Notrocetam, 200 mg/ml 5 ml 10 pcs

Pharmacotherapeutic group: nootropic agent

ATX code: [N06BX03]

Pharmacological properties

Pharmacodynamics

Piracetam is a nootropic drug that affects the central nervous system in different ways: modifies neurotransmission in the brain; improves conditions that promote neuronal plasticity; improves microcirculation, affecting blood rheological characteristics and without causing vasodilation. Piracetam administration in patients with cerebral dysfunction increases attention concentration and improves cognitive functions, which is accompanied by changes on the electroencephalogram (increased α and β activity, reduced δ activity).

It promotes cognitive recovery due to various disorders such as hypoxia, intoxication or electroconvulsive therapy.

Piracetam is indicated for the treatment of cortical myoclonias both as monotherapy and as part of complex therapy. It reduces the duration of induced vestibular neuronitis.

Piracetam inhibits increased aggregation of activated platelets and, in case of pathological erythrocyte stiffness, improves their deformability and filtration capacity.

Pharmacokinetics

The pharmacokinetic profile of piracetam is linear and independent of time. Low variability over a large dose range is characteristic.

The steady-state plasma concentration is reached 3 days after the start of administration. The volume of distribution (Vd) is about 0.6 l/kg. Piracetam penetrates through the blood-brain and placental barriers, as well as hemodialysis membranes.

In animal studies 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 is not bound to plasma proteins, is not metabolized in the body and is excreted unchanged by the kidneys. Period of half-life (T1/2) is 4-5 hours from plasma and 8.5 hours from cerebrospinal fluid. The elimination half-life does not depend on the route of administration.

80-100 % of piracetam is excreted unchanged by the kidneys through glomerular filtration. Total clearance of piracetam in healthy volunteers is 80-90 ml/min. Renal excretion is almost complete (> 95%) within 30 h.

The T1/2 is prolonged in renal insufficiency (in terminal chronic renal failure up to 59 h). Pharmacokinetics of piracetam does not change in patients with hepatic insufficiency.

Indications

– symptomatic treatment of intellectual and mental disorders in the absence of an established diagnosis of dementia;

– reduction of manifestations of cortical myoclonias in patients sensitive to piracetam both as monotherapy and as part of complex therapy (in order to determine the sensitivity to piracetam in a particular case a trial course of treatment may be conducted).

Active ingredient

How to take, the dosage

Intravenously or intramuscularly.

Parenteral administration of piracetam is prescribed when oral forms of the drug cannot be used (unconsciousness, difficulty in swallowing).

Intravenous administration is preferable.

The daily dose is infused intravenously through a catheter at a constant rate for 24 hours a day (e.g., in the initial phase of treatment of severe myoclonias).

The drug is pre-diluted in one of the compatible infusion solutions: dextrose 5%, 10%, or 20%;

fructose 5%, 10%, 20%; sodium chloride 0.9%;

dextran 40 10% (in 0.9% sodium chloride solution);

Ringer’s solution; mannitol solution 20%.

The total volume of solution to be administered is determined taking into account the clinical indications and the patient’s condition.

Intramuscularly, the drug is administered if insertion through a vein is difficult or the patient is agitated. The volume of the solution administered intramuscularly shall not exceed 5 ml. The frequency of administration of the drug is similar to that for intravenous or oral administration.

If possible, switch to oral administration of the drug (see instructions for medical use of the respective forms of release of the drug).

The duration of treatment is determined by the physician depending on the disease and taking into account the dynamics of symptoms.

In case of memory disorders, intellectual disorders:

At 2.4-4.8 g/day in several doses for the first few weeks, then switch to maintenance therapy of 2.4 g/day in 2-3 doses, 1.2 g/day is possible. Treatment of cortical myoclonias:

The treatment starts with 7.2 g/day, every 3-4 days the dose is increased by 4.8 g/day until the maximum dose of 24 g/day, divided into 2-3 injections. The dose of other drugs for treatment of myoclonias is not changed. Subsequently, based on the results of treatment, the dose of myoclonia medications should be decreased, if possible.

After initiation of piracetam treatment, treatment is continued as long as the symptoms of the disease persist. In patients with an acute episode, the course of the disease may change over time, so attempts should be made every 6 months to reduce the dose or withdraw the drug. To avoid a sudden relapse, the dose is reduced by 1.2 g every 2 days (to prevent the possibility of a sudden relapse of seizures in Lance-Adams syndrome, every 3-4 days).

Elderly patients:

Elderly patients with renal impairment should have their dosage adjusted (see “Renal Impairment”). In long-term treatment, creatinine clearance should be assessed regularly to determine if dose adjustment is necessary. Renal Impairment:

Piracetam is excreted almost exclusively by the kidneys; caution should be exercised when treating patients with renal impairment or requiring renal function monitoring.

The elimination half-life increases in direct proportion to worsening renal function and creatinine clearance, and this is also true for elderly patients in whom creatinine excretion is age-related.

The dose should be adjusted according to creatinine clearance (CK): Creatinine clearance for men can be calculated based on serum creatinine concentration using the following formula:

[140 – age (years)] x body weight (kg)

CK (ml/min) =

72 x CKsyvorot (mg/dL)

Creatinine clearance for women can be calculated by multiplying the resulting value by a factor of 0.85.

Renal function

CK (ml/min)

Dosing regimen

Norm

> 80

Normal dose in 2-4 doses

Mild renal failure

50-79

2/3 of the usual dose in 2-3 doses

Moderate renal failure

insufficiency

30-49

1/3 of the usual dose in 2 doses

Severe renal failure

˂30

1/6 of the usual dose once

Terminal renal failure

–

contraindicated

Hepatic failure:

Patients with isolated hepatic impairment do not require dose adjustment. In patients with both renal and hepatic impairment, dosing is according to the regimen (see “Renal Impairment”).

Interaction

The possibility of changes in pharmacokinetics of piracetam under the influence of other drugs is low because 90% of piracetam is excreted unchanged by the kidneys.

In concomitant use with thyroid hormones, there have been reports of confusion, irritability and sleep disturbance.

. According to a published study of patients with recurrent venous thrombosis, piracetam at a dose of 9.6 g/day does not alter the dose of acenocoumarol needed to achieve an INR (international normalized ratio) of 2.5-35, but compared with the effects of acenocoumarol alone, the addition of piracetam at a dose of 9.6 g/day significantly reduces platelet aggregation, ß-thromboglobin release, fibrinogen and Willebrand factor concentrations (VIII: C; VIII: vW: Ag; VIII: vW: RCo) as well as blood and serum viscosity.

At concentrations of 142, 426 and 1422 mg/ml, piracetam does not inhibit cytochrome P450 isoenzymes.

For the 1422 mg/ml concentration, minimal inhibition of CYP 2A6 (21%) and 3A4/5 (11%) was observed. However, normal values of the inhibition constant (Ki) can probably be achieved at a higher concentration. Thus, metabolic effects of piracetam with other drugs are unlikely. Administration of piracetam at a dose of 20 g/day for 4 weeks in patients with epilepsy receiving stable doses of antiepileptic drugs did not alter the maximum serum concentration and AUC (area under the curve) of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital and valproate).

Co-administration with alcohol had no effect on serum concentrations of piracetam; serum ethanol concentrations were not altered by 1.6 g of piracetam.

Special Instructions

Because of its antiaggregant effect, piracetam should be administered with caution in patients with severe hemorrhagic disorders, risk of bleeding (e.g., peptic ulcer), hemostasis disorders, hemorrhagic cerebrovascular disorders in the history, in patients with surgical interventions, including dental interventions, in patients taking anticoagulants and antiaggregants, including low-dose aspirin.

In the treatment of cortical myoclonias, abrupt interruption of treatment should be avoided because it may cause seizures to recur.

Because piracetam is excreted through the kidneys, caution should be exercised when prescribing the drug in patients with renal impairment.

In long-term treatment of elderly patients, regular monitoring of creatinine clearance is necessary, since dosage adjustment may be necessary.

Piracetam passes through the filter membranes of hemodialysis machines.

Influence on driving and operating machinery

At the time of treatment, caution should be exercised when driving motor vehicles and engaging in other potentially dangerous activities requiring increased concentration and rapid psychomotor reactions.

Synopsis

Contraindications

– individual intolerance to piracetam or pyrrolidone derivatives or other components of the drug;

– psychomotor agitation at the time of administration of the drug;

– Huntington’s chorea;

– acute impairment of cerebral circulation (hemorrhagic stroke);

– end-stage renal failure (with creatinine clearance less than 20 ml/min);

– children under 18 years of age.

With caution

. With caution in patients with severe hemorrhagic disorders, risk of bleeding (e.g., gastric ulcer), hemostasis disorders, hemorrhagic cerebrovascular disorders in the history, in patients with surgical interventions, including dental interventions, in patients taking anticoagulants and antiaggregants, includingincluding low doses of acetylsalicylic acid. Caution should be exercised when prescribing the drug in patients with renal insufficiency.

Side effects

The adverse drug reactions listed below have been identified in clinical trials and from post-registration follow-up and are grouped into systemic organ classes. The frequency gradation is defined as follows:

Very common (≥10%), common (≥1% and < 10%), infrequent (≥0.1% and < 1%), rare (≥0.01% and < 0.1%), very rare (< 0.01%) and frequency unknown (cannot be estimated from available clinical trial data).

In post-registration use, due to insufficient data, the incidence cannot be estimated.

The blood and lymphatic system:

The incidence is unknown – bleeding.

Immune system disorders:

incidence unknown – anaphylactoid reactions, hypersensitivity.

Psychiatric disorders:

frequently – nervousness; infrequently – depression;

frequency unknown – agitation, anxiety, confusion, hallucinations.

Nervous system disorders:

often – hyperactivity; infrequent – somnolence;

frequency unknown – ataxia, balance disorders, worsening of the course of epilepsy, headache, insomnia, tremor.

Hearing organ and labyrinth disorders:

frequency unknown – vertigo.

Vascular disorders:

rare – thrombophlebitis, arterial hypotension.

Digestive system disorders:

incidence unknown – abdominal pain, including in the upper parts, diarrhea, nausea, vomiting.

Skin and subcutaneous tissue disorders:

incidence unknown – angioedema, dermatitis, pruritus, urticaria.

Reproductive system disorders:

incidence unknown – increased sexual desire.

General disorders and disorders at the site of administration:

infrequent – asthenia;

rare – pain at the injection site, fever.

Laboratory and instrumental data:

often – increase in body weight.

If any of the side effects listed in the instructions worsen or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

Increase possible side effects.

The first aid is symptomatic therapy, hemodialysis is possible (effectiveness 50-60%). There is no specific antidote.

Pregnancy use

Pregnancy

There are no sufficient data on the use of the drug during pregnancy. Animal studies have shown no direct or indirect effect on pregnancy, embryo/fetal development, labor or postnatal development.

Piracetam penetrates the placental barrier. Plasma concentrations of piracetam in the newborn reach 70-90% of that in the mother. Piracetam should be administered 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 piracetam treatment.

Breastfeeding

Piracetam penetrates into the breast milk. Piracetam should not be used while breastfeeding or breastfeeding should be discontinued during treatment with piracetam. When deciding whether to stop breastfeeding or to discontinue treatment with piracetam, the benefit of breastfeeding for the baby should be weighed against the benefit of therapy for the woman.

Similarities