Indications:
Adults:
Supportive treatment of chronic symptoms of cognitive and neurosensory impairment in the elderly (excluding Alzheimer’s disease and other dementias).
Symptomatic improvement of vertigo.
Treatment of cortical myoclonus.
Children over 30 kg (from 9 years of age):
Treatment of dyslexia
Administration, dosage:
Administration:
The drug is taken orally and can be taken with or without food. The dose should be divided into 2-4 times a day.
Dilute the solution in a little water.
Use the graduated dropper to measure the dose:
| Amount of Criatam solution | 1 ml | 2 ml | 3 ml | 4 ml | 5 ml |
| Equivalent amount of active ingredient Piracetam | 200 mg | 400 mg | 600 mg | 800 mg | 1000 mg |
Or use pre-divided sachets of 4 ml (equivalent to 800 mg piracetam) and 12 ml (equivalent to 2.4 g).
Dosage:
The recommended dosages by indication:
Supportive treatment of chronic symptoms of cognitive and neurosensory impairment in the elderly and vertigo:
Dose 800 mg/once (4 ml sachet can be used) every morning, noon and evening, or 2.4 g daily.
Treatment of cortical myoclonus:
The initial daily dose is 7.2 g and then increased by 4.8 g every 3 – 4 days to a maximum dose of 24 g, divided into 2 – 3 times a day (12 ml sachet can be used). Treatment with other antimyoclonic drugs should be maintained at the same dosage. Depending on the clinical benefit achieved, the dosage of these drugs should be reduced, if possible.
Once started, treatment with piracetam should be continued as long as the initial brain disease persists. In patients with an acute episode, spontaneous improvement may occur over time and will require try to decrease or stop medication every six months. For this case, the dose of piracetam will have to be reduced by 1.2 g every other day (every three or four days in the case of Lance and Adams syndrome), to prevent the risk of sudden recurrence of myoclonus or withdrawal convulsions.
Special populations:
Elderly:
Dose adjustment is recommended in elderly patients with impaired renal function (see “Warnings and precautions for use, renal impairment”). During long-term treatment in the elderly, creatinine clearance should be regularly assessed to adjust the dose appropriately when necessary.
Renal failure:
The daily dose is adjusted for individual patient according to renal function. Consult to 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. Creatinine clearance (ml/min) can be estimated from serum creatinine concentration (mg/dl) using the following formula:
| Clcr = | [140 – age (years)] * weight (kg) | (* 0.85 for women) |
| 72 * serum creatinine (mg/dl)) |
| Group | Clearance of the
creatinine (ml/min) |
Dosage and frequency |
| Normal kidney function | > 80 | Usual daily dose divided into 2 to 4 doses |
| Mild renal failure | 50 ‒ 79 | 2/3 of the usual daily dose divided into 2 or 3 doses |
| Moderate renal failure | 30 ‒ 49 | 1/3 of the usual daily dose divided into 2 doses |
| Severe renal failure | < 30 | Contraindication |
| End stage renal disease | ‒ | Contraindication |
Hepatic failure:
No dosage adjustment is necessary in patients with only hepatic impairment. Dosage adjustment is recommended in patients with hepatic and renal impairment.
Children:
Treatment of dyslexia: 50 mg/kg/day divided into 3 times.
For example, for a 30 kg child, the dose is 500 mg/time, 3 times/day.
Some special attention on the handling of the medicine before and after use:
There are no special requirements for handling the drug after use.
Contraindications:
Hypersensitivity to piracetam, other pyrrolidone derivatives or any ingredient of the drug.
Patients with severe renal failure or end-stage renal failure.
Cerebral hemorrhage.
Huntington’s chorea (worsening of symptoms).
Warnings and precautions for use:
Effect on platelet aggregation:
Due to the effect of piracetam on platelet aggregation, caution is recommended in patients with severe bleeding, patients at risk for bleeding such as a gastrointestinal ulcer, patients with hemostatic disorders, a history of hemorrhagic stroke, patients undergoing surgery (including dental surgery) and patients on anticoagulants or antiplatelet agents, including low-dose acetylsalicylic acid.
Renal failure:
Piracetam is excreted by the kidneys, therefore caution should be exercised in patients with renal impairment.
In mild to moderate renal impairment, doses will be decreased and / or spaced if the clearance of creatinine is less than 80 ml/min.
Elderly:
In case of long-term treatment, creatinine clearance should be regularly assessed to adjust the dose, if necessary.
Stop treatment:
Sudden discontinuation of treatment should be avoided in patients with myoclonus, as this may cause sudden recurrence of these or withdrawal convulsions.
Warnings relating to excipients:
Each ml of the medicine contains 40 mg of betadex. Due to limited safety information in children under 2 years of age, the medicine should not be used for this group unless directed by a doctor.
Each ml of the medicine contains 420 mg of sorbitol. Due to sorbitol is a source of fructose, if you have an intolerance to some sugars or a rare hereditary fructose intolerance, where you cannot break down fructose, you should inform your doctor before taking it. In addition, sorbitol may cause gastrointestinal upset or a mild laxative effect.
The medication contains methylparaben and propylparaben, which may cause allergic reactions.
The medication contains glycerin, which can cause headache, stomach upset, and diarrhea.
Each ml of the drug contains 4 mg propylene glycol, concomitant use with any alcohol dehydrogenase substrate such as ethanol may cause serious adverse reactions in newborns.
Pregnancy and lactation:
Pregnancy:
There are no adequate data on the use of piracetam in pregnant women. Studies in animals have not shown any direct or indirect deleterious effects on pregnancy, the development of the embryo or fetal, childbirth or postnatal development.
Piracetam crosses the placental barrier. Drug concentrations in the newborn are approximately 70% to 90% of maternal concentrations. Piracetam is not recommended during pregnancy unless there is a real need, when the expected benefit for the mother is greater than the potential risks.
Lactation:
Piracetam is excreted in breast milk. Therefore, piracetam should not be used while breastfeeding or breastfeeding should be discontinued during treatment with piracetam. A decision whether to discontinue breast-feeding or to discontinue piracetam should be made taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Fertility:
Studies 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.
Effects on ability to drive, use machines:
The drug has moderate influence on the ability to drive and use machines.
Interactions, incompatibilities of medicine:
Interaction of the drug with other drugs and other types of interactions:
Pharmacokinetic interactions:
The potential for drug interactions leading to changes in the pharmacokinetics of piracetam is considered low because approximately 90% of the piracetam dose is excreted in the urine unchanged.
In vitro, piracetam did not inhibit 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 a concentration of 1422 μg/ml, minor inhibitory effects were observed on CYP 2A6 (21%) and 3A4/5 (11%). However, it is likely that the Ki values required to inhibit these two CYP isoforms are well greater than 1422 μg/ml. Therefore, a metabolic interaction of piracetam with other drugs is unlikely.
Thyroid hormones:
Confusion, irritability and sleep disorders have been reported when this medicine was used concomitantly with thyroid hormones (T3+T4).
Acenocoumarol:
In a published single-blind study in patients with severe recurrent venous thromboembolism, piracetam 9.6 g/day did not alter the dose of acenocoumarol required to achieve an INR of 2.5 to 3.5. However, compared with the effects of acenocoumarol alone, the addition of piracetam 9.6 g/day significantly decreased platelet aggregation, β-thromboglobulin release, fibrinogen and von Willebrand factors (VIII: VS; VIII: vW: Ag; VIII: vW: RCo) as well as the viscosity of whole blood and plasma.
Antiepileptic:
Use of piracetam over 4 weeks at a daily dose of 20 g did not change the peak and trough serum concentrations of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, valproic acid) in epileptic patients who received stable doses.
Alcohol:
Concomitant use of alcohol did not affect serum piracetam and alcohol concentrations were not altered by oral doses of 1.6 g piracetam.
Incompatibilities:
Because there are no studies of drug incompatibility, do not mix this drug with other drugs.
Undesirable effects:
Safety profile summary:
Double-blind, placebo-controlled clinical pharmacology studies or clinical trials with available data (extracted from the UCB data bank as of June 1997) included more than 3,000 subjects taking piracetam, regardless of indication, formulation, daily dose or characteristics of the study population.
Undesirable effects are classified according to frequency: Very common (ADR ≥ 1/10), common (1/100 ≤ ADR < 1/10), uncommon (1/1,000 ≤ ADR < 1/100), rare (1/10,000 ≤ ADR < 1/1,000), very rare (ADR < 1/10,000); cannot be estimated from the available data “Not known”.
Blood and lymphatic system disorders:
Unknown: Bleeding disorders.
Immune system disorders:
Unknown: Anaphylactoid reaction, hypersensitivity.
Psychiatric disorders:
Common: Nervousness.
Uncommon: Depression.
Unknown: Agitation, anxiety, confusion, hallucination.
Nervous system disorders:
Common: Hyperkinesia.
Uncommon: Nervousness.
Unknown: Ataxia, balance disorder, aggravated epilepsy, headache, insomnia, drowsiness.
Disorders of the ear and labyrinth:
Unknown: Fear of heights.
Gastrointestinal disorders:
Unknown: Abdominal pain, upper abdominal pain, diarrhea, nausea, vomiting.
Skin and subcutaneous tissue disorders:
Unknown: Angioedema, dermatitis, pruritus, urticaria.
Systemic and local disorders:
Uncommon: Asthenia.
Investigations:
Common: Weight gain
Contact your doctor if you experience these side effects.
Overdose and management:
Overdose:
Symptoms: The highest reported overdose was a piracetam dose of 75 g. Bloody diarrhea with abdominal pain appeared, but most likely related to the very high dose of sorbitol in the drug.
No additional adverse reactions related to overdose have been reported with piracetam.
Management:
In case of acute and severe overdose, the stomach may be emptied by induction of vomiting. There is no specific antidote for piracetam. Treatment of overdose is primarily symptomatic and may include hemodialysis. The dialysis efficiency is 50 to 60% for piracetam.
Pharmacodynamics:
Pharmacological group: Other psychostimulants and nootropics.
ATC code: N06BX03.
Action mechanism:
The mechanism of action of the therapeutic effects is unknown.
Pharmacodynamic effects:
In animals, under conditions different from therapeutic use, especially at dosages or concentrations often high, the following pharmacological effects have been observed:
Improves neurotransmission in the GABAergic, cholinergic and glutamatergic systems.
Increases the ability to absorb and speed of processing intra- and inter-hemispheric information.
Pharmacokinetics:
Absorption:
After oral administration, the drug is completely and rapidly reabsorbed. Maximum plasma concentrations are achieved within 45 minutes.
Distribution:
The plasma half-life of piracetam is 4 to 5 hours. The doubling time increases for creatinine clearance below 60 ml/min.
Piracetam crosses the blood-brain barrier and the placental barrier.
Elimination:
Excreted in urine within 30 hours.
