Topapepsin - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline - 12.5 mg; corn starch - 7.5 mg; pregelatinized starch - 12 mg; lactose monohydrate - 17.5 mg; crospovidone - 2.5 mg; silicon dioxide colloidal - 1 mg; croscarmellose sodium - 1.5 mg; magnesium stearate - 0.5 mg.

Shell composition: hypromellose - 2 mg, macrogol 6000 - 0.32 mg; glycerol 0.32 mg; talc 0.68 mg; titanium dioxide - 0.432 mg; dye iron oxide red - 0.008 mg; lactose monohydrate 0.24 mg.

One 50 mg tablet contains:

active substance: Topiramate in terms of 100% of the substance - 50 mg;

Excipients: cellulose microcrystalline - 25 mg; corn starch - 15 mg; pregelatinized starch - 24 mg; lactose monohydrate 35 mg; crospovidone - 5 mg; silicon dioxide colloidal - 2 mg; croscarmellose sodium - 3 mg; magnesium stearate - 1 mg.

Shell composition: hypromellose - 4 mg, macrogol 6000 - 0.64 mg; glycerol - 0.64 mg; talc - 1.36 mg; titanium dioxide - 0.864 mg; ferric oxide red oxide - 0.016 mg; lactose monohydrate 0.48 mg.

One 100 mg tablet contains:

active substance: Topiramate in terms of 100% of the substance - 100 mg;

Excipients: cellulose microcrystalline - 50 mg; corn starch - 30 mg; Pregelatinized starch - 48 mg; lactose monohydrate - 70 mg; crospovidone - 10 mg; silicon dioxide colloidal - 4 mg; croscarmellose sodium - 6 mg; magnesium stearate - 2 mg.

Shell composition: hypromellose - 8 mg, macrogol 6000 - 1.28 mg; glycerol 1.28 mg; talc - 2.72 mg; titanium dioxide - 1.728 mg; iron dye oxide red - 0.032 mg; lactose monohydrate 0.96 mg.

One 200 mg tablet contains:

active substance: Topiramate in terms of 100% substance - 200 mg;

Excipients: cellulose microcrystalline - 100 mg; corn starch - 60 mg; pregelatinized starch 96 mg; lactose monohydrate - 140 mg; crospovidone - 20 mg; silicon dioxide colloid - 8 mg; croscarmellose sodium - 12 mg; magnesium stearate - 4 mg.

Shell composition: hypromellose - 16 mg, macrogol 6000 - 2.56 mg; glycerol - 2.56 mg; talc - 5.44 mg; titanium dioxide - 3.456 mg; ferric oxide red oxide - 0.064 mg; lactose monohydrate - 1.92 mg.

Description:

The tablets covered with a film cover, from light pink to pink with kremovatym a shade of color, round, biconcave. On the fracture of the tablet from white to white with a creamy or grayish hue of color.

Pharmacotherapeutic group:antiepileptic agent

ATX: & nbsp

N.03.A.X Other antiepileptic drugs

N.03.A.X.11 Topiramate

Pharmacodynamics:

Antiepileptic agent. Reduces the frequency of occurrence of action potentials that are characteristic of a neuron in a state of persistent depolarization, which indicates the dependence of the blocking effect of topiramate on sodium channels on the state of the neuron. Increases the activity of gamma-aminobutyric acid (GABA) with respect to some subtypes of GABA receptors (incl. GABA_A-receptors), and also modulates the activity of the GABA_A-receptors; prevents the activation of kainate sensitivity of kainate / AMPK receptors (alpha-amino-3-hydroxy-5 methylisoxazole-4-propionic acid) to glutamate, does not affect activity N-methyl-Daspartate NMDA receptors. These effects are dose-dependent with a concentration of Topiramate in plasma of 1-200 μM, with a minimum activity of 1-10 μM.

Inhibits the activity of certain isoenzymes of carbonic anhydrase (II-IV), but this effect is weaker, in acetazolamide, and probably is not the main one in the anticonvulsant activity of topiramate.

Pharmacokinetics:

Absorption is high, bioavailability is 80%. Eating does not have a clinically significant effect on bioavailability. Time to reach the maximum concentration in the blood plasma - 2 hours after ingestion at a dose of 400 mg. The maximum concentration in the blood after repeated ingestion of 100 mg twice a day - 6.76 μg / ml.

The connection with plasma proteins is 13-17%. The volume of distribution (after taking 1,2 g) - 0,55-0,8 l / kg, depends on the sex (in women - 50% from the values observed in men). Equilibrium concentration is achieved after 4-8 days, with renal insufficiency - 10-15 days. Penetrates into breast milk.

Metabolised in the liver by hydroxylation, hydrolysis and glucuronation with the formation of 6 pharmacologically inactive metabolites. Pharmacokinetics after a single oral intake is linear, plasma clearance remains constant - 20-30 ml / min; the area under the concentration-time curve (AUC) in the dose range of 100-400 mg increases in proportion to the dose.

Half-life after repeated intake of 50 and 100 mg twice a day -21h. With severe hepatic and renal (creatinine clearance less than 60 ml / min), plasma and kidney clearance are reduced. It is excreted by the kidneys in unchanged form (70%) and in the form of metabolites. It is removed from the plasma by hemodialysis.

Indications:

As a monotherapy - first diagnosed epilepsy.

As an auxiliary drug in adults and children older than 3 years - partial or generalized tonic-clonic seizures; epileptic seizures against the background of the Lennox-Gastaut syndrome.

Contraindications:

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

Carefully:

Renal or hepatic insufficiency, nephrourolythiasis (in the anamnesis, including in the family), hypercalciuria.

Dosing and Administration:

Inside, regardless of food intake. Tablets should not be divided.

When applying as a monotherapy it is necessary to take into account the possible effect of withdrawal of concomitant anticonvulsant therapy on the frequency of seizures. In those cases where it is undesirable to abruptly cancel concomitant anticonvulsant therapy, the dose of the drug is reduced gradually, reducing the dose by 1/3 every 2 weeks.

With the withdrawal of drugs that are inducers of microsomal "hepatic" enzymes, the concentrations of topiramate in plasma will increase. In such situations, in the presence of clinical indications, the dose can be reduced.

Adults at the beginning of monotherapy - 25 mg 1 time per day before bedtime for 1 week. Then the dose is increased at intervals of 1-2 weeks at 25-50 mg / day (the daily dose is divided into 2 divided doses). If this mode of treatment is intolerant, the dose is increased by a smaller amount or at large intervals. The dose is selected depending on the effect. The recommended dose is 100 mg / day, the maximum daily dose is 500 mg. In some cases with monotherapy of refractory to the treatment of epilepsy, the dose of topiramate is 1 g / day.

Children older than 3 years with monotherapy in the first week of treatment - 0.5-1 mg / kg / day (daily dose divided into 2 divided doses). The magnitude of the dose and the rate of its increase are determined by the clinical efficacy and tolerability of therapy. The recommended range of doses for monotherapy with topiramate in children older than 3 years is 3-6 mg / kg / day. With newly diagnosed partial seizures, up to 500 mg / day.

When appointing in combination with other anticonvulsant drugs in adults initial dose - 50 mg once a day at night for 1 week. The dose is then increased by 25-50 mg every other week until an effective dose is reached. The average daily dose is 200-400 mg, the frequency of administration is 2 times a day. If necessary, an increase in the daily dose to a maximum of 1600 mg is possible.The criterion for choosing a dose is the clinical effect, in some patients it can be achieved with the drug once a day.

When carrying out combined anticonvulsant therapy in children older than 3 years the recommended total daily dose is 5-9 mg / kg for 2 divided doses. Selection of the dose begins with 25 mg / day at night for 1 week. In the future, the dose can be increased by 1-3 mg / kg in 1-2 weeks and taken in 2 divided doses. The daily dose of 30 mg / kg is usually well tolerated.

On the days of hemodialysis topiramate should be prescribed additionally at a dose equal to 1/2 the daily dose, in 2 doses (before and after the procedure).

The drug should be discontinued gradually to minimize the possibility of an increase in the frequency of seizures (by 100 mg / week).

Side effects:

Ataxia, decreased ability to concentrate, confusion, dizziness, increased fatigue, paresthesia, drowsiness, impaired thinking; rarely, excitation, amnesia, decreased appetite, aphasia, depression, emotional lability, speech impairment, nystagmus, impaired vision (including diplopia), perversion of taste sensations, nausea, nephrourolythiasis, weight loss.

There may be a syndrome (usually 1 month after the start of therapy), characterized by myopia with increased intraocular hypertension. There was also a sharp decrease in visual acuity and / or pain in the eye area.

Ophthalmic manifestations included: myopia, a decrease in the depth of the anterior chamber of the eye, hyperemia of the mucous membrane of the eye, and increased intraocular pressure. In some cases - mydriasis. A possible mechanism of this syndrome is an increase in supraciliary eudhotia, which leads to a shift in the lens and iris and, as a result, the development of secondary, closed-angle glaucoma. Treatment includes discontinuation of the drug and measures aimed at reducing intraocular pressure.

Perhaps the development of allergic reactions.

Overdose:

Symptoms: increased side effects.

Treatment: gastric lavage, symptomatic therapy. The use of activated carbon is ineffective, because in experiments in vitro it has been shown that it does not adsorb topiramate. An effective way to remove topiramate from the body is hemodialysis.

Interaction:

Reduces the effectiveness of oral estrogen-containing contraceptives.

Reduces AUC digoxin by 12%.

It is not recommended simultaneous administration of ethanol or other drugs that depress the central nervous system.

When taken concomitantly with carbamazepine AUC carbamazepine remained unchanged or slightly changed (less than 10%), whereas AUC Topiramate is reduced by 40%.

When co-appointed AUC phenytoin remains unchanged or increased by 25%, whereas AUC topiramate is reduced by 48%; it may be necessary to correct the dosage regimen of the latter.

When used concomitantly with valproic acid AUC Valproic acid is reduced by 11%, topiramate - by 14%.

Inhibitors of carbonic anhydrase (acetazolamide) increase the risk of formation of renal calculi.

Special instructions:

In patients with a predisposition to nephrourolythiasis, the risk of kidney stones is increased, and an adequate increase in the amount of kidney stones is necessary to prevent this. liquid.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Film-coated tablets, 25 mg, 50 mg, 100 mg and 200 mg.

Packaging:

For 10 tablets with a dosage of 25 mg, 50 mg and 100 mg, or 4 tablets with a dosage of 200 mg in a contour, cell pack.

For 28 tablets with a dosage of 200 mg in a can of polypropylene or polyethylene.

Each bank or 3 contiguous cell packs of 10 tablets, or 7 contour packs of cells of 4 tablets, together with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006458/09

Date of registration:13.08.2009 / 13.10.2016

Expiration Date:Unlimited

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp02.01.2017

Illustrated instructions

Instructions

Topalepsin® (Topalepsin®)