Lucetam®

International Non-Proprietary Name (INN): piracetam
Dosage form: solution for intravenous and intramuscular injections Structure
1 ml of the solution contains:
Active ingredient: piracetam 200 mg;
Excipients: sodium acetate trihydrate, glacial acetic acid, water.
Description
Transparent liquid without color or with a slight greenish tint color.
Pharmacological classification: nootropic
ATC code: N06BX03
Pharmacological action: nootropic, antihypoxic, cerebroprotective

nootropil-package-3


Pharmacodynamics

The active ingredient is piracetam, a cyclic derivative of gamma-aminobutyric acid (GABA). Improves cognitive processes, such as learning ability, memory, attention, and mental performance, without having a sedative or psychostimulating effect.

Lucetam® has an effect on the central nervous system in various ways: it changes the speed of brain excitation spreading, improves neuronal plasticity and metabolic processes in nerve cells.
It improves communication between the cerebral hemispheres and synaptic conduction in neocortical structures, improves mental performance and cerebral blood flow.

Lucetam® improves microcirculation in the brain by influencing the blood rheology without having a vasorelaxant action.

Lucetam® inhibits platelet aggregation, restores the elasticity of the erythrocyte membrane, and erythrocyte capability to transit through the microvasculature. It reduces red cell adherence.

At a dose of 9.6 g, it decreases the fibrinogen level and the von Willebrand factors by 30–40% and increases the bleeding time.

Lucetam® provides protective and restorative action in case of impaired brain function caused by hypoxia, intoxication, or trauma. It reduces the severity and duration of vestibular nystagmus.

Pharmacokinetics

Distribution
It does not bind with blood plasma proteins. Piracetam accumulates selectively in tissues of the cerebral cortex, mainly in the frontal, parietal and occipital lobes, in the cerebellum, and in basal nuclei. Piracetam penetrates through the blood-brain barrier and placental barrier.

Metabolism
Does not metabolize in the body.

Excretion
The half-life is 4-5 hours from the blood plasma and 8.5 hours from the cerebrospinal fluid. 80–100% of piracetam is excreted in the unchanged form by the kidneys through kidney filtration. The total clearance of piracetam in healthy volunteers is 86 ml/min. The half-life is prolonged in case of kidney failure. Pharmacokinetics in patients with liver failure does not change.

Intended uses

  • symptomatic treatment of the psycho-organic syndrome (including elderly patients with memory loss, dizziness, reduced ability to concentrate, mood changes, behavioral disorder, gait disorder, as well as patients with Alzheimer’s disease and senile Alzheimer-type dementia);
  • treatment of consequences of an ischemic stroke, such as speech disorders, emotional, motor and mental disorders;
  • treatment of withdrawal syndrome and psycho-organic syndrome in case of chronic alcohol addiction;
  • during trauma and intoxication of the brain recovery therapy;
  • treatment of dizziness and related equilibrium disorders (excluding cases of dizziness of vasomotor and psychogenic origin);
  • (as a part of complex therapy) treatment of low learning ability in children;
  • treatment of cortical myoclonia (both in the form of monotherapy, and as part of combination therapy);
  • preventive treatment and arresting of the sickle cell vaso-occlusive crisis.


Contraindications

  • haemorrhagic stroke;
  • terminal stage of kidney failure (CC<20 ml/min);
  • psychomotor agitation at the time of prescribing;
  • Huntington’s chorea;
  • children under 3 year old;
  • pregnancy and lactation;
  • hypersensitivity to the drug ingredients.


With caution: hemostasis disorder, extensive surgical interventions, severe bleeding.

Dosage and administration

Intravenous injections. Daily doses vary within the range of 30–160 mg/kg (3–12 g/day). Dosage frequency is 2–4 times/day.

The parenteral injection is prescribed when oral administration is not possible (for example in case of coma or swallowing problem).

The drug is diluted in one of the matching infusion solutions: glucose 5%, 10% or 20%; fructose 5%, 10%, 20%; levulose 5%; sodium chloride 0.9%; dextran 40 10% (in a sodium chloride solution 0.9%); dextran 100 6% (in a sodium chloride solution 0.9%); Ringer’s solution; dextran-mannitol; hydroxiethyl starch 6%. Infusion solutions with piracetam are stable for at least 24 hours.

Adults

Chronic psycho-organic syndrome
2.4–4.8 g/day (divided into 2 or 3 sub-doses).

Dizziness and related equilibrium disorders
2.4–4.8 g/day (divided into 2 or 3 sub-doses).

Cortical myoclonia
The treatment starts with a dose of 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 is reached. Then the patient is transferred to oral administration of the drug. The treatment continues throughout the whole period of the disease. Abrupt discontinuation of the therapy should be avoided. This can cause episode relapse. The dosage is reduced gradually. In case of lack of efficacy or a slight therapeutic effect, the treatment is discontinued.

For arresting (parenterally) the sickle cell vaso-occlusive crisis
The drug is taken at a dose of 300 mg/kg, divided into 4 intakes.

Children

Complex therapy for treating dyslexia in children above 8 years old
A daily dose of 3.2 g divided into 2 injections.

Arresting the sickle cell vaso-occlusive crisis in children above 3 years old
300 mg/kg, divided into 4 intakes.

Special groups of patients

Dose adjustment is not required for patients with the compromised liver function.

In patients with kidney disorders, the dose should be adjusted depending on the amount of creatinine clearance (see the table below).

The creatinine clearance for men can be calculated based on the serum creatinine concentration, according to the following formula: Creatinine clearance, ml/min = [(140 – age, years) × body weight, kg] / (72 × serum creatinine concentration, mg/dL)

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

Kidney failureCreatinine clearance, ml/minDose regimen
Missing (norm)> 80Usual Dose
Light50–792/3 of the usual dose in 2-3 intakes
Average30–491/3 of the usual dose in 2 intakes
Severe<301/6 of the usual dose in a single intake
End-stageContraindicated


The dose for elderly patients is adjusted in case of kidney failure. The monitoring of the functional state of the kidneys is necessary in case of long-term therapy.

Side effects

Central nervous system disorders
Rare: Hyperkinesia, nervousness, drowsiness, depression, asthenia. These side effects often occur in elderly patients who received the drug at a dose of more than 2.4 g/day. In most cases, the reduction of the dose can lower these side effects. In some cases, dizziness, headache, ataxia, balance disorder, and acute condition of epilepsy, insomnia, tremor, confusion, agitation, anxiety, panic, hallucinations, and increased libido are reported.

Metabolism disorders
Rare: Increase in body weight.

Digestive system disorders
Rare: Nausea, vomiting, diarrhea, abdominal and epigastric pains.

Dermatological reactions
Rare: Dermatitis, itching, urticaria.

Blood and lymphatic system
Rare: Bleeding.

Immune system disorders
Rare: Anaphylactoid reactions, hypersensitivity.

Hearing disorders
Rare: Vertigo.

Allergic reactions
Rare: Angioneurotic edema.

Сardiovascular system disorders
Rare: Hypertension; hypotension.

Other
Rare: Pain in the area of ​​injection, thrombophlebitis, hyperthermia.

Overdose

Lucetam® is a low toxic drug. In case of severe overdose (possible symptoms: abdominal pain, diarrhea with blood admixtures) symptomatic therapy, which may include hemodialysis, is recommended. No specific antidote exists. The efficiency of hemodialysis is 50–60%.

Interaction with other drugs

Acute irritation, disorientation, and sleep disturbance are reported when the drug is used simultaneously with thyroid extract.

No interaction of Lucetam® with Clonazepam, Phenytoin, Phenobarbital, sodium valproate was reported.

Piracetam in high doses (9.6 g/day) increases the effectiveness of acenocoumarol in patients with venous thrombosis: reports showed a greater reduction in the level of aggregation of platelets, in fibrinogen level, in von Willebrand factors, and in blood and plasma viscosity, compared with the case when Acenocoumarol only was prescribed.

The possibility of changing the pharmacodynamics of piracetam under the influence of other drugs is low because 90% of its dose is excreted in the urine in the unchanged form.
In vitro, piracetam at concentrations of 142, 426, and 1422 μg/ml does not inhibit the activity of the isoenzymes CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 4A9/11. At a concentration of 1422 μg/ml, slight inhibition of the activity of the isoenzymes CYP2A6 (21%) and 3A4/5 (11%) is reported. However, the level of the inhibition constant (Ki) of these two isoenzymes is sufficient in case there is an exceeding of 1422 μg/ml. Therefore, metabolic interaction with other drugs is unlikely.

When piracetam is taken at a dose of 20 mg/day, there is no changing of the maximum concentrations in the blood plasma and of the nature of the pharmacokinetic curve of antispasmatic medications (carbamazepine, phenytoin, phenobarbital, valproate) in patients with epilepsy receiving constant doses of the drug. When piracetam was taken at a dose of 1.6 g with ethanol, the concentrations of piracetam and ethanol in the serum remained unchanged.

Special precaution

Lucetam® should be taken no later than 5 pm to prevent sleep disturbances.

Since piracetam has an influence on the aggregation of platelets, it should be prescribed with caution to patients with hemostasis disorders, during major surgical interference, and to patients with severe bleeding symptoms.

When treating patients with cortical myoclonia, abrupt discontinuation of the therapy should be avoided. This can cause episode relapse.

In case of long-term therapy of elderly patients, regular monitoring of kidney function indicators is recommended; if necessary, the dose is adjusted depending on the results of the creatinine clearance study.

Lucetam® penetrates through the filtration membranes of the hemodialysis apparatus.

Pregnancy and lactation

Adequate and strictly controlled studies of the safety of the use of Lucetam® during pregnancy have not been conducted. Therefore the drug should not be prescribed during pregnancy, except cases of emergency. Piracetam penetrates through the placental barrier and is excreted in breast milk. The concentration of piracetam in newborns reaches 70–90% of its concentration in the blood of the mother. If the taking of the drug is required during lactation, breastfeeding should be discontinued.

Influence on the ability to drive vehicles and operate mechanisms

Taking into account possible undesirable effects, the patient should be careful when operating mechanisms and driving vehicles.

Terms of release from pharmacy

On prescription.

Storage conditions

Store at temperatures of 15–30°C. Keep out of reach of children.

Shelf life

5 years. Do not use beyond the expiration date.

Country of manufacture

Hungary.

Instructions