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

Piracetam - 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, without inducing vasodilation with the atom.The use of piracetam in patients with cerebral dysfunction increases concentration of attention and improves cognitive functions, which is accompanied by changes in the electroencephalogram (increase in α and β-activity, decrease in δ-activity). Pyracetam contributes to the restoration of cognitive functions due to various disorders, such as hypoxia, intoxication or electroconvulsive therapy.

It is indicated for the treatment of cortical myoclonia as an ionotherapy, as well as in complex therapy. Reduces the duration of vestibular neuronitis caused.

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 administration of piracetam in 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

The half-life of blood (T1) is 4-5 hours, and of cerebrospinal fluid - 8.5 hours. 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 myoclonias in piracetam sensitive patients both as monotherapy and as part of complex therapy (in order to determine sensitivity to pyracetam, a trial course of treatment can be conducted in a specific case).

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.

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.

Piracetam 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, so it should not be used during breastfeeding or should stop feeding when treated with piracetam. When deciding whether to abort breastfeeding or refusing piracetam treatment, the benefits of breastfeeding for a child should be correlated withbenefit therapy for a woman.

Dosing and Administration:

Inside, during the intake of food or on an empty stomach. Capsules are swallowed, not chewed, washed down with water.

In memory disorders, intellectual disorders

2.4-4.8 g / day (6-12 capsules / day) in several doses during the first few weeks, then pass to maintenance therapy 2.4 g / day (6 capsules / day) in 2-3 doses, 1.2 g / day (3 capsules per day).

Treatment of cortical myoclonia

Treatment begins with 7.2 grams per day (18 capsules per day), increasing it by 4.8 g (12 capsules) every 3-4 days up to 24 grams (60 capsules) divided into 2-3 doses. The dose of other drugs for the treatment of myoclonus does not change. Further on the results of treatment, it is necessary, if possible, to reduce 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. In patients with acute episodes, the course of the disease may change with time, therefore every 6 months, attempts should be made to reduce the dose or to cancel the drug. To avoid sudden relapse, the dose is reduced by 1.2 g (3 capsules) every 2 days (to prevent the possibility of sudden recurrence of seizures in the Lansa-Adams syndrome - every 3-4 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 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.

The dose of pyracetam should be adjusted depending on the creatinine clearance (CC). 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 КК_serum (mg / ml)]

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

Kidney function	CK (ml / min)	Dosing regimen
Norm	>80	the usual dose of 2-4 admission
Mild renal insufficiency	50-79	2/3 of the usual dose in 2-3 doses
Mean renal insufficiency	30-19	1/3 of the usual dose in 2 divided doses
Severe renal insufficiency	<30	1/6 of the usual dose once
Terminal Renal Failure	-	contraindicated

Liver failure

Patients with isolated impaired liver function do not need dose adjustment. Patients with impaired function and kidneys, 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 / 10000 to <1 / 1000), very rarely (up to <1/10000) and the frequency is unknown (it is impossible to estimate based on the available clinical trial data).

The data of post-registration observations 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 eagle's ears and maze

Frequency unknown: vertigo.

From the side of the vessels

Rarely: thrombophlebitis.

From the digestive system

The frequency is unknown; abdominal pain (including in the upper parts), 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.

Common violations

Infrequently: asthenia.

Laboratory and instrumental data

Often: weight gain.

Overdose:

Symptoms

An isolated case of development of dyspeptic phenomena in the form of diarrhea with blood and abdominal pain with piratsetam taken insidea daily dose of 75 g, presumably because of the large total dose of sorbitol. In this preparation sorbitol There is no, but you should be careful. Other symptoms of overdose are not registered

Treatment

If there is a significant overdose, rinse the stomach or induce vomiting. There is no specific antidote. It is recommended to carry out symptomatic therapy, which may include hemodialysis. The efficiency of hemodialysis for the removal of 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 did not affect the dose of acenocoumarol necessary to achieve an international normalized ratio equal to 2.5-3.5, but compared to the affects atsenokumarola alone, the addition of piracetam in a dose of 9.6 g / day significantly reduces platelet aggregation, release of β-tromboglobina, fibrinogen concentration and von Willebrand factor (VIII CVIII: vW: Ag; VIII: vW: RCo), as well as the viscosity of whole blood and plasma.

Pharmacokinetic interactions

The possibility of changing the pharmacokinetics of pyracetam under the influence of other drugs is low, since 90% of pyracetam is excreted unchanged in urine.

In concentrations of 142, 426 and 1422 mg / ml piracetam does not inhibit cytochrome P450 proenzymes (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 4A9 / 11) in vitro.

At a concentration of 1422 mg / ml, minimal inhibition of the proenzyme CYP2A6 (21%) and 3A4 / 5 (11%) was observed. However, the values of the inhibition constant (Ki), probably go far 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 the plasma; when taking 1.6 g of pyracetam, the concentration of ethanol in the plasma did not change.

Pharmaceutical compatibility

There is no information on pharmaceutical incompatibility.

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, including low doses of acetylsalicylic acid.

Renal insufficiency

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

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.

It penetrates the hemodialysis apparatus through the filter membranes.

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

Given the profile of adverse reactions, during the treatment period, care must be taken when driving vehicles, working with mechanisms and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:Capsules 400 mg.

Packaging:

10 capsules per contour cell package.

For 60, 80, 100 capsules in cans of polymer.

Each jar, 2, 6, 8, 10 contour squares with instruction for use is placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

Shelf life 5 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N001902 / 01

Date of registration:22.01.2008

The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Information update date: & nbsp17.09.2015

Illustrated instructions

Instructions

Pyracetam (Piracetam)