Pyracetam - instructions for use, dose, side effects, contraindications

Active substance: piracetam 0.2 g; excipients: potato starch, povidone, magnesium carbonate, calcium stearate - to obtain a tablet weighing 0.25 g (excluding shell); excipients: sucrose (sugar), povidone, magnesium carbonate, silicon dioxide colloid (aerosil), titanium dioxide, tropeolin stain O, sunflower oil, beeswax - enough to obtain a tablet weighing 0.46 grams (with a shell).

Pharmacotherapeutic group:Nootropic agent.

ATX: & nbsp

N.06.B.X.03 Pyracetam

Pharmacodynamics:

Pyracetam - nootropic agent, has an effect on the central nervous system in various ways: it modifies neurotransmission in the brain; improves conditions,promoting neuronal plasticity; improves microcirculation, affecting the rheological characteristics of the blood and not causing vasodilation. The use of piracetam in patients with cerebral dysfunction increases attention concentration and improves cognitive function, which is accompanied by changes in the electroencephalogram (increase in α and β activity, decrease in δ activity). Promotes restoration of cognitive functions due to various disorders, such as hypoxia, intoxication or electroconvulsive therapy. Reduces the duration of induced vestibular neuronitis. Pyracetam inhibits increased aggregation of activated platelets and, in the case of abnormal rigidity of erythrocytes, improves their deformability and ability to filter.

Pharmacokinetics:

Absorption. After oral administration piracetam quickly and almost completely absorbed from the gastrointestinal tract. Bioavailability is about 100%. After a single dose of piracetam at a dose of 2 g, the maximum concentration (C_max) is reached in 30 minutes and is 40-60 μg / ml, after 2-8 hours it is found in the cerebrospinal fluid.

Distribution.The volume of the distribution (Vd) is about 0.6 l / kg. Does not bind to plasma proteins. Pyracetam penetrates through blood-brain and placental barriers, as well as hemodialysis membranes. In an animal study, it was found that piracetam selectively accumulates in the tissues of the cerebral cortex, mainly in the frontal, parietal and occipital lobes, in the cerebellum and basal nuclei.

Metabolism. It is not metabolized. Excretion. Half-life of blood (T1) is 4-5 h and 8.5 h - from the cerebrospinal fluid. T1 is prolonged with renal failure. It is excreted unchanged by the kidneys. Excretion by the kidneys is almost complete (> 95%) for 30 hours. The total clearance of piracetam in healthy volunteers is 86 ml / min.

Indications:

Symptomatic treatment of intellectual-mnestic disorders in the absence of an established diagnosis of dementia.

Reduction of the manifestations of cortical myoclonia in piracetam sensitive patients both as monotherapy and as part of complex therapy. (In order to determine sensitivity to pyracetam in a particular case, a trial treatment course can be performed).

Contraindications:

hypersensitivity to pyracetam or pyrrolidone derivatives, as well as other components of the drug;
terminal stage of chronic renal failure;
hemorrhagic stroke;
Huntington's chorea;
deficiency of sucrose / isomaltase, intolerance to fructose, glucose-galactose malabsorption.

Carefully:

In the treatment of cortical myoclonia, sudden cessation of treatment should be avoided, as this may cause the resumption of seizures.

Effect on platelet aggregation. Due to the antiaggregant effect (see the section "Pharmacodynamics"), piracetam should be administered with caution to patients with severe hemorrhagic disorders, risk of bleeding (eg, gastric ulcer), hemostasis disorders, in patients with surgical interventions, including dental interventions, in patients taking anticoagulants and antiaggregants, incl. low doses of acetylsalicylic acid.

Renal failure. Because the piracetam is excreted by the kidneys, care should be taken when prescribing the drug to patients with renal insufficiency (see section "Method of administration and dose").

With prolonged therapy in elderly patients, regular monitoring of renal function is recommended, if necessary, dose adjustment is performed depending on the creatinine clearance (see section "Method of administration and dose"). Pyracetam penetrates the filtration membranes of hemodialysis apparatus.

Pregnancy and lactation:

Pregnancy.

Sufficient data on the use of piracetam during pregnancy are absent. Studies in animals have not shown a direct or indirect effect on pregnancy, embryo / fetal development, childbirth or postnatal development. Pyracetam penetrates the placental barrier. The plasma concentration of piracetam in neonates reaches 70-90% of that of the mother. Pyracetam should be prescribed during pregnancy only in exceptional cases if the benefit to the mother exceeds the potential risk to the fetus, and the clinical condition of the pregnant woman requires treatment with piracetam.

Lactation.

Piracetam penetrates into breast milk. Pyracetam should not be used during breastfeeding or should stop breastfeeding while treating piracetam.When deciding whether to abort breastfeeding or refusing piracetam treatment, the benefits of breastfeeding for a child and the benefits of therapy for a woman should be correlated.

Dosing and Administration:

Inside with food or on an empty stomach, with water. The daily dose is divided into 2-4 admission.

In memory disorders, intellectual disorders - 2.4 - 4.8 g / day in 2-3 doses during the first few weeks, then go on maintenance therapy 2.4 g / day, taking 1.2 g / day.

Treatment of cortical myoclonia: treatment starts with a dose of 7.2 g / day, gradually increasing by 4.8 g every 3-4 days until a maximum dose of 24 g / day is reached. With little or no therapeutic effect, treatment is stopped on the 7th day, in case of a positive response to treatment, a dose of 24 g is reduced by 1.2 g every 2 days, until the occurrence of myoclonus. This allows you to know the average effective dose. The daily dose of piracetam should be divided into 2-3 doses. The dose of other drugs for the treatment of myoclonus does not change. Then, later on the results of treatment, it is allowed to review the dose of other drugs for the treatment of myoclonus. After initiation of piracetam treatment, treatment is continued as long as the symptoms of the disease persist.However, every 6 months, attempts should be made to reduce the dose or cancel the drug. To avoid sudden relapse, the dose is reduced by 1.2 g every 2 days. If oral administration is not possible, the drug is administered intravenously at the same dose.

Renal failure. Pyracetam is excreted exclusively by the kidneys, care should be taken when treating patients with renal insufficiency or requiring renal function control. The elimination half-life increases in direct proportion to the impairment of kidney function and creatinine clearance; this is also true for the elderly, in whom the excretion of creatinine depends on age.

A dosage adjustment is required depending on the amount of creatinine clearance (CK). The creatinine clearance for men can be calculated based on the serum creatinine concentration (K_serum), according to the following formula:

CK (ml / min) = [140 - age (years) х body weight (kg)] / [72 х К_serum (mg / ml)]

The creatinine clearance for women can be calculated by multiplying the obtained value by a factor of 0.85.

Renal insufficiency	Creatinine clearance (ml / min)	Dose and frequency of application
Norm	>80	Usual Dose
Lightweight	50-79	2/3 of the usual dose in 2-3 doses
Average	30-49	1/3 of the usual dose in 2 divided doses
Heavy	20-30	1/6 of the usual dose once
Terminal	<20	Contraindicated

Dosing to elderly patients: the dose is adjusted in the presence of renal failure in accordance with the scheme (see section "Renal failure").

Dosing to patients with impaired hepatic function: dose adjustment is not it takes. Patients with impaired functions of the kidneys and liver, the drug is prescribed according to the scheme (see section "Renal failure").

Side effects:

The undesirable drug reactions listed below were detected in clinical trials and post-detection observations and grouped according to system-organ classes. The frequency gradient is defined as follows: very often (≥1 / 10), often (≥1 / 100 to <1/10), infrequently (≥1 / 1000 to <1/100), rarely (≥1 / 10,000 to < 1/1000), very rarely (up to <1/10 000) and the frequency is unknown (it is impossible to estimate based on available data).

From the side of the blood and lymphatic system: frequency unknown: bleeding.

From the immune system: frequency unknown: anaphylactoid reactions, hypersensitivity.

From the side of the psyche: often: nervousness; infrequently: depression; frequency unknown: agitation, anxiety, confusion, hallucinations.

From the nervous system: often: hyperactivity; infrequently: drowsiness; frequency unknown: ataxia, imbalance, exacerbation of epilepsy, headache, insomnia, tremor.

From the side of the organ of hearing and labyrinth: frequency unknown: vertigo.

From the digestive system: frequency unknown: abdominal pain (including in the upper divisions), diarrhea, nausea, vomiting.

From the skin and subcutaneous tissues: frequency unknown: angioedema, dermatitis, itching, hives.

On the part of the reproductive system: frequency unknown: increased sexual desire.

Common disorders and disorders at the site of administration: rarely: pain at the injection site, fever (only with parenteral administration).

Laboratory and instrumental data: often: weight gain.

Overdose:

A single case of development of diarrhea in the form of diarrhea with blood and abdominal pain with piracetam taken inside at a daily dose of 75 g. Apparently, this was due to the receipt of a large total dose of sorbitol,which previously was part of the solution for oral administration. Other symptoms of overdose are not registered.

First aid: gastric lavage, artificial vomiting, symptomatic treatment, including hemodialysis. There is no specific antidote. The efficiency of hemodialysis is 50-60%.

Interaction:

With the simultaneous use of piracetam with iodine-containing thyroid hormones, confusion, irritability and sleep disturbance can occur.

Acenocoumarol. According to a published blind clinical trial in patients with recurrent venous thrombosis piracetam at a dose of 9.6 g / day does not affect the dose of acenocoumarol necessary to achieve an international normalized ratio of 2.5-3.5, but compared with the effects of acenocoumarol alone, the addition of pyracetam at a dose of 9.6 g / day significantly reduces platelet aggregation, β-thromboglobin release, fibrinogen concentration and von Willebrand factors (VIII: C; VIII: vW: Ag; VIII: vW: RCo); and the viscosity of whole blood and plasma.

Pharmacokinetic interaction.

The possibility of changing the pharmacokinetics of piracetam under the influence of other drugsof the drugs is low, since 90% of the piracetam is excreted unchanged in the urine. In concentrations of 142, 426 and 1422 mg / ml

Pyracetam does not inhibit cytochrome P450 isoenzymes (CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 4A9 / 11) in vitro. At a concentration of 1422 mg / ml, a minimal inhibition of the isoenzyme CYP2A6 (21%) and SA4 / 5 (11%) was observed. However, the values of the inhibition constant (Ki) probably go well beyond the concentration of 1422 mg / ml. Thus, the metabolic interactions of piracetam with other drugs are unlikely.

Admission of piracetam at a dose of 20 g / day for 4 weeks in patients with epilepsy who received stable doses of antiepileptic drugs did not change the maximum serum concentration and area under the concentration-time curve of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital and valproic acid).

Joint intake with alcohol did not affect the concentration of piracetam in the serum; the concentration of ethanol in the serum did not change with the intake of 1.6 g of piracetam. There is no information on pharmaceutical incompatibility.

Special instructions:

In the treatment of cortical myoclonia avoid abrupt cessation of treatment, as this may cause a resumption of seizures.

Effect on platelet aggregation.

Due to the antiaggregant effect (see Fig.section "Pharmacodynamics"), piracetam should be administered with caution to patients with severe hemorrhagic disorders, risk of bleeding (eg, gastric ulcer), hemostasis disorders, in patients with surgical interventions, including dental interventions, in patients taking anticoagulants and antiaggregants, incl. low doses of acetylsalicylic acid.

Renal failure.

Because the piracetam is excreted by the kidneys, care should be taken when prescribing the drug to patients with renal insufficiency (see section "Method of administration and dose").

With prolonged therapy in elderly patients it is recommended that the kidney function is regularly monitored, if necessary, dose adjustment is performed depending on the creatinine clearance (see section "Method of administration and dose"). Pyracetam penetrates the filtration membranes of hemodialysis apparatus.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles, performing work with mechanisms, engaging in other potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:The coated tablets, 0.2 g

Packaging:

For 60 tablets in a can of light-protective glass or 6 contour squares for 10 tablets together with instructions for use in a pack of cardboard box.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N003097 / 01

Date of registration:14.07.2009

The owner of the registration certificate:IRBITSK HFZ, OJSC IRBITSK HFZ, OJSC Russia

Manufacturer: & nbsp

IRBITSK HFZ, OJSC Russia

Information update date: & nbsp22.09.2015

Illustrated instructions

Instructions

Pyracetam (Piracetam)