Nootropil®

INSTRUCTIONS for medical use of the medicinal product NOOTROPI L® (Nootropil®)

Composition:

Active substance: piracetam;

One tablet contains 800 or 1200 mg of piracetam;

Excipients: macrogol 6000, colloidal silicon dioxide anhydrous, magnesium stearate, sodium croscarmellose, Opadry Y-1-7000 (hypromellose (E 464), titanium dioxide (E 171), macrogol 400), Opadry OY-S-29019 (hypromellose (E 464), macrogol 6000).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: elongated, film-coated white tablets with a score line on both sides; on one side of the tablet there is an imprint "N" on both sides of the score line.

Pharmacotherapeutic group. Psychostimulants and nootropic agents.

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 mechanisms of its 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 blood rheological properties without vasodilatory effects. Long-term or single administration of piracetam to patients with cerebral dysfunction leads to 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 erythrocyte rigidity, piracetam improves their filterability and elasticity. Piracetam exerts a protective and restorative effect on impaired brain functions caused by hypoxia, intoxication, and electroconvulsive therapy.

Piracetam is used either as a monotherapy or as part of combined treatment for cortical myoclonia to reduce the impact of triggering factors—vestibular neuronitis.

Pharmacokinetics.

Absorption

After oral administration, piracetam is rapidly and almost completely absorbed from the gastrointestinal tract. Bioavailability is nearly 100%.

Following a single 2 g dose, Cmax is reached in plasma within 30 minutes and in cerebrospinal fluid within 2–8 hours, reaching 40–60 μg/mL.

Distribution

Piracetam does not bind to plasma proteins, and its apparent volume of distribution is approximately 0.6 L/kg. Piracetam distributes throughout all tissues and crosses the blood-brain barrier, placental barrier, and membranes used during hemodialysis. Piracetam accumulates in cerebral cortical 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 does not undergo metabolism in animals.

Elimination

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 impairment. Piracetam is excreted 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 course of treatment may be administered for a limited period of time.

Contraindications.

Hypersensitivity to piracetam or pyrrolidone derivatives, as well as to other components of the drug.

Acute impairment of cerebral circulation (hemorrhagic stroke).

Terminal stage of renal failure.

Huntington's chorea.

Interaction with other medicinal products and other forms of interaction.

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 piracetam at doses of 9.6 g/day did not affect the required dosage of acenocoumarol to achieve an INR value of 2.5–3.5. However, when used concomitantly, a significant reduction was observed in platelet aggregation, β-thromboglobulin release, fibrinogen levels, von Willebrand factors (VIII:C; VIII:vW:Ag; VIII:vW:Rco), and whole blood and plasma viscosity.

Pharmacokinetic interactions.

The likelihood of other medicinal products altering the pharmacokinetics of piracetam is low, as approximately 90% of the drug is excreted unchanged in urine.

In vitro, piracetam does not inhibit the major isoforms of human liver cytochrome P450 enzymes 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 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/day for four weeks or longer did not alter the concentration-time curve or maximum plasma concentration (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 alcohol concentration was 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 coagulation disorders, conditions that may be associated with bleeding (e.g. gastrointestinal ulcer), during major surgical procedures (including dental interventions), patients with signs of severe hemorrhage, or those with a history of hemorrhagic stroke; and to patients receiving anticoagulants, platelet antiaggregants, including low-dose acetylsalicylic acid.

Renal impairment.

The drug is eliminated 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; dosage adjustment may be necessary based on creatinine clearance test results (see section "Dosage and administration").

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.

Precautions related to excipients.

Noötropil®, film-coated tablets 800 mg contain 1.5 mg of sodium per tablet, equivalent to 0.08% of the WHO recommended maximum daily sodium intake of 2 g for adults.

Noötropil®, film-coated tablets 1200 mg contain 2.3 mg of sodium per tablet, equivalent to 0.12% of the WHO recommended maximum daily sodium intake of 2 g for adults. Caution is advised when administering to patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding.

The drug should not be used during pregnancy or breastfeeding.

Ability to affect reaction rate while driving or operating machinery.

Due to adverse reactions observed with this medicinal product, an effect on the ability to drive vehicles or operate machinery is possible and should be taken into account.

Method of Administration and Dosage.

NoötrOpil®, film-coated tablets, can be taken independently of food intake. The drug is administered orally, swallowed with a small amount of water.

Adults.

Treatment of conditions associated with memory impairment and cognitive disorders.

The recommended daily dose is 2.4–4.8 g. The dose is usually divided into 2–3 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 agents should be maintained at previously prescribed doses. Depending on the therapeutic effect achieved, and if possible, the dose of other antimyoclonic medicinal products should be reduced.

Treatment should continue until symptoms of the disease disappear. 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 occurrence of seizures associated with drug withdrawal).

Special patient groups.

Use in elderly patients.

Dose adjustment is recommended for elderly patients with diagnosed or suspected renal function disorders (see section "Dosage in patients with renal impairment"). In long-term treatment, if necessary, such patients should have their creatinine clearance monitored to ensure adequate dose adjustment.

Dosage in 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; in such patients, renal function should be monitored.

Prolongation of elimination half-life is directly related to deterioration of 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.

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

Treatment for such patients is prescribed according to the degree of renal impairment, following these recommendations:

Dosage in patients with hepatic impairment.

Dose adjustment is not required for patients with hepatic impairment alone. In cases of diagnosed or suspected concurrent hepatic and renal impairment, dosage adjustment should be performed as indicated in the section «Dosage in patients with renal impairment».

Children.

Not applicable.

Overdose.

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

Treatment: symptomatic management: gastric lavage, induction of emesis. There is no specific antidote; hemodialysis may be used (eliminates 50–60% of piracetam).

Adverse Reactions

Adverse reactions observed during clinical trials and post-marketing surveillance are listed by system organ classes 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 calculate the frequency of adverse reactions in the treated 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.

General disorders

Uncommon: asthenia.

Investigations

Common: weight increased.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicine has been authorized is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 4 years.

Storage conditions. No special storage conditions required.
Keep out of reach of children.

Incompatibilities.

Not known.

Packaging. Film-coated tablets, 800 mg, 15 tablets in a blister pack, pack of 30 (15x2) in a cardboard box; or 1200 mg, 10 tablets in a blister pack, pack of 20 (10x2) in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

1. UCB Pharma, Belgium;
2. Aesica Pharmaceuticals GmbH, Germany.

Manufacturer's address and location.

1. Chemin Du Foriest 1, Braine-L’alleud, 1420, Belgium;
2. Alfred-Nobel-Str. 10, 40789 Monheim am Rhein, Germany.

Marketing Authorization Holder.

UCB Pharma S.A., Belgium.

Address of the Marketing Authorization Holder.

Allee de la Recherche 60, B-1070 Brussels, Belgium.