Levetinol oral solution 100mg / ml, 300ml

• As a monotherapy for the treatment of partial seizures with or without secondary generalization in patients over 16 years of age with a newly diagnosed epilepsy.

As part of additional therapy during treatment:

• partial seizures with or without secondary generalization in patients older than 1 month (in the appropriate dosage form for this age) with epilepsy;

• myoclonic seizures in patients over 12 years old with juvenile myoclonic epilepsy;

• primary generalized tonic-clonic seizures in patients from 12 years of age with idiopathic generalized epilepsy.

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

For oral administration.

Depending on the indications and the patient's age, a single dose is 250-750 mg. Frequency rate of application - 2 times / day.

In children, levetiracetam should be used in the appropriate dosage form depending on age.

The oral solution is transparent, almost colorless, with a characteristic odor.

1 ml

Active ingredient: levetiracetam - 100 mg

Excipients: sodium citrate dihydrate - 1.05 mg, citric acid monohydrate - 0.066 mg (in terms of citric acid - 0.06 mg), methyl parahydroxybenzoate - 2.7 mg, propyl parahydroxybenzoate - 0.3 mg, ammonium glycyrrhizinate - 1.5 mg, glycerol malt - 235.5 mg, - 300 mg, acesulfame potassium - 4.5 mg, grape flavor (Grape Flavor 597303C or Lydia Grape MA / 1 273) - 0.3 mg, purified water - up to 1 ml.

• Hypersensitivity to levetiracetam or other pyrrolidone derivatives,

• children's age up to 1 month.

Carefully

Elderly patients (over 65 years old); liver disease in the stage of decompensation; renal failure.

Clinical and pharmacological group: Anticonvulsant drug

Pharmaco-therapeutic group: Antiepileptic drug

pharmachologic effect

Antiepileptic agent, pyrrolidone derivative (S-enantiomer of ?-ethyl-2-oxo-1-pyrrolidine-acetamide). The chemical structure differs from the known antiepileptic drugs. The mechanism of action of levetiracetam is not fully understood, but it is obvious that it differs from the mechanism of action of known antiepileptic drugs.

In vitro studies have shown that levetiracetam affects the intraneuronal concentration of Ca2 + ions, partially inhibiting Ca2 + flow through N-type channels and reducing the release of calcium from intraneuronal stores. In addition, levetiracetam partially restores currents through GABA- and glycine-dependent channels, reduced by zinc and ?-carbolines.

One of the proposed mechanisms is based on the proven binding to the SV2A synaptic vesicle glycoprotein, which is contained in the gray matter of the brain and spinal cord. It is believed that in this way the anticonvulsant effect is realized, which is expressed in counteracting the hypersynchronization of neural activity. Does not alter normal neurotransmission, but suppresses epileptiform neuronal outbursts induced by the GABA agonist bikuculin and the excitation of glutamate receptors. The activity of levetiracitam has been confirmed in relation to both focal and generalized epileptic seizures (epileptiform manifestations / photoparoxysmal reaction).

Pharmacokinetics

After oral administration, levetiracetam is well absorbed from the gastrointestinal tract. Absorption is complete and linear; therefore, the concentration in blood plasma can be predicted based on the applied dose of the drug in mg / kg of body weight. The degree of absorption does not depend on the dose and time of the meal. Bioavailability is about 100%.

After taking a dose of 1 g, Cmax in blood plasma is reached after 1.3 hours and is 31 ?g / ml, after repeated administration (2 times / day) - 43 ?g / ml.

Plasma protein binding of levetiracetam and its main metabolite is less than 10%. The Vd of levetiracetam is about 0.5-0.7 l / kg. The equilibrium state is achieved after 2 days when taken 2 times / day.

The formation of a primary pharmacologically inactive metabolite occurs without the participation of cytochrome P450 isoenzymes in the liver. Levetiracetam does not affect the enzymatic activity of hepatocytes.

In adults, T1 / 2 from blood plasma is 7 ± 1 hour and does not change depending on the dose, route of administration or repeated administration. The average clearance is 0.96 ml / min / kg. 95% of the dose is excreted by the kidneys. The renal clearance of levetiracetam and its inactive metabolite is 0.6 ml / min / kg and 4.2 ml / min / kg, respectively.

In elderly patients, T1 / 2 increases by 40% and is 10-11 hours, which is associated with a decrease in renal function in this category of patients. In patients with impaired renal function, the clearance of levetiracetam and its primary metabolite correlates with CC. In end-stage renal failure in adult patients, T1 / 2 is 25 hours between dialysis sessions and 3.1 hours during dialysis. During a 4-hour dialysis session, up to 51% of levetiracetam is removed.

During 4-hour dialysis, 51% of levetiracetam is removed from the body.

In patients with mild to moderate impaired liver function, significant changes in the clearance of levetiracetam do not occur. In severe liver dysfunction with concomitant renal failure, the clearance of levetiracetam decreases by more than 50%.

Pharmacokinetics of levetiracetam in children is linear in the dose range from 20 to 60 mg / kg / day. Cmax is reached after 0.5-1 hours. T1 / 2 in children after a single oral intake at a dose of 20 mg / kg body weight is 5-6 hours. The total clearance of levetiracetam in children is about 40% higher than in adults and is in direct proportion from body weight.

Indications

• As a monotherapy for the treatment of partial seizures with or without secondary generalization in patients over 16 years of age with a newly diagnosed epilepsy.

As part of additional therapy during treatment:

• partial seizures with or without secondary generalization in patients older than 1 month (in the appropriate dosage form for this age) with epilepsy;

• myoclonic seizures in patients over 12 years old with juvenile myoclonic epilepsy;

• primary generalized tonic-clonic seizures in patients from 12 years of age with idiopathic generalized epilepsy.

Dosage regimen

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

For oral administration.

Depending on the indications and the patient's age, a single dose is 250-750 mg. Frequency rate of application - 2 times / day.

In children, levetiracetam should be used in the appropriate dosage form depending on age.

Side effect

From the hematopoietic system: infrequently - thrombocytopenia, leukopenia; rarely - neutropenia, pancytopemia.

From the side of metabolism: often - anorexia; infrequently - increase / decrease in body weight.

From the side of the central nervous system: very often - drowsiness, headache; often - mood swings, emotional lability, depression, aggressiveness, insomnia, nervousness; infrequently - conduct disorder, anger, anxiety, hallucinations, psychotic disorders, memory impairment, suicide attempt. obsessions, amnesia, disorder of tactile sensitivity, dizziness, headache, hyperkinesia, tremor, imbalance, distraction, paresthesia; rarely - personality disorder, incl. thought disorder, suicide, hyperkinesis, choreoathetosis.

From the senses: often - dizziness; infrequently - diplopia, blurred vision.

From the respiratory system: often - cough.

From the digestive system: often - nausea, vomiting, diarrhea, abdominal pain, dyspepsia; infrequently - deviations of laboratory parameters of liver function from the norm; rarely - pancreatitis, hepatitis, liver failure.

On the part of the skin and subcutaneous tissues: often - skin rash; infrequently - eczema, pruritus; rarely - alopecia (in some cases, disappearing after discontinuation of levetiracetam), toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome.

From the musculoskeletal system: infrequently - myalgia, muscle weakness.

Others: often - general weakness, fatigue; infrequently - nasopharyngitis, accidental trauma.

In children, the most common: vomiting, agitation, mood swings, aggression, emotional lability, behavioral disorder, lethargy.

Contraindications for use

• Hypersensitivity to levetiracetam or other pyrrolidone derivatives,

• children's age up to 1 month.

Carefully

Elderly patients (over 65 years old); liver disease in the stage of decompensation; renal failure.

Application during pregnancy and lactation

Adequate and strictly controlled clinical studies on the safety of using levetiracetam in pregnant women have not been conducted, therefore, levetiracetam should not be used during pregnancy, unless absolutely necessary.

Physiological changes in a woman's body during pregnancy can affect the plasma concentration of levetiracetam, as well as other antiepileptic drugs. During pregnancy, a decrease in the concentration of levetiracetam in plasma was noted. This decrease is more pronounced in the first trimester (up to 60% of the baseline concentration in the period preceding pregnancy).

Treatment with levetiracetam in pregnant women should be carried out under special supervision. It should be borne in mind that interruptions in antiepileptic therapy can lead to a worsening of the course of the disease, which is harmful to both the mother and the fetus.

Levetiracetam is excreted in breast milk; therefore, breastfeeding during treatment is not recommended. However, if treatment with levetiracetam is necessary during lactation, then the risk / benefit ratio of treatment should be carefully weighed against the importance of breastfeeding.

Application for violations of liver function

Use with caution in liver diseases in the stage of decompensation.

Application for impaired renal function

Use with caution in renal failure.

Application in children

Contraindicated for use in children under 1 month of age.

It is intended for use in children over 1 month old in the appropriate dosage form.

Use in elderly patients

Elderly patients (over 65 years old).

special instructions

Concomitant antiepileptic drugs (during the period of transfer of patients to taking levetiracetam) should be canceled gradually.

For patients with kidney disease and decompensated liver disease, a renal function test is recommended before starting treatment. In connection with the existing reports of cases of suicide, suicidal intent and attempted suicide during treatment with levetiracetam, patients should be warned about the need to immediately inform their doctor about the appearance of any symptoms of depression or suicidal intent.

Influence on the ability to drive vehicles and mechanisms

Due to the different individual sensitivity to levetiracetam on the part of the central nervous system during the period of treatment, patients should refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Drug interactions

When taken together with topiramate, the likelihood of developing anorexia is higher.

The completeness of absorption of levetiracetam does not change under the influence of food, while the rate of absorption is somewhat reduced.

Contacts for inquiries

GEROPHARM LLC (Russia)