ТОПСАВЕР

Active material: Topiramate
When ATH: N03AX11
CCF: Anticonvulsants
ICD-10 codes (testimony): G40
When CSF: 02.05.11
Manufacturer: PLIVA HRVATSKA d.o.o. (Croatia)

DOSAGE FORM, COMPOSITION AND PACKAGING

Pills, Film-coated white, round, lenticular, labeled “TO” on one side and “25” – another.

Excipients: lactose monohydrate, pre-gelatinized starch, partially pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate.

The composition of the shell: gipromelloza, polysorbate 80, talc, Titanium dioxide (E171).

14 PC. – blisters (2) – packs cardboard.

Pills, Film-coated light yellow, round, lenticular, labeled “TO” on one side and “50” – another.

Excipients: lactose monohydrate, pre-gelatinized starch, partially pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate.

The composition of the shell: gipromelloza, polysorbate 80, talc, Titanium dioxide (E171), iron oxide yellow (E172).

14 PC. – blisters (2) – packs cardboard.

Pills, Film-coated yellow color, round biconvex, labeled “TO” on one side and “100” – another.

Excipients: lactose monohydrate, pre-gelatinized starch, partially pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate.

The composition of the shell: gipromelloza, polysorbate 80, talc, Titanium dioxide (E171), iron oxide yellow (E172).

14 PC. – blisters (2) – packs cardboard.

Pills, Film-coated grayish-pink, round, lenticular, labeled “TO” on one side and “200” – another.

Excipients: lactose monohydrate, pre-gelatinized starch, partially pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate.

The composition of the shell: gipromelloza, polysorbate 80, talc, Titanium dioxide (E171), iron oxide red (E172).

7 PC. – blisters (4) – packs cardboard.

Pharmacological action

The antiepileptic drug. Topiramate refers to substituted sulfate monosaharidam. Does sodium channels and suppresses emergence of repetitive action potentials against the backdrop of a prolonged membrane depolarization of the neuron. Increases the activity of GABA in respect of certain subtypes of GABA-a receptors. Prevents the activation of the kainatom subtype sensitivity 60/AMPK (Alpha-amino-3-Hydroxy-5-metilizoksazol-4-propionic acid) ^ receptors, without affecting the activity of N-methyl-D-aspartata (NMDA) against NMDA-receptors. These effects dozozawisima. Besides, topiramate inhibits carbonic anhydrase isoenzymes activity by some. This effect is much weaker, carbonic anhydrase inhibitor than azetazolamida and is not the main component of protivojepilepticheskoj topiramata activity.

Pharmacokinetics

Absorption

Topiramate is quickly absorbed and. Food intake has no clinically significant effect on its bioavailability, which is about 80%. The average value of C_max After repeated intake dose 100 mg 2 times per day is 6.76 ug / ml.

Distribution

Plasma protein binding – 13-17%. Average V_d – 0.55-0.8 l/kg in a single dose to 1.2 g. V_d It depends on gender: in women, these values are 50% from the values, observed in men, that is associated with higher content of fat tissue in women. After a single dose, pharmacokinetics is linear in nature, plasma clearance is constant, The AUC in the range of doses from 100 mg 400 mg increases with the dose. Normal renal function, patients may require 4-8 days to achieve C_ss.

Topiramate enters breast milk.

Metabolism

Metabolised about 20% topiramate. To 50% topiramata metabolized in patients, at the same time receiving other antiepileptic drugs (PEP), inducing enzymes to metabolize. From plasma, human urine and faeces are highlighted 6 almost inactive metabolites topiramata.

Deduction

Unchanged topiramate and its metabolites, primarily, excreted through the kidneys. Plasma clearance is about 20-30 ml / min.

T_1/2 After repeated dose 50 mg 100 mg 2 times per day is 21 no. Effectively eliminated from the blood plasma during hemodialysis.

Pharmacokinetics in special clinical situations

V_d It depends on gender: in women, these values are 50% from the values, observed in men, that is associated with higher content of fat tissue in women.

In patients with impaired renal function (CC < 60 ml / min) reduced plasma and kidney klirens topiramata; in patients with end stage renal failure decreases plasma clearance topiramata.

Plasma clearance topiramata does not change in elderly patients in the absence of violations of kidney function.

Topiramata decreases plasma clearance in patients with moderate and severe violations of the liver.

Pharmacokinetics topiramata in children, as well as in adults, whereby the. Clearance of the drug does not depend on the dose, equilibrium concentration in the plasma increases with the dose. But, for children is characterized by higher values of clearance and a shorter elimination half-life. Hence, topiramata concentration in plasma when receiving the same doses per kg body weight may be lower in children compared to adults.

Testimony

-monotherapy in children with epilepsy 7 years and adults (incl. first established in patients with epilepsy);

— auxiliary therapy in children with 3 years and adults with the ineffectiveness of the PROBE first choice when partial or tonico-klonicakih generalized pripadkah, as well as when pripadkah amid Lennox-Gastaut syndrome.

Dosage regimen

The drug is prescribed inside. Swallow whole tablets, without chewing, take regardless of mealtimes. For optimal control of seizures, It is recommended to begin treatment with low doses, followed by an increase to effective dose.

In the combined therapy

To Adult the minimum effective dose of 200 mg / day. The usual daily dose – 200-400 mg (in 2 admission). The maximum daily dose – 1.6 g. Treatment starts with 25-50 mg daily at night for 1 of the week. Thereafter, the dosage is increased by 25-50 mg / day for 1-2 weeks, with multiplicity of admission 2 times / day. In rejecting such a dosage, increase the dose or less through large intervals. Dose and frequency reception picked depending on clinical effect.

Children over 3 years The recommended daily dose is 5-9 mg / kg body weight, razdelennaya of 2 admission. Treatment is initiated with a dose of 25 mg at night for 1 of the week. Thereafter, the dosage is increased by 1 -3 mg / kg / day for 1-2 weeks, with multiplicity of admission 2 times / day, to achieve an optimal clinical effect.

Monotherapy

Adults treatment is initiated with 25 mg at night for 1 of the week. Thereafter, the dosage is increased by 25-50 mg / day for 1-2 weeks, with multiplicity of admission 2 times / day. In rejecting such a dosage, increase the dose or take less through large intervals. Dose and frequency reception picked depending on clinical effect. The recommended initial dose topiramata for monotherapy in adults with for the first time established epilepsy is 100 mg / day, the maximum recommended dose – 500 mg / day. These doses are recommended for all adults, including seniors with normal renal function.

In children 7 and older treatment is initiated with dosages 0.5-1 mg/kg body weight overnight throughout 1 of the week. Thereafter, the dosage is increased by 0.5-1 mg/kg/day for 1-2 weeks, the multiplicity of reception – 2 times / day. In rejecting such a dosage, increase the dose or less through large intervals. Dose and frequency reception picked depending on clinical effect. The recommended dose range 3-6 mg / kg body weight. Babies with recently established by parcialnymi torments You can assign up to 500 mg / day.

Side effect

CNS: hypererethism, dizziness, headache, speech and vision, psychomotor retardation, ataxia, fatiguability, difficulty concentrating, confusion, paraesthesia, drowsiness, thought disorders, diplopia, anorexia, nistagmo, depression, perversion of taste sensations, excitation, cognitive abnormality, emotional lability, apathy, psychotic symptoms, violent behavior, suicidal ideation or attempts; additional children – personality disorders, increased salivation, giperkineziya, hallucinations.

From the digestive system: dyspepsia, nausea, abdominal pain, diarrhea, xerochilia, increase in liver transaminases, hepatitis, hepatic failure.

On the part of the organ of vision: myopia syndrome may occur against a background of increased intraocular pressure with a sharp decrease in visual acuity and pain in the eye. Myopia, reducing the depth of the anterior chamber of the eye, hyperemia of the mucous membrane of the eye and increased intraocular pressure, midriaz. A possible mechanism is the increase in data breaches supratsiliarnogo effusion, which leads to the forward shift of the lens and the iris, and as a consequence – the development of a secondary angle-closure glaucoma.

Dermatological reactions: erythema multiforme, pemphigus, Stevens-Johnson syndrome and toksičeskij épidermalʹnyj necrolysis.

Other: weight loss, leukopenia, nephrolithiasis, oligogidroz (mainly in children), metabolic acidosis.

Contraindications

- Children under 3 years;

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to any component of the drug.

FROM caution should be prescribed in patients with renal or hepatic insufficiency, nefrourolitiaze (incl. history), hypercalciuria.

Pregnancy and lactation

The drug is contraindicated in pregnancy and lactation (breast-feeding).

Cautions

Before the drug is recommended for women to use adequate contraception.

Topiramate, as well as other AEDs, it is recommended to cancel, gradually reducing the dose, to reduce the potential risk of increased frequency of seizures.

Patients with kidney failure moderate or severe it may be necessary 10-15 days to reach an equilibrium concentration in the plasma, in contrast to 4-8 days for patients with normal renal function. Like all patients, a gradual increase in dose should be administered in accordance with the clinical results (such as the control of seizures, the incidence of adverse effects), considering, that patients with renal failure secondary to severe may require a longer time to reach steady-state after each dose.

Some patients, especially predisposed to nephrolithiasis, may increase the risk of forming kidney stones, accompanied by symptoms such as renal colic, flank pain and kidney in. It is recommended that adequate hydration to reduce the risk of kidney stones.

In patients with impaired liver clearance of topiramate is reduced.

In the development of myopia, We recommend that you cancel the topiramate as fast, as clinically possible and take action, aimed at reducing intraocular pressure.

When applying topiramata may occur giperhloremicheskij, not associated with deficiency of anions, metabolic acidosis (eg, reduction of the concentration of hydrocarbons in the plasma below normal levels in the absence of respiratory alkalosis). This decrease of the concentration of serum hydrocarbonate is a consequence of inhibiting effect on kidney topiramata carbonic anhydrase. Concerning, When treating topiramatom periodically to determine the concentration of hydrocarbons in the serum.

With the decrease in body weight during therapy topiramatom be useful to consider the possibility of appointing additional food.

Effects on ability to drive vehicles and management mechanisms

During treatment advised to refrain from driving and work requiring high concentration and psychomotor speed reactions.

Overdose

Symptoms: convulsions, impairment of consciousness up to coma, lowering blood pressure, severe metabolic acidosis, increased severity of side effects.

Treatment: gastric lavage, administration of activated charcoal, simptomaticheskaya therapy, hemodialysis.

Drug Interactions

Influence on other PROBE topiramata

Does not affect the concentrations of carbamazepine, valproic acid, fenoʙarʙitala, prymydona. In some cases,, When applying with phenytoin, perhaps increasing the concentration fenitoina plasma.

The influence of other PROBES on topiramate

When coupled with topiramata phenytoin and carbamazepine may reduce concentration in plasma topiramata. When adding or canceling fenitoin or carbamazepine dose adjustment is recommended topiramata.

When taking other PROBES, inducing liver enzymes, reduced C_max topiramata in plasma.

Interaction with other drugs

When coupled with topiramatom AUC of Digoxin is reduced by 12%.

Topiramate dose 50-800 mg/day had no significant impact on the effectiveness of norethindrone and dose 50-200 mg / day – on the effectiveness of ethinyl estradiol. Significant dose-related decrease in the effectiveness of ethinyl estradiol were observed when taking topiramata in dose 200-800 mg / day. Patients, taking oral contraceptives, must inform the doctor about any changes in the nature of bleeding.

Together with the use of topiramatom averages (C)_max and AUC of metformin increases the 18% and 25% respectively, While the average value of the total clearance decreases by 20%. Topiramate had no impact on TC_makh metformin. Plasma clearance topiramata under the influence of metformin decreases. The clinical significance of the effects of metformin on farmakokinetiku topiramata not clear. In appointing or revoking topiramata on metformin therapy, it was necessary to monitor the State of carbohydrate metabolism.

Together with the admission of hydrochlorothiazide, increase C_max on 27% and AUC topiramata 29%.

Not recommended Simultaneous with topiramatom ethanol and other means, CNS depressants.

Revealed a decrease AUC pioglitazon on 15%, without changing C_max topiramate. For active gidroksimetabolita pioglitazon decrease C_max and AUC of 13% and 16% respectively, and for active decrease ketometabolita and C_max, and AUC of 60%. The clinical significance of these data is unknown.

Topiramate, When used together with other drugs, predisposing to nephrolithiasis, in particular, carbonic anhydrase inhibitors (aцetazolamid) may increase the risk of nefrolitiaza. While using topiramata patients should avoid receiving these drugs, because they can create physiological conditions, increase the risk of forming kidney stones.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 3 year.