Brand name Lucetam

Form tablets, film-coated

Active substance / Dosage

piracetam · 400 mg

Prescription type prescription only

ATC code

N06BX03

Registration number UA/8165/01/01

Manufacturer PJSC Pharmaceutical Plant EGIS

Table of Contents

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LUCETAM Ò (LUCETAM Ò)
Composition:
Clinical characteristics.
Special precautions for use.
Method of Administration and Dosage
Adverse Reactions

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LUCETAM Ò (LUCETAM Ò)

Composition:

Active substance: piracetam;

1 tablet contains 400 mg or 800 mg or 1200 mg of piracetam;

Excipients: magnesium stearate, povidone, dibutyl sebacate;

coating composition: Opadry 03F28561 white (macrogol, titanium dioxide (E 171), talc, aqueous dispersion of ethylcellulose, hypromellose).

Pharmaceutical form.
Film-coated tablets.

Main physico-chemical properties:

400 mg tablets –
white or almost white, oval-shaped, biconvex film-coated tablets with a bevel, engraved «E 241» on one side of the tablet, odorless;

800 mg tablets –
white or almost white, oval-shaped, biconvex film-coated tablets with a bevel, with a line on both sides, engraved «E 242» on one side of the tablet, odorless;

1200 mg tablets –
white or almost white, oval-shaped, biconvex film-coated tablets with a bevel, engraved «E 243» on one side of the tablet, odorless.

Pharmacotherapeutic group.
Psychostimulants and nootropic agents.

ATC code: N06BX03.

Pharmacological properties.

Pharmacodynamics.

The active component of Lucetam® is piracetam, a cyclic derivative of gamma-aminobutyric acid. Piracetam is a nootropic agent acting on the brain, improving cognitive functions such as learning ability, memory, attention, and mental performance in both healthy individuals and patients with cognitive impairments. These effects are not related to sedative or stimulant actions. The effects of piracetam are associated with stimulation of nucleotide metabolism in neurons, increased levels of glucose and oxygen utilization in the brain, as well as enhancement of cholinergic and dopaminergic mechanisms of excitation transmission in nervous tissue. Piracetam has the property of dose-dependent binding to the phospholipid bilayer of cell membranes, thereby restoring their structure, increasing membrane fluidity, and improving membrane function.

The mechanisms of the drug's action on the central nervous system are likely multiple: alteration of the rate of excitation spread in the brain; enhancement of metabolic processes in nerve cells; improvement of microcirculation by influencing the rheological properties of blood without causing vasodilatory effects. It improves interhemispheric connections and synaptic conduction in neocortical structures. Piracetam inhibits platelet aggregation and restores erythrocyte membrane elasticity, reducing erythrocyte adhesion. At a dose of 9.6 g, it reduces fibrinogen and von Willebrand factor levels by 30–40% and prolongs bleeding time. Piracetam exerts a protective or restorative cognitive effect in cases of impaired brain function (e.g., hypoxia, poisoning, electroconvulsive therapy) or following these conditions. Piracetam reduces the intensity and duration of vestibular nystagmus.

Animal experiments have shown that piracetam protects the central nervous system from hypoxia, traumatic brain injury, toxic and electroconvulsive influences, and also reduces the harmful effects of these factors.

Pharmacokinetics.

After oral administration, piracetam is rapidly and almost completely absorbed. Maximum plasma concentration (C_max) is reached approximately 30 minutes after administration; C_max in cerebrospinal fluid is achieved within 5 hours and amounts to 40–60 µg/mL. The bioavailability of the drug is nearly 100%.

The volume of distribution of piracetam is approximately 0.6 L/kg. Concomitant food intake does not affect the extent of drug absorption, although it reduces C_max and increases t_max.

The elimination half-life of the drug from plasma is 4–5 hours and from cerebrospinal fluid is 8.5 hours. This half-life may be 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 and placental barriers (fetal concentrations reach 70–90% of maternal concentrations) and is excreted into breast milk. Piracetam undergoes dialysis (elimination efficiency is 50–60%). Animal studies have shown that piracetam selectively accumulates in cerebral cortex tissues, primarily in the frontal, parietal, and occipital regions, cerebellum, basal ganglia, caudate nucleus, hippocampus, lateral geniculate body, and choroid plexus of the brain.

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.

Contraindications.

Hypersensitivity to piracetam and other derivatives of pyrrolidone, 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 types of interactions.

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 affect the required dosage of acenocoumarol to achieve a prothrombin time (INR) of 2.5–3.5. However, when administered concomitantly, a significant reduction in platelet aggregation, fibrinogen levels, von Willebrand factors (VIII:C; VIII:vW:Ag; VIII:vW:Rco), and blood and plasma viscosity was observed.

Pharmacokinetic interactions

The likelihood of changes in the pharmacodynamics of piracetam due to other medicinal products is low, as 90% of the drug 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 above 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 mg daily for 4 weeks or longer did not alter the concentration-time curves or Cmax of antiepileptic drugs in blood plasma (carbamazepine, phenytoin, phenobarbital, sodium valproate) in patients with epilepsy.

Alcohol

Concomitant intake with alcohol did not affect the plasma concentration of piracetam, and serum alcohol concentration was 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 "Pharmacological properties"), the drug should be prescribed with caution to patients with coagulation disorders, conditions that may be associated with bleeding (e.g. peptic ulcer of the gastrointestinal tract), during major surgical procedures (including dental interventions), patients with symptoms of severe bleeding or those with a history of hemorrhagic stroke; and patients taking anticoagulants, platelet antiaggregants, including low-dose acetylsalicylic acid. The drug is excreted by the kidneys; therefore, special attention should be paid to patients with renal impairment.

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").

Discontinuation of treatment

In the treatment of patients with cortical myoclonus, abrupt discontinuation of therapy should be avoided due to the risk of myoclonus generalization or seizure occurrence.

Precautions related to excipients

The product contains 2 mmol (46 mg) of sodium per 24 g of piracetam. This should be taken into account by patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Do not use the drug during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Caution should be exercised when driving or operating machinery.

Method of Administration and Dosage

Administer the drug orally, swallowing with a small amount of water.

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 usually be divided into 2–3 doses.

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 daily dose is 24 g for 3 days. If the desired therapeutic effect is not achieved within this period, continue administration of the drug at the same dosage (24 g/day) for up to 7 days. If the desired therapeutic effect is not achieved by day 7 of treatment, therapy should be discontinued. If a therapeutic effect is achieved, starting from the day when stable improvement is observed, begin reducing the dose by 1.2 g every 2 days until symptoms of cortical myoclonus reappear. This allows determination of the average effective dose.

Divide the daily dose into 2–3 doses. Concomitant treatment with other antimyoclonic agents should be maintained at previously prescribed doses. Continue treatment until symptoms of the disease disappear. To prevent worsening of the patient's condition, abrupt discontinuation of the drug 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 diminish.

Use in elderly patients .

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

Dosage in patients with impaired renal function .

Since the drug is eliminated via the kidneys, caution should be exercised when treating patients with renal insufficiency.

Prolongation of the 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 estimation of the patient's creatinine clearance using the following formula:

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

Renal impairment	Creatinine clearance (mL/min)	Dosage
Normal renal function	> 80	Usual dose divided into 2 or 4 administrations
Mild	50–79	2/3 of usual dose in 2–3 administrations
Moderate	30–49	1/3 of usual dose in 2 administrations
Severe	< 30	1/6 of usual dose as a single administration
End-stage	–	Contraindicated

Dosage in patients with impaired liver function

Dose adjustment is not required solely for patients with impaired liver function.

In cases of diagnosed or suspected hepatic and renal dysfunction, adjust dosage as indicated in the section "Dosage in patients with impaired renal function".

Children.
Not applicable.

Overdose.

Symptoms:
Exacerbation of the drug's adverse effects. Symptoms of overdose have been observed following oral administration of the drug at a dose of 75 g.

Treatment:
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 of piracetam.

Nervous system disorders: Hyperkinesia.

Metabolism and nutrition disorders: Weight gain.

Psychiatric disorders: Nervousness, depression.

General disorders and administration site conditions: Asthenia.

Adverse reactions reported during post-marketing surveillance, listed below by system organ class:

Blood and lymphatic system disorders: Hemorrhagic disorders.

Immune system disorders: Hypersensitivity, anaphylactoid reactions.

Psychiatric disorders: Nervousness, depression; increased excitability, anxiety, confusion, hallucinations.

Nervous system disorders: Hyperkinesia; somnolence; ataxia, loss of balance, increased frequency of epileptic seizures, headache, insomnia, tremor.

Ear and labyrinth disorders: Dizziness.

Gastrointestinal disorders: Abdominal pain, upper abdominal pain, diarrhea, nausea, vomiting.

Skin and subcutaneous tissue disorders: Angioneurotic edema, dermatitis, rash, urticaria, pruritus.

Reproductive system and breastfeeding disorders: Increased sexual drive.

Investigations: Weight gain.

Shelf life.

5 years.

Storage conditions.

Store at temperatures not exceeding 30°C, in a place inaccessible to children.

Packaging.

Tablets 400 mg: 60 tablets in a glass bottle or 15 tablets in a blister pack (4 blisters) in a cardboard box.

Tablets 800 mg: 30 tablets in a glass bottle or 15 tablets in a blister pack (2 blisters) in a cardboard box.

Tablets 1200 mg: 20 tablets in a glass bottle or 10 tablets in a blister pack (2 blisters) in a cardboard box.

Prescription category. Prescription only.

Manufacturer

Egis Pharmaceuticals PLC, Hungary.

Manufacturer's address and place of business.

65 Matyas kiraly Street, Kermend, 9900, Hungary.