Lucetam

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 of the tablet: Opadry 03F28561 white (polyethylene glycol, titanium dioxide (E 171), talc, aqueous dispersion of ethylcellulose, hypromellose).

Pharmaceutical form.
Film-coated tablets.

Main physicochemical properties:

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

Pharmacotherapeutic group.
Psychostimulants and nootropic agents.

ATC code N06B X03.

Clinical characteristics.

Indications.

• symptomatic treatment of pathological conditions associated with impaired memory and cognitive disorders, excluding diagnosed dementia;
• treatment of cortical myoclonia: as monotherapy or as part of combination therapy.

Contraindications.

Hypersensitivity to piracetam and other 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 forms of interactions.

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

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 ratio (INR) of 2.5–3.5. However, when used 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.

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.

Administration of piracetam at a dose of 20 mg daily for 4 weeks or longer did not alter the concentration-time curves or Cmax levels of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, sodium valproate) in serum of patients with epilepsy.

Concomitant intake with alcohol did not affect serum concentrations of piracetam, and serum alcohol concentrations were not altered following administration of 1.6 g of piracetam.

Special precautions for use.

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 signs of severe hemorrhage, or in patients with a history of hemorrhagic stroke; and in patients receiving anticoagulants or platelet antiaggregants, including low-dose acetylsalicylic acid. As the drug is excreted by the kidneys, particular attention should be paid to patients with renal impairment.

During long-term therapy in elderly patients, regular monitoring of renal function parameters is recommended; dosage adjustment based on creatinine clearance results may be necessary (see section "Dosage and administration").

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.

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

Use during pregnancy or breastfeeding.

Do not use the drug during pregnancy or breastfeeding.

Ability to influence reaction rate while 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.

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, 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 has not been 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 has been achieved, starting from the day when stable improvement is observed, the dose should be reduced by 1.2 g every 2 days until symptoms of cortical myoclonus 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 is not permitted. 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 diminish.

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, such patients should have creatinine clearance monitored as needed to ensure appropriate dose adjustment.

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

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.

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:

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

In case of diagnosed or suspected hepatic and renal dysfunction, dose adjustment should be performed as indicated in the section «Dosage in patients with renal impairment».

Children.
Not to be used.

Overdose.

Symptoms:
Exaggeration 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 with piracetam.

Nervous system disorders:
Hyperkinesis.

Metabolism and nutrition disorders:
Weight gain.

Psychiatric disorders:
Nervousness, depression.

General disorders and administration site conditions:
Asthenia.

Adverse reactions observed during post-marketing surveillance, listed below by organ systems.

Blood and lymphatic system disorders:
Haemorrhagic disorders.

Immune system disorders:
Hypersensitivity, anaphylactoid reactions.

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

Nervous system disorders:
Hyperkinesis; 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, diarrhoea, nausea, vomiting.

Skin and subcutaneous tissue disorders:
Angioneurotic oedema, 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 u., Kermend, Hungary, H-9900.