Keep out of reach of children.
Read the directions carefully before use.
For prescription only.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Active ingredient
Piracetam .................................. 800 mg
Excipients q.s ……………………… 1 tablet
Film coated tablet.
Product description
A capsule-shaped, white to off-white, film-coated tablet, scored on one side, imprinted with on the other side, undamaged edges.
Box of 3 blisters x 10 film coated tablets.
Pharmacotherapeutic group: Other psychostimulants and nootropics. ATC code: N06B X03.
Piracetam's mode of action in cortical myoclonus is as yet unknown.
Pharmacodynamic effects
Piracetam exerts its haemorrheological effects on the platelets, red blood cells, and vessel walls by increasing erythrocyte deformability and by decreasing platelet aggregation, erythrocyte adhesion to vessel walls and capillary vasospasm.
+ Effects on the red blood cells: In patients with sickle cell anaemia, piracetam improves the deformability of the erythrocyte membrane, decreases blood viscosity, and prevents rouleaux formation.
+ Effects on platelets: In open studies in healthy volunteers and in patients with Raynaud's phenomenon, increasing doses of piracetam up to 12 g was associated with a dose-dependent reduction in platelet functions compared with pre-treatment values (tests of aggregation induced by ADP, collagen, epinephrine and ßTG release), without significant change in platelet count. In these studies, piracetam prolonged bleeding time.
+ Effects on blood vessels: In animal studies, piracetam inhibited vasospasm and counteracted the effects of various spasmogenic agents. It lacked any vasodilatory action and did not induce “steal” phenomenon, nor low or no reflow, nor hypotensive effects.
In healthy volunteers, piracetam reduced the adhesion of RBCs to vascular endothelium and possessed also a direct stimulant effect on prostacycline synthesis in healthy endothelium.
+ Effects on coagulation factors: In healthy volunteers, compared with pre-treatment values, piracetam up to 9.6 g reduced plasma levels of fibrinogen and von Willebrand's factors (VIII : C; VIII R : AG; VIII R : vW) by 30 to 40%, and increased bleeding time.
In patients with both primary and secondary Raynaud phenomenon, compared with pre-treatment values, piracetam 8 g/d during 6 months reduced plasma levels of fibrinogen and von Willebrand's factors (VIII : C; VIII R : AG; VIII R : vW (RCF)) by 30 to 40%, reduced plasma viscosity, and increased bleeding time.
Absorption
Piracetam is rapidly and almost completely absorbed. Peak plasma levels are reached within 1.5 hours after administration. The extent of oral bioavailability is close to 100%. Peak levels and AUC are proportional to the dose given.
Distribution
The volume of distribution of piracetam is 0.7 L/kg. Piracetam crosses the blood-brain and the placental barrier and diffuses across membranes used in renal dialysis.
Biotransformation
Up to now, no metabolite of piracetam has been found.
Elimination
Piracetam is excreted almost completely in urine and the fraction of the dose excreted in urine is independent of the dose given. Excretion half-life values are consistent with those calculated from plasma/blood data. The plasma half-life is 5.0 hours, in young adult men. Clearance of the compound is dependent on the renal creatinine clearance and would be expected to diminish with renal insufficiency.
In clinical studies, at dosages between 1.6 - 15 grams per day, hyperkalemia, somnolence, nervousness and depression were reported more frequently in patients on piracetam than on placebo. There is no experience on driving ability in dosages between 15 and 20 grams daily. Caution should therefore be exercised by patients intending to drive or use machinery whilst taking 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 or foetal development, parturition or post-natal development.
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.
Breast-feeding
Piracetam is excreted in human breast milk. Therefore, piracetam should not be used during breast-feeding 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.
Fertility
There are no available clinical data on the effect of piracetam on fertility. Animal studies indicate that piracetam has no effect on fertility in male or female rats.
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.
Undesirable effects are listed 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), not know (cannot be estimated from the available).
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, hypotension.
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: fever, pain at injection site.
Investigations
Common: weight increased.
Please inform your doctor of all undesirable effects upon drug administration.
Symptoms
No additional adverse events specifically related to overdose have been reported with piracetam.
The highest reported overdose with piracetam was oral intake of 75 g. One case of bloody diarrhoea with abdominal pain, associated with the oral intake of 75 g piracetam daily, was most probably related to the extreme high dose of sorbitol contained in the used formulation.
Management of overdose
In acute, significant overdosage, the stomach may be emptied by induction of emesis. There is no specific antidote for overdose with piracetam. Treatment for an overdose will be symptomatic treatment and may include hemodialysis. The extraction efficiency of the dialyser is 50 to 60% for piracetam.
Store in dry places, not exceeding 30oC, protect from light.
Effects on platelet aggregation
Due to the effect of piracetam on platelet aggregation, 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 cerebro-vascular accident (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.
Elderly
For long-term treatment in the elderly, regular evaluation of the creatinine clearance is required to allow dosage adaptation if needed.
Discontinuation
Abrupt discontinuation of treatment should be avoided as this may induce myoclonic or generalised seizures in some myoclonic patients.
Excipients
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, that is to say essentially "sodium-free".
Adults
Piracetam is indicated for
- symptomatic treatment of the psycho-organic syndrome whose features, improved by treatment, are memory loss, attention disorders and lack of drive,
- treatment of cortical myoclonus, alone or in combination,
- treatment of vertigo and associated disorders of balance, with the exception of dizziness of vasomotor or psychic origin,
- prophylaxis and remission of sickle cell vaso-occlusive crises.
Children
Piracetam is indicated for
- treatment of dyslexia, in combination with appropriate measures such as speech therapy,
- prophylaxis and remission of sickle cell vaso-occlusive crises.
Hypersensitivity to the active substance, other pyrroline derivatives, or to any of the excipients of the medicine.
Piracetam is contra-indicated in patients with severe renal impairment (renal creatinine clearance of less than 20 ml per minute).
It is also contraindicated in patients with cerebral haemorrhage and in patients suffering from Huntington's Chorea.
Piracetam may be taken with or without food. The film-coated tablets should be swallowed with liquid.
Method of administration
For oral use.
Adults
Symptomatic treatment of the psycho-organic syndrome
The recommended daily dose ranges from 2.4 g to 4.8 g, in two or three divided doses.
Treatment of cortical myoclonus
The daily dosage should begin at 7.2 g, increasingly by 4.8 g every three to four days up to a maximum of 20 g, in two or three divided doses. Treatment with other anti-myoclonic medicinal products should be maintained at the same dosage. Depending on the clinical benefit obtained, the dosage of other such medicinal products should be reduced, if possible. The dosage must be set individually for each patient by a therapeutic trial.
Once started, treatment with piracetam should be continued for as long as the original cerebral disease persists. In patients with an acute episode, spontaneous evolution may occur over time and an attempt should be made every 6 hours to decrease or discontinue the medicinal treatment. This should be done by reducing the dose of piracetam by 1.2 g every two days (every three or four days in the case of a Lance-Adams syndrome, in order to prevent the possibility of sudden relapse or withdrawal seizures).
Treatment of vertigo
The recommended daily dose ranges from 2.4 g to 4.8 g, in two or three divided doses.
Prophylaxis and remission of sickle cell vaso-occlusive crises
The recommended daily dose for prophylaxis and remission of crises is 160 mg/kg, orally, in four divided doses.
The recommended daily dose for prophylaxis and remission of crises is 300 mg/kg, intravenously, in four divided doses. For sickle cell anaemia the prophylactic dosage must be permanent.
A dose lower than 160 mg/kg/day or irregular intake may result in relapse of crises.
Children
Dyslexia in combination with appropriate measures such as speech therapy
The recommended dosage for school age children (from 8 years old) and adolescents is 3.2 g per day, that means 2 tablets of 800 mg in the morning and in the evening, usually during the whole period of the school year.
Prophylaxis and remission of sickle cell vaso-occlusive crises
For children from 3 years old onwards the prophylactic dosage is 160 mg/kg/day, in four divided doses. In case of remission a dose of 300 mg/kg/day is administered intravenously, in four divided doses. The prophylactic administration in sickle cell anaemia must be permanent.
A dose lower than 160 mg/kg/day or an irregular intake may cause a relapse of the illness. Piracetam is administered to children with sickle cell anaemia indication in recommended daily doses (mg/kg - see above). Piracetam has been administered only to a limited number of children in the age range of 1 - 3 years.
Elderly
Adjustment of the dose is recommended in elderly patients with compromised renal function (see section Special warnings and precautions for use; Renal impairment below). For long-term treatment in the elderly, regular evaluation of the creatinine clearance is required to allow dosage adaption if needed.
Renal impairment
Piracetam is contraindicated in severe renal impairment (renal creatinine clearance of less than 20 ml per minute) (see sections Contraindications; Special warnings and precautions for use). The daily dose must be individualized according to the renal function. Refer to the following table and adjust the dose as indicated. To use this dosing table, an estimate of the patient’s creatinine clearance (Clcr) in ml/min is needed.
The Clcr in ml/min may be estimated from serum clearance (mg/dl) determination using the following formula:
Clcr = {[140 - age (years)] x weight (kg) / [72 x serum creatinine (mg/dl)]} x 0.85 (for women).
Hepatic impairment
No dose adjustment is needed in patients with solely hepatic impairment. In patients with hepatic impairment and renal impairment, adjustment of dose is recommended (see section Dose adjustment in renal impairment above).
Or as directed by the physician.
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