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

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 abnormal rigidity of erythrocytes, improves their deformability and ability to filter.

Pharmacokinetics:

The pharmacokinetic profile of pyracetam is linear and does not depend on time. Characteristic of low variability in a large range of doses. Constant concentration in the plasma is achieved after 3 days from the beginning of the reception. The volume of distribution (Vd) is about 0.6 l / kg. Pyracetam penetrates through blood-brain and placental barriers. When studying animals, 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. It does not bind to blood plasma proteins, it is not metabolized in the body. The half-life (T_1/2) is 4-5 hours from the blood plasma and 8.5 hours from the cerebrospinal fluid. The half-life does not depend on the route of administration. 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. T_1/2lengthened with renal failure (with terminal CRF - up to 59 hours). The pharmacokinetics of pyracetam does not change in patients with hepatic insufficiency.

Indications:

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 other components of the drug.
Hemorrhagic stroke.
Terminal stage of chronic renal failure.
Huntington's disease.

Carefully:

Violation of hemostasis.
Extensive surgical interventions.
Severe bleeding.

If you have any of the listed diseases before taking the drug, be sure to consult a doctor.

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. 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:

Intravenously.

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. Treatment begins with a dose of 7.2 g / day, every 3-4 days the dose is increased by 4.8 g / day until a maximum concentration of 24 g / day in 2-3 doses. Treatment continues throughout the period of the disease. Every 6 months, attempts should be made to reduce the dose or discontinue the drug. The dose is reduced by 1.2 g every 2 days to avoid a sudden relapse (to prevent the possibility of sudden recurrence of seizures in the Lansa-Adams syndrome - every 3-4 days).

Dosing to patients with impaired renal function

Dosage to patients with impaired renal function should be adjusted depending on the amount of creatinine clearance (CC). The creatinine clearance for men can be calculated based on the serum creatinine concentration (K_serum), using 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.

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

Elderly patients are adjusted the dose in the presence of renal failure, with prolonged therapy, it is necessary to monitor the functional state of the kidneys.

Dosing to patients with impaired liver function

Patients with a dysfunction of the liver do not need a dose adjustment. Patients with impaired function of the kidneys and liver, dosing is carried out according to the scheme (see section (Dosing to patients with impaired renal function ").

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 hearing and labyrinth organs: 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.

After intravenous injection, rare cases of pain at the injection site, thrombophlebitis, fever, and lowering of blood pressure were recorded.

Overdose:

Symptoms: registered a single case of development of diarrhea in the form of diarrhea with blood and pain in the abdomen when taking the drug inside at a daily dose of 75 g. Apparently, this was due to the use of a large total dose of sorbitol, which is part of the drug previously for the dosage form solution for reception inside. There were no other cases of drug overdose.

Treatment: In case of an overdose, symptomatic therapy is recommended, 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 platelet aggregation, release (3-thromboglobin, fibrinogen concentration and von Willebrand factor (VIII: C; VIII: vW: Ag; VIII: vW: RCo), and the viscosity of whole blood and plasma.

Pharmacokinetic interactions

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 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 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, 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").

Hyponodium diet

When treating patients on a hyponatric diet, it is recommended that the piracetam solution for intravenous and intramuscular administration contain sodium acetate.

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.

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 concentration and speed of psychomotor reactions.

Form release / dosage:

Solution for intravenous administration 200 mg / ml.

Packaging:

5 ml per ampoule.

For 10 ampoules together with a knife for opening ampoules and instructions for medical use in a cardboard box.

For 10 ampoules together with a knife for opening ampoules and instructions for medical use in a pack with a cardboard insert for fixing ampoules.

5 ampoules in the outline of the cell. 2 contour mesh packages together with a knife for opening ampoules and instructions for medical use in a pack of cardboard.

In case of using ampoules with a break ring or a notch and a break point, the insertion of the knife for opening ampoules is not provided.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

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

Terms of leave from pharmacies:On prescription

Registration number:P N 015439/01

Date of registration:17.03.2009

The owner of the registration certificate:BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus

Manufacturer: & nbsp

BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus

Information update date: & nbsp22.09.2015

Illustrated instructions

Instructions

Pyracetam (Piracetam)