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

Active substance: piracetam - 400 mg. Excipients: calcium stearate, magnesium hydroxycarbonate. Capsules, hard gelatin: gelatin, purified water, methyl parahydroxybenzoate (nipagin), propyl parahydroxybenzoate (nipazole), titanium dioxide.

Description:

Capsules of white color. The contents of capsules are white or almost white powder.

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 the conditions conducive to 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 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.

Pyracetam is indicated for the treatment of cortical myoclonus both as monotherapy and as part of complex therapy. Reduces the duration of induced vestibular neuronitis.

Piracetam 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 distribution (V_d) 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 (T_1/2) is 4-5 hours and 8.5 hours - from cerebrospinal fluid. T_1/2 lengthened with renal

insufficiency.

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.

A decrease in 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 course of treatment can be performed).

Contraindications:

hypersensitivity to pyracetam or pyrrolidone derivatives, as well as other components of the drug;
hemorrhagic stroke;
terminal stage of chronic renal failure; Huntington's disease.

Carefully:

violation of hemostasis;
extensive surgical interventions;
heavy bleeding.

Pregnancy and lactation:

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 quit breastfeeding or refuse treatment with piracetam, the benefits of breastfeeding for a child and the benefits of therapy for a woman should be correlated.

Dosing and Administration:

Inside. Capsules are swallowed, not liquid, squeezed with water. During a meal or on an empty stomach.

In memory disorders, intellectual disorders

On 2,4-4,8 g / day in several receptions during the first several weeks, then pass to supporting therapy of 2,4 g / day in 2-3 receptions, reception of 1,2 g / day is possible.

Treatment of cortical myoclonia

Treatment is started from 7.2-24 g per day, with little therapeutic effect or its absence, 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 appearance 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.

Elderly patients

Elderly patients with renal insufficiency should be corrected for the dose (see below "Renal failure"). With long-term treatment to assess the need for dose adjustment, creatinine clearance should be assessed regularly.

Renal insufficiency

Piracetam is excreted almost exclusively by the kidneys, care should be taken when treating patients with renal insufficiency or requiring renal function control.

The half-life period increases in direct proportion to the decrease in kidney function and creatinine clearance; this is also true for elderly patients whose creatinine excretion depends on age.

In this regard, the dose is adjusted in accordance with the following table:

Renal insufficiency	CK (ml / min)	Dosing regimen
Norm	>80	the usual dose of 2-4 admission
Lightweight	50-79	2/3 of the usual dose in 2-3 doses
Average	30-19	1/3 of the usual dose in 2 divided doses
Heavy	<30	1/6 of the usual dose once
The final stage	-	contraindicated

Creatinine clearance for men can be Calculate 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 КК_serum (mg / ml)]

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

Liver failure

Patients with isolated dysfunction of the liver do not need correction of the dose. Patients with impaired function and kidney and liver dosing is carried out according to the scheme (see above "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); frequency is unknown (can not be estimated based on available data from clinical trials).

Post-registration data are not sufficient to determine the frequency of undesired reactions.

On the part of the blood and lymphatic system

The frequency is unknown: bleeding.

From the immune system

The frequency is unknown: anaphylactoid reactions, hypersensitivity.

From the side of the psyche

Often: nervousness. Infrequently: depression.The frequency is unknown: agitation, anxiety, confusion, hallucinations.

From the nervous system

Often: hyperactivity. Infrequently: drowsiness. The frequency is unknown: ataxia, imbalance, exacerbation of epilepsy, headache, insomnia, tremor.

From the side of the hearing and labyrinth organs

Frequency unknown: vertigo.

From the side of the vessels

Rarely: thrombophlebitis, arterial hypotension (only with parenteral administration).

From the digestive system

The frequency is unknown: abdominal pain (including in the upper divisions), diarrhea, nausea, vomiting.

From the skin and subcutaneous tissues

The frequency is unknown: angioedema, dermatitis, itching, urticaria.

From the side of the reproductive system

Frequency unknown: increased sexual desire.

General disorders and disorders at the site of administration

Infrequently: asthenia. Rarely: pain at the injection site, fever (only with parenteral administration).

Laboratory and instrumental data

Often: weight gain.

Overdose:

After oral administration of piracetam at a dose of 75 g, dyspeptic phenomena such as diarrhea with blood, abdominal pain are noted.

Treatment: Immediately after taking the drug inside, you can flush the stomach or cause artificial vomiting. It is recommended to carry out symptomatic therapy, which may include hemodialysis. There is no specific antidote.

The efficacy of hemodialysis for piracetam is 50-60%.

Interaction:

Thyroid hormones

With the simultaneous use of pyracetam and thyroid extract (triiodothyronine + thyroxine), confusion, irritability and sleep disturbance were noted.

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 aggregation of platelets, release of | 3-thromboglobin, fibrinogen concentration and von Willebrand factor (VIII: C; VIII: vW: Ag; VIII: vW: RCo), as well as the viscosity of whole blood and plasma. Pharmacokinetic interactions The possibility of changing the pharmacokinetics of piracetam under the influence of other drugs is low,Since 90% of the piracetam is excreted unchanged in the urine.

In concentrations of 142, 426 and 1422 mg / ml piracetam 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.

Anticonvulsants

Admission piracetam at a dose of 20 g / day for 4 weeks in patients with epilepsy, taking a constant dose of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital and valproic acid), did not change their maximum and minimum concentrations.

Alcohol

Simultaneous reception with alcohol did not affect the concentration of pyracetam in plasma; when taking 1.6 g of pyracetam, the concentration of ethanol in the plasma did not change.

Special instructions:

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 insufficiency

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

Elderly patients

Long-term treatment of elderly patients requires regular monitoring of creatinine clearance, since dose adjustment may be required.

Abolition of therapy

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

Penetrates the filtration membranes of hemodialysis machines

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

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Capsules of 400 mg.

Packaging:

10 capsules in a planar cell package. 6 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

List B. In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3,5 years.

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

Terms of leave from pharmacies:On prescription

Registration number:P N002598 / 01

Date of registration:07.10.2008

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp22.09.2015

Illustrated instructions

Instructions

Pyracetam (Piracetam)