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

Excipients: potato starch - 17,11mg, polyvinylpyrrolidone low molecular weight medical 12600 ± 2700 (povidone) - 9.28 mg, magnesium hydroxycarbonate (magnesium carbonate basic) - 21.29 mg, calcium stearate - 2.48 mg, Tablet composition composition: sucrose ) - 193.96 mg, polyvinylpyrrolidone low molecular weight medical 12600 ± 2700 (povidone) - 2.05 mg, magnesium hydroxycarbonate (magnesium carbonate basic) - 29.08 mg, silicon dioxide colloid (aerosil) - 2.9 mg, titanium dioxide titanium dioxide pigment) - 1.45 mg, beeswax - 0.3 mg, tropeolin 0-0.1 mg.

Description:

The tablets covered with a cover, from light yellow up to yellow-orange color.On the cross-section two layers are visible: the inner one is white, the outer one is from light yellow to yellow-orange 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 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 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 pathological rigidity of red blood cells, improves their deformity 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 mcg / ml, after repeated intake of 3.2 g 3 times a day - 115 mcg / ml and is achieved after 1 hour in the serum and after 5 hours in the cerebrospinal 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 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 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 piracetam 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 almost complete (> 95%) for 30 h T? Elongates with renal insufficiency (renal failure at a terminal - 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 piracetam in case trial treatment may be conducted.)

Contraindications:

hypersensitivity to pyracetam or pyrrolidone derivatives, as well as other components of the drug;
end-stage chronic renal failure (creatinine clearance less than 20 mL / min);
hemorrhagic stroke;
Huntington's chorea;
deficiency of sucrose / isomaltase,
intolerance to fructose, glucose-galactose malabsorption.

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. Pyracetam 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. 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 disturbances of 2.4-4.8 g / day in several doses during the first few weeks, then pass to maintenance therapy 2.4 g / day in 2-3 doses, it is possible to take 1,2 g / day.

Treatment begins with 7.2 grams per day, increasing it by 4.8 g every 3-4 days up to 24 g, divided into 2-3 injections. 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. 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. Intravenous administration is carried out for several minutes; for intravenous infusion, the daily dose is administered for 24 hours through the catheter at a constant rate. Elderly patients with renal insufficiency should be corrected for the dose (see Fig.below "Renal failure"). With long-term treatment to assess the need for dose adjustment, creatinine clearance should be assessed regularly.

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 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 КК_serum (mg / ml)]

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

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

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 evaluate based on the available clinical trial data).

The data of post-registration observations are not sufficient to determine the frequency of undesired reactions.

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 side of the vessels: rarely: thrombophlebitis, arterial hypotension (only with parenteral administration).

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

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

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

Common 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:

An isolated 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:

The possibility of changing the pharmacokinetics of piracetam under the influence of other drugs is low, since 90% of the drug is excreted unchanged in 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 platelet aggregation, β-thromboglobin release, fibrinogen concentration 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 CYP 2A6 (21%) and 3A4 / 5 (11%) was observed.However, the values of the inhibition constant (K(i), probably go far 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 piracetam 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:

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

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. Pyracetam penetrates the filtration membranes of hemodialysis apparatus.

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 antiplatelet agents, including 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").

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 treatment period, 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:

The tablets covered with a cover, 200 mg.

Packaging:

10 tablets in a planar cell package.

60 tablets in a jar of glass-melt type BV or in a jar of orange glass type BDS, or in a jar of polymer type BP.

Each jar or 6 contour packs of 10 tablets together with the instructions for use are placed in a pack of cardboard.

Storage conditions:

Store in a 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.

Terms of leave from pharmacies:On prescription

Registration number:LSR-004348/10

Date of registration:17.05.2010

The owner of the registration certificate:Anzhero-Sudzhensky Chemical-Pharmaceutical Plant, LLC Anzhero-Sudzhensky Chemical-Pharmaceutical Plant, LLC

Manufacturer: & nbsp

Anzhero-Sudzhensky Chemical-Pharmaceutical Plant, LLC Russia

Information update date: & nbsp23.09.2015

Illustrated instructions

Instructions

Pyracetam of Avexime (Piracetam Avexima)