Piracetam (Nootropil) 800 mg Film-Coated Tablet: Each film-coated tablet contains 800 mg of piracetam.
Piracetam (Nootropil) 1.2 g Film Coated Tablet: Each film-coated tablet contains 1200 mg of piracetam.
Pharmacology: Pharmacodynamics: Mechanism of Action: Available data suggest that piracetam basic mechanism of action is neither cell nor organ specific. Piracetam binds physically in a dose-dependent manner to the polar head of phospholipids membrane models, inducing the restoration of the membrane lamellar structure characterized by the formation of mobile drug phospholipid complexes. This probably accounts for an improved membrane stability, allowing the membrane and transmembrane proteins to maintain or recover the 3-dimensional structure or folding essential to exert their function. Piracetam has neuronal and vascular effects.
Neuronal Effect: At the neuronal level, piracetam exerts its membrane activity in various ways. In animals, piracetam enhances a variety of types of neurotransmission, primarily through postsynaptic modulation of receptor density and activity. In both animals and man, the functions involved in cognitive processes eg, learning, memory, attention and consciousness were enhanced in the normal subject as well as in deficiency states without the development of sedative or psychostimulant effects. Piracetam protects and restores cognitive abilities in animals and man after various cerebral insults such as hypoxia, intoxications and electroconvulsive therapy. It protects against hypoxia-induced changes in brain function and performance as assessed by electroencephalograph (EEG) and psychometric evaluations.
Vascular Effects: Piracetam applies its haemorrhagic effect to thrombocytes, erythrocytes and the walls of the blood vessels by increasing the deformability of erythrocytes, reducing the aggregability of throbocytes, reduces the adhesion of erythrocytes to the walls of vessels and reduces capillary vasospasm.
Effects on the Red Blood Cells: In patients with sickle cell anemia, 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 βTG 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's phenomenon, compared with pretreatment 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.
Pharmacokinetics: The pharmacokinetic profile of piracetam is linear and time-dependent with low intersubject variability over a large range of doses. This is consistent with the high permeability, high solubility and minimal metabolism of piracetam. Plasma half-life of piracetam is 5 hours. It is similar in adult volunteers and in patients. It is increased in the elderly (primarily due to impaired renal clearance) and in subjects with renal impairment. Steady-state plasma concentrations are achieved within 3 days of dosing.
Absorption: Piracetam is rapidly and extensively absorbed following oral administration. In fasted subjects, the peak plasma concentrations are achieved 1 hour after dosing. The absolute bioavailability of piracetam oral formulations is close to 100%. Food does not affect the extent of absorption of piracetam but it decreases Cmax by 17% and increases Tmax from 1 to 1.5 hours. Peak concentrations are typically 84 μg/mL and 115 μg/mL following a single oral dose of 3.2 g and repeat dose of 3.2 g twice daily, respectively.
Distribution: Piracetam is not bound to plasma proteins and its volume of distribution is approximately 0.6 L/kg. Piracetam crosses the blood brain barrier as it has been measured in cerebrospinal fluid following intravenous administration. In cerebrospinal fluid, the Tmax was achieved about 5 hours post-dose and the half-life was about 8.5 hours. In animals, piracetam's highest concentrations in the brain were in the cerebral cortex (frontal, parietal and occipital lobes), in the cerebellar cortex and basal ganglia. Piracetam diffuses to all tissues except adipose tissues, crosses placental barrier and penetrates the membranes of isolated red blood cells.
Metabolism: Piracetam is not known to be metabolized in the human body. This lack of metabolism is supported by the lengthy plasma half-life in anuric patients and the high recovery of parent compound in urine.
Elimination: The plasma half-life of piracetam in adults is about 5 hours following either intravenous or oral administration. The apparent total body clearance is 80-90 mL/min. The major route of excretion is via urine, accounting for 80 to 100% of the dose. Piracetam is excreted by glomerular filtration.
Linearity: The pharmacokinetics of piracetam are linear over the dose range of 0.8 to 12 g. Pharmacokinetic variables like half-life and clearance are not changed with respect to the dose and the duration of treatment.
Special Patient Populations: Children: No formal pharmacokinetic study has been conducted in children.
Elderly: In the elderly, the half-life of piracetam is increased and the increased is related to the decrease in renal function in this population (see Dosage & Administration).
Renal Impairment: Piracetam clearance is correlated to CrCl. It is therefore recommended to adjust the daily dose of piracetam based on creatinine clearance in patients with renal impairment (see Dosage & Administration). In anuric end-stage renal disease subjects, the half-life of piracetam is increased up to 59 hours. The fractional removal of piracetam was 50 to 60% during a typical 4-hour dialysis session.
Hepatic Impairment: The influence of hepatic impairment on the pharmacokinetics of piracetam has not been evaluated. Because 80 to 100% of the dose is excreted in the urine as unchanged drug, hepatic impairment solely would not be expected to have a significant effect on piracetam elimination.
Other patient characteristics: Gender: In a bioequivalence study comparing formulations at a dose of 2.4 g, Cmax and AUC were approximately 30% higher in women (N=6) compared to men (N=6). However, clearances adjusted for body weight were comparable.
Race: Formal pharmacokinetic studies of the effects of race have not been conducted. Cross study comparisons involving Caucasians and Asians, however, show that pharmacokinetics of piracetam were comparable between the two races. Because piracetam is primarily renally excreted and there are no important racial differences in creatinine clearance, pharmacokinetic differences due to race are not expected.
Toxicology: Non-Clinical Information: The preclinical data indicate that piracetam has a low toxicity potential. Single dose studies showed no irreversible toxicity after oral doses of 10 g/kg in mice, rats and dogs. No target organ for toxicity was observed in repeated dose, chronic toxicity studies in mice (up to 4.8 g/kg/day) and in rats (up to 2.4 g/kg/day). Mild gastrointestinal effects (emesis, change in stool consistency, increased water consumption) were observed in dogs when piracetam was administered orally for one year at a dose increasing from 1 to 10 g/kg/day. Similarly, IV administration of up to 1 g/kg/day for 4-5 weeks in rats and dogs did not produce toxicity. In vitro and in vivo studies have shown no potential for genotoxicity and carcinogenicity.
Adults: 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; vertigo and associated disorders of balance, with the exception of dizziness of vasomotor or psychic origin.
Children: Treatment of dyslexia, in combination with appropriate measures such as speech therapy.
Symptomatic Treatment of Psycho-Organic Syndromes: The recommended daily dose ranges from 2.4 g up to 4.8 g, in two or three subdoses.
Treatment of Myoclonus of Cortical Origin: The daily dosage should begin at 7.2 g, increasing by 4.8 g every 3 or 4 days up to a maximum of 24 g, in two or three subdoses. Treatment with other antimyoclonic medicinal products should be maintained at the same dosage. Depending on the clinical benefit obtained, the dosage of the other such medicinal products should be reduced, if possible. 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 months to decrease or discontinue the medicinal treatment. This should be done by reducing the dose of piracetam by 1.2 g every 2 days (every 3 or 4 days in the case of a Lance and Adams syndrome, in order to prevent the possibility of sudden relapse or withdrawal seizures).
Treatment of Vertigo: The recommended daily dose ranges from 2.4-4.8 g in two or three subdoses.
Treatment of Dyslexia in Combination with Speech Therapy: Adolescents and Children from 8 years: The recommended daily dose is about 3.2 g, in two subdoses.
Elderly: Adjustment of the dose is recommended in elderly patients with compromised renal function (see Table 1). For long-term treatment in the elderly, regular evaluation of the CrCl is required to allow dosage adaptation if needed.
Renal Impairment: The daily dose must be individualized according to renal function. Refer to the following table and adjust the dose as indicated. To use this dosing table, an estimate of the patient's CrCl in mL/min is needed. The CrCl in mL/min may be estimated from the serum creatinine (mg/dL) determination using the following formula:
Click on icon to see table/diagram/image
Click on icon to see table/diagram/image
Hepatic Impairment: No dose adjustment is needed in patients with solely hepatic impairment. In patients with hepatic and renal impairment, adjustment dose is recommended (see Table 1).
Administration: Oral Formulations: Piracetam (Nootropil) may be taken with or without food. The film-coated tablet should be swallowed with liquid.
Route of Administration: Oral Formulations: For oral use.
Symptoms: No additional adverse events specifically related to overdose have been reported with piracetam (Nootropil).
The highest reported overdose with piracetam (Nootropil) was oral intake of 75 g wherein bloody diarrhoea with abdominal pain, was most probably related to the extreme high dose of sorbitol contained in the used formulation.
Treatment: There is no specific antidote for overdose with piracetam (Nootropil). Treatment for an overdose should be symptomatic and may include haemodialysis. The extraction efficiency of the dialyser is 50 to 60% for piracetam (Nootropil).
Further management should be as clinically indicated or as recommended by the national poisons centre, where available.
Piracetam (Nootropil) is contraindicated in: Hypersensitivity to piracetam, other pyrrolidone derivatives or any of the excipients, severe renal impairment (renal creatinine clearance of less than 20 mL per minute), cerebral haemorrhage, patients suffering from Huntington's Chorea.
Effects on platelet aggregation: Due to the effect of piracetam (Nootropil) 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 CVA, patients undergoing major surgery including dental surgery, and patients using anticoagulants or platelet antiaggregant drugs including low dose acetylsalicylic acid.
Renal insufficiency: Piracetam (Nootropil) is eliminated via the kidneys and care should thus be taken in cases of renal insufficiency (see Dosage & Administration).
Discontinuation: Abrupt discontinuation of treatment should be avoided as this may induce myoclonic or generalised seizures in some myoclonic patients.
Ability to perform tasks that require judgement, motor or cognitive skills: In view of the undesirable side effects, which were observed after the administration of the preparation, there is the possibility of
influence on the ability to drive and to operate machinery and this should be taken into consideration.
Use in Elderly: For long-term treatment in the elderly, regular evaluation of the creatinine clearance is required to allow dosage adaptation if needed (see Dosage & Administration).
Fertility: There are no relevant data available.
Pregnancy: Piracetam (Nootropil) 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 (Nootropil). Piracetam (Nootropil) crosses the placental barrier. Drug levels in the newborn are approximately 70% to 90% of maternal levels.
There are no adequate data from the use of piracetam (Nootropil) 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.
Lactation: Piracetam (Nootropil) should not be used during breastfeeding or breastfeeding should be discontinued, while receiving treatment with piracetam (Nootropil). Piracetam (Nootropil) is excreted in human breast milk. A decision must be made whether to discontinue breast-feeding or to discontinue piracetam (Nootropil) therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Clinical Trial and Post Marketing Data: Double-blind placebo-controlled clinical or pharmaco-clinical trials, of which quantified safety data are available, included more than 3000 subjects receiving Piracetam (Nootropil), regardless of indication, dosage form, daily dosage or population characteristics.
Adverse drug reactions (ADRs) are listed below by MedDRA system organ class and by frequency.
Frequencies are defined as: Very common ≥1/10, Common ≥1/100 to <1/10, Uncommon ≥1/1000 to <1/100, Rare ≥1/10000 to <1/1000, Very rare <1/10000, Not known (cannot be estimated from the available data) (see Table 2).
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Pharmacokinetic interactions: The drug interaction potential resulting in changes of piracetam (Nootropil) pharmacokinetics is expected to be low because approximately 90% of the dose of piracetam (Nootropil) is excreted in the urine as unchanged drug.
In vitro, piracetam (Nootropil) 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 (Nootropil) 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 (Nootropil) 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 (Nootropil) 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 (Nootropil) 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 (Nootropil) serum levels and alcohol levels were not modified by a 1.6 g oral dose of piracetam (Nootropil).
Incompatibilities: None known.
Piracetam (Nootropil) 800 mg and 1200 mg film coated tablet: Store at temperatures not exceeding 30°C.
N06BX03 - piracetam ; Belongs to the class of other psychostimulants and nootropics.
Nootropil FC tab 1200 mg
30's
Nootropil FC tab 800 mg
30's
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