Vimpat tablets p / o 200mg, No. 14

As part of the complex therapy of partial seizures, accompanied or not accompanied by secondary generalization, in patients with epilepsy aged 16 years and older.

Inside. The daily dose is divided into 2 doses - in the morning and in the evening, regardless of the time of the meal. The recommended starting dose is 50 mg 2 times a day. After 1 week, the dose is increased to 100 mg 2 times a day. Taking into account efficacy and tolerability, the maintenance dose can be increased to 150 mg 2 times a day in the third week of administration and to a maximum daily dose of 400 mg / day (200 mg 2 times a day) from the fourth week. It is recommended to cancel VimpatЃ gradually, reducing the dose by 200 mg per week.

Application in patients with renal insufficiency
Patients with mild and moderate renal impairment (creatinine clearance> 30 ml / min) do not require dose adjustment. In patients with severe renal impairment (creatinine clearance Use in patients with impaired liver function
Patients with mild to moderate impairment of liver function do not need dose adjustment. Titration of the dose in such patients should be done with caution, given that impaired liver function is often accompanied by impaired renal function. lacosamide has not been studied in patients with severe hepatic impairment.

Use in the elderly
Elderly people do not need dose reduction Experience with lacosamide in elderly patients with epilepsy is limited. In the elderly, it is necessary to take into account the possibility of an age-related decrease in renal clearance and, as a result, an increase in the concentration of lacosamide in blood plasma.

Use in children
Lacosamide is not recommended for children and adolescents under the age of 16 years, since the safety and efficacy of the drug in these age groups have not been studied.

Active substance: lacosamide - 200 mg

Excipients: microcrystalline cellulose, low-substituted hyprolose, salting HD 90 [microcrystalline cellulose and anhydrous colloidal silicon dioxide], crospovidone, magnesium stearate, hyprolose.

Sheath: opadry II (colored) [polyvinyl alcohol; talc; macrogol 3350; soy lecithin; titanium dioxide, E 171; iron dye yellow oxide, E 172 (tablets 100 mg and 150 mg); iron dye red oxide, E 172 (tablets 50 mg and 150 mg); iron dye black oxide (tablets 50 mg and 150 mg); FD&C blue 2 indigo carmine dye (tablets 50 mg and 200 mg)]; opadry transparent [macrogol 400, macrogol 8000, hypromellose 3 cf, hypromellose 6 cf and hypromellose 50 cf].

Hypersensitivity to any component of the drug, incl. soybeans (included in the tablet shell), as well as peanuts. Atrioventricular block II or III degree. Age under 16.

With caution in patients with severe renal impairment (creatinine clearance

Trade (proprietary) name: Vimpat

International (non-proprietary) name: lacosamide

Dosage form:

film-coated tablets

Composition
1 film-coated tablet contains:

Active ingredient: lacosamide 50 mg, 100 mg, 150 mg or 200 mg;

Excipients: microcrystalline cellulose, low-substituted hyprolose, salting HD 90 [microcrystalline cellulose and anhydrous colloidal silicon dioxide], crospovidone, magnesium stearate, hyprolose.

Sheath: opadry II (colored) [polyvinyl alcohol; talc; macrogol 3350; soy lecithin; titanium dioxide, E 171; iron dye yellow oxide, E 172 (tablets 100 mg and 150 mg); iron dye red oxide, E 172 (tablets 50 mg and 150 mg); iron dye black oxide (tablets 50 mg and 150 mg); FD&C blue 2 indigo carmine dye (tablets 50 mg and 200 mg)]; opadry transparent [macrogol 400, macrogol 8000, hypromellose 3 cf, hypromellose 6 cf and hypromellose 50 cf].

Description
Tablets 50 mg: pinkish oval, biconvex film-coated tablets. On one side of the tablet, the marking У50Ф is embossed, and on the other УSPФ.

Tablets 100 mg: oval, biconvex, dark yellow film-coated tablets. On one side of the tablet, the marking '100' is embossed, and on the other 'SP'.

Tablets 150 mg: pale orange, oval, biconvex film-coated tablets. On one side of the tablet, the marking У150Ф is embossed, and on the other УSPФ.

Tablets 200 mg: blue oval, biconvex film-coated tablets. On one side of the tablet is embossed У200Ф and on the other УSPФ.

Pharmacotherapeutic group:

antiepileptic drug.

ATX code: N03 AX 18

Pharmacological properties
The exact mechanism of the antiepileptic action of lacosamide has not been established. Lacosamide selectively enhances the slow inactivation of voltage-dependent sodium channels, which leads to stabilization of the hyperexcitable membranes of neurons.

In addition, lacosamide binds to the phosphoprotein CRMP-2, which is expressed predominantly in the nervous system and is involved in the regulation of neuronal differentiation and axonal growth.

Pharmacodynamics
It has been shown that lacosamide delays the development of increased convulsive readiness. Lacosamide has a synergistic or additive anticonvulsant effect in combination with levetiracetam, carbamazepine, phenytoin, valproic acid, lamotrigine, topiramate, or gabapentin.

Pharmacokinetics

Absorption
Lacosamide is rapidly and completely absorbed after oral administration. The bioavailability of lacosamide in tablets is approximately 100%. After oral administration, the concentration of lacosamide in plasma rapidly increases, the maximum concentration (Cmax) is reached in 0.5-4 hours. Food intake does not affect the rate and degree of absorption.

Distribution
The volume of distribution is approximately 0.6 l / kg, the degree of binding to plasma proteins is less than 15%. When applied twice a day, equilibrium plasma concentrations are reached within 3 days.

Metabolism
95% of the dose is excreted through the kidneys, both unchanged (about 40% of the dose) and in the form of metabolites (O-desmethyl metabolite - less than 30%). The proportion of the polar fraction in urine (presumably serine derivatives) was approximately 20%. Other metabolites are determined in urine in the amount of 0.5-2%. The formation of the O-desmethyl metabolite occurs mainly under the action of the cytochrome CYP2C19 isoenzyme. Other enzymes involved in the metabolism of lacosamide have not been established. The concentration of the O-desmethyl metabolite in plasma is approximately 15% of the concentration of lacosamide. This metabolite has no pharmacological activity.

Excretion
Lacosamide is excreted by renal excretion and biotransformation. The half-life is approximately 13 hours. Pharmacokinetic parameters are directly proportional to the dose used, do not change over time and are characterized by low individual variability.

Indications for use
As part of the complex therapy of partial convulsive seizures, accompanied or not accompanied by secondary generalization, in patients with epilepsy aged 16 years and older.

Contraindications
Hypersensitivity to any component of the drug, incl. soybeans (included in the tablet shell), as well as peanuts. Atrioventricular block II or III degree. Age under 16.

With caution in patients with severe renal impairment (creatinine clearance

Pregnancy and lactation

Pregnancy There are no
clinical data on the use of lacosamide in pregnant women. In animal studies, no teratogenic effects were recorded, however, embryotoxicity was noted when using high (toxic) doses. Lacosamide should not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the fetus. If a woman is planning a pregnancy, then it is necessary to carefully weigh the appropriateness of using this drug.

Lactation period There are no
data on the excretion of lacosamide in human breast milk. In animal studies, excretion of lacosamide in milk has been noted. During treatment with lacosamide, breastfeeding should be discontinued.

Dosing and Administration
Inside. The daily dose is divided into 2 doses - in the morning and in the evening, regardless of the meal time. The recommended starting dose is 50 mg 2 times a day. After 1 week, the dose is increased to 100 mg 2 times a day. Taking into account efficacy and tolerability, the maintenance dose can be increased to 150 mg 2 times a day in the third week of administration and to a maximum daily dose of 400 mg / day (200 mg 2 times a day) from the fourth week. It is recommended to cancel VimpatЃ gradually, reducing the dose by 200 mg per week.

Application in patients with renal insufficiency
Patients with mild and moderate renal impairment (creatinine clearance> 30 ml / min) do not require dose adjustment. In patients with severe renal impairment (creatinine clearance Use in patients with impaired liver function
Patients with mild to moderate impairment of liver function do not need dose adjustment. Titration of the dose in such patients should be done with caution, given that impaired liver function is often accompanied by impaired renal function. lacosamide has not been studied in patients with severe hepatic impairment.

Use in the elderly
Elderly people do not need dose reduction Experience with lacosamide in elderly patients with epilepsy is limited. In the elderly, it is necessary to take into account the possibility of an age-related decrease in renal clearance and, as a result, an increase in the concentration of lacosamide in blood plasma.

Use in children
Lacosamide is not recommended for children and adolescents under the age of 16 years, since the safety and efficacy of the drug in these age groups have not been studied.

Adverse reactions
in the treatment lakosamidom most common adverse reactions were dizziness, headache, nausea and diplopia. As a rule, they were mild or moderately pronounced. The severity of some adverse reactions depended on the dose and decreased after its reduction. The frequency and severity of central nervous system (CNS) and gastrointestinal adverse reactions generally decreased over time.

The use of lacosamide is accompanied by a dose-dependent lengthening of the PR interval, as a result of which the development of such clinical conditions as atrioventricular blockade, syncope and bradycardia is possible.

Adverse reactions reported in more than 1% of patients in clinical trials are listed below. Adverse reactions are classified by frequency according to the following categories: Very common (> 1/10); Often (from> 1/100 to 1/1000 to From the central nervous system and psyche
Very often: dizziness, headache.
Often: depression, irritability, imbalance, impaired coordination of movements, memory impairment, impaired attention, cognitive impairment, hypesthesia , drowsiness, confusion, tremors, nystagmus, dysarthria.

From the side of the visual organs
Very often: diplopia.
Often: blurred vision.

On the part of the hearing organs and vestibular apparatus
Often: vertigo, tinnitus.

From the gastrointestinal tract
Very often: nausea.
Often: vomiting, constipation, flatulence, dyspepsia, dry mouth.

On the part of the skin and subcutaneous fat
Often: itching.

From the musculoskeletal system
Often: muscle spasms.

Other
Common: gait disturbance, asthenia, fatigue, falls, increased risk of injury (due to impaired coordination of movements and dizziness).

Overdose
Clinical data on overdose of lacosamide are limited. After taking the drug at a dose of 1200 mg / day, clinical symptoms were mainly represented by the central nervous system and the gastrointestinal tract (dizziness and nausea) and disappeared after lowering the dose. There is no antidote to lacosamide. Overdose treatment is symptomatic. If necessary, it is possible to use hemodialysis.

Interaction with other drugs
Research results indicate a low probability of interaction of lacosamide with other drugs. Lacosamide should be used with caution in combination with drugs that cause prolongation of the PR interval (eg, carbamazepine, lamotrigine, pregabalin) and class I antiarrhythmic drugs. However, in clinical studies, there was no additional lengthening of the PR interval in patients who simultaneously took lacosamide in combination with carbamazepine or lamotrigine.

Lacosamide is a cytochrome P450 (CYP2C19) substrate. Potent enzyme inducers such as rifampicin or St. John's wort (Hypericum perforatum) can cause a moderate decrease in the systemic concentration of lacosamide. In this regard, caution should be exercised when prescribing or discontinuing such drugs.

Antiepileptic drugs
Lacosamide at any therapeutic dose does not affect the equilibrium concentration of levetiracetam, carbamazepine, carbamazepine epoxide, lamotrigine, topiramate, oxcarbazepine, phenytoin, valproic acid, phenobarbital, gabapentin, clondaazepam and zonisamam.

Carbamazepine and valproic acid had no effect on the plasma concentration of lacosamide.

Concomitant therapy with antiepileptic drugs that induce enzymes (carbamazepine, phenytoin, phenobarbital, in various doses), reduced the total systemic exposure of lacosamide by 25%.

Oral contraceptives
There was no evidence of significant interaction between lacosamide and oral contraceptives ethinyl estradiol and levonorgestrel. Lacosamide has no effect on progesterone concentration.

Other
lacosamide does not affect the pharmacokinetics of digoxin. No clinically significant interaction between lacosamide and metformin has been identified. There are no data on the interaction of lacosamide with alcohol.

Omeprazole 40 mg once a day increased the area under the concentration-time curve of lacosamide by 19%. This effect may not be clinically relevant. When taking a single dose, lacosamide did not affect the pharmacokinetics of omeprazole. The effect of other isoenzymes of cytochrome P450 and other enzymes on the metabolism of lacosamide has not been precisely established. Lacosamide is not a substrate or inhibitor of P-glycoprotein.

The degree of binding of lacosamide to blood plasma proteins is less than 15%. Therefore, a clinically significant interaction with other drugs that bind to proteins is unlikely.

Special instructions
Treatment with lacosamide can be accompanied by dizziness, potentially leading to injury and falls. In this regard, patients should be careful.

Analysis of data from clinical trials of antiepileptic drugs indicates a slight increase in the risk of suicidal thoughts and suicidal behavior. The mechanism for increasing the risk is not clear, the existing data do not allow to deny the existence of such a risk when taking lacosamide. Caregivers of patients should be warned about the existing risk and the need to consult a specialist if suicidal behavior occurs. Patients receiving lacosamide treatment should be closely monitored and warned about the need to consult a specialist in case of suicidal thoughts.

Given the possibility of prolonging the PR interval during therapy with Vimpat, patients are recommended to periodically monitor the ECG.

Influence on the ability to drive a car and other mechanical means
The drug may affect the ability to drive a car or use complex equipment. Treatment with this drug may be accompanied by the development of dizziness or blurred vision. Accordingly, patients are not advised to drive a car or operate complex equipment.

Release form
Film-coated tablets 50 mg, 100 mg, 150 mg or 200 mg.
14 tablets in a blister of PVC / PVDC - aluminum foil.
1 or 4 blisters in a cardboard box along with instructions for use.

Storage
conditions Store at a temperature not exceeding 30 ? —. Keep out of the reach of children.

Shelf life is
3 years. Do not use the drug after the expiration date.

Terms of dispensing from pharmacies
Prescription.