Levetiracetam, 1000 mg 30 pcs

As monotherapy in the treatment of:

• partial seizures with or without secondary generalization in adults and adolescents over 16 years of age with newly diagnosed epilepsy.

As part of complex therapy in the treatment of:

• partial seizures with or without secondary generalization in adults and children over 4 years of age with epilepsy;
• myoclonic seizures in adults and adolescents over 12 years of age with juvenile myoclonic epilepsy;
• primary generalized tonic-clonic seizures in adults and adolescents over 12 years of age with idiopathic generalized epilepsy.

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Active ingredient

Composition

How to take, the dosage

Orally, regardless of meals, with plenty of fluids. The daily dose of the drug is divided into two equal doses.

Monotherapy

Adults and adolescents over 16 years of age should start treatment with a daily dose of 500 mg divided into 2 doses (250 mg twice daily). In 2 weeks the dose can be increased to the initial therapeutic one – 1000 mg (500 mg twice a day). The maximum daily dose is 3000 mg (but 1500 mg 2 times a day).

In combination therapy

Children over 4 years old and adolescents (12 to 17 years old) with body weight less than 50 kg should start treatment with a daily dose of 20 mg/kg body weight divided into 2 doses (10 mg/kg body weight 2 times a day). The dose may be changed by 20 mg/kg of body weight every 2 weeks until the recommended daily dose of 60 mg/kg of body weight (30 mg/kg of body weight 2 times/day) is reached. In case of intolerance to the recommended daily dose, it may be reduced. The minimum effective dose should be used.

The physician should prescribe the drug in the most appropriate dosage form according to the patient’s body weight and the required therapeutic dose.

In children with a body weight of more than 50 kg, the dosage is according to the dosage regimen for adults.

Adults and adolescents (12 to 17 years) with body weight over 50 kg should start treatment with daily dose of 1000 mg divided into 2 doses (500 mg twice daily). Depending on clinical reaction and tolerability of the drug, daily dose can be increased up to maximum 3000 mg (1500 mg 2 times per day). Changing the dose to 500 mg 2 times a day may be carried out every 2-4 weeks.

Because levetiracetam is excreted by the kidneys, when prescribing the drug in patients with renal insufficiency and elderly patients, the dose should be adjusted according to the CKR value.

The CK for men can be calculated based on serum creatinine concentration using the following formula:

CK (ml/min) = [140 – age (years)] x body weight (kg)/ 72 x CK serum creatinine (mg/dL)

CK for women can be calculated by multiplying the resulting value by factor 085.

The CK is then adjusted for body surface area (BSA) using the following formula:

CK (ml/min/173 m2) = CK (ml/min)/PPT facility (m2) x 173

Dose adjustment for adults

Renal insufficiency

CKC (ml/min)

Dosing regimen

Norm

>80

500 to 1500 mg 2 times daily

Mild

50 to 79

500 to 1000 mg 2 times daily

Moderate

30-49

/td>

250 to 750 mg 2 times daily

Severe

< 30

/td>

250 to 500 mg 2 times daily

Terminal stage (dialysis patients*)

–

500 to 1000 mg once daily**

*On the first day of treatment, a saturation dose of 750 mg is recommended.

** An additional dose of 250-500 mg is recommended after dialysis.

In children with renal impairment, the dose of levetiracetam should be adjusted according to the degree of renal impairment using the recommendations given for adults.

The following formula (Schwartz formula) is used for young adolescents and children:

CK (ml/min/173 m2) = height (cm) x ks/ CK-syvom (mg/dL)

in children under 13 years of age and adolescent girls, ks = 055;

in adolescent boys, ks = 07.

Recommendations for dose adjustment for children and adolescents with impaired renal function and a body weight of less than 50 kg

Moderate

30-49

5-15 mg/kg 2 times daily

Severe

< 30

5-10 mg/kg 2 times daily

Terminal stage (patients on dialysis)

–

10-20 mg/kg 1 time per day***

*On the first day of treatment, a loading dose of levetiracetam 15 mg/kg is recommended.

** An additional dose of 5-10 mg/kg is recommended after dialysis.

Patients with mild to moderate hepatic dysfunction do not require dosing adjustments.

In patients with decompensated hepatic impairment and renal failure, the level of CK reduction may not fully reflect the severity of renal failure. In such cases, in CK< 60 ml/min/173 m2 it is recommended to reduce the daily dose by 50%.

Interaction

Anticonvulsants

According to pre-registration clinical studies, levetiracetam has no effect on serum concentrations of other anticonvulsants: phenytoin carbamazepine valproic acid phenobarbital lamotrigine gabapentin topiramate and primidone and these anticonvulsants do not affect the pharmacokinetics of levetiracetam.

Like in adults in children at doses up to 60 mg/kg/day levetiracetam does not interact with other medications. Retrospective evaluation of pharmacokinetic interactions in children and adolescents with epilepsy (4-16 years old) confirms that levetiracetam as adjuvant therapy does not influence serum Css of simultaneously used carbamazepine and valproic acid. However, there is data that clearance of levetiracetam in children taking anticonvulsants – inducers of microsomal liver enzymes – is increased by 20%. No dose adjustment is required.

Probenecid

Probenecid (500 mg 4 times daily) is a blocker of tubular secretion in nocturnal studies have shown that it inhibits renal clearance of the main metabolite but not levetiracetam. However, the concentration of the main metabolite remains low. It is expected that other drugs that are excreted by active tubular secretion may decrease the renal clearance of the main metabolite. The effect of levetiracetam on probenecid has not been studied; the effect of levetiracetam on other drugs excreted by active tubular secretion including nonsteroidal anti-inflammatory drugs sulfonamide and methotrexate is unknown.

Peroral contraceptives and other pharmacokinetic interactions

Levetiracetam at a dose of 1000 mg/day has no effect on the pharmacokinetics of oral contraceptives (ethinylestradiol and levonorgestrel); hormonal status (luteinizing hormone and progesterone levels) is not changed. Levetiracetam at a dose of 2000 mg/day had no effect on the pharmacokinetics of digoxin and warfarin. Concomitant use of digoxin oral contraceptives and warfarin has no effect on the pharmacokinetics of levetiracetam.

Antacids

There are no data on the effect of antacids on absorption of levetiracetam.

Food and alcohol

Food does not affect the degree of absorption of levetiracetam but slightly reduces its rate. There are no data on the interaction of levetiracetam with ethanol. There are single reports of decreased efficacy of levetiracetam when used topically with osmotic laxatives; therefore, it is not recommended to take osmotic laxatives for one hour before and one hour after levetiracetam administration simultaneously.

Special Instructions

Cancellation of therapy

Cancellation of the drug is recommended to be done gradually. For example, in adults and adolescents with a body weight over 50 kg: dose reduction should be carried out in increments of 500 mg 2 times daily at most every 2-4 weeks; in children from 6 years of age with a body weight less than 50 kg: dose reduction should be carried out in increments of no more than 10 mg/kg 2 times daily at most every 2 weeks.

Renal failure

The use of levetiracetam in patients with renal failure may require dose adjustment. In patients with severe hepatic impairment, it is recommended that renal function be evaluated prior to dose adjustment (see Dosage and Administration)

Suicide

Patients who have taken anticonvulsants (including levetiracetam) have experienced suicidal attempts, suicidal thoughts and behavior.

A meta-analysis of randomized placebo-controlled trials of anticonvulsant medications showed a small increase in the risk of suicidal thoughts and behavior. Its mechanism is unknown.

In view of the above, patients with symptoms of depression or suicidal thoughts and/or behaviors should be monitored and appropriate therapy should be administered. Patients (and their caregivers) should be informed to seek medical attention when they have symptoms of depression and/or suicidal thoughts and behaviors.

Children

The tablet dosage form has age restrictions for use in children (see “Indications”). Levetiracetam is not reported to affect growth and puberty. However, the long-term effect on learning intelligence growth endocrine function puberty and fertility in children is unknown.

The concomitant antiepileptic medications (while patients are being switched to levetiracetam) should preferably be withdrawn gradually.

There have been no studies on the effect on the ability to drive and operate machinery. Due to individual differences in susceptibility, somnolence and other central nervous system disturbances may occur in some patients especially at the beginning of therapy and after increasing the dose. Therefore, it is recommended to be cautious when driving vehicles and engaging in other activities that require high concentration and quick psychomotor reactions. If these symptoms occur, patients should abstain from such activities until they are sure that these symptoms have no significant effect on them.

Contraindications

– Hypersensitivity to levetiracetam or other pyrrolidone derivatives as well as to any of the drug components;

– Children under 4 years of age (safety and efficacy not established).

– Elderly patients (over 65 years);

– Liver disease in decompensation stage;

– Renal failure.

Side effects

Based on data from clinical studies and postmarketing experience with levetiracetam, the most common adverse reactions were nasopharyngitis drowsiness headache fatigue and dizziness. The safety profile of levetiracetam is generally similar for different age groups of adults and children.

The incidence of adverse effects: very common (≥1/10) common (≥1/100 to< 1/10) infrequent (≥1/1000 to < 1/100) rare (≥1/10000 to < 1/1000) very rare (< 1/10000) frequency not determined (currently no data on the incidence of adverse reactions).

Blood and lymphatic system disorders

Infrequent: thrombocytopenia leukopenia.

Rarely: agranulocytosis pancytopenia (in some cases with suppression of bone marrow function) neutropenia.

Immune system disorders

Rare: drug reaction with eosinophilia and systemic manifestations (DRESS syndrome).

Metabolic disorders

Often: anorexia.

Infrequent: weight gain weight loss.

Rarely: hyponatremia.

Mental disorders

Often: depression mood changes hostility aggression insomnia nervousness irritability anxiety.

Infrequent: confusion agitation hallucinations emotional instability psychotic disorders suicide attempts and suicidal thoughts behavioral disorders anger panic attacks mood swings.

Rarely: completed suicide personality disorder thought disorder.

Nervous system disorders

Very common: drowsiness headache.

Often: seizures dizziness tremor impaired balance lethargy.

Infrequent: paresthesias amnesia impaired coordination/ataxia impairment of memory decreased concentration.

Rare: hyperkinesia choreoathetosis dyskinesia.

Visual organ disorders

Infrequent: diplopia impaired accommodation.

Hearing organ disorders

Often: vertigo.

Respiratory system disorders

Often: cough.

Digestive system disorders

Often: abdominal pain diarrhea dyspepsia nausea vomiting.

Infrequent: pancreatitis change in functional liver function tests.

Rarely: liver failure hepatitis weight loss.

Skin disorders

Often: skin rash.

Infrequent: eczema pruritus alopecia (in some cases hair regrowth was observed after discontinuation of the drug).

Rarely: toxic epidermal necrolysis Stevens-Johnson syndrome erythema multiforme.

Muscular system disorders

Infrequent: muscle weakness myalgia.

Infections and invasions

Very common: nasopharyngitis.

Rarely: infections.

General disorders

Infrequent: asthenia fatigue accidental injury.

The risk of anorexia is higher when levetiracetam is coadministered with topiramate.

In placebo-controlled studies, the safety profile of levetiracetam in children (patients aged 4-16 years) was comparable to that of adults, except for behavioral and psychiatric adverse reactions, which occurred more often in children than in adults. In children and adolescents aged 4-16 years, adverse reactions such as vomiting (very often 112%) agitation (often 34%) mood changes (often 21%) emotional lability (often 17%) aggression (often 82%) conduct disorder (often 56%) and lethargy (often 39%) were more frequent than in other age ranges.

. An evaluation of the cognitive and neuropsychological effects of levetiracetam in children 4-16 years of age with partial seizures (based on double-blind placebo-controlled safety profile studies) showed that levetiracetam was not different (no less safe) from placebo on changes from baseline on the Leiter-R Attention and Memory Screen Composite scale. The results of the study of behavioral and emotional functions confirming that aggressive behavior occurs against the background of levetiracetam use were obtained using a standardized method with a validated instrument – Achenbach Child Behavior Checklist. However, patients who took levetiracetam long-term in open studies did not show abnormal behavioral and emotional functions, in particular the level of aggressive behavior did not differ from baseline.

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

Symptoms: drowsiness agitation anxiety aggression depression of consciousness respiratory depression coma.

Treatment: in the acute period – induced vomiting and gastric lavage followed by administration of activated charcoal. There is no specific antidote for levetiracetam. If necessary, symptomatic treatment under hospital conditions using hemodialysis (dialysis efficiency for levetiracetam is 60% for its primary metabolite – 74%).

Pregnancy use

Post-marketing data from several prospective pregnancy registries have documented more than 1000 cases of levetiracetam monotherapy in the first trimester of pregnancy.

In general, these data do not indicate a significant increase in the risk of serious congenital malformations, although teratogenic risk cannot be completely excluded. Therapy with multiple antiepileptic agents is associated with a higher risk of birth defects than monotherapy, so monotherapy in pregnant women is more appropriate. No adequate and strictly controlled clinical trials concerning safety of levetiracetam use in pregnant women have been conducted, therefore the drug should not be administered during pregnancy and also in fertile women who do not use reliable contraceptive methods except in case of emergency.

Physiological changes in the woman’s body during pregnancy may affect the plasma concentration of levetiracetam as well as that of other antiepileptic drugs. A decrease in plasma concentrations of levetiracetam has been noted during pregnancy. Treatment of pregnant women with levetiracetam should be performed under special supervision. Interruptions in antiepileptic therapy may worsen the course of the disease, which may be harmful to the health of both mother and fetus.

Levetiracetam is excreted with breast milk, so breast-feeding with the drug is not recommended.

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