PIRACETAM TEVA 800 mg Film-coated scored tablet B/45

Piracetam......................................................................................................................................................800 mg

For one scored film-coated tablet.

In adults :

• adjunctive treatment with symptomatic aim for the pathological chronic cognitive and neurosensory deficit in the elderly (excluding Alzheimer's disease and other dementias);

• symptomatic improvement of vertigo.

In children weighing more than 30 kg (i.e. from approximately 9 years of age):

• adjunctive treatment of dyslexia.

Dosage

The recommended dosages by indication are:

• Adjunctive treatment with symptomatic aim for the pathological chronic cognitive and neurosensory deficit in the elderly and vertigo:

• 1 tablet at 800 mg morning, noon and evening, i.e. 3 tablets per day.

Special populations

Elderly subject

A dose adjustment is recommended in elderly patients with impaired renal function (see "Renal impairment" below). For long-term treatments, regular assessment of creatinine clearance is necessary to allow dose adjustment, where appropriate.

Renal impairment

The daily dose must be adjusted individually and taking renal function into account. Consult the following table and adjust the dose as indicated. To use this table, it is necessary to estimate the patient's creatinine clearance (CLcr) in mL/min. The CLcr in mL/min can be estimated from the serum creatinine value (mg/dL) using the following formula:

CLcr =

Hepatic impairment

No dose adjustment is necessary in patients with hepatic impairment alone. Dose adjustment is recommended in patients with both hepatic impairment and renal impairment (see "Renal impairment" above).

Paediatric population

• Treatment of dyslexia:

• 50 mg/kg/day in 3 doses.

In children, the oral solution is the most suitable form. In addition, this dosage (800 mg tablet) is not suitable for this dosage regimen.

Method of administration

PIRACETAM TEVA 800 mg, scored film-coated tablet must be taken orally, with or without food. The tablets must be swallowed whole with a drink. It is recommended to take the daily dose in 2 to 4 intakes.

• Hypersensitivity to the active substance, to a pyrrolidone derivative or to any of the excipients listed in section Composition.

• Severe renal impairment or end-stage renal failure.

• Cerebral haemorrhage.

• Huntington's chorea (worsening of symptoms).

Effects on platelet aggregation

Due to the effect of piracetam on platelet aggregation (see section Interactions), caution is recommended in patients with severe haemorrhage, patients at risk of bleeding such as gastrointestinal ulcer, patients with haemostasis disorders, a history of haemorrhagic stroke, patients scheduled to undergo surgery (including dental surgery), and patients taking anticoagulants or antiplatelet agents, including low-dose acetylsalicylic acid.

Renal impairment

Piracetam is eliminated via the kidneys and precautions should be taken in cases of renal impairment.

In case of mild to moderate renal impairment, doses will be decreased and/or spaced out if creatinine clearance is below 80 ml/min (see section Dosage and administration).

Elderly subject

For long-term treatment in elderly subjects, regular assessment of creatinine clearance is necessary to allow dose adjustment, if required (see section Dosage and administration).

Discontinuation of treatment

Sudden discontinuation of treatment should be avoided in patients with myoclonus, as this may cause a sudden recurrence of myoclonus or withdrawal seizures (see section Dosage and administration.).

Pharmacokinetic interactions

The risk of drug interactions that could alter the pharmacokinetics of piracetam is expected to be low, as approximately 90 % of the piracetam dose is excreted unchanged in the urine.

In vitro, piracetam does not inhibit the isoforms of human hepatic cytochrome P450 (CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 4A9/11) at concentrations of 142, 426 and 1 422 µg/mL.

At a concentration of 1422 µg/mL, minor inhibitory effects were observed on CYP 2A6 (21 %) and 3A4/5 (11 %). However, the Ki values required for inhibition of these two CYP isoforms are likely to be well above 1422 µg/mL. Consequently, a metabolic interaction of piracetam with other medicinal products is unlikely.

Thyroid hormones

Confusion-type effects, irritability and sleep disturbances have been reported with concomitant administration of thyroid extracts (T3 + T4).

Acenocoumarol

In a single-blind study in patients with severe recurrent venous thromboses, piracetam (9,6 g/day) did not change the doses of acenocoumarol required to reach an INR between 2,5 and 3,5. However, compared with the effects of acenocoumarol alone, the addition of piracetam (9,6 g/day) significantly decreased platelet aggregation, release of β-thromboglobulin, fibrinogen levels and von Willebrand factor levels (VIII: C; VIII: vW: Ag; VIII: vW: RCo) as well as the viscosity of whole blood and plasma.

Antiepileptics

Piracetam, administered at a daily dose of 20 g for four weeks, did not change the maximum and residual serum levels of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, valproic acid) in epileptic patients receiving stable doses.

Alcohol

Concomitant administration of alcohol had no effect on serum piracetam levels, and alcohol levels were not modified by an oral dose of 1,6 g of piracetam.

Pregnancy

There are no adequate data on the use of piracetam in pregnant women. Animal studies have not shown direct or indirect harmful effects on pregnancy, embryonic/foetal development, parturition or postnatal development (see section Preclinical safety).

Piracetam crosses the placental barrier. Drug levels in the newborn represent approximately 70 to 90% of maternal levels. Piracetam is not recommended during pregnancy unless there is a real need, when the expected benefit to the mother outweighs the potential risks.

Breast-feeding

Piracetam is excreted in human breast milk. Therefore, piracetam should not be used during breastfeeding, or breastfeeding should be interrupted during treatment. A decision must be made either to interrupt breastfeeding or to interrupt piracetam, taking into account the benefit of breastfeeding for the child relative to the benefit of treatment for the mother.

Fertility

Studies performed in animals indicate that piracetam has no effect on the fertility of male or female rats.

There are no clinical data on the effects of piracetam on fertility.

PIRACETAM TEVA has a moderate influence on the ability to drive vehicles and use machines.

Summary of the safety profile

Placebo-controlled, double-blind pharmacological or clinical studies that provided tolerability data (from the UCB database, as of June 1997) included more than 3000 subjects who received piracetam, without distinction of indication, pharmaceutical form, daily dosage or population.

Summary list of adverse effects

Adverse reactions reported during clinical studies and since marketing are presented by system organ class and by frequency in the table below. Frequency is defined as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data). Data collected since marketing are insufficient to determine their incidence in the treated population.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr/.

Symptoms

The largest reported overdose of piracetam was an oral intake of 75 g. One case of bloody diarrhoea with abdominal pain was observed following daily oral intake of 75 g of piracetam, but this was most likely due to the extreme dose of sorbitol contained in the formulation used.

No additional adverse events specifically related to overdose have been reported with piracetam.

Management of overdose

In case of acute and significant overdose, the stomach may be emptied by gastric lavage or induction of vomiting. There is no specific antidote for piracetam. Treatment of an overdose will be symptomatic and may include haemodialysis. The extraction efficiency by dialysis is 50 to 60 % for piracetam.

Pharmacotherapeutic class: OTHER PSYCHOSTIMULANTS AND NOOTROPICS, ATC code: N06BX03.

Mechanism of action

The mechanism of action underlying the therapeutic effects is not known.

Pharmacodynamic effects

In animals, under conditions different from therapeutic use, particularly at dosages or concentrations often high, the following pharmacological effects have been observed:

• improvement of GABAergic, cholinergic and glutamatergic neurotransmission;

• facilitation of learning and of the speed of information processing within and between hemispheres.

Absorption

After oral administration, absorption is complete and rapid. The maximum plasma concentration is reached in 45 minutes.

Distribution

The plasma half-life of piracetam is 4 to 5 hours. It is doubled for a creatinine clearance below 60 mL/min.

Piracetam crosses the blood-brain barrier.

It readily crosses the placenta.

Elimination

Mainly urinary within 30 hours.

Acute toxicity in rodents, by both intravenous and oral routes, is observed at doses above 8 g/kg.

Repeated-dose toxicity studies in dogs, by oral route, revealed no deleterious effect at a dose of 10 g/kg/day.

Studies performed in animals indicate that piracetam has no effect on the fertility of male or female rats.

3 years.

No special precautions for storage.

No special requirements.