Piracetam-darnitsa

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

Composition:

active substance: piracetam;

1 tablet contains 200 mg of piracetam;

excipients: magnesium carbonate heavy, potato starch, povidone, calcium stearate, hypromellose, macrogol 4000, titanium dioxide (E 171), quinoline yellow (E 104).

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties: film-coated tablets, from light yellow to yellow or yellow with reddish tinge, round-shaped with biconvex surface. Two layers are visible in cross-section.

Pharmacotherapeutic group.

Psychostimulants and nootropic agents. Piracetam. 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: altering the rate of excitation propagation in the brain, improving metabolic processes in nerve cells, enhancing microcirculation by influencing the rheological properties of blood without causing vasodilatory effects.

It improves interhemispheric connectivity and synaptic transmission in neocortical structures. Piracetam inhibits platelet aggregation and restores erythrocyte membrane elasticity, reducing erythrocyte adhesion. Piracetam exerts protective and restorative effects on impaired brain function caused by hypoxia and intoxication. Piracetam reduces the intensity and duration of vestibular nystagmus.

Pharmacokinetics.

After oral administration, piracetam is rapidly and almost completely absorbed, with peak plasma concentration reached within 1 hour after intake. Bioavailability is nearly 100% following 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 plasma is 4–5 hours and 6–8 hours from cerebrospinal fluid, which is prolonged 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 insufficiency. Piracetam crosses the blood-brain barrier, placental barrier, and membranes used during hemodialysis. In animal studies, piracetam selectively accumulates in cerebral cortex tissues, predominantly in the frontal, parietal, and occipital lobes, as well as in the cerebellum and basal ganglia.

Clinical characteristics.

Indications.

In adults:

− symptomatic treatment of pathological conditions associated with memory impairment and cognitive disorders, excluding diagnosed dementia;

− treatment of cortical myoclonus: as monotherapy or as part of combination therapy.

Contraindications.

− Individual hypersensitivity to piracetam or to pyrrolidone derivatives, as well as to other components of the medicinal product.

− Acute cerebrovascular accident (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 the pharmacodynamics of piracetam 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 values for these two CYP isoenzymes are sufficiently high when exceeding 1422 µg/ml. Therefore, metabolic interactions with drugs undergoing biotransformation by these enzymes are unlikely.

Thyroid hormones

When used concomitantly with thyroid hormones (T3+T4), 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 require adjustment of acenocoumarol dosage to achieve a prothrombin time ratio (INR) of 2.5–3.5. However, when used concomitantly, a significant reduction in platelet aggregation, fibrinogen levels, von Willebrand factor [coagulation activity (VIII:C); ristocetin cofactor (VIII:vW:Rco); and plasma protein (VIII:vW:Ag)], blood and plasma viscosity was observed.

Antiepileptic medicinal products

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

Alcohol

Concomitant intake with alcohol does not affect the serum concentration of piracetam, and the serum alcohol concentration is not altered after 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 medicinal product should be administered with caution to patients with disorders of hemostasis; conditions that may be associated with hemorrhage (e.g., peptic ulcer of the gastrointestinal tract); during major surgical procedures (including dental surgery); patients with signs of severe bleeding; patients with a history of hemorrhagic stroke; and patients receiving anticoagulants, platelet antiaggregants, including low-dose acetylsalicylic acid.

Renal impairment.

The medicinal product is eliminated by the kidneys; therefore, special attention should be given to patients with renal insufficiency.

Elderly patients.

During long-term therapy, regular monitoring of renal function parameters is recommended in elderly patients. Dose adjustments should be made as 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 generalized myoclonus or seizure occurrence.

The medicinal product penetrates through the filtering membranes of hemodialysis equipment.

Important information about excipients.

This medicinal product contains sodium compounds. Caution is advised when administering to patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding.

Do not use the medicinal product 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 potential for adverse reactions affecting the central nervous system.

Method of Administration and Dosage

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

Use in 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. The dose should be divided into 2–3 administrations per day. The maintenance dose is 2.4 g per day (divided into 2–3 doses). Subsequently, the dose may be gradually reduced by 1.2 g per day.

Treatment of cortical myoclonus.

The initial dose is 24 g over 3 days. If the desired therapeutic effect has not been achieved within this period, continue administration of the drug at the same dosage (24 g/day) for up to 7 days. If the therapeutic effect is weak or absent, continue treatment at the same dose for up to 7 days. If the desired therapeutic effect has not been achieved by day 7 of treatment, treatment with piracetam should be discontinued. If a therapeutic effect has been achieved, starting from the day when stable improvement is observed, the dose 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.

The daily dose must be divided into 2–3 administrations. Concomitant treatment with other antimyoclonic agents should be maintained at previously prescribed doses. Treatment should be continued until symptoms of the disease disappear. To prevent worsening of the patient's condition, abrupt discontinuation of the medicinal product must be avoided. The dose should be gradually reduced by 1–2 g every 2–3 days. Repeat treatment courses should be prescribed every 6 months, adjusting the dose according to the patient's condition, until symptoms disappear or are reduced.

Use in Elderly Patients

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

Dosage in Patients with Renal Impairment

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 based on renal function parameters.

Dose calculation should be based on assessment of the patient's creatinine clearance using the following formula:

[140 − age (years)] × body weight (kg)

Ccr = ───────────────────────────── (× 0.85 for women)

72 × plasma creatinine (mg/dL)

Treatment should be prescribed according to the severity of renal insufficiency, following these recommendations:

Patients with hepatic impairment, dose adjustment is not required. In case of diagnosed or suspected hepatic or renal disorders, dose adjustment should be performed as indicated in the section "Dosage in patients with renal impairment".

Children

The drug is not to be used in children.

Overdose

Symptoms: intensification of adverse drug reactions. After oral administration of 75 g of piracetam, gastrointestinal disturbances were observed, such as diarrhea with blood and abdominal pain. Symptoms of overdose occurred following oral administration of the drug at a dose of 75 g.

Treatment: symptomatic. After 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).

Side effects

Adverse effects are classified by organ systems and frequency of occurrence.

Frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1000), very rare (< 1/10,000), isolated cases (frequency cannot be estimated from available data).

Adverse reactions reported during post-marketing surveillance are listed below by organ systems.

Vestibular system.

Isolated cases: vertigo.

Gastrointestinal tract.

Isolated cases: anorexia, abdominal pain, upper abdominal pain, nausea, diarrhea, vomiting, constipation.

Metabolism and nutrition disorders.

Common: weight gain.

Nervous system.

Common: hyperkinesia.

Uncommon: somnolence.

Isolated cases: 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.

Isolated cases: increased excitability, confusion, anxiety, disorientation, hallucinations.

Cardiovascular system.

Isolated cases: worsening of angina pectoris, arterial hypertension.

Blood and lymphatic system.

Isolated cases: thrombophlebitis, hemorrhagic disorders.

Immune system.

Isolated cases: hypersensitivity reactions, including anaphylaxis.

Skin and subcutaneous tissue.

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

Reproductive system.

Isolated cases: increased sexual activity.

General disorders.

Isolated cases: hyperthermia, asthenia.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization is an important procedure. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Shelf life. 5 years.

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 blister packs in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and location of its business activity.

13, Boryspilska Street, Kyiv, 02093, Ukraine.