Топалепсин®

General characteristics. Structure:

Active agent: 25 mg, 50 mg, 100 mg or 200 mg of a topiramat in terms of 100% substance.

Excipients: cellulose microcrystallic, starch corn, starch prezhelatinizirovanny, lactose (sugar milk), кросповидон, silicon dioxide colloid (aerosil), croscarmellose sodium, magnesium stearate.

Structure of a cover: gipromelloz (gidroksipropilmetiltsellyuloz), macrogoal (polietilengli-if 6000), глицерол (glycerin), talc, titanium dioxide, dye ferrous oxide red, lactose (sugar milk).

Pharmacological properties:

Pharmacodynamics. Antiepileptic means. Reduces the frequency of emergence of the action potentials characteristic of neuron is able permanent depolarization that testifies to dependence of the blocking action of a topiramat on natrium channels from a condition of neuron. Increases activity of piperidic acid (GAMK) concerning the GAMK-some subtypes of receptors (including GAMK and - receptors), and also modulates activity of GAMK and - receptors; interferes with activation kainaty sensitivity of kainat/AMPK-receptors (alpha amino-Z-gidroksi-5 metilizoksazol-4-propionic acid) to a glutamate, does not influence activity of M-metil-D-aspartata concerning NMDA-receptors.

These effects of a dozozavisima at concentration of a topiramat in plasma of 1-200 microns, with the minimum activity within 1 - 10 micron.

Activity of some isoenzymes of a karboangidraza (II-IV), however this effect boyoly weak, than at acetazoleamide oppresses, and it is probable, is not the basic in an anticonvulsant akyotivnost of a topiramat.

Pharmacokinetics. Absorption — high, bioavailability — 80%. Meal has no clinically significant effect on bioavailability. Time of achievement of the maximum concentration in a blood plasma — 2 h after intake in a dose of 400 mg. The maximum concentration in blood after multiple dose in 100 mg 2 times a day — 6,76 mkg/ml. Communication with proteins of plasma — 13-17%. Distribution volume (after reception of 1,2 g) — 0,55-0,8 l/kg, depends on a floor (women have 50% of the sizes observed at men). Equilibrium concentration is reached in 4-8 days, at a renal failure — 10-15 days. Gets into breast milk.

It is metabolized in a liver by a hydroxylation, hydrolysis and a glyukuronirovaniye with education 6 pharmacological of inactive metabolites. The pharmacokinetics after a single dose inside has linear character, the plasma clearance remains constant — 20-30 ml/min.; area size under a curve "concentration — time" (AUC) increases in range of doses of 100-400 mg in proportion to a dose. An elimination half-life after multiple dose of 50 and 100 mg 2 times a day — 21 h. At heavy hepatic and renal (clearance of creatinine less than 60 ml/min.) insufficiency plasma and renal clearance decrease. It is removed by kidneys in not changed look (70%) and in the form of metabolites. Is removed from plasma by means of a hemodialysis.

Indications to use:

As monotherapy — for the first time the diagnosed epilepsy.

As auxiliary medicine at adults and children 3 years — partial or generalized toniko-clonic attacks are more senior; epileptic seizures against the background of Lennox-Gasto's syndrome.

Route of administration and doses:

Inside, regardless of meal. Tablets should not be divided. At use as monotherapy it is necessary to consider possible influence of cancellation of the accompanying anticonvulsant therapy on the frequency of attacks. When it is undesirable to cancel sharply accompanying anticonvulsant therapy, drug doses reduce gradually, reducing a dose for 1/3 each 2 weeks. At cancellation of the medicines which are inductors of microsomal "hepatic" enzymes, concentration of a topiramat will increase in plasma. In such situations in the presence of clinical indications the dose can be reduced.

The adult at the beginning of performing monotherapy — on 25 mg of 1 times a day before going to bed within 1 week. Then the dose is raised at an interval of 1 - 2 week on 25-50 mg/days (the daily dose is divided into 2 receptions). At intolerance of such mode of therapy the dose is raised at a smaller size or through big intervals. The dose is selected depending on effect. The recommended dose — 100 mg/days, the maximum daily dose — 500 mg. In certain cases at monotherapy of epilepsy, refractory to treatment, the dose of a topiramat makes 1 g/days. To children 3 years at monotherapy in the first week of treatment are more senior — on 0,5-1 mg/kg/days (the daily dose is divided into 2 receptions). The size of a dose and speed of its increase are defined by clinical performance and portability of therapy. The recommended range of doses at monotherapy topiramaty at children is more senior than 3 years — 3-6 mg/kg/days. At recently diagnosed partial attacks — to 500 mg/days.

At appointment in a combination with other anticonvulsant medicines at adults an initial dose — 50 mg of 1 times a day for the night within 1 week. Further the dose is increased by 25-50 mg every week before achievement of an effective dose. An average daily dose — 200-400 mg, frequency rate of reception — 2 times a day. If necessary increase in a daily dose to maximum — 1600 mg is possible. As criterion of selection of a dose serves the clinical effect, at some patients it can be reached at administration of drug of 1 times a day.

When performing the combined anticonvulsant therapy at children 3 years the recommended total daily dose — 5-9 mg/kg for 2 receptions are more senior. Selection of a dose is begun with 25 mg/days for the night within 1 week. Further the dose can be increased by 1-3 mg/kg in 1-2 weeks and to accept in 2 receptions. The day dose of 30 mg/kg is usually well transferred. In days of carrying out a hemodialysis топирамат it is necessary to appoint in addition in a dose, equal 1/2 daily doses, in 2 receptions (before and after the procedure).

It is necessary to cancel drug gradually to minimize a possibility of increase in frequency of attacks (on 100 mg/week).

Features of use:

At patients with predisposition to a nefrourolitiaz the risk of formation of stones in kidneys which prevention requires adequate increase in volume of the consumed liquid increases.

Influence on ability to drive the car and other mechanisms. During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Ataxy, decline in the ability to concentration of attention, confusion of consciousness, dizziness, increased fatigue, paresthesias, drowsiness, disturbance of thinking; seldom — excitement, amnesia, a loss of appetite, aphasia, a depression, emotional lability, disturbance of the speech, a nystagmus, a vision disorder (including a diplopia), a perversion of flavoring feelings, nausea, нефроуролитиаз, decrease in body weight.

Emergence of the syndrome (usually in 1 month from the beginning of therapy) which is characterized by a myopia against the background of increase in intraocular hypertensia is possible. At the same time acute decrease in visual acuity and/or pain in an eye was also noted.

Ophthalmologic manifestations included: myopia, reduction of depth of an anterior chamber of an eye, hyperemia of a mucous membrane of an eye and increase in intraocular pressure. In certain cases — a mydriasis.

The possible mechanism of this syndrome is increase in a supratsiliarny exudate that leads to anteposition of a crystalline lens and an iris of the eye and as a result to development of secondary closed-angle glaucoma.

Treatment includes the termination of administration of drug and an action directed to decrease in intraocular pressure. Development of allergic reactions is possible.

Interaction with other medicines:

Reduces efficiency of oral estrogensoderzhashchy contraceptives. Reduces AUC digoxin by 12%.

The concomitant use of ethanol or other medicines oppressing the central nervous system is not recommended.

At a concomitant use with AUC carbamazepine of carbamazepine remains invariable or slightly changes (less than for 10%) whereas AUC of a topiramat decreases by 40%. At joint appointment of AUC of Phenytoinum remains invariable or increases by 25% whereas AUC of a topiramat decreases by 48%; correction of the mode of dosing of the last can be required.

At simultaneous use with AUC valproic acid of valproic acid the topiramata — for 14% decreases by 11%.

Inhibitors of a karboangidraza (acetazoleamide) increase risk of formation of renal concrements.

Contraindications:

Hypersensitivity, pregnancy, the lactation period, children's age (up to 3 years).

With care. A renal or liver failure, нефроуролитиаз (in the anamnesis, including in family), a hypercalcuria.

Overdose:

Symptoms: strengthening of side effects.

Treatment: gastric lavage, symptomatic therapy. Use of absorbent carbon is inefficient since in experiments of in vitro it was shown that it does not adsorb топирамат. An effective way of removal of a topiramat from an organism — a hemodialysis.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. Not to use after expiry date. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 25 mg, 50 mg, 100 mg and 200 mg. On 10 tablets with a dosage of 25 mg, 50 mg and 100 mg or on 4 tablets with a dosage of 200 mg in a blister strip packaging.

On 28 tablets with a dosage of 200 mg in bank from polypropylene or polyethylene. Each can or 3 blister strip packagings on 10 tablets, or 7 blister strip packagings on 4 tablets together with the application instruction in a pack from a cardboard.