Maxitopyr - instructions for use, doses, side effects, contraindications

Excipients: mannitol 37.81 mg, pregelatinized starch 8.55-mg, microcrystalline cellulose 19 mg, croscarmellose sodium 2.85 mg, silicon dioxide colloid 0.36 mg, magnesium stearate 1.43 mg, opedrai II white dye 85F18422 3.8 mg (alcohol polyvinyl, titanium dioxide, macrogol 3350, talc).

1 tablet, film-coated, 50 mg contains:

active substance: topiramate 50 mg;

Excipients: mannitol 75.64 mg, pregelatinized starch 17.1 mg, microcrystalline cellulose 38 mg, croscarmellose sodium 7 mg, silicon dioxide colloid 0.71 mg, magnesium stearate 2.85 mg, opedrai II yellow dye 85G32312 7.6 mg (polyvinyl alcohol , talc, titanium dioxide, macrogol 3350, soy lecithin E322, iron oxide yellow E172).

1 tablet, film-coated, 100 mg contains:

active substance: topiramate 100 mg;

Excipients: mannitol 151.28 mg, starch re-gelatinized 34.2 mg, cellulose microcrystalline 76 mg, croscarmellose sodium l1.4 mg, silicon dioxide colloid 1.42 mg, magnesium stearate 5.7 mg,dye opedrai II yellow 85G32313 15.2 mg (polyvinyl alcohol, talc, titanium dioxide, macrogol 3350, iron oxide yellow E172, soy lecithin E322).

1 tablet, film-coated, 200 mg contains:

active substance: topiramate 200 mg;

Excipients: mannitol 302.55 mg, pre-gelatinized starch 68.4 mg, microcrystalline cellulose 152 mg, croscarmellose sodium 22.8 mg, silicon dioxide colloid 2.85 mg, magnesium stearate 11.4 mg, colorless opadrai II pink 85G34776 (polyvinyl alcohol, talcum powder , titanium dioxide, macrogol 3350, soy lecithin E322, iron oxide red E172).

Description:

Tablets 25 mg: Round biconvex tablets covered with a film shell, white with the inscription "V1" on one side;

Tablets 50 mg: Round biconvex tablets covered with a film coating, light yellow color with the inscription "V3" on one side;

Tablets 100 mg: Round biconvex tablets covered with a film membrane, yellow with the inscription "V4" on one side;

Tablets 200 mg: Oval biconvex tablets covered with a film membrane, brownish-pink color with the inscription "V5" on one side.

Pharmacotherapeutic group:Antiepileptic remedy

ATX: & nbsp

N.03.A.X Other antiepileptic drugs

N.03.A.X.11 Topiramate

Pharmacodynamics:Topiramate refers to sulfate-substituted monosaccharides. It blocks sodium channels and suppresses the appearance of action potentials against the background of a prolonged depolarization of the neuron membrane. Increases the activity of γ-aminobutyric acid (GABA) against certain subtypes of GABA receptors. Prevents the activation of kainate by the sensitivity of the kainate / AMPK subtype (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptors to glutamate, without affecting NMDA receptor activity of N-methyl-D-aspartate (NMDA) -. These effects are dose-dependent, In addition, topiramate inhibits the activity of certain isoenzymes of carbonic anhydrase. This effect is much weaker than that of the acetoazolamide carbonic anhydride inhibitor and is not the main component of the antiepileptic activity of topiramate.

Pharmacokinetics:

Topiramate is quickly and well absorbed. Eating 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 the sex: in women, these values are 50% of the values observed in men, which is associated with a higher content of adipose tissue in women.Presumably penetrates into breast milk. About 20% of the topiramate is metabolized. Up to 50% of topiramate is metabolized in patients taking other antiepileptic drugs (PEP) simultaneously, inducing metabolic enzymes. Of the plasma, urine and human feces, six practically inactive metabolites of topiramate were isolated. Unaltered topiramate and its metabolites are mainly excreted through the kidneys. Plasma clearance is about 20-30 ml / min.

After a single dose, the pharmacokinetics is linear, the plasma clearance is constant, and the area under the concentration / time curve in the dosage range of 100 to 400 mg increases in proportion to the dose. With normal kidney function, patients may need 4-8 days to achieve an equilibrium plasma concentration. The average value of the maximum concentration after repeated intake of 100 mg of topiramate twice a day is 6.76 μg / 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), the plasma and renal clearance of topiramate decreases; in patients with the final stage of renal failure, the plasma clearance of topiramate decreases.Plasma clearance of topiramate does not change in elderly patients in the absence of renal dysfunction. Plasma clearance of topiramate is reduced in patients with moderate and severe impairment of liver function.

The 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 are characterized by higher clearance values and a shorter half-life. Therefore, 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. As in adults, when taking other PEPs that induce liver enzymes, the equilibrium concentration of topiramate in the blood plasma decreases.

Topiramate is effectively excreted from the blood plasma during hemodialysis.

Indications:

- Monotherapy of epilepsy in children from 3 years old and adults (including patients with newly established epilepsy);

- Auxiliary therapy in children from 3 years of age and adults with inadequate PEP effectiveness of the first choice of partial or generalized tonic-clonic seizures, as well as seizures with Lennox-Gastaut syndrome.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- Children up to 3 years;

- Pregnancy and lactation.

Carefully:Hepatic or renal failure, nephrourolythiasis (including past or family history), hypercalciuria.

Dosing and Administration:

Are common

Inside, swallowing the pill entirely without chewing, Regardless of the meal. For optimal control of seizures, it is recommended to begin treatment with low doses with subsequent increase to an effective dose.

As part of complex therapy

Adults: minimum effective dose of 200 mg / day. The usual daily dose of 200-400 mg (for 2 admission). The maximum daily dose is 1600 mg. Treatment begins with 25-50 mg daily for the night for 1 week. Then the dose is increased by 25-50 mg per day for 1-2 weeks, with a frequency of reception 2 times a day. If this dosage regimen is necessary, the dose is increased by a smaller amount or at large intervals. The dose and the frequency of reception are selected depending on the clinical effect.

Children over 3 years: the recommended daily dose is 5-9 mg / kg body weight, divided into 2 doses. Treatment begins with a dose of 25 mg per night for 1 week.

Then the dose is increased by 1-3 mg / kg / day for 1-2 weeks, with the frequency of reception 2 times a day, until the optimal clinical effect is achieved.

Monotherapy

Adults: treatment is started with 25 mg per night for 1 week. Then the dose is increased by 25-50 mg per day for 1-2 weeks, with a frequency of reception 2 times a day. If this dosage regimen is intolerant, the dose is increased by a smaller amount or at large intervals. The dose and the frequency of reception are selected depending on the clinical effect. The recommended initial dose of topiramate for monotherapy in adults with newly established epilepsy is 100 mg / day, the maximum recommended dose is 500 mg / day. These doses are recommended for all adults, including the elderly with normal kidney function.

Children from 3 years: treatment is started with a dose of 0.5-1 mg / kg 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 reception is 2 times a day. If this dosage regimen is intolerant, the dose is increased by a smaller amount or at large intervals. The dose and the frequency of reception are selected depending on the clinical effect. The recommended dose range is 3-6 mg / kg body weight. Children with newly established partial seizures can be prescribed up to 500 mg per day.

In 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:

Neurological and psychiatric disorders: Increased excitability, dizziness, headache, speech and vision impairment, psychomotor inhibition, ataxia, fatigue, difficulty concentrating, confusion, paresthesia, drowsiness, thinking disorders, diplopia, anorexia, nystagmus, depression, perversion of taste sensations, arousal, cognitive disorders , emotional lability, apathy, psychotic symptoms, aggressive behavior, suicidal ideation or attempts; In addition, in children - personality disorders, increased salivation, hyperkinesia, hallucinations.

Gastrointestinal disorders: 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 myopia syndrome on the background of increased intraocular pressure with acute reduction 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 eudhotia, which leads to a shift in the lens and iris and, as a consequence, 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.

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 was shown that it does not adsorb topiramate. An effective way to remove topiramate from the body is hemodialysis.

Interaction:

Influence of topiramate on other PEPs

Does not affect the concentrations 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, i.e. When adding or removing phenytoin or carbamazepine, a dose correction for topiramate is recommended.

Other interactions

Digoxin: the area under the pharmacological curve of 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. Patients taking oral contraceptives should inform the doctor of any changes in the nature of the bleeding.

Metformin: When used simultaneously with topiramate, the mean values of the maximum concentration and area under the concentration curvemetformin increased by 18% and 25%, respectively, while the average value of total clearance is reduced by 20%. Topiramate did not affect the time to achieve C_max 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. With the value or elimination of topiramate against the background of metformin therapy, it is necessary to monitor the state of carbohydrate metabolism.

Hydrochlorothiazide: with simultaneous administration, the maximum concentration of topiramate is increased by 27% and the area under the curve of the concentration of topiramate is 29%.

Means that depress the central nervous system (CNS): simultaneous administration with ethanol topiramate and other CNS depressant medications is not recommended. Pioglitazone: a decrease in the area under the curve of the concentration of pioglitazone by 15%, without changing the maximum concentration of the drug. For active pioglitazone hydroxymetabol, the maximum concentration and area under the concentration curve decreased by 13% and 16%, respectively, and the active ketometabolite showed a decrease in both the maximum concentration and the area under the curveconcentration 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, as they can create physiological conditions that increase the risk of kidney stones.

With simultaneous application with valproic acid, the area under the concentration curve of valproic acid decreases by 11%, topiramate by 14%.

Special instructions:

When taking the drug, women are recommended to use adequate contraception, Topiramate, like other PEPs, it is recommended to cancel, gradually reducing the dose, to reduce the potential risk of increasing the frequency of seizures.

Renal failure: Patients with mild to severe renal impairment may need 10-15 days to achieve a steady state plasma concentration, unlike 4-8 days for patients with normal renal function.As with all patients, a gradual increase in dose should be consistent with clinical outcomes (such as seizure control, the incidence of side effects), given that patients with moderate or severe renal failure may need more time to reach a stable state after each dose.

Nephrolithiasis: In some patients, especially those prone to nephrolithiasis, the risk of kidney stones may increase, accompanied by symptoms such as renal colic, lateral pain, and kidney problems. It is recommended to conduct adequate hydration to reduce the risk of kidney stones. Hepatic insufficiency: in patients with impaired liver function, the clearance of topiramate is reduced.

Myopathy and secondary closed angle glaucoma: with the development of myopia, it is recommended to cancel topiramate as quickly as clinically possible and take measures aimed at reducing intraocular pressure.

Metabolic acidosis: when using topiramate, hyperchloremic, not associated with an anion deficiency, metabolic acidosis (eg, a decrease in the bicarbonate concentration in the plasma below the normal level in the absence of respiratory alkalosis) may occur.This decrease in serum bicarbonate concentration is a consequence of the inhibitory effect of topiramate on renal carboanhydrase. In this regard, in the treatment of 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 appointing supplementary nutrition.

Effect on the ability to drive transp. cf. and fur:During treatment it is recommended to abstain from driving a car and works requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Film coated tablets 25 mg, 50 mg, 100 mg and 200 mg.

Packaging:10 tablets per strips of aluminum foil (A1 / -A1); 10, 50, 60, 100 or 200 tablets in high pressure polyethylene or low pressure polyethylene containers with a low pressure polyethylene lid with a desiccant (activated silica gel) placed in a plastic container of high pressure polyethylene. 1 strip or 1 container with instructions for use is placed in a cardboard box.

Storage conditions:At a temperature of no higher than 25 ° C.Keep out of the reach of children!

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001044/08

Date of registration:26.02.2008 / 17.11.2009

Expiration Date:Unlimited

The owner of the registration certificate:Aktavis, AOAktavis, AO Iceland

Manufacturer: & nbsp

ACTAVIS, Ltd. Iceland

Representation: & nbspAktavis, Open Company Aktavis, Open Company

Information update date: & nbsp29.03.2018

Illustrated instructions

Instructions

Maxitopyr® (Maxitopir®)