Lucetam: detailed information

Brand name Lucetam

Form tablets, film-coated

Active substance / Dosage

piracetam · 1200 mg

Prescription type prescription only

ATC code

N06BX03

Registration number UA/8165/01/03

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 edge, with inscription "E 241" engraved on one side, odorless;

800 mg tablets –
white or almost white, oval-shaped, biconvex film-coated tablets with a bevel edge, with a notch on both sides, with inscription "E 242" engraved on one side, odorless;

1200 mg tablets –
white or almost white, oval-shaped, biconvex film-coated tablets with a bevel edge, with inscription "E 243" engraved on one side, 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 (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 effects, and also reduces the harmful impact of these factors.

Pharmacokinetics.

After oral administration, piracetam is rapidly and almost completely absorbed. Maximum plasma concentration (Cmax) is reached approximately 30 minutes after administration; Cmax 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 Cmax and increases tmax.

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, predominantly in the frontal, parietal, and occipital regions, cerebellum, basal ganglia, caudate nucleus, hippocampus, lateral geniculate bodies, and choroid plexus of the brain.

Clinical characteristics.

Indications.

Adults:

symptomatic treatment of pathological conditions accompanied by memory impairment and cognitive disorders, with the exception of diagnosed dementia;
treatment of cortical myoclonia: 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 cerebral circulation disorders (hemorrhagic stroke).

Terminal stage of renal failure.

Huntington's chorea.

Interaction with other medicinal products and other forms 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 used concomitantly, a significant reduction was observed in platelet aggregation, fibrinogen levels, von Willebrand factors (VIII:C; VIII:vW:Ag; VIII:vW:Rco), and blood and plasma viscosity.

Pharmacokinetic interactions

The likelihood of changes in the pharmacodynamics of piracetam due to other medicinal products is low, since 90% of the drug is excreted unchanged in the urine.

In vitro, piracetam does not inhibit the 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 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 mg daily for 4 weeks or longer did not alter the concentration-time curve or Cmax of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, sodium valproate) in the blood serum of patients with epilepsy.

Alcohol

Concomitant intake with alcohol did not affect the serum concentration of piracetam, and the 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"), caution is required when prescribing the drug to patients with coagulation disorders, conditions that may be associated with bleeding (e.g. gastrointestinal ulcer), during major surgical procedures (including dental interventions), in patients with symptoms of severe hemorrhage or those with a history of hemorrhagic stroke, and in patients receiving anticoagulants or 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. Dose adjustments should be made 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 generalized myoclonus or seizure occurrence.

\u> Warnings 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-controlled 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.

The drug should be administered orally, taken 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 is usually divided into 2–3 doses.

The maintenance dose is 2.4 g per day, divided into 2–3 doses.

Subsequently, gradual reduction of the dose by 1.2 g per day is possible.

Treatment of cortical myoclonia.

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, treatment 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 myoclonia reappear. This allows determination of the average effective dose.

The daily dose should be divided into 2–3 doses. Treatment with other antimyoclonic agents should be continued at previously prescribed doses. Treatment should continue 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 courses of treatment should be prescribed every 6 months, adjusting the dose according to the patient's condition, until symptoms disappear or decrease.

Administration to 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"). In long-term treatment, such patients may require monitoring of creatinine clearance to ensure adequate dose adjustment.

Dosage in patients with impaired renal function .

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

Prolongation of the elimination half-life is directly related to worsening 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 assessment of the patient's creatinine clearance using the following formula:

Treatment for such patients should be prescribed depending on the severity 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 hepatic impairment

Dose adjustment is not required only for patients with hepatic impairment.

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

Children.
Not recommended.

Overdose.

Symptoms:
Exaggeration of adverse drug reactions. Symptoms of overdose were 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 (removes 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 are 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 breast disorders: Increased sexual drive.

Investigations: Weight gain.

Shelf life.

5 years.

Storage conditions.

Store at a temperature 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 Ltd., Hungary.

Address of manufacturer and site of activity.

65 Matyas Kiraly Street, Keremennd, H-9900, Hungary.