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

Excipients: potato starch 17 mg, magnesium carbonate 67.22 mg, low molecular weight polyvinylpyrrolidone 11.8 mg, calcium stearate 2.5 mg, polysorbate Tween 80 1.25 mg, sucrose 87, 41 mg, silicon dioxide colloid (aerosil) - 1.09 mg, titanium dioxide (titanium dioxide pigment) - 1.09 mg, tropeolin 0-0.05 mg, talc 0.4 mg, beeswax 0.19 mg .

Description:Round tablets of biconvex form, covered with a shell of yellow color.

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 concentration and improves cognitive function, which is accompanied by changes in the electroencephalogram (increase in alpha and beta activity, decrease in delta 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 of the drug 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 in cerebrospinal fluid. Eating reduces C_max by 17% and increases the time to reach the maximum concentration (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. Pyracetam selectively accumulates in the tissues of the cerebral cortex, mainly in the frontal, parietal and occipital lobes, in the cerebellum and basal nuclei. It does not bind to blood plasma proteins, it is not metabolized in the body.

Excretion. The half-life of blood (T1) is 4-5 hours and 8.5 hours of 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 hours. T1 is prolonged with renal failure (with terminal renal failure - up to 59 hours). The pharmacokinetics of pyracetam do 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.

Carefully:

Pregnancy and lactation:

Piracetam should be given 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.

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.The tablets covered with a cover swallow, without chewing, washing down with water. During a meal or on an empty stomach.

In memory disorders, intellectual disorders 2.4 - 4.8 g / day in several doses during the first several weeks, then they switch to maintenance therapy 2.4 g / day in 2-3 doses, 1.2 g / day can be taken.

Treatment cortical myoclonia begin with 7.2 g - 24 grams 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 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 failure. Pyracetam 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 in 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	Creatinine clearance (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

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.

Allergic reactions: hypersensitivity, anaphylactic reactions, angioedema.

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.

From the side of the reproductive system: increased sexual desire.

Overdose:

Symptoms: abdominal pain, diarrhea with an admixture of blood.

Treatment: symptomatic therapy, which may include hemodialysis (the efficiency of hemodialysis for piracetam is 50-60%). There is no specific antidote.

Interaction:

No interaction with clonazepam, phenytoin, phenobarbital, sodium valproate was noted.

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, the release of P-thromboglobin, the concentration of fibrinogen and von Willebrand factor (VIII: C; vW: Ag; VIII: vW: RCo), and the viscosity of whole blood and plasma.

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

The possibility of changing the pharmacodynamics of piracetam under the influence of other drugs is low, since 90% of the drug is excreted unchanged in urine. In vitro piracetam does not inhibit cytochrome P450 isoforms CYP1A2, 2B6, 2C8, 2C9, 2D6, 2E1 and 4A9 / 11 at a concentration of 142, 426 and 1422 μg / ml. At a concentration of 1422 μg / ml, slight inhibition of CYP2A6 (21%) and SA4 / 5 (11%) was noted. However, the correlation level of these CYP isomers is sufficient at an increase of 1422 μg / ml. Therefore, metabolic interaction with other drugs is unlikely.

The administration of piracetam at a dose of 20 mg / day did not alter the peak and the concentration curve of antiepileptic drugs in serum (carbamazepine, phenytoin, phenobarbital, valproic acid) in patients with epilepsy receiving a constant dosage.

Joint intake with alcohol did not affect the level of serum piracetam concentration, and the serum concentration of alcohol did not change with the intake of 1.6 g of piracetam. With simultaneous use with drugs that stimulate the central nervous system, excessive stimulation of the central nervous system is possible.

When administered with neuroleptics reduces the risk of extrapyramidal disorders.

Special instructions:

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 disorder, in patients with surgical interventions, including dental interventions, in patients taking anticoagulants and antiaggregants, incl. low doses of acetylsalicylic acid.

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").

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

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

Form release / dosage:

The tablets covered with a cover of 200 mg.

Packaging:

For 10 or 24 tablets, coated in a contour acrylic packaging of polyvinylchloride film and aluminum foil printed lacquered.

For 60 tablets, coated with a shell in a polymer can.

Each jar or 2, 3, 5 or 6 contour squares (10 tablets, coated),or 1 circuit cell package (24 coated tablets) together with the instructions for use are placed in a pack of cardboard.

Storage conditions:

In dry, the dark 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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N000382 / 01

Date of registration:27.04.2007

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

Manufacturer: & nbsp

DALHIMFARM, OJSC Russia

Information update date: & nbsp16.09.2015

Illustrated instructions

Instructions

Pyracetam (Piracetam)