Nootropil^® (Tablets, Capsules, Solution) Instructions for Use

ATC Code

N06BX03 (Piracetam)

Active Substance

Piracetam (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Nootropic drug

Pharmacotherapeutic Group

Nootropic agent

Pharmacological Action

Nootropic drug, a cyclic derivative of gamma-aminobutyric acid (GABA).

Available data indicate that the primary mechanism of action of piracetam is not cell-specific or organ-specific.

Piracetam binds to the polar heads of phospholipids and forms mobile Piracetam-phospholipid complexes. As a result, the bilayer structure of the cell membrane and its stability are restored, which in turn leads to the restoration of the three-dimensional structure of membrane and transmembrane proteins and the restoration of their function.

At the neuronal level, Piracetam facilitates various types of synaptic transmission, exerting a predominant effect on the density and activity of postsynaptic receptors (data obtained from animal studies).

Piracetam improves functions such as learning, memory, attention, and consciousness, without exerting a sedative or psychostimulant effect.

The hemorheological effects of piracetam are associated with its influence on erythrocytes, platelets, and the vascular wall.

In patients with sickle cell anemia, Piracetam increases the deformability of erythrocytes, reduces blood viscosity, and prevents the formation of “rouleaux”. Furthermore, it reduces platelet aggregation without significantly affecting their count.

Animal studies have shown that Piracetam prevents vasospasm and counteracts various vasospastic substances.

In studies on healthy volunteers, Piracetam reduced erythrocyte adhesion to the vascular endothelium and stimulated the production of prostacyclin by healthy endothelium.

Pharmacokinetics

Absorption

After oral administration, Piracetam is rapidly and almost completely absorbed from the gastrointestinal tract. After a single dose of 3.2 g, C_max is 84 µg/ml, after multiple doses of 3.2 mg 3 times/day – 115 µg/ml and is reached in 1 hour in plasma and in 5 hours in cerebrospinal fluid. Food intake reduces C_max by 17% and increases T_max to 1.5 hours. In women taking piracetam at a dose of 2.4 g, C_max and AUC are 30% higher than in men.

Distribution and Metabolism

Does not bind to plasma proteins.

The V_d of piracetam is about 0.6 L/kg.

Animal studies have found that Piracetam selectively accumulates in the tissues of the cerebral cortex, mainly in the frontal, parietal, and occipital lobes, the cerebellum, and the basal ganglia.

It is not metabolized in the body.

Penetrates the blood-brain barrier and the placental barrier.

Elimination

T_1/2 from plasma is 4-5 hours, from cerebrospinal fluid – 8.5 hours. T_1/2 does not depend on the route of administration.

80-100% of piracetam is excreted by the kidneys unchanged via renal filtration. The total clearance of piracetam in healthy volunteers is 80-90 ml/min.

Pharmacokinetics in Special Clinical Cases

T_1/2 is prolonged in renal failure; in the terminal stage of chronic renal failure – up to 59 hours.

The pharmacokinetics of piracetam are not altered in patients with hepatic impairment.

Penetrates through the filtering membranes of hemodialysis apparatus.

Indications

Adults

• Symptomatic treatment of psycho-organic syndrome, particularly in elderly patients, accompanied by memory impairment, dizziness, decreased concentration and activity, mood changes, behavioral disorders, gait disturbance (these symptoms may be early signs of age-related diseases such as Alzheimer’s disease and senile dementia of the Alzheimer’s type);
• Treatment of dizziness and associated balance disorders, excluding vasomotor and psychogenic dizziness;
• Treatment of cortical myoclonus (as monotherapy or as part of combination therapy);
• Prevention of sickle-cell vaso-occlusive crisis.

Children

• Treatment of dyslexia (as part of combination therapy);
• Prevention of sickle-cell vaso-occlusive crisis.

ICD codes

Dosage Regimen

Tablets

The drug is administered orally, during meals or on an empty stomach, with liquid.

Symptomatic treatment of psycho-organic syndrome: 2.4-4.8 g/day in 2-3 divided doses.

Treatment of dizziness and associated balance disorders: 2.4-4.8 g/day in 2-3 divided doses.

Treatment of cortical myoclonus starts with a dose of 7.2 g/day, the dose is increased by 4.8 g/day every 3-4 days until a maximum dose of 24 g/day in 2-3 divided doses is reached. Treatment continues throughout the entire period of the disease. Every 6 months, attempts should be made to reduce the dose or discontinue the drug, gradually reducing the dose by 1.2 g/day every 2 days.

Prevention of sickle-cell vaso-occlusive crisis: the daily dose is 160 mg/kg of body weight, divided into 4 equal doses.

Treatment of dyslexia in children (as part of combination therapy): the recommended daily dose for children from 8 years and adolescents is 3.2 g, divided into 2 doses.

For patients with impaired renal function, the dose should be adjusted depending on the CrCl value.

CrCl can be calculated based on serum creatinine concentration using the following formula.

For men CrCl (ml/min) = [140 – age (years)] × body weight (kg)/72 × serum creatinine (mg/dl);

CrCl for women can be calculated by multiplying the obtained value by a coefficient of 0.85.

Patients with renal failure require dose adjustment of the drug according to the following scheme.

In elderly patients, the dose is adjusted in the presence of renal failure; during long-term therapy, monitoring of renal functional status is necessary.

Patients with impaired hepatic function do not require dose adjustment.

Patients with impaired renal and hepatic function are prescribed the drug in the same way as patients with impaired renal function only.

Capsules

Administered orally, IM or IV. The dose, method and scheme of administration, duration of therapy are determined individually, depending on the indications, clinical situation, patient’s age and the dosage form used.

Parenteral administration of piracetam is prescribed when oral forms cannot be used (unconscious state, difficulty swallowing). IV administration is preferred.

Solution

The drug is administered IV and IM.

Parenteral administration of piracetam is prescribed when oral forms of the drug cannot be used (unconscious state, difficulty swallowing). IV administration is preferred.

IV infusion of the drug at the daily dose is performed through a catheter at a constant rate over 24 hours (e.g., in the initial stage of treatment of severe myoclonus). The drug is preliminarily diluted in one of the compatible infusion solutions: dextrose 5%, 10% or 20%; fructose 5%, 10%, 20%; sodium chloride 0.9%; dextran 40 10% (in sodium chloride 0.9% solution); Ringer’s solution; mannitol 20% solution. The total volume of the solution intended for administration is determined taking into account clinical indications and the patient’s condition.

Bolus IV administration (e.g., emergency treatment of crisis in sickle cell anemia) is performed over at least 2 minutes, the daily dose is distributed over several administrations (2-4) at equal intervals so that the dose per administration does not exceed 3 g.

The drug is administered IM if venous administration is difficult. The volume of the solution for IM administration should not exceed 5 ml. The frequency of drug administration is similar to that for its IV or oral administration.

When possible, switch to oral administration of the drug (in accordance with the instructions for medical use of the respective drug forms).

The duration of treatment is determined by the doctor individually depending on the disease and taking into account the dynamics of symptoms.

Symptomatic treatment of chronic psycho-organic syndrome: 2.4-4.8 g/day.

Treatment of dizziness and associated balance disorders: 2.4-4.8 g/day.

Cortical myoclonus: treatment starts with a dose of 7.2 g/day, the dose is increased by 4.8 g/day every 3-4 days until a maximum dose of 24 g/day is reached. Treatment continues throughout the entire period of the disease. Every 6 months, attempts should be made to reduce the dose or discontinue the drug, gradually reducing the dose by 1.2 g/day every 2 days.

Sickle cell anemia: during crisis – IV at a dose of 300 mg/kg in 4 divided equal doses.

For patients with impaired renal function, the dose should be adjusted depending on the CrCl value.

CrCl can be calculated based on serum creatinine concentration using the following formula.

For men CrCl (ml/min) = [140 – age (years)] × body weight (kg)/72 × serum creatinine (mg/dl);

CrCl for women can be calculated by multiplying the obtained value by a coefficient of 0.85.

Patients with renal failure require dose adjustment of the drug according to the following scheme.

In elderly patients, the dose is adjusted in the presence of renal failure; during long-term therapy, monitoring of renal functional status is necessary.

Patients with impaired hepatic function do not require dose adjustment.

Patients with impaired renal and hepatic function are prescribed the drug in the same way as patients with impaired renal function only.

Adverse Reactions

Nervous system disorders motor disinhibition (1.72%), irritability (1.13%), somnolence (0.96%), depression (0.83%), asthenia (0.23%); in isolated cases – dizziness, headache, ataxia, balance disorder, exacerbation of epilepsy, insomnia, confusion, agitation, anxiety, hallucinations, increased libido. In post-marketing practice, the following side effects have been observed, the frequency of which is not established (due to insufficient data): headache, insomnia, agitation, balance disorder, ataxia, exacerbation of epilepsy, anxiety, hallucinations, confusion.

Gastrointestinal disorders: nausea, vomiting, diarrhea, abdominal pain (including gastralgia).

Metabolism and nutrition disorders: weight increase (1.29%).

Ear and labyrinth disorders: vertigo.

Skin and subcutaneous tissue disorders: dermatitis, pruritus, urticaria.

Allergic reactions: angioedema, hypersensitivity, anaphylactic reactions.

Other: in rare cases – pain at the injection site, thrombophlebitis, hyperthermia, arterial hypotension (with IV administration).

In most cases, it is possible to achieve regression of such symptoms by reducing the dose of the drug.

Contraindications

• Psychomotor agitation at the time of prescribing the drug;
• Huntington’s chorea;
• Acute cerebrovascular accident (hemorrhagic stroke);
• End-stage chronic renal failure (with CrCl < 20 ml/min);
• Children under 1 year of age (for oral solution);
• Children under 3 years of age (for tablets);
• Hypersensitivity to the components of the drug;
• Hypersensitivity to pyrrolidone derivatives.

With caution the drug should be used in case of hemostasis disorders, extensive surgical interventions, severe bleeding, in chronic renal failure (CrCl 20-80 ml/min).

Use in Pregnancy and Lactation

Adequate and strictly controlled studies on the safety of Nootropil^® use during pregnancy have not been conducted. Controlled studies of the drug use during pregnancy have not been conducted.

Piracetam penetrates the placental barrier. The concentration of the drug in newborns reaches 70-90% of its concentration in the mother’s blood. Nootropil^® should not be prescribed during pregnancy.

Piracetam is excreted in breast milk. When prescribing the drug during lactation, breastfeeding should be avoided.

Use in Hepatic Impairment

Patients with impaired hepatic function do not require dose adjustment.

Use in Renal Impairment

Patients with renal failure require dose adjustment of the drug according to the following scheme.

Pediatric Use

Contraindication: children under 1 year of age (for oral solution); children under 3 years of age (for tablets).

Geriatric Use

In elderly patients, the dose is adjusted in the presence of renal failure; during long-term therapy, monitoring of renal functional status is necessary.

Special Precautions

Due to the effect of piracetam on platelet aggregation, the drug should be prescribed with caution to patients with hemostasis disorders, during extensive surgical interventions, or to patients with symptoms of severe bleeding.

When treating cortical myoclonus, abrupt interruption of treatment should be avoided, as this may cause recurrence of seizures.

When treating sickle cell anemia, a dose of less than 160 mg/kg or irregular intake of the drug may cause exacerbation of the disease.

During long-term therapy, elderly patients are recommended to have regular monitoring of renal function parameters; if necessary, dose adjustment is carried out depending on the results of CrCl testing.

When treating patients on a hyposodic diet, it should be taken into account that the piracetam oral solution at a dose of 24 g contains 80.5 mg of sodium.

Piracetam penetrates through the filtering membranes of hemodialysis apparatus.

Effect on ability to drive vehicles and operate machinery

During treatment, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms a single case of dyspeptic phenomena in the form of diarrhea with blood and abdominal pain has been recorded after oral administration of the drug at a daily dose of 75 g. This was apparently associated with the intake of a large total dose of sorbitol, previously part of the oral solution dosage form.

Treatment immediately after significant oral overdose, gastric lavage or induction of artificial vomiting can be performed. There is no specific antidote. The effectiveness of hemodialysis is 50-60%.

Drug Interactions

The possibility of changes in the pharmacokinetics of piracetam under the influence of other drugs is low, since 90% of the drug is excreted unchanged in the urine.

When used concomitantly with thyroid hormones, reports of confusion, irritability, and sleep disturbances have been noted.

According to a published study of patients with recurrent venous thrombosis, Piracetam at a dose of 9.6 g/day increases the effectiveness of indirect anticoagulants (a more pronounced decrease in platelet aggregation, fibrinogen concentration, von Willebrand factors, blood and plasma viscosity was noted compared to the use of only indirect anticoagulants).

Piracetam does not inhibit cytochrome P450 isoenzymes. Metabolic interaction with other drugs is unlikely.

Administration of piracetam at a dose of 20 g/day for 4 weeks did not change the C_max in serum and AUC of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, valproate).

Concomitant use with alcohol did not affect the serum concentration of piracetam; serum ethanol concentration was not altered by the intake of 1.6 g of piracetam.

Storage Conditions

The drug should be stored out of the reach of children, in a dry place at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 4 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.