Nootropil

Nootropil

piracetam

Manufacturer:

GlaxoSmithKline

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Piracetam.
Description
FC tab: Each film-coated tablet contains 800 mg of piracetam.
Each film-coated tablet contains 1200 mg of piracetam.
Inj: Each 5 ml solution for injection contains 1 g of piracetam.
Each 15 ml solution for injection contains 3 g of piracetam.
Infusion: Each 60 ml solution for infusion contains 12 g of piracetam.
Excipients/Inactive Ingredients: FC tab: Macrogol 6000, Opadry Y-1-7000 White, Opadry OY-S 29019 Clear, Sodium Croscarmellose, Colloidal anhydrous silica (Aerosil), Magnesium Stearate.
Inj: Water for injection, Sodium acetate, Glacial acetic acid.
Infusion: Water for injections, Sodium chloride, Sodium acetate, Glacial acetic acid.
Action
Pharmacology: Pharmacodynamics: Piracetam is a "nootrope" that is to say it is a psychotropic agent which acts directly on the brain to improve efficacy of the telencephalon in both normal subjects and those suffering from some functional deficit. This area of the brain is involved in cognition and also has a role to play in learning and memory, in alertness and in consciousness. Piracetam does not produce either sedation or stimulation.
Piracetam can act on the Central Nervous System in a variety of ways. It will modify neurotransmission within the brain, and can help to improve the metabolic environment essential for good neuronal function. It is also a haemorrheological agent and can improve microcirculation without producing vasodilation.
When given as acute or long term treatment for patients suffering from a functional CNS deficit, it will heighten alertness and increase cognitive function. These changes are seen as a significant increase in the alpha and beta activity, with a reduction in delta activity, on an EEG trace.
Piracetam will protect and restore cognitive functional capacity after cerebral trauma such as hypoxia or intoxication, and after electroshock therapy.
Piracetam may be given alone, or together with other drugs when treating cortical myoclonia. NOOTROPIL will reduce the duration of vestibular nystagmus.
Piracetam will improve regional oxygen and glucose uptake in the brain in patients suffering from dementia subsequent to multiple infarcts, or in those with cerebral ischaemia.
Piracetam will inhibit the increased aggregation of activated platelets and, in conditions where there is abnormal rigidity of the red blood cell, it can restore deformability and the ability to pass through the microvasculature.
Clinical Studies: see Pharmacology: Pharmacodynamic effects under Actions.
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, i.v. 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.
Pharmacokinetics: The pharmacokinetic profile of piracetam is linear and time-independent 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 highest concentrations in the brain were in the cerebral cortex (frontal, parietal and occipital lobes), in the cerebellar cortex and in the 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 increase is related to the decrease in renal function in this population (see Dosage & Administration).
Renal impairment: Piracetam clearance is correlated to creatinine clearance. 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.
Indications/Uses
Treatment of the elderly with some degree of cerebral functional impairment such as loss of memory, a lack of concentration or alertness and vertigo.
NOOTROPIL is indicated for patients suffering from myoclonus of cortical origin, irrespective of aetiology and should be used in combination with other anti-myoclonic therapies.
Dosage/Direction for Use
Oral formulations: Piracetam may be taken with or without food. The film-coated tablets should be swallowed with liquid. It is recommended to take the daily dose in two to four sub-doses.
Parenteral formulations: When parenteral administration is needed (e.g. swallowing difficulties, unconsciousness) piracetam can be administered intravenously at the same recommended daily dose.
The solution for injection will be administered intravenously over several minutes.
The solution for infusion will be administered continuously at the recommended daily dose over a 24 hour period.
Route of Administration: Oral formulations: For oral use.
Parenteral formulations: For intravenous use.
Adults: The daily dosage should begin at 7.2 g, increasing by 4.8 g every three or four days up to a maximum of 24 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.
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 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).
Elderly: Adjustment of the dose is recommended in elderly patients with compromised renal function (see Precautions; Renal impairment as follows).
For long term treatment in the elderly, regular evaluation of the creatinine clearance is required to allow dosage adaptation if needed.
Renal impairment: The daily dose must be individualised 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 creatinine clearance (Clcr) in ml/min is needed. The Clcr in ml/min may be estimated from serum creatinine (mg/dl) determination using the following formula (see equation):

Click on icon to see table/diagram/image

(See table.)

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 impairment and renal impairment, adjustment of dose is recommended (see dose adjustment in Renal Impairment previously).
Overdosage
Symptoms and signs: 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 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. Treatment for an overdose should be symptomatic and may include haemodialysis. The extraction efficiency of the dialyser is 50 to 60% for piracetam.
FC tab: Further management should be as clinically indicated or as recommended by the national poisons centre, where available.
Inj & Infusion: In acute, significant overdosage, the stomach may be emptied by induction of emesis.
Contraindications
Piracetam is contraindicated in: hypersensitivity to piracetam, other pyrrolidone derivates or any of the excipient.
Severe renal impairment (renal creatinine clearance of less than 20 ml per minute).
Cerebral haemorrhage.
Patients suffering from Huntington's Chorea.
Special Precautions
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 a 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 is eliminated via the kidneys and care should thus be taken in cases of renal insufficiency (see Dosage & Administration).
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).
Discontinuation: Abrupt discontinuation of treatment should be avoided as this may induce myoclonic or generalised seizures in some myoclonic patients.
Excipients: FC tab: Sodium: These products contain about 2 mmol (or about 46 mg) sodium per 24 g piracetam. This should be taken into consideration by patients on a controlled sodium diet.
Inj: Sodium: This product contains less than 1 mmol (23 mg) sodium per 24 g piracetam. This should be taken into consideration by patients on a controlled sodium diet.
Infusion: Sodium: This product contains about 19 mmol (or about 445 mg) sodium per 24 g piracetam. This should be taken into consideration by patients on a controlled sodium diet.
Effects on ability to drive and use machines: In view of the undesirable side effects, which were observed after the administration of the prepartion, there is the possibility of influence on the ability to drive and to operate machinery and this should be taken into consideration.
Use In Pregnancy & Lactation
Fertility: There are no relevant data available.
Pregnancy: 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. 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.
Piracetam crosses the placental barrier. Drug levels in the newborn are approximately 70% to 90% of maternal levels.
Lactation: 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.
Piracetam is excreted in human breast milk.
Adverse Reactions
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, regardless of indication, dosage form, daily dosage or population characteristics.
Adverse drug reactions (ADRs) are listed as follows 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).
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 disorder, 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: pyrexia (only for injectable form), injection site pain (only for injectable form).
Investigations: Common: weight increased.
Drug Interactions
Pharmacokinetic 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.
Caution For Usage
Instruction for Use and Handling: There are no special requirements for use or handling of this product.
Incompatibilities: None known.
Storage
FC tab: Store below 30°C.
Inj: Store below 30°C.
Infusion: Store below 25°C.
ATC Classification
N06BX03 - piracetam ; Belongs to the class of other psychostimulants and nootropics.
Presentation/Packing
FC tab 800 mg (white oblong, imprinted with a bisect line and N/N on one side and plain on the other side) x 90's. 1200 mg (white oblong scored, marked N/N on one side and plain on the other side) x 20's. Soln for inj (amp) (clear, colourless) 1 g/5 mL x 12's, 3 g/15 mL x 4's. Soln for infusion 12 g/60 mL (clear, colorless) x 1's.
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