Topsaver tablets p / o 50mg, No. 28

- monotherapy of epilepsy in children from 7 years of age and adults (including patients with newly diagnosed epilepsy);

- auxiliary therapy in children from 3 years of age and in adults with insufficient effectiveness of the first choice AED in partial or generalized tonic-clonic seizures, as well as in seizures against the background of Lennox-Gastaut syndrome.

Dosage and administration
General
Inside, swallowing the whole tablet without chewing, regardless of food intake. For optimal seizure control, it is recommended that treatment be started at low doses and then increased to the effective dose.
As part of complex therapy
Adults: the minimum effective dose is 200 mg / day. The usual daily dose is 200-400 mg (for 2 doses). The maximum daily dose is 1600 mg. Treatment begins with 25-50 mg daily at night for 1 week. Then the dose is increased by 25-50 mg per day for 1-2 weeks, with a frequency of administration 2 times a day. If such a dosage regimen is intolerant, the dose is increased by a smaller amount or at longer intervals. The dose and frequency of administration are selected depending on the clinical effect.
Children over 3 years old:the recommended daily dose is 5-9 mg / kg of body weight, divided into 2 doses. Treatment begins with a dose of 25 mg at night for 1 week. Then the dose is increased by 1-3 mg / kg / day for 1-2 weeks, with a frequency of 2 times a day, until the optimal clinical effect is achieved.
Monotherapy
Adults: Treatment begins with 25 mg at night for 1 week. Then the dose is increased by 25-50 mg per day for 1-2 weeks, with a frequency of administration 2 times a day. If such a dosage regimen is intolerant, the dose is increased by a smaller amount or at longer intervals. The dose and frequency of administration are selected depending on the clinical effect. The recommended starting dose of topiramate for monotherapy in adults with newly diagnosed epilepsy is 100 mg / day, and the maximum recommended dose is 500 mg / day. These doses are recommended for all adults, including the elderly, with normal renal function.
Children from 7 years old:treatment begins with a dose of 0.5-1 mg / kg of body weight at night for 1 week. Then the dose is increased by 0.5-1 mg / kg / day for 1-2 weeks, the frequency of administration is 2 times a day. If such a dosage regimen is intolerant, the dose is increased by a smaller amount or at longer intervals. The dose and frequency of administration are selected depending on the clinical effect. The recommended dose range is 3-6 mg / kg body weight. Children with recently established partial seizures can be prescribed up to 500 mg per day.

Each tablet of 50 mg contains: active substance - topiramate 50 mg; auxiliary substances - lactose monohydrate, pregelatinized starch, partially pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate, shell - hypromellose, polysorbate 80, talc, titanium dioxide (E171), iron dye yellow oxide (E172);

- hypersensitivity to any component of the drug;

- children's age up to 3 years;

- pregnancy and lactation.

With caution: renal or hepatic failure, nephrourolithiasis (including past or family history), hypercalciuria.

Drug name:

Topsaver

International non-proprietary name:

topiramate

Dosage form:

film-coated tablets

Composition:

Each 25mg tablet contains: and the active substance - topiramate 25mg; auxiliary substances - lactose monohydrate, pregelatinized starch, partially pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate, shell - hypromellose, polysorbate17 80, taloxide (taloxide) (
Each tablet of 50 mg contains: active substance - topiramate 50 mg; auxiliary substances - lactose monohydrate, pregelatinized starch, partially pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate, shell- hypromellose, polysorbate 80, talc, titanium dioxide (E171), iron dye yellow oxide (E172);
Each 100 mg tablet contains: the active substance is topiramate 100 mg; excipients - lactose monohydrate, pregelatinized starch, partially pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate, shell - hypromellose, polysorbate 80, talc, titanium dioxide (E171), iron oxide yellow (E172);
Each 200 mg tablet contains: active substance - 200 mg of topiramate, excipients:lactose monohydrate, pregelatinized starch, partially pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate, shell - hypromellose, polysorbate 80, talc, titanium dioxide (E171), iron oxide red (E172);

Description:
Tablets 25 mg: white, round, biconvex film-coated tablets marked 'TO' on one side and '25' on the other.
Tablets 50 mg: light yellow, round, biconvex film-coated tablets, marked 'TO' on one side and '50' on the other.
Tablets 100 mg: yellow, round, biconvex film-coated tablets marked 'TO' on one side and '100' on the other.
Tablets 200 mg: grayish pink, round, biconvex film-coated tablets marked 'TO' on one side and '200' on the other.

Pharmacotherapeutic group:

antiepileptic drug

Pharmacological properties
Pharmacodynamic.
Topiramate refers to sulfate-substituted monosaccharides. Blocks sodium channels and suppresses the occurrence of repeated action potentials against the background of prolonged depolarization of the neuron membrane. Increases the activity of gamma-aminobutyric acid (GABA) against some subtypes of GABA receptors. Prevents kainate from activating the sensitivity of the kainate / AMPK subtype (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptors to glutamate, without affecting the activity of N-methyl-D-aspartate (NMDA) towards NMDA receptors ... These effects are dose-dependent. In addition, topiramate inhibits the activity of some isoenzymes of carbonic anhydrase. This effect is significantly weaker than that of the carbonic anhydrase inhibitor acetazolamide and is not the main component of the antiepileptic activity of topiramate.

Pharmacokinetics.
Topiramate is rapidly and well absorbed. Food intake does not have a clinically significant effect on its bioavailability, which is about 80%. The connection with plasma proteins is 13-17%. The average volume of distribution is 0.55-0.8 l / kg for a single dose up to 1200 mg. This indicator depends on gender; in women, these values ??are 50% of the values ??observed in men, which is associated with a higher content of adipose tissue in women. About 20% of topiramate is metabolized. Up to 50% of topiramate is metabolized in patients who are simultaneously taking other antiepileptic drugs (AEDs) that induce metabolizing enzymes. Six practically inactive metabolites of topiramate have been isolated from human plasma, urine and feces. Unchanged topiramate and its metabolites are mainly excreted through the kidneys. Plasma clearance is about 20-30 ml / min.After a single dose, pharmacokinetics are linear, plasma clearance is constant, and the area under the concentration / time curve in the dose range from 100 to 400 mg increases in proportion to the dose. With normal renal function, patients may need 4-8 days to reach equilibrium plasma concentrations. The average value of the maximum concentration after repeated oral administration of 100 mg of topiramate twice a day is 6.76 ?g / ml. The half-life after repeated administration of 50 and 100 mg twice a day is 21 hours. In patients with impaired renal function (creatinine clearance <60 ml / min), plasma and renal clearance of topiramate decreases; in patients with end-stage renal failure, plasma clearance of topiramate decreases.Plasma clearance of topiramate does not change in elderly patients in the absence of impaired renal function. Plasma clearance of topiramate is reduced in patients with moderate to severe hepatic impairment. Pharmacokinetics of topiramate in children, as well as in adults, is linear. The clearance of the drug does not depend on the dose, the equilibrium concentration in the blood plasma increases in proportion to the dose. However, children have higher clearance values ??and a shorter half-life. Consequently, the concentration of topiramate in blood plasma when taking the same doses per kg of body weight may be lower in children than in adults. Topiramate is effectively eliminated from blood plasma during hemodialysis. Presumably passes into breast milk.Plasma clearance of topiramate is reduced in patients with moderate to severe hepatic impairment. Pharmacokinetics of topiramate in children, as well as in adults, is linear. The clearance of the drug does not depend on the dose, the equilibrium concentration in the blood plasma increases in proportion to the dose. However, children have higher clearance values ??and a shorter half-life. Consequently, the concentration of topiramate in blood plasma when taking the same doses per kg of body weight may be lower in children than in adults. Topiramate is effectively eliminated from blood plasma during hemodialysis. Presumably passes into breast milk.Plasma clearance of topiramate is reduced in patients with moderate to severe hepatic impairment. Pharmacokinetics of topiramate in children, as well as in adults, is linear. The clearance of the drug does not depend on the dose, the equilibrium concentration in the blood plasma increases in proportion to the dose. However, children have higher clearance values ??and a shorter half-life. Consequently, the concentration of topiramate in the blood plasma when taking the same doses per kg of body weight may be lower in children than in adults. Topiramate is effectively eliminated from blood plasma during hemodialysis. Presumably passes into breast milk.the equilibrium concentration in blood plasma increases in proportion to the dose. However, children have higher clearance values ??and a shorter half-life. Consequently, the concentration of topiramate in the blood plasma when taking the same doses per kg of body weight may be lower in children than in adults. Topiramate is effectively eliminated from blood plasma during hemodialysis. Presumably passes into breast milk.the equilibrium concentration in blood plasma increases in proportion to the dose. However, children have higher clearance values ??and a shorter half-life. Consequently, the concentration of topiramate in blood plasma when taking the same doses per kg of body weight may be lower in children than in adults. Topiramate is effectively eliminated from blood plasma during hemodialysis. Presumably passes into breast milk.

Indications for use

- monotherapy of epilepsy in children from 7 years of age and adults (including patients with newly diagnosed epilepsy);

- auxiliary therapy in children from 3 years of age and in adults with insufficient effectiveness of the first choice AED in partial or generalized tonic-clonic seizures, as well as in seizures against the background of Lennox-Gastaut syndrome.

Contraindications

- hypersensitivity to any component of the drug;

- children's age up to 3 years;

- pregnancy and lactation.

With caution: renal or hepatic failure, nephrourolithiasis (including past or family history), hypercalciuria.

Dosage and administration
General
Inside, swallowing the whole tablet without chewing, regardless of food intake. For optimal seizure control, it is recommended that treatment be started at low doses and then increased to the effective dose.
As part of complex therapy
Adults: the minimum effective dose is 200 mg / day. The usual daily dose is 200-400 mg (for 2 doses). The maximum daily dose is 1600 mg. Treatment begins with 25-50 mg daily at night for 1 week. Then the dose is increased by 25-50 mg per day for 1-2 weeks, with a frequency of administration 2 times a day. If such a dosage regimen is intolerant, the dose is increased by a smaller amount or at longer intervals. The dose and frequency of administration are selected depending on the clinical effect.
Children over 3 years old:the recommended daily dose is 5-9 mg / kg of body weight, divided into 2 doses. Treatment begins with a dose of 25 mg at night for 1 week. Then the dose is increased by 1-3 mg / kg / day for 1-2 weeks, with a frequency of 2 times a day, until the optimal clinical effect is achieved.
Monotherapy
Adults: Treatment begins with 25 mg at night for 1 week. Then the dose is increased by 25-50 mg per day for 1-2 weeks, with a frequency of administration 2 times a day. If such a dosage regimen is intolerant, the dose is increased by a smaller amount or at longer intervals. The dose and frequency of administration are selected depending on the clinical effect. The recommended starting dose of topiramate for monotherapy in adults with newly diagnosed epilepsy is 100 mg / day, and the maximum recommended dose is 500 mg / day. These doses are recommended for all adults, including the elderly, with normal renal function.
Children from 7 years old:treatment begins with a dose of 0.5-1 mg / kg of body weight at night for 1 week. Then the dose is increased by 0.5-1 mg / kg / day for 1-2 weeks, the frequency of administration is 2 times a day. If such a dosage regimen is intolerant, the dose is increased by a smaller amount or at longer intervals. The dose and frequency of administration are selected depending on the clinical effect. The recommended dose range is 3-6 mg / kg body weight. Children with recently established partial seizures can be prescribed up to 500 mg per day.

Side effect
Neurological and mental disorders: increased excitability, dizziness, headache, speech and vision disorders, psychomotor retardation, ataxia, fatigue, difficulty concentrating, confusion, paresthesia, drowsiness, thinking disorders, diplopia, anorexia, nystagmus, depression, perversion taste sensations, agitation, cognitive impairment, emotional lability, apathy, psychotic symptoms, aggressive behavior, suicidal ideation or attempts; additionally in children - personality disorders, increased salivation, hyperkinesia, hallucinations.
Gastrointestinal Disorders:dyspeptic symptoms, nausea, abdominal pain, diarrhea, dry lips, increased activity of 'liver' transaminases, hepatitis, liver failure.
From the side of the eyes: the occurrence of myopia syndrome is possible against the background of an increase in intraocular pressure with an acute decrease in visual acuity and pain in the eye area. 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, mydriasis. A possible mechanism of these disorders is an increase in supraciliary effusion, which leads to anterior displacement of the lens and iris and, as a consequence, the development of secondary angle-closure glaucoma.
On the part of the skin and mucous membranes: erythema multiforme, pemphigus, Stevens-Johnson syndrome and toxic epidermal necrolysis
Others: weight loss, leukopenia, nephrolithiasis, oligohydrosis (mainly in children), metabolic acidosis.

Overdose
Symptoms: convulsions, impaired consciousness up to coma, decreased blood pressure, severe metabolic acidosis, increased severity of side effects.
Treatment: gastric lavage, intake of activated charcoal, symptomatic therapy, hemodialysis.

Interaction with other medicinal products
Effect of topiramate on other AEDs Does not affect the concentration of carbamazepine, valproic acid, phenobarbital, primidone. In some cases, when used with phenytoin, it is possible to increase the concentration of phenytoin in plasma.
Influence of other AEDs on topiramate With the combined use of topiramate with phenytoin and carbamazepine, it is possible to reduce the plasma concentration of topiramate, i.e. when adding or canceling phenytoin or carbamazepine, a dose adjustment of topiramate is recommended.
When taking other AEDs that induce liver enzymes, the maximum concentration of topiramate in the blood plasma decreases.
Other interactions
Digoxin: The AUC (area under the concentration-time curve) of digoxin is reduced by 12%.
Oral contraceptives: Topiramate at a dose of 50-800 mg / day had no significant effect on the efficacy of norethindrone and at a dose of 50-200 mg / day on the efficacy of ethinyl estradiol. A significant dose-dependent decrease in the effectiveness of ethinylestradiol was observed with topiramate at a dose of 200-800 mg / day. Patients taking oral contraceptives should inform their doctor about any changes in bleeding patterns.
Metformin: When used simultaneously with topiramate, the mean values ??of the maximum concentration and AUC (area under the concentration-time curve) of metformin increase by 18% and 25%, respectively, while the mean value of total clearance decreases by 20%. Topiramate had no effect on the time to reach TS metformin. 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 prescribing or canceling topiramate against the background of metformin therapy, it is necessary to monitor the state of carbohydrate metabolism. Hydrochlorothiazide: when taken simultaneously, there is an increase in the maximum concentration of topiramate by 27% and the AUC (area under the concentration-time curve) of topiramate by 29%.
Drugs that depress the central nervous system (CNS): it is not recommended to take ethanol and other drugs that depress the central nervous system with topiramate. Pioglitazone: a 15% decrease in the AUC (area under the concentration-time curve) of pioglitazone was detected, without changing the maximum concentration of the drug. For the active hydroxymetabolite pioglitazone, a decrease in the maximum concentration and the area under the concentration curve by 13% and 16%, respectively, was revealed, and for the active ketometabolite, a decrease in both the maximum concentration and AUC (area under the concentration-time curve) by 60% was revealed. The clinical relevance of these findings is unknown. Other drugs: topiramate, when used together with other drugs that predispose to nephrolithiasis, in particular with carbonic anhydrase inhibitors (acetazolamide), may increase the risk of nephrolithiasis.While using topiramate, patients should avoid taking such drugs, as they can create physiological conditions that increase the risk of kidney stones.

Special instructions
When taking the drug, women are advised to use adequate contraception. Topiramate, like other AEDs, is recommended to be discontinued with a gradual dose reduction to reduce the potential risk of increased seizure frequency.
Renal failure:Patients with moderate to severe renal impairment may take 10-15 days to reach an equilibrium plasma concentration, as opposed to 4-8 days for patients with normal renal function. As with all patients, gradual dose escalation should be carried out according to clinical outcomes (such as seizure control, frequency of side effects), given that patients with moderate to severe renal impairment may take longer to reach a steady state after each dose.
Nephrolithiasis:in some patients, especially those who are prone to nephrolithiasis, the risk of formation of kidney stones may increase, accompanied by symptoms such as renal colic, pain in the side and in the region of the kidney. Adequate hydration is recommended to reduce the risk of kidney stones.
Hepatic impairment: in patients with impaired liver function, the clearance of topiramate is reduced.
Myopia and secondary angle-closure glaucoma: If myopia develops, it is recommended to discontinue topiramate as quickly as clinically possible and take measures to reduce intraocular pressure.
Metabolic acidosis:when using topiramate, hyperchloremic, not associated with anion deficiency, metabolic acidosis may occur (for example, a decrease in the concentration of bicarbonates in plasma below normal levels in the absence of respiratory alkalosis). This decrease in the concentration of blood serum bicarbonates is a consequence of the inhibitory effect of topiramate on renal carbonic anhydrase. In this regard, when treating with topiramate, it is recommended to periodically determine the concentration of bicarbonates in the blood serum.
Diet: with a decrease in body weight during therapy with topiramate, it is advisable to consider the possibility of prescribing additional nutrition.
During treatment, it is recommended to refrain from driving and work requiring increased concentration of attention and speed of psychomotor reactions.

Release form
Tablets 25 mg, 50 mg. 100 mg:
14 tablets in blister of oriented polyamide / aluminum foil / PVC / aluminum foil. 2 blisters with instructions for use in a cardboard box.
Tablets 200 mg:
7 tablets each in a blister of oriented polyamide / aluminum foil / PVC / aluminum foil. 4 blisters with instructions for use in a cardboard box.

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

Storage conditions
List B. At a temperature not higher than 25 ? C.
Keep out of the reach of children.

Terms of dispensing from pharmacies
Prescription.