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

1 tablet contains: active substance: topiramate 25.0 mg or 100.0 mg; Excipients: microcrystalline cellulose (avicel PH-102) 12.0 / 48.0 mg, mannitol 27.5 / 110.0 mg, sodium carboxymethyl starch 10.0 / 40.0 'mg, - pregelatinized starch 1500 LM 10.0 / 40.0 mg, crospovidone (kollidone CL) 8.5 / 34.0 mg, povidone 5.0 / 20.0 mg, magnesium stearate 0.5 / 2.0 mg, carnauba wax 1.5 / 6.0 mg; shell: for tablets 25 mg: opadrai II white OY-LS-28908 2.0 mg: titanium dioxide 0.5 mg, lactose monohydrate 0.4 mg, macrogol 4000 0.3 mg, hypromellose 15 cP 0.3 mg, hypromellose 3 cp 0.25 mg, hypromellose 50 cp 0.25 mg; for tablets 100, mg: opadrai orange 02H23314 8.0 mg: hypromellose 5 cP 3.8784 mg, titanium dioxide 1.9362 mg, talc 1.1632 mg, propylene glycol 0.9969 mg, dye sunset yellow (15-18% ) 0.0336 mg, dye solar sunset yellow (38-42%) 0.0160 mg.

Description:

Tablets, 25 mg: Round biconvex tablets, covered with a film coating of white color. On the cross section, the core of the tablet is white or almost white in color.

Tablets of 100 mg: Oval biconcave tablets covered with a film membrane of orange color. On the cross section, the core of the tablet is white or almost white in color.

Pharmacotherapeutic group:Antiepileptic agent.

ATX: & nbsp

N.03.A.X Other antiepileptic drugs

N.03.A.X.11 Topiramate

Pharmacodynamics:Antiepileptic agent. The drug blocks sodium channels and reduces the frequency of occurrence of action potentials against a background of prolonged depolarization of the neuron membrane. Increases the activity of gamma-aminobutyric acid (GABA), with respect to some subtypes of GABA receptors, and also simulates the activity of GABA A receptors. Prevents the activation of kainate sensitivity of kainate / AMPK receptors (alpha-amino-Z-hydroxy-5-methylisoxazole-4-propionic acid) to glutamate, does not affect the activity of N-methyl-D-acanthate against NMDA receptors. These effects are dose-dependent with a plasma topiramate concentration of 1-200 μM, with a minimum activity of 1-10 μM.

Pharmacokinetics:

Topiramate is rapidly absorbed in the gastrointestinal tract. Bioavailability - 80%. Eating does not affect the bioavailability of the drug. The time to reach the maximum concentration (C max) after taking a single dose of 400 mg of the drug for 2 hours. Cmax after repeated use at a dose of 100 mg twice a day - 6.76 μg / ml.

The connection with plasma proteins is 13-17%. The volume of distribution after a single dose of 1200 mg is 0.55-0.8 l / kg. The value depends on sex (in women 50% of the values observed in men). Equilibrium concentration in plasma is achieved after 4-8 days, with renal failure - 10-15 days. Topiramate 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 application is linear, plasma clearance remains constant - 20-30 ml / min; the area under the pharmacokinetic curve (AUC) in the dose range of 100-400 mg increases in proportion to the dose. The half-life (T1 / 2) after repeated intake of 50 and 100 mg twice a day -21h. In severe hepatic and renal failure (creatinine clearance less than 60 ml / min), plasma and renal clearance is reduced. It is excreted by the kidneys and unchanged (70%) and in the form of metabolites. Topiramate is effectively excreted by hemodialysis.

Indications:

Partial or generalized tonic-clonic seizures in adults and children older than 3 years as a monotherapy and in combination with other anticonvulsants;

For the first time diagnosed epilepsy (in adults and children older than 3 years); Auxiliary therapy of epileptic seizures against the background of the Lennox-Gastaut syndrome (in adults and children over 3 years old).

Contraindications:Hypersensitivity to any of the components of the drug, pregnancy, lactation, children under 3 years.

Carefully:With caution, the drug should be used for renal / hepatic insufficiency, nephrourolythisis (in anamnesis, including in the family), hypercalciuria.

Pregnancy and lactation:Since combined treatment with antiepileptic drugs increases the risk of developing congenital malformations, it is important to adhere to monotherapy whenever possible. Topiramate has a teratogenic effect in the studied laboratory animals (mice, rats, rabbits). In rats topiramate penetrates the placental barrier. Women of childbearing age in the treatment of Epitope should use reliable contraception. The drug is contraindicated in pregnancy and lactation (breastfeeding).

Dosing and Administration:The drug is taken orally regardless of food intake. Tablets do not divide, swallow whole, without chewing.To achieve optimal control of seizures, it is recommended to start treatment with taking lower doses of the drug and then increasing them to an effective dose. In cases of transition from treatment with other antiepileptic drugs (PEP) to monotherapy, Epitope should take into account the possible effect of withdrawal of antiepileptic therapy on the frequency of seizures. In cases where it is undesirable to abruptly abolish previous therapy, the doses of drugs are reduced gradually, reducing the dose by 1/3 every 2 weeks. With the abolition of PET, which are inducers of microsomal "hepatic" enzymes, the concentrations of topiramate in plasma will increase. In these cases, in the presence of clinical indications, the dose of Epitope can be reduced. Adults with monotherapy Epitope should be taken at 25 mg 1 time per day before bedtime for 1 week. Then the dose is increased with an interval of 1-2 weeks for 25-50 mg / day (the daily dose is divided into 2 doses). The dose is selected individually 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 the drug can be 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 in children older than 3 years is 3-6 mg / kg / day. With newly diagnosed partial seizures, up to 500 mg / day.

When combined with other PEP in adults, the initial dose is 50 mg once a day at night during the week. The dose is then increased by 25-50 mg every week until the effective dose is reached. The average daily dose of 200-400 mg, the frequency of reception 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 a clinically significant effect, in some patients it is achieved with the drug once a day.

When combined anticonvulsant therapy is administered 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 (or less at a rate of 1-3 mg / kg / 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 tolerated well.

To cancel Epitope, you need to gradually, 100 mg per week, to minimize the risk of an increase in the frequency of seizures.

Side effects:

From the side of the central nervous system and the peripheral nervous system: ataxia, decrease, concentration of attention, psychomotor retardation, confusion, dizziness, increased fatigue, paresthesia, drowsiness, impaired thinking; may occur: agitation, amnesia, decreased appetite, aphasia, depression, cognitive disorders, emotional lability, speech disorders, nystagmus, visual impairment (including diplopia), perversion of taste sensations, suicidal ideation or attempts; In addition, in children - personality disorders, increased salivation, hyperkinesia, hallucinations.

From the digestive system: dyspepsia, nausea, abdominal pain, diarrhea, dry lips, increased activity of hepatic transaminases, hepatitis, liver failure.

From the side of the eyes: there may be a syndrome (1 month after initiation of therapy), characterized by myopia in the background, increased intraocular pressure with acute reduction in visual acuity and pain in the eye area.Ophthalmic manifestations included: myopia, a decrease in the depth of the subject chamber, eyes, 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 euda, leading to a shift in the lens and iris, and, as a result, to the development of secondary, closed-angle glaucoma.

From the skin and mucous membranes: erythema multiforme, pemphigus, Stephen-Johnson syndrome and toxic epidermal necrolysis.

Other: weight loss, leukopenia, nephrolithiasis, oligohydrosis (mainly in children), metabolic acidosis, allergic reactions.

Overdose:

Symptoms: convulsions, impaired consciousness up to coma, lower blood pressure, severe metabolic acidosis, increased severity of 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 the drug from the body is hemodialysis.

Interaction:

Influence of topiramate on other PEPs

Does not affect the concentration of carbamazepine, valproic acid, phenobarbital, primidone. In some cases, when used with phenytoin, an increase in the concentration of phenytoin in the plasma is possible.

The influence of other PEPs on topiramate

With the combined use of topiramate with phenytoin and carbamazepine, a decrease in the concentration of topiramate in plasma is possible. When adding or removing phenytoin or carbamazepine, a dose correction for topiramate is recommended. When receiving other PEP that induce liver enzymes, the maximum concentration decreases (C_m_Oh) topiramate in blood plasma. With simultaneous application valproic acid practically does not affect the concentration of topiramate in plasma - the area under the concentration curve (AUC) Valproic acid is reduced by 11%, topiramate - by 14%.

Interaction with other drugs

Digoxin: AUC digoxin is reduced by 12%.

Oral contraceptives: topiramate in a dose of 50-800 mg / day had no significant effect on the effectiveness of norethindrone and at a dose of 50-200 mg / day - on the efficacy of ethinylestradiol. A significant dose-dependent reduction in the efficacy of ethinylestradiol was observed with the administration of topiramate at a dose of 200-800 mg / day.Thus, with the simultaneous administration of the Epitope with oral contraceptives, the efficacy of the latter can be reduced. Patients taking oral contraceptives should inform the doctor of any changes in the nature of the bleeding.

Metformin: when used simultaneously with the topiramate, the average values of C_m_Oh and AUC metformin increased by 18% and 25%, respectively, while the average value of total clearance is reduced by 20%. Topiramate did not affect the time to reach C_m_Ohmetformin. Plasma clearance of topiramate under the influence of metformin decreases. The clinical significance of the effects of metformin on the pharmacokinetics of topiramate is not clear. When appointing or canceling topiramate against the background of metformin therapy, it is necessary to monitor the state of carbohydrate metabolism.

Hydrochlorothiazide: with simultaneous admission an increase in C_m_Ohof topiramate by 27% and AUC of topiramate by 29%.

Means that depress the central nervous system (CNS): simultaneous administration with ethanol topiramate and other CNS depressant medications is not recommended.

Pioglitazone: decreased AUC pioglitazone by 15%, without change in C_m_Oh preparation.For the active hydroxymetabolite of pioglitazone, a decrease in C_m_Oh and AUC by 13% and 16%, respectively, and for active ketometabolite, a decrease in C_m_Ohand AUC by 60%.

The clinical significance of this data is unknown.

Other means: topiramate, when combined with other drugs predisposing to nephrolithiasis, in particular with inhibitors of carbonic anhydrase (acetazolamide), may increase the risk of nephrolithiasis. When using topiramate, patients should avoid taking such drugs because they may create physiological conditions that increase the risk of kidney stones.

Special instructions:

In patients with a predisposition to nephrourolythiasis, the risk of kidney stones is increased, which requires an adequate increase in the amount of fluid consumed to prevent it.

Effect on the ability to drive transp. cf. and fur:With caution should prescribe the drug to patients engaged in potentially dangerous activities that require increased attention and speed of psychomotor reactions, tk. the drug may cause drowsiness, dizziness.Do not use during work drivers of vehicles and people whose profession is associated with increased concentration of attention.

Form release / dosage:Tablets, film-coated 25 mg, 100 mg.

Packaging:For 10 tablets in PVC / PVDC / PE / Al blister. For 3 blisters together with instructions for use in a cardboard box.

Storage conditions:At a temperature of no higher than 30 ° C. Keep out of the reach of children.

Shelf life:

Three years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:PL-000927

Date of registration:18.10.2011

The owner of the registration certificate:Geroth Pharmacetica GmbHGeroth Pharmacetica GmbH Greece

Manufacturer: & nbsp

GEROT PHARMAZEUTIKA, GmbH Greece

Representation: & nbspHEROTH PHARMACOUTICS GmbHHEROTH PHARMACOUTICS GmbHRussia

Information update date: & nbsp10.09.2015

Illustrated instructions

Instructions

Epitope (Epitope)