.

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

Treatment for such patients is prescribed depending on the degree of renal impairment:

Patients with hepatic impairment.

Dose adjustment is not required for patients with hepatic impairment only. In case 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 adverse drug reactions. Symptoms of overdose were observed following oral administration of the drug at a dose of 75 g.

Treatment is 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 by system organ class and frequency.

Frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to <1/100), rare (≥ 1/10,000 to <1/1000), 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 exposed population.

Blood and lymphatic system disorders

Frequency not known: haemorrhagic 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, 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 activity

Vascular disorders

Rare: hypotension, thrombophlebitis

General disorders and administration site conditions

Uncommon: asthenia
Rare: pain at injection site, chills

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 reach of children.

Incompatibilities.

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

Packaging. 5 ml in an ampoule; 5 ampoules in a blister pack; 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Halychpharm"

Manufacturer's address and location of operations.

6/8 Opryshkivska Street, Lviv, 79024, Ukraine