Nootropil

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

Composition:

Active substance: piracetam;

1 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 break line on both sides; on one side of the tablet, the imprint “N” is applied on both sides of the break 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 improves the efficiency of cognitive functions. 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 blood rheological characteristics 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 conditions of pathological erythrocyte rigidity, piracetam enhances their filterability and elasticity. Piracetam exerts protective and restorative effects in impaired brain function due to hypoxia, intoxication, and electroconvulsive therapy.

Piracetam is used either as a monotherapy or as part of complex treatment of cortical myoclonus to reduce the severity of the triggering factor—vestibular neuronitis.

Pharmacokinetics.

Absorption

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

After a single 2 g dose, Cmax is achieved 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 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 does not undergo metabolism 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. It is eliminated in urine almost completely (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, with the exception of diagnosed dementia;
• treatment of cortical myoclonia either 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 to pyrrolidone derivatives, as well as to any 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 types of interactions.

Thyroid hormones.

Concomitant use with thyroid hormones (T3+T4) may result in increased irritability, disorientation, and sleep disturbances.

Ace­no­cumarol.

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 hepatic 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 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 plasma concentrations of piracetam, and alcohol concentrations were not altered when 1.6 g of piracetam was administered.

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 impaired hemostasis, 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 patients with a history of hemorrhagic stroke; and to patients receiving anticoagulants, platelet anti-aggregating agents, including low-dose acetylsalicylic acid.

Renal impairment.

The drug is eliminated by the kidneys; therefore, special attention should be paid 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; the dose should be adjusted as 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 generalization of myoclonus or development of seizures.

Precautions related to excipients.

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

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

Use during pregnancy or breast-feeding.

The drug should not be used during pregnancy or breast-feeding.

Ability to influence reaction speed when 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 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 disappear. 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 dose of piracetam 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).

Special patient groups.

Use in elderly patients.

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

Dosage in patients with renal function impairment.

Since the drug is eliminated 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 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.

Dosage 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 hepatic and renal dysfunction, dosage adjustment should be performed as specified in the section "Dosage in patients with renal impairment".

Children.

Not applicable.

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 is symptomatic: 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 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 based on 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: hemorrhagic 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: hyperkinesia
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, diarrhea, nausea, vomiting

Skin and subcutaneous tissue disorders

Frequency not known: angioneurotic edema, dermatitis, urticaria, pruritus

Reproductive system and breast disorders

Frequency not known: increased sexual drive

General disorders

Uncommon: asthenia

Investigations

Common: weight increase

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: 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 per blister, pack of 30 (15x2) in a cardboard box; or 1200 mg, 10 tablets per blister, 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 of operations:

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 Marketing Authorization Holder:

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