Levetinol - Instructions For Use, Price, Reviews, Tablets, Solution

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Levetinol

Levetinol: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Levetinol

ATX code: N03AX14

Active ingredient: Levetiracetam (Levetiracetam)

Manufacturer: CJSC "Moscow Pharmaceutical Factory" (Russia); LLC "GEROPHARM" (Russia)

Description and photo update: 2019-24-07

Prices in pharmacies: from 380 rubles.

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Levetinol is an antiepileptic drug.

Release form and composition

• film-coated tablets: biconvex, oval, blue (250 mg), yellow (500 mg) or white (1000 mg) coated tablets, marked on one side with an engraving L, and on the other, in accordance with the dosage, the numbers 250, 500 are applied or 1000; the core at a break is white with a yellow tinge or white [10 pcs. in a blister strip made of aluminum foil and polyvinyl chloride film; in a carton box 3 or 6 blisters];
• oral solution: almost colorless transparent liquid with a characteristic odor (100, 125, 150 or 300 ml each in a dark glass vial of hydrolytic class III, closed with a white screw cap with an inner lining and a first opening control ring, equipped with a childproof protection; c box of cardboard box 1 bottle complete with adapter and measuring syringe).

Each pack also contains instructions for the use of Levetinol.

1 film-coated tablet contains:

• active substance: levetiracetam - 250, 500 or 1000 mg;
• additional components: povidone, crospovidone, magnesium stearate, colloidal anhydrous silicon dioxide;
• film shell: titanium dioxide (E171), partially hydrolyzed polyvinyl alcohol, talc, macrogol 4000; additionally for 250 and 500 mg - indigo carmine dye (E132), for 500 mg - iron oxide yellow dye (E172).

1 ml of solution contains:

• active substance: levetiracetam - 100 mg;
• additional components: methyl parahydroxybenzoate, citric acid monohydrate, propyl parahydroxybenzoate, sodium citrate dihydrate, ammonium glycyrrhizinate, liquid maltitol, glycerol, acesulfame potassium, purified water, grape flavor (grape Lydia MA / 1273 or Grape3 Flavor 597)

Pharmacological properties

Pharmacodynamics

The active substance of Levetinol, levetiracetam, belongs to the group of pyrrolidone derivatives (S-enantiomer of α-ethyl-2-oxo-1-pyrrolidineacetamide) and has a chemical structure that is different from other antiepileptic agents. The mechanism of action of levetiracetam is currently not fully understood, but it has been established that it differs from the mechanism of action of many antiepileptic drugs.

In experiments in vitro and in vivo, it was demonstrated that levetiracetam does not lead to a change in the basic properties of cells and normal nerve transmission. According to the results of in vitro studies, it affects the intraneuronal concentration of Ca ^{2+ ions}, partially reducing their current through N-type channels and weakening the release of calcium from intraneuronal stores, changing the level of Ca ²⁺ ions inside neurons. In addition, it partially promotes the restoration of currents through GABA (gamma-aminobutyric acid) - and glycine-dependent channels, inhibited by β-carbolines and zinc.

In vitro studies also revealed that levetiracetam communicates with a specific area in the brain tissue. The binding site is represented by the 2A protein of synaptic vesicles, which is presumably involved in neurotransmitter exocytosis and vesicle fusion. Levetinol and its analogs differ in binding affinity for synaptic vesicle protein 2A, which is correlated with the degree of antiepileptic protection in an audiogenic model of epilepsy in mice. These facts indicate that the binding of the active substance to this protein ensures the implementation of the anticonvulsant action of Levetinol.

The activity of the drug has been confirmed in relation to both focal and generalized epileptic seizures (epileptiform burst / photoparoxysmal reaction). The anticonvulsant effect of levetiracetam has been confirmed in a variety of animal models of disease.

In adult patients with epilepsy, as an adjunctive therapy for partial seizures with or without secondary generalization, the efficacy of Levetinol was determined in 3 blinded placebo-controlled studies. As a result, it was found that the ratio of patients who had a 50% or more decrease in the frequency of partial seizures per week compared with the baseline level, against the background of constant use of levetiracetam in daily doses of 1000, 2000 or 3000 mg in 2 doses for 12– 14 weeks, it was 27.7, respectively; 31.6% and 41.3%, and in persons receiving placebo, this figure was 12.6%.

In patients 4-16 years old with epilepsy to determine the effectiveness of levetiracetam as an adjunctive therapy for partial seizures with or without secondary generalization, a double-blind, placebo-controlled study with a duration of 14 weeks was conducted in which participants were 198 volunteers. The drug was taken in a daily dose of 60 mg / kg in 2 divided doses. In the levetiracetam group, 44.6%, and in the placebo group, 19.6% of patients, showed a 50% or more reduction in the frequency of partial seizures per week when compared with the initial level. For 6 months during the period of therapy, 11.4% of patients had no seizures, and, at least, within 12 months - 7.2%.

The effect of Levetinol for the adjunctive treatment of partial seizures with or without secondary generalization in children with epilepsy from 1 month to 4 years was determined over 5 days in a study involving 116 participants. Oral solution infants from 1 to 6 months were taken in a daily dose of 20 mg / kg in 2 divided doses with further dose titration up to 40 mg / kg, children from 6 months to 4 years - 25 mg / kg in 2 divided doses with subsequent dose increase up to 50 mg / kg. The efficacy index was established according to the analysis in 109 children who underwent video electroencephalography for at least 24 hours. Relative to the baseline level, a decrease in the frequency of partial seizures by 50% or more per week was recorded in 43.6% of patients in the levetiracetam group and in 19.6% of patients receiving placebo. Have had no seizures during long-term treatment 8,6% of patients within 6 months, and 7.8% - for at least 12 months.

The effect of levetiracetam as a monotherapy drug for partial seizures with or without secondary generalization was comparable to the effect of controlled-release carbamazepine. The study involved 576 patients over 16 years of age with newly diagnosed epilepsy with generalized tonic-clonic seizures or unprovoked partial seizures. Carbamazepine was taken in a daily dose of 400–1200 mg, levetiracetam - 1000–3000 mg, the duration of drug administration was up to 121 weeks and depended on the clinical response. For 6 months, the absence of seizures was recorded in 73% of patients receiving therapy with levetiracetam and 72.8% with carbamazepine. More than 50% of patients had no seizures within 12 months.

In a double placebo-controlled study lasting 16 weeks, the efficacy of levetiracetam, received in a daily dose of 3000 mg in 2 divided doses, was studied in patients over 12 years of age with idiopathic generalized epilepsy with various myoclonic seizure syndromes. The majority of patients were diagnosed with juvenile myoclonic epilepsy. In the levetiracetam group, 58.3% of patients and in the placebo group, 23.3% of patients had at least 50% reduction in myoclonic seizures within a week. With continuous long-term treatment, 28.6% of patients had no seizures for 6 months or more, 21% for at least 12 months.

In a placebo-controlled study, which lasted 24 weeks, the efficacy of levetiracetam was established in a limited number of children, as well as adolescents and adults with idiopathic generalized epilepsy with tonic-clonic seizures, juvenile myoclonic epilepsy, juvenile absence epilepsy, childhood absence epilepsy or epilepsy in childhood. generalized convulsive seizures on awakening. Adults and adolescents received the drug in a daily dose of 3000 mg, children - 60 mg / kg in 2 divided doses. A decrease in the frequency of seizures per week by 50% or more was observed in 72.2% of patients receiving levetiracetam, and in 45.2% in the placebo group. There were no seizures for at least 6 months in 47.4% of patients, and within 12 months in 31.5%.

Pharmacokinetics

The dependence of the pharmacokinetic parameters of Levetinol on race, gender and time of day was not recorded.

The pharmacokinetic profile of the drug is linear, with low variability, and is comparable in healthy volunteers and patients with epilepsy. There were no changes in the clearance of levetiracetam after repeated administration. It belongs to highly soluble substances that demonstrate high penetrating power.

After oral administration, levetiracetam is rapidly absorbed from the gastrointestinal tract (GIT). It is almost completely absorbed, so that as a result of complete and linear absorption, the plasma level can be predicted from the administered dose, expressed in mg / kg. The time of the meal and the dose of the drug do not affect the degree of its absorption. When taken orally, the bioavailability of levetiracetam approaches 100%. The maximum concentration (C _max) in plasma is observed 1.3 hours after taking the drug at a dose of 1000 mg. As a rule, the C _max value is 31 and 43 μg / ml after single and repeated (2 times a day) administration of levetiracetam at a dose of 1000 mg, respectively. With oral administration of the drug 2 times a day, the equilibrium state is noted after 2 days.

In children and adults, a high correlation is shown between the content of levetiracetam in plasma and saliva - the saliva / plasma ratio fluctuates in the range of 1–1.7 for tablets and solution 4 hours after its administration. The active substance and its main metabolite are characterized by a weak connection with plasma proteins - less than 10%, the volume of distribution (V _d) of levetiracetam is approximately 0.5-0.7 l / kg.

In the human body, the drug is metabolized to a weak extent. The main pathway of biotransformation (24% of the dose) is the process of enzymatic hydrolysis of the acetamide group. Enzymes of the P450 family of the liver are not involved in the formation of the main metabolite (ucb L057), the latter does not have pharmacological activity. Also, the drug has two minor metabolites: the first is the result of hydroxylation of the pyrrolidone cycle (1.6% of the dose), the second is formed by opening the pyrrolidone ring (0.9% of the dose). Other biotransformation products of the agent make up only 0.6% of the dose. In vivo, optical isomerization was not detected in levetiracetam and ucb L057.

Levetiracetam does not impair the enzymatic activity of hepatocytes. The active substance and its main metabolite in vitro did not inhibit cytochrome P450 isoenzymes (CYP1A2, CYP2E1, CYP2D6, CYP2C19, CYP2C9, CYP2A6 and CYP3A4), as well as the effect of glucuronyl transferase (UGT1A1) and UGT. It also did not affect in vitro the glucuronidation process of valproic acid. And in the culture of human hepatocytes, it did not interact or only slightly affected the enzymatic activity of UGT1A1, CYP1A2 and SULT1E1. The drug can cause weak induction of CYP3A4 and CYP2B6.

The half-life of the substance from plasma (T _1/2) in adults is 7 ± 1 h, regardless of the route of administration or dosage regimen; the average total clearance is 0.96 ml / min / kg. Most of the drug is eliminated in the urine, approximately 95% of the dose received, of which 93% - within 48 hours. 0.3% is excreted with feces. The share of total excretion of levetiracetam and ucb L057 is 66 and 24% of the administered dose, respectively, during the first 48 hours.

The renal clearance of levetiracetam and its main metabolite is 0.6 and 4.2 ml / min / kg, respectively, which is evidence of the excretion of levetiracetam by glomerular filtration (CF) with further tubular reabsorption, as well as the fact that the primary metabolite is also excreted through active tubular secretion in addition to CF. Elimination of the basic substance correlates with creatinine clearance (CC).

In patients 4–12 years old, after a single oral administration of levetiracetam at a dose of 20 mg / kg, its T1 / 2 is 6 hours. In children of this age group, the total clearance of the active substance is approximately 30% higher than that in adults and is directly proportional to body weight. After repeated oral administration of the drug in a daily dose of 20-60 mg / kg Cmax in plasma is observed 0.5-1 hours after administration. The area under the concentration-time curve (AUC) and Cmax of the drug are linear and proportional to the dose taken. The average value of the total clearance is 1.1 ml / min / kg.

In children over the age of 1 month and up to 4 years after a single oral dose of 20 mg / kg solution, T½ is 5.3 hours, plasma Cmax is reached on average 1 hour after administration of the drug. The average total clearance is 1.5 ml / min / kg.

Indications for use

As a monotherapy drug, Levetinol is recommended for the treatment of partial seizures with or without secondary generalization in adolescents from 16 years of age and adults with newly diagnosed epilepsy.

As a means of additional therapy, Levetinol is prescribed for the treatment of the following conditions:

• myoclonic seizures in adolescents over 12 years of age and adults with juvenile myoclonic epilepsy;
• primary generalized convulsive tonic-clonic seizures in adolescents after 12 years of age and adults with idiopathic generalized epilepsy;
• partial convulsions with or without secondary generalization in children (over 1 month - for solution, over 6 years - for tablets) and adults with epilepsy.

Contraindications

Absolute:

• violation of fructose tolerance (solution, since it contains maltitol);
• age up to 1 month (solution);
• age up to 6 years (Levetinol tablets due to the impossibility of correctly selecting the dose);
• hypersensitivity to levetiracetam or other pyrrolidone derivatives, or to any of the excipients in the drug.

Relative (Levetinol is recommended to be taken with caution): liver disease in the stage of decompensation, renal failure, old age (over 65 years).

Levetinol, instructions for use: method and dosage

All forms of release of the drug Levetinol are intended for oral administration. Food intake does not affect the effectiveness of the drug. The tablets should be taken with a sufficient amount of liquid. The daily dose is required to be divided into 2 doses in equal parts.

Monotherapy

When carrying out monotherapy, patients over 16 years of age are advised to start treatment with a daily dose of Levetinol 500 mg - 2 times 250 mg. 2 weeks after the start of the course, the dose can be increased to 1000 mg - 2 times 500 mg.

The maximum allowable daily dose should not exceed 3000 mg, divided into 2 doses.

As part of additional therapy

Adolescents over 12 years old and adults weighing more than 50 kg should begin treatment with a daily dose of 1000 mg, divided into 2 doses. Taking into account the tolerance of Levetinol and the clinical response, it can be increased to the maximum allowable - 3000 mg, used in 2 doses. Dose adjustments, in increments of 500 mg 2 times a day, can be done every 2–4 weeks.

Children aged 6 months to 6 years (for solution), as well as children and adolescents from 6 to 17 years (for both dosage forms), with a body weight of less than 50 kg are recommended to start treatment with a daily dose of 20 mg / kg, divided by 2 receptions. A dose change of 20 mg / kg in 2 divided doses can be carried out every 2 weeks until a daily dose of 60 mg / kg is reached (2 times 30 mg / kg). In case of intolerance to the recommended dose, it may be reduced. The minimum effective dose should be used.

Levetinol should be taken based on age, body weight and the desired therapeutic dose, in the most appropriate dosage and dosage form.

Due to the lack of the required dosage, Levetinol tablets are not prescribed for children with a body weight of less than 25 kg, if it is necessary to take a dose of less than 250 mg, and also if there are difficulties in swallowing this form of the drug. Treatment in such cases is recommended to start with a solution.

Recommended single doses of Levetinol solution (initial dose 10 mg / kg; maximum dose 30 mg / kg) in children aged 6 months and adolescents, depending on body weight, with a frequency of administration 2 times a day:

• 6 kg: 60 mg (0.6 ml); 180 mg (1.8 ml);
• 10 kg: 100 mg (1 ml); 300 mg (3 ml);
• 15 kg: 150 mg (1.5 ml); 450 mg (4.5 ml);
• 20 kg: 200 mg (2 ml); 600 mg (6 ml);
• 25 kg: 250 mg / 750 mg.

Children and adolescents with a body weight of more than 50 kg are recommended to take the drug in doses the same as in adults.

In children aged 1 to 6 months, the initial dose of Levetinol solution is 7 mg / kg 2 times a day. In the future, depending on the therapeutic effect and tolerability of the drug, it may be increased to 21 mg / kg 2 times a day. The change should not be higher than ± 7 mg / kg 2 times a day every 2 weeks, while taking the minimum effective dose.

Recommended single doses of oral solution [initial (7 mg / kg) / maximum (21 mg / kg)] in pediatric patients aged 1 to 6 months, depending on body weight, with a frequency of 2 times a day:

• 4 kg: 28 mg (0.3 ml) / 84 mg (0.85 ml);
• 5 kg: 35 mg (0.35 ml) / 105 mg (1.05 ml);
• 7 kg: 49 mg (0.5 ml) / 147 mg (1.5 ml).

Dosing of the solution is carried out using measuring syringes that are attached to the drug. Syringes of the following nominal capacity are included in the delivery set of Levetinol:

1. 1.5 ml with a graduation of 0.05 ml (5 mg) for babies from 1 to 6 months.
2. 3 ml, graduated with 0.1 ml (10 mg) for children from 6 months to 4 years.
3. 10 ml graduated in 0.25 ml (25 mg) for children over 4 years of age.

The measured dose of the solution should be diluted in a baby bottle or glass of water.

To dispense the solution using a measuring syringe, you should:

1. Open the bottle by pressing the cap and turning it counterclockwise.
2. Insert the syringe adapter into the neck of the bottle, make sure it is securely seated, and place the syringe in the adapter.
3. Turning the bottle upside down, and pulling the syringe plunger down, fill it with a small volume of solution, and then move the plunger up to remove air bubbles.
4. Pull the plunger down until the division, which corresponds to the number of milliliters of the drug, the dose recommended by the doctor, and fill the syringe with the solution.
5. Holding the bottle vertically, neck up, remove the syringe from the adapter.
6. Pressing the plunger all the way, inject the solution collected into the syringe into a glass of water or a baby bottle.
7. Take the prepared solution in full.
8. Then rinse the syringe with water and close the bottle with a lid.

In patients with renal insufficiency, the dose of Levetinol should be adjusted depending on the CC value. For men, CC can be calculated using the following formula, taking into account the serum creatinine content:

CC (ml / min) = [140 - age (years)] × body weight (kg) ÷ 72 × serum creatinine level (mg / dl)

For women, the resulting value should be multiplied by a factor of 0.85.

Then the correction of the QC calculation is carried out taking into account the body surface area (PPT) according to the following formula:

CC (ml / min / 1.73 m2) = CC (ml / min) ÷ PPT (m2) × 1.73

Correction of the dose of Levetinol for adults depending on the degree of impaired renal function and CC ml / min / 1.73 m² (a single dose is indicated with a frequency of administration 2 times a day):

• norm (K> 80): 500-1500 mg;
• light (CC = 50–79): 500–1500 mg (solution), 500–1000 mg (tablets);
• moderate (CC = 30–49): 250–750 mg;
• severe (CC <30): 250-500 mg;
• terminal stage (patients on dialysis *): 500–1000 mg ** (once a day).

* on the first day of therapy, a saturating dose of 750 mg is recommended.

** after the end of the dialysis session, an additional dose of 250-500 mg is recommended.

Changing the dose of Levetinol in children with renal failure is required to take into account the severity of renal impairment.

CC (ml / min / 1.73 m²) for children and adolescents can be estimated based on the determination of serum creatinine (mg / dL) using the following formula (Schwartz formula):

CC (ml / min / 1.73 m²) = height (cm) × ks ÷ serum creatinine level (mg / dl)

Where ks is a constant, depending on the sex and age of the child, is: for children of both sexes under the age of 1 year = 0.45; for children under 13 and teenage girls = 0.55; for teenage boys = 0.7.

Correction of the dose of Levetinol in children and adolescents with a body weight of less than 50 kg in the presence of impaired renal function, taking into account the severity of the disease and CC (ml / min / 1.73 m2) with a frequency of administration 2 times a day (aged from 1 to 6 months; ages 6 months and older):

• CC> 80 (normal renal function): 7–21 mg / kg (0.07–0.21 ml / kg); 10-30 mg / kg (0.1-0.3 ml / kg);
• CC = 50–79 (mild renal failure): 7–14 mg / kg (0.07–0.14 ml / kg); 10–20 mg / kg (0.1–0.2 ml / kg);
• CC = 30–49 (moderate renal failure): 3.5–10.5 mg / kg (0.035–0.105 ml / kg); 5-15 mg / kg (0.05-0.15 ml / kg);
• CC <30 (severe renal failure): 3.5-7 mg / kg (0.035-0.07 ml / kg); 5-10 mg / kg (0.05-0.1 ml / kg);
• patients on dialysis (end-stage renal failure): 7-14 mg / kg (0.07-0.14 ml / kg) once a day ^{a, c}; 10–20 mg / kg (0.1–0.2 ml / kg) once a day ^{b, d}.

^a on the first day of therapy, a loading dose of 10.5 mg / kg (0.105 ml / kg) is recommended.

^b on the first day of the course, a loading dose of 15 mg / kg (0.15 ml / kg) is recommended.

^c after dialysis, a maintenance dose of 3.5–7 mg / kg (0.035–0.07 ml / kg) is recommended.

^d after dialysis, a maintenance dose of 5–10 mg / kg (0.05–0.1 ml / kg) is recommended.

Side effects

The following profile of side effects is based on an analysis of the results of placebo-controlled studies, as well as the experience of post-marketing use of Levetinol. The most common adverse events were drowsiness, dizziness, fatigue, headache, and nasopharyngitis. According to the results of clinical studies, the safety profile of levetiracetam in children was comparable to that in adults.

Adverse reactions in systems and organs (frequency of occurrence: very often - not less than 0.1; often - from 0.01 to 0.1; infrequently - from 0.001 to 0.01; rarely - from 0.0001 to 0.001; extremely rare - less than 0.00001):

• metabolism: often - anorexia (the threat of development is aggravated by the combination of levetiracetam and topiramate); infrequently - increase / decrease in body weight; rarely, hyponatremia;
• blood and lymphatic system: infrequently - leukopenia, thrombocytopenia; rarely - neutropenia, pancytopenia (with pancytopenia, bone marrow suppression was sometimes recorded), agranulocytosis;
• infectious and parasitic lesions: very often - nasopharyngitis; rarely - infections;
• immune system: rarely - a drug reaction with eosinophilia and systemic manifestations (DRESS syndrome);
• organ of hearing and labyrinthine disorders: often - vertigo;
• organ of vision: infrequently - blurred vision, diplopia;
• nervous system: very often - headache, drowsiness; often - dizziness, imbalance, tremors, lethargy, convulsions; infrequently - memory impairment, amnesia, weakening of concentration, paresthesia, impaired coordination / ataxia; rarely - dyskinesia, choreoathetosis, hyperkinesia;
• mental disorders: often - nervousness, insomnia, irritability, anxiety, hostility / aggressiveness, depression; infrequently - agitation, mood swings, emotional lability, panic attacks, confusion, anger, hallucinations, behavioral disorders, psychotic disorders, suicidal intentions, attempts at suicide; rarely - thought disorder, personality disorder, suicide;
• Gastrointestinal tract: often - vomiting, nausea, abdominal pain, dyspepsia, diarrhea; rarely - pancreatitis;
• respiratory system, chest and mediastinal organs: often - cough;
• liver and biliary tract: infrequently - changes in liver function tests; rarely - hepatitis, liver failure;
• skin and subcutaneous tissue: often - rash; infrequently - itching, eczema, alopecia (in many cases, hair restoration was noted after discontinuation of Levetinol); rarely - erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis;
• kidneys and urinary tract: rarely - acute renal failure;
• general disorders: often - fatigue, asthenia;
• musculoskeletal system and connective tissue: infrequently - muscle weakness, myalgia; rarely - an increase in the content of creatine phosphokinase (CPK) in the blood, rhabdomyolysis;
• injuries, complications of manipulations: infrequently - accidental injuries.

It was found that the increase in the level of CPK in the blood and the prevalence of rhabdomyolysis are significantly higher in the Japanese when compared with representatives of other nationalities.

In children and adolescents 4-16 years old, the following undesirable effects were most often recorded: very often - vomiting (11.2%), often - emotional lability (1.7%), mood swings (2.1%), agitation (3, 4%), lethargy (3.9%), behavioral disorders (5.6%), aggressiveness (8.2%). In children aged 1 month to 4 years, such adverse reactions as irritability (11.7%) and impaired coordination (3.3%) were more often observed.

After analyzing the behavioral and emotional status using the Achenbach questionnaire, aggressive behavior was found in the group of patients receiving Levetinol. At the same time, in patients who used the drug during long-term follow-up, no aggravation of disturbances in the emotional-behavioral status was recorded, for example, there was no deterioration in indicators of aggressive behavior when compared with the initial level.

Overdose

Symptoms of an overdose of Levetinol may include aggression, agitation, drowsiness, respiratory depression, depression of consciousness, coma.

In the acute period of intoxication, induction of vomiting and / or gastric lavage with further intake of activated charcoal is prescribed. There is no specific antidote for levetiracetam. If necessary, symptomatic treatment is carried out in a hospital, including the use of hemodialysis. The effectiveness of the latter for the active substance is 60%, and for its main metabolite - 74%.

special instructions

If it is required to complete therapy, Levetinol should be withdrawn gradually, reducing every 2-4 weeks in adolescents and adults weighing more than 50 kg, a single dose of 500 mg. In children older than 6 months, a single dose reduction every 2 weeks should not be more than 10 mg / kg, in infants under 6 months - more than 7 mg / kg, provided that the drug is taken 2 times a day.

During the transfer to treatment with Levetinol, concomitant antiepileptic drugs should be canceled gradually.

Against the background of the use of levetiracetam, cases of a decrease in the number of blood cells were recorded - thrombocytopenia, neutropenia, leukopenia, agranulocytosis, pancytopenia. A blood test with the establishment of the number of corpuscles is recommended for patients who have experienced hyperthermia, severe weakness, recurrent infections or blood clotting disorders.

In patients receiving treatment with antiepileptic drugs (including levetiracetam), such undesirable effects as suicidal thoughts and behavior, suicidal attempts, and suicide were observed. Analysis of studies on the use of these drugs has shown a slight aggravation of the risk of suicidal thoughts and attempts, the mechanism of this phenomenon is unknown. Due to the above, during the period of taking Levetinol, it is necessary to carefully monitor the condition of patients with symptoms of depression and / or the presence of suicidal thoughts and intentions, and to provide them, if necessary, with appropriate treatment. The observing physician should be informed of the development of any signs of depression or suicidal tendencies.

The oral solution contains propyl parahydroxybenzoate and methyl parahydroxybenzoate, which can provoke allergic reactions, including delayed action.

Influence on the ability to drive vehicles and complex mechanisms

The influence of Levetinol on the ability to drive complex and potentially dangerous vehicles, including driving a car, has not been studied. However, due to individual sensitivity to the drug on the part of the central nervous system (including the possible development of drowsiness) during therapy, it is necessary to abandon activities that require increased concentration of attention and high speed of psychomotor reactions.

Application during pregnancy and lactation

There are no data indicating a significant aggravation of the risk of severe congenital malformations when prescribing levetiracetam in the first trimester of pregnancy in monotherapy regimen. At the same time, the teratogenic threat cannot be completely excluded. Treatment with several antiepileptic drugs causes a higher risk of congenital malformations of the fetus, when compared with monotherapy, so the latter is more appropriate in pregnant women.

Strictly controlled and adequate clinical studies on the safety of using Levetinol during pregnancy have not been carried out, therefore, in pregnant women and women with preserved reproductive function, drug therapy should not be carried out, except in cases of clinical necessity.

Physiological changes during pregnancy may contribute to a decrease in the plasma level of levetiracetam. This decrease is most pronounced during the third trimester (up to 60% of the baseline content observed before pregnancy).

Levetinol intake by pregnant women should be closely monitored. Intervals in anticonvulsant treatment can worsen the course of the disease, and thereby harm the health of the woman and the fetus.

Levetiracetam is excreted in breast milk, as a result of which breastfeeding is not recommended during drug treatment. However, if the administration of Levetinol is necessary during lactation, the intended benefits and possible threat of treatment should be carefully weighed against the importance of breastfeeding.

The effect of levetiracetam on fertility has not been identified in animal studies, the possible risk to humans is unknown.

Pediatric use

Children under 6 years of age are advised to use Levetinol in the form of an oral solution.

According to the currently available information on the use of Levetinol in children, levetiracetam does not adversely affect growth and puberty. At the same time, the long-term effects of therapy on intellectual development, endocrine gland function, growth, sexual development, the ability of children to learn are unknown.

With impaired renal function

In patients with renal insufficiency, it is necessary to adjust the maintenance dose taking into account CC, since the elimination of the main substance and its primary metabolite correlates with the latter. In the presence of end-stage renal failure in adult patients, T _{1/2 of the} drug is 25 hours in the intervals between hemodialysis sessions and 3.1 hours during the procedure itself. During a 4-hour hemodialysis session, approximately 51% of levetiracetam is excreted.

In patients with renal failure, the degree of CC decrease may not fully reflect the severity of renal impairment. In such cases, with CC below 60 ml / min / 1.73 m², the daily dose should be reduced by 50%.

Before starting the course of treatment with the drug, patients with renal lesions are recommended to investigate their function; in case of identified violations, dose adjustment may be necessary.

In extremely rare cases, therapy with Levetinol was accompanied by acute kidney damage, observed from several days to several months.

For violations of liver function

In the presence of mild to moderate liver dysfunctions, there is a slight change in the clearance of levetiracetam. In the overwhelming majority of patients with severe hepatic impairment against the background of concomitant renal failure, the clearance of the active substance decreases by more than 50%.

Before starting treatment, patients with decompensated liver disease are recommended to conduct a study of renal function. If impaired renal function is found, it may be necessary to change the dose of Levetinol.

Patients with mild to moderate hepatic impairment do not require dosage adjustment.

Use in the elderly

In elderly patients, T _1/2 increases by 40% and can be 10–11 hours, which is due to impaired renal function in people of this age category.

Patients 65 years of age and older should adjust the dose of Levetinol in accordance with the CC value.

Drug interactions

• other antiepileptic drugs (valproic acid, carbamazepine, phenytoin, lamotrigine, phenobarbital, gabapentin, primidone, topiramate): the effect of levetiracetam on the plasma content of these drugs, as well as their effect on the pharmacokinetics of levetiracetam, has not been established; according to a retrospective analysis of pharmacokinetic interactions in patients 4–17 years old with epilepsy, oral use of Levetinol as an adjunctive therapy did not affect the equilibrium serum concentration of simultaneously administered valproate and carbamazepine; however, in children taking enzyme-inducing antiepileptic drugs, levetiracetam was cleared 20% higher compared to children not receiving them; dose changes are not required;
• methotrexate: a decrease in its clearance was recorded, causing an increase in blood levels to possible toxic levels or an extension of the time for maintaining such concentrations; it is required to control the plasma content of levetiracetam and methotrexate in the blood;
• probenecid (blocker of tubular secretion in the kidneys) 4 times a day, 500 mg: there was a suppression of renal clearance of the main metabolite of levetiracetam - ucb L057, but not the active substance itself; the level of ucb L057 remains low, it is assumed that other substances, the elimination of which occurs by active tubular secretion, are also able to reduce the renal clearance of ucb L057; the effect of levetiracetam on probenecid has not been studied;
• sulfonamides, non-steroidal anti-inflammatory drugs: the effect of levetiracetam on these drugs has not been established;
• digoxin and warfarin: no change in prothrombin time was recorded - when combined with levetiracetam in a daily dose of 2000 mg, the pharmacokinetics of the latter and these substances remained unchanged;
• antacids: there is no evidence of the effect of these drugs on the absorption of levetiracetam;
• oral contraceptives (ethinylestradiol and levonorgestrel): there was no effect of levetiracetam, used in a dose of 1000 mg per day, on the pharmacokinetics of these drugs; hormonal status (progesterone and luteinizing hormone levels) did not change; the pharmacokinetics of levetiracetam also did not change;
• ethanol: there is no information on the interaction of levetiracetam with ethyl alcohol;
• food: there is no change in the completeness of absorption of levetiracetam, but its rate is slightly reduced.

Analogs

The analogues of Levetinol are Keppra, Komviron, Kepaira-Vero, Tirapol, Convilept, Epiterra Long, Levetiracetam, Epitropil, Levetiracetam Canon, etc.

Terms and conditions of storage

Store out of the reach of children and protected from light, at a temperature not exceeding 25 ° C (film-coated tablets) or 30 ° C (oral solution).

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Levetinol

According to the few reviews of Levetinol found on medical sites, the drug in most cases effectively stops epileptic seizures or helps to reduce their number. Along with this, against the background of treatment with the drug, the development of such undesirable effects as headache, irritability, severe dizziness, drowsiness, nervousness is often noted, due to which, in some cases, patients had to stop taking this anticonvulsant.

Price for Levetinol in pharmacies

The price of Levetinol can be:

• film-coated tablets: dosage 250 mg - 450–550 rubles, 500 mg - 900–100 rubles, 1000 mg - 2200–2400 rubles, per package containing 30 pieces;
• oral solution: 2500–2600 rubles. per bottle of 300 ml.

Levetinol: prices in online pharmacies

Drug name Price Pharmacy

Levetinol 250 mg film-coated tablets 30 pcs. RUB 380 Buy

Levetinol tablets p.p. 250mg 30 pcs. RUB 471 Buy

Levetinol 500 mg film-coated tablets 30 pcs. 637 RUB Buy

Levetinol 1 g film-coated tablets 30 pcs. 723 RUB Buy

Levetinol tablets p.p. 500mg 30 pcs. 827 RUB Buy

Levetinol tablets p.p. 1000mg 30 pcs. RUB 938 Buy

Levetinol 100 mg / ml oral solution 300 ml 1 pc. 1889 RUB Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!