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

Hard gelatin capsules of white color number 0. The capsule case is white, the cap of the capsule is white. 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 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 at a dose of 3.2 g, the maximum concentration (C_max) is 84 μg / ml, after repeated intake of 3.2 g 3 times a day - 115 μg / ml and is achieved after 1 hour in serum and after 5 hours incerebrospinal fluid. Eating reduces C_max by 17% and increases the time it is reached (T_max) up to 1.5 hours. In women with piracetam at a dose of 2.4 g C_max and the area under the concentration-time curve (AUC) is 30% larger than that of men.

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 does not bind to blood plasma proteins, it is not metabolized in the body.

Excretion. Half-life of blood (T_1/2) is 4-5 hours and 8.5 hours - from cerebrospinal fluid. 80-100% of pyracetam is excreted by the kidneys unchanged by glomerular filtration. The total clearance of piracetam in healthy volunteers is 80-90 ml / min. Excretion by the kidneys is almost complete (> 95%) for 30 h. T_1/2 lengthened with renal failure (with terminal renal failure - up to 59 hours).The pharmacokinetics of pyracetam does not change in patients with hepatic insufficiency.

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 to other components of the drug, acute cerebrovascular accident (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. 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. 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 begins with 7.2 grams - 24 grams per day, with little therapeutic effect or its absence, treatment is stopped on the 7th day, in the case of a positive response to treatment, a dose of 24 g is reduced by 1.2 g every 2 days, until the appearance myoclonia.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 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 should be adjusted 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) x body weight (kg)] / [72 x KK_serum (mg / ml)]

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

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

Kidney function	CK (ml / min)	Dosing regimen
Norm	>80	The standard dose of 2-4 admission
Mild renal insufficiency	50-79	2/3 of the standard dose in 2-3 doses
Mean renal insufficiency	30-49	1/3 of the standard dose in 2 divided doses
Severe renal insufficiency	<30	1/6 of the standard dose once
Terminal Renal Failure	---	Contraindicated

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:

In clinical trials, the most common adverse reactions occurred in the following systemic and organ classes (according to the WHO classification):

Mental disorders
Disorders of the central and peripheral nervous system
Disorders of metabolism and nutrition
General disorders

Below are the undesirable drug reactions (NLR), whose frequency in the piracetam group exceeded the frequency in the placebo group.

Classification of NLR by system-organ classes	Often (> 1, <10 %)	Infrequently (> 0.1, <1%)
From the central and peripheral nervous system	Hyperkinesis (1.72%, placebo - 0.42%)
From the side of metabolism and nutrition	Weight gain (1.29 / 0.39%)
From the side of the psyche	Nervousness (1.13 / 0.25%)	Drowsiness (0.96 / 0.25%) Depression (0.83 / 0.21%)
General disorders		Asthenia (0.23 / 0%)

Post-registration experience

Post-registration studies identified the following adverse reactions (grouped according to the Medical Dictionary for regulatory activity, MedDRA). Due to insufficient data, it is not possible to estimate the frequency.

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

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

From the immune system: anaphylactoid reactions, hypersensitivity.

From the nervous system: ataxia, imbalance, exacerbation of epilepsy, headache, insomnia, drowsiness, tremor.

From the side of the psyche: agitation, anxiety, confusion, hallucinations.

From the skin and subcutaneous tissues: Quincke's edema, dermatitis, itching, hives.

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

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. It seems that this was due to the receipt of a large total dose of sorbitol, which was previously part of the solution for oral administration. Other symptoms of overdose are not registered. 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 efficacy of hemodialysis for piracetam is 50-60%.

Interaction:

When used simultaneously with iodine-containing hormones of the thyroid gland, confusion, irritability and sleep disturbance may occur.

In high doses (9.6 g / day) in patients with venous thrombosis increases the anticoagulant effect of indirect anticoagulants (more pronounced decrease in platelet aggregation, fibrinogen content, von Willebrand factor, viscosity of blood and plasma).

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

Hormones of the thyroid gland. 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 in 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 β-thromboglobin,the concentration of fibrinogen and von Willebrand factor (VIII: C; VIII: vW: Ag; VIII: vW: RCo), and the viscosity of whole blood and plasma.

Pharmacokinetic interaction. 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. 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. 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.

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, 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 "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.

It penetrates the hemodialysis apparatus through the filter membranes.

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

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

Form release / dosage:

Capsules of 400 mg.

Packaging:

10 capsules in a planar cell package.

For 60, 100 or 120 capsules in a can of polymeric or in a vial polymer, or an imported vial.

Each bank or vial, 5, 6, 9 or 10 contour cell packs together with instructions for use in a cardboard pack.

Storage conditions:

In dry, dark place at a temperature of no higher than 25 ° 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:LS-000165

Date of registration:25.02.2010

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Information update date: & nbsp22.09.2015

Illustrated instructions

Instructions

Piracetam-SZ (Piracetam-SZ)