Piracetam-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PIRACETAM-DARNITSA (Pyracetam-Darnitsa)

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. Solution for injection.

Main physicochemical properties: clear, colorless liquid.

Pharmacotherapeutic group. Psychostimulants and nootropic agents.

ATC code N06BX03.

Pharmacological properties.

Pharmacodynamics.

The active component of the medicinal product is piracetam, a cyclic derivative of gamma-aminobutyric acid.

Piracetam is a nootropic agent, i.e. a psychotropic drug acting on the brain and improving cognitive functions such as learning ability, memory, attention, and mental performance. The mechanisms of the drug's action on the central nervous system are likely multiple: alteration of the rate of excitation propagation in the brain; enhancement of metabolic processes in nerve cells; improvement of microcirculation by influencing the rheological properties of blood without causing vasodilatory effects.

Piracetam improves interhemispheric connections and synaptic conduction in neocortical structures. Long-term or single 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 platelet aggregation and restores erythrocyte membrane elasticity, reducing erythrocyte adhesion. Piracetam exerts a protective and restorative effect on impaired brain function due to hypoxia, intoxication, and electroshock therapy. Piracetam reduces the intensity and duration of vestibular nystagmus.

Piracetam may be used as monotherapy or as part of combined therapy for cortical myoclonus, as well as a means to reduce the severity of triggering factors—vestibular neuronitis.

Pharmacokinetics.

Absorption

Cmax after administration of 2 g of the drug is reached in blood plasma within 30 minutes and in cerebrospinal fluid within 2–8 hours, amounting to 40–60 µg/mL. The volume of distribution of piracetam is approximately 0.6 L/kg.

Distribution

Piracetam does not bind to plasma proteins and is not metabolized in the body. The pharmacokinetics of piracetam are not altered in patients with hepatic insufficiency. Piracetam crosses the blood-brain barrier, placental barrier, and membranes used in hemodialysis. Animal studies have shown that piracetam selectively accumulates in cerebral cortex tissues, primarily in the frontal, parietal, and occipital regions, cerebellum, and basal ganglia.

Biotransformation

Piracetam is active in its unchanged form and is not metabolized in animals.

Elimination

The elimination half-life of the drug from blood plasma is 4–5 hours and correspondingly 6–8 hours from cerebrospinal fluid. This period may be prolonged in renal insufficiency. 80–100% of piracetam is excreted unchanged by the kidneys via glomerular filtration 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, with the exception of diagnosed dementia;
• treatment of cortical myoclonia, either as monotherapy or as part of combination therapy.

Contraindications.

Hypersensitivity to piracetam or to 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.

Piracetam therapy may be combined, if necessary, with cardiovascular drugs. In the treatment of psychiatric disorders – with appropriate psychotropic agents.

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 per 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, β-thromboglobulin release, fibrinogen levels, von Willebrand factor (coagulation activity (VIII:C); ristocetin cofactor activity (VIII:vW:Rco); and plasma protein levels (VIII:vW:Ag)), as well as blood and plasma viscosity.

Pharmacokinetic interactions.

The likelihood of changes in piracetam pharmacokinetics 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 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 medicinal products metabolized by these enzymes are unlikely.

Antiepileptic medicinal products.

No interaction has been observed with clonazepam, phenytoin, phenobarbital, or sodium valproate.

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 receiving stable doses.

Alcohol.

Concomitant intake with alcohol did not affect the serum concentration of piracetam, and alcohol serum concentration was not altered after administration of 1.6 g 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 (see section "Pharmacodynamic properties"), caution is required when prescribing the medicinal product to patients with disorders of haemostasis, conditions that may be associated with bleeding (e.g. gastrointestinal ulcer), during major surgical procedures (including dental interventions), patients with signs of severe haemorrhage or patients with a history of haemorrhagic stroke; and patients receiving anticoagulants, platelet antiaggregants, including low-dose acetylsalicylic acid.

Renal function impairment.

The drug is excreted by the kidneys; therefore, special attention should be given 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. If necessary, the dose should be adjusted according to creatinine clearance test results (see section "Dosage and administration"). The drug penetrates through the filtering membranes of hemodialysis equipment.

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 occurrence of seizures.

The medicinal product contains sodium. This should be taken into account in patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding.

The medicinal product should not be used during pregnancy and 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.

Method of Administration and Dosage

The medicinal product in the form of an injectable solution should be used in acute cases or when oral forms of piracetam cannot be administered.

The medicinal product should be administered intravenously (given slowly over several minutes) or by infusion (administered continuously over 24 hours).

The medicinal product is intended for use in adults.

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 should be increased by 4.8 g every three or four days up to a maximum dose of 24 g, divided into two or three administrations. Treatment with other antimyoclonic medicinal products should be continued at the same doses. Depending on the therapeutic effect achieved, and if possible, the dose of other antimyoclonic medicinal products should be reduced.

Piracetam treatment should be continued until symptoms of the underlying brain disorder have resolved. In patients with acute disease course, 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 piracetam dose should be reduced by 1.2 g every two days (every three or four days in cases of Lenz–Adams syndrome) to prevent sudden relapse or withdrawal-related seizures.

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 allow appropriate dose adjustment when necessary.

Patients with Renal Impairment.

Since the medicinal product is eliminated by 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 reduced creatinine clearance. This also applies to elderly patients, in whom creatinine clearance is age-dependent. The dosing interval should be adjusted based on the degree of renal impairment.

Dose calculation should be based on the patient's creatinine clearance. Calculate using the formula:

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

Patients with impaired liver function

Dose adjustment is not required solely for patients with impaired liver function. In case of diagnosed or suspected disorders of liver and kidney function, dose adjustment should be performed as indicated in the section "Patients with impaired renal 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 are most commonly observed in elderly patients at doses exceeding 2–4 g per day.

Frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100 < 1/10), uncommon (≥ 1/1000 < 1/100), rare (≥ 1/10000 < 1/1000), very rare (< 1/10000), isolated cases (frequency cannot be estimated based on available data).

Adverse reactions observed during post-marketing surveillance are listed below by system organ class.

Ear and labyrinth disorders.

Single cases: dizziness.

Gastrointestinal disorders.

Single cases: abdominal pain, upper abdominal pain, diarrhea, nausea, vomiting.

Nervous system disorders.

Frequent: hyperkinesia.

Uncommon: somnolence.

Single cases: ataxia, loss of balance, increased frequency of epileptic seizures, headache, insomnia, tremor.

Psychiatric disorders.

Frequent: irritability.

Uncommon: depression.

Single cases: increased excitability, anxiety, confusion, hallucinations.

Cardiac and vascular disorders.

Very rare: hypotension, thrombophlebitis.

Blood and lymphatic system disorders.

Single cases: haemorrhagic disorders.

Immune system disorders.

Single cases: hypersensitivity, anaphylactoid reactions.

Skin and subcutaneous tissue disorders.

Single cases: angioneurotic edema, dermatitis, rash, urticaria, pruritus.

Reproductive system and breast disorders.

Single cases: increased sexual drive.

General disorders and administration site conditions.

Uncommon: asthenia.

Very rare: malaise, injection site reactions including pruritus, pain, hyperemia, induration at injection site.

Investigations.

Frequent: weight gain.

Shelf life. 3 years.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 °C. Do not freeze. Keep out of reach of children.

Incompatibility.

Studies have not been conducted. The medicinal product should not be mixed with other drugs.

Incompatible with acid and alkali solutions, which lead to degradation of the active substance.

Packaging.

5 ml in a vial; 5 vials in a blister pack; 2 blister packs in a carton.

Prescription category. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's name and address of manufacturing site.

13, Boryspylska Street, Kyiv, 02093, Ukraine.