NOOTROPIL Film-coated tablet / Oral solution / Solution for injection Ref.[7770] Active ingredients: Piracetam

Effects on platelet aggregation

Due to the effect of piracetam on platelet aggregation (see section 5.1), caution is recommended in patients with severe haemorrhage, patients at risk of bleeding such as gastrointestinal ulcer, patients with underlying disorders of haemostasis, patients with history of haemorrhagic CVA, patients undergoing major surgery including dental surgery, and patients using anticoagulants or platelet antiaggregant drugs including low dose aspirin.

Renal insufficiency

Piracetam is eliminated via the kidneys and care should thus be taken in cases of renal insufficiency (see section 4.2).

Elderly

For long-term treatment in the elderly, regular evaluation of the creatinine clearance is required to allow dosage adaptation if needed (see section 4.2).

Discontinuation

Abrupt discontinuation of treatment should be avoided in myoclonic patients as this may induce sudden relapse or withdrawal seizures.

Warnings related to excipients

• Sunset Yellow FCF (E110): May cause allergic reactions
• Mannitol (E421): May have a mild laxative effect from an intake of 6.5g piracetam or more, daily.
• Aspartam (E951): Contains a source of phenylalanine equivalent to 50mg for a dose of 2.4g piracetam. May be harmful for people with phenylketonuria.
• Methyl parahydroxybenzoate and propyoparahydroxybenzoate: May cause allergic reactions (possible delayed).
• Glycerol: may cause headache, stomach upset and diarrhoea
• Sodium:

Piracetam 800mg and 1200mg film-coated tablets: this medicinal product contains 46mg sodium per 24g piracetam, equivalent to 2.3% of the WHO recommended maximum daily intake of 2 g sodium for an adult. To be taken in consideration by patients on a controlled sodium diet.

Piracetam 20% oral solution: this medicinal product contains 80.5mg sodium per 24g piracetam, equivalent to 4.03% of the WHO recommended maximum daily intake of 2 g sodium for an adult. To be taken into consideration by patients on a controlled sodium diet.

Piracetam 1g/5ml, 3g/15ml solution for injection: This medicinal product contains less than 1 mmol sodium (23mg) per 24 g piracetam, that is to say essentially ‘sodium-free’. To be taken into consideration by patients on a controlled low-sodium diet.

Pharmacokinetics Interactions

The drug interaction potential resulting in changes of piracetam pharmacokinetics is expected to be low because approximately 90% of the dose of piracetam is excreted in the urine as unchanged drug.

In vitro, piracetam does not inhibit the human liver cytochrome P450 isoforms CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 4A9/11 at concentrations of 142, 426 and 1422 µg/ml.

At 1422 µg/ml, minor inhibitory effects on CYP 2A6 (21%) and 3A4/5 (11%) were observed. However, the Ki values for inhibition of these two CYP isoforms are likely to be well in excess of 1422 µg/ml. Therefore, metabolic interaction of piracetam with other drugs is unlikely.

Thyroid Hormones

Confusion, irritability and sleep disorder have been reported during concomitant treatment with thyroid extract (T3 + T4).

Acenocoumarol

In a published single-blind study on patients with severe recurrent venous thrombosis, piracetam 9.6 g/d did not modify the doses of acenocoumarol necessary to reach INR 2.5 to 3.5, but compared with the effects of acenocoumarol alone, the addition of piracetam 9.6 g/d significantly decreased platelet aggregation, β-thromboglobulin release, levels of fibrinogen and von Willebrand.s factors (VIII : C; VIII : vW : Ag; VIII : vW : RCo) and whole blood and plasma viscosity.

Antiepileptic Drugs

A 20 g daily dose of piracetam over 4 weeks did not modify the peak and trough serum levels of antiepileptic drugs (carbamazepine, phenytoin, phenobarbitone, valproate) in epileptic patients who were receiving stable doses.

Alcohol

Concomitant administration of alcohol had no effect on piracetam serum levels and alcohol levels were not modified by a 1.6 g oral dose of piracetam.

Pregnancy

There are no adequate data from the use of piracetam in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or post-natal development (see Section 5.3).

Piracetam crosses the placental barrier. Drug levels in the newborn are approximately 70% to 90% of maternal levels. Piracetam should not be used during pregnancy unless clearly necessary, when benefit exceeds the risks and the clinical condition of the pregnant mother requires treatment with piracetam.

Lactation

Piracetam is excreted in human breast milk. Therefore, piracetam should not be used during breastfeeding or breastfeeding should be discontinued, while receiving treatment with piracetam. A decision must be made whether to discontinue breast-feeding or to discontinue piracetam therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Given the adverse events observed with the drug, an influence on driving and using machines is possible and should be taken into account.

a. Summary of safety profile

Double-blind placebo-controlled clinical or pharmacoclinical trials, of which quantified safety data are available (extracted from the UCB Documentation Data Bank on June 1997), included more than 3000 subjects receiving piracetam, regardless of indication, dosage form, daily dosage or population characteristics.

b. Tabulated list of adverse reactions

Undesirable effects reported in clinical studies and from post-marketing experience are listed in the following table per System Organ Class and per frequency. The 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).

Data from post-marketing experience are insufficient to support an estimate of their incidence in the population to be treated.

Blood and lymphatic system disorders

Not known: haemorrhagic disorder

Immune system disorders

Not known: anaphylactoid reaction, hypersensitivity

Psychiatric disorders

Common: nervousness

Uncommon: depression

Not known: agitation, anxiety, confusion, hallucination

Nervous system disorders

Common: hyperkinesia

Uncommon: somnolence

Not known: ataxia, balance impaired, epilepsy aggravated, headache, insomnia,

Ear and labyrinth disorders

Not known: vertigo

Vascular disorders

Rare: Thrombophlebitis (only for injectable form), hypotension (only for injectable form)

Gastrointestinal disorders

Not known: abdominal pain, abdominal pain upper, diarrhoea, nausea, vomiting

Skin and subcutaneous tissue disorders

Not known: angioneurotic oedema, dermatitis, pruritus, urticaria

General disorders and administration site conditions

Uncommon: asthenia

Rare: injection site pain (only for injectable form), pyrexia (only for injectablet form)

Investigations

Common: weight increased

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 reactions to the Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs Fax: +357 22608649.

None known.

Piracetam is compatible (physico-chemical compatibility) with the perfusions of:

Glucose 5%, 10%, 20%
Fructose 5%, 10%, 20%
Sodium chloride 0.9%
Dextran 40 (10% in a 0.9% NaCl solution)
Ringer
Mannitol 20%
HES solution (Hydroxy Ethyl Starch) 6% and 10%

The stability of these solutions has been demonstrated for a minimum period of 24 h.

Effects on diagnostic examinations: none known.