Topiramate-Teva - instructions for use, dose, side effects, contraindications

1 tablet contains: active substance topiramate 25.0 / 50.0 / 100.0 / 200.0 mg; Excipients: lactose monohydrate 30.00 / 22.25 / 44.50 / 89.00 mg; starch corn pregelatinized 15.00 / 11.00 / 22.00 / 44.00 mg; cellulose microcrystalline 25.50 / 12.25 / 24.50 / 49.00 mg; sodium carboxymethyl starch (type A) 3.00 / 3.00 / 6.00 / 12.00 mg; Silica colloidal dioxide 0.50 / 0.50 / 1.00 / 2.00 mg; magnesium stearate 1.00 / 1.00 / 2.00 / 4.00 mg; shell Opadry OYGM-28900 white / Opadrai II 85F22055 yellow / Opadrai II45F22481 yellow / Opadrai II45F24512 pink. Shell Opadry OYGM white: polydextrose 0.938 mg; hypromellose (E464) 0.938 mg; titanium dioxide (E171) 0.938 mg; Macrogol-4000 0.188 mg.

The shell of Opadrij II 85F22055 yellow: polyvinyl alcohol partially hydrolyzed 1,200 mg; titanium dioxide (E171) 0.725 mg; macrogol-3350 0.606 mg; talc 0.444 mg; ferric iron oxide yellow (E172) 0.026 mg.

The shell of Opadrij II 45F22481 yellow: polydextrose 1,875 mg; hypromellose (E464) 1.875 mg; titanium dioxide (E171) 1.549 mg; Macrogol-4000 0.375 mg; ferric iron oxide yellow (E172) 0.325 mg; ferric oxide black oxide (E172) 0.0012 mg. The shell of Opadrij II 45F24512 pink: polydextrose 3,750 mg; hypromellose (E464) 3.750 mg; titanium dioxide (E171) 3.367 mg; Macrogol-4000 0.750 mg; ferric dye oxide red (E172) 0.305 mg; dye red charming (E129) 0.060 mg; indigocarmine 0.018 mg.

Description:

Tablets 25 mg. White or almost white capsules in the form of capsules, covered with a film sheath. On one side - engraving "T 25".

Tablets 50 mg. Light-yellow capsules in the form of capsules, coated with a film sheath. On one side - risk and engraving "T" and "50" on each side of the risks.

Tablets of 100 mg. Yellow capsules in capsule form, film-coated. On

one side - risk and engraving "T" and "100" on each side of the risks.

Tablets 200 mg. Light red capsules in capsule form, coated with film shell. On one side - risk and engraving "T" and "200" on each side of the risks.

Pharmacotherapeutic group:Antiepileptic agent.

ATX: & nbsp

N.03.A.X Other antiepileptic drugs

N.03.A.X.11 Topiramate

Pharmacodynamics:

Topiramate belongs to the class of sulfate-substituted monosaccharides. It blocks sodium channels and suppresses occurrence of repeated potentials of action against the background of prolonged depolarization of the neuron membrane. Topiramate increases the activity of gamma-aminobutyric acid (GABA) with respect to some subtypes of GABA receptors (including GABA receptors), and also modulates the activity of the GABA receptors themselves, hinders activation kainate / AMPK

(a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptors for glutamate, does not affect the activity of N-methyl-D-aspartate (NMDA) with respect to the NMDA receptor subtype. These effects of topiramate are dose-dependent with a plasma topiramate concentration of 1-200 μmol / L, with a minimum activity ranging from 1 to 200 μmol.

Besides, topiramate inhibits the activity of some isoenzymes of carbonic anhydrase. By the severity of this pharmacological effect topiramate is significantly inferior to acetazolamide - a known inhibitor of carbonic anhydrase, therefore this action of topiramate is not the main component of its antiepileptic activity.

Pharmacokinetics:

After oral administration topiramate quickly and well absorbed from the gastrointestinal tract. Bioavailability is about 80%. After oral administration of 100 mg of topiramate, the maximum concentration in the plasma (C_m_Oh) 1.5 mg / min is achieved within 2-3 hours. Eating does not have a clinically significant effect on the bioavailability of topiramate. The pharmacokinetics of topiramate is linear in nature with a dose-dependent increase in the concentration of topiramate in plasma at a dose of 200-800 mg / day.After repeated administration of topiramate in a dose of 100 mg 2 times a day C_m_Oh on average is 6.76 μg / ml.

The connection with blood plasma proteins for topiramate is 13-17%. The average volume of distribution is 0.55-0.8 l / kg. The size of the distribution is due to gender, in women it is approximately 50% of the values observed in men because of the higher fat content in the body. Topiramate binds to erythrocytes in an amount of 3-10 μg / ml. The equilibrium concentration of topiramate in the blood plasma is reached within 4-8 days, with renal insufficiency - within 10-15 days. Topiramate penetrates into breast milk and through the placental barrier. After oral administration topiramate is metabolized on average by 20% by hydroxylation, hydrolysis and glucuronation with the formation of 6 inactive metabolites found in urine, blood plasma and feces. With simultaneous application of inducers of cytochrome P450 isoenzymes, the rate of metabolism of topiramate is increased up to 1.5 times. Kidney clearance is an average of 18 ml / min, plasma clearance - 20-30 ml / min after ingestion. Topiramate reabsorbed in the renal tubules.About 70% of the accepted topiramate is excreted by the kidneys. After repeated intake of 50 and 100 mg twice a day, the half-life (T_1/2) is 21 hours. Topiramate is output by hemodialysis.

Pharmacokinetics in special clinical cases.

Renal and plasma clearance of topiramate with mild renal insufficiency (creatinine clearance more than 70 ml / min) is not changed. The renal and plasma clearance of topiramate is reduced by 42% with an average degree of renal insufficiency (KC 30-69 ml / min), and with renal and plasma clearance of topiramate reduced by 54% or more with a severe degree of renal insufficiency (KC less than 30 ml / min).

With moderate and severe hepatic insufficiency, the plasma clearance of topiramate is reduced by 20-30%.

In elderly patients without renal and hepatic insufficiency, the clearance of topiramate is not changed.

The pharmacokinetics of topiramate in children, as in adults receiving supplementary therapy, is linear in nature with a dose-independent clearance; the equilibrium concentration of topiramate in the blood plasma increases in proportion to the increase in dose. It should be borne in mind that in children the clearance of topiramate is elevated, and T_1/2is reduced, so at the same dose, based on 1 kg of body weight, the concentration of topiramate in blood plasma in children will be lower than in adults. In children, as in adults, anti-epileptic drugs (PEP) inducing cytochrome P450 cause a decrease in the concentration of topiramate in the blood plasma and increase the degree of its metabolism.

Indications:

Monotherapy:

- partial and / or generalized tonic-clonic seizures in adults and children over 6 years of age.

In the combination therapy:

- partial and / or generalized tonic-clonic seizures in adults and children over 3 years of age;

- seizures associated with Lennox-Gastaut syndrome, in adults and children older than 3 years.

Preventing migraines after excluding the possibility of using alternative medications (only in adults, is not intended for the treatment of acute attacks).

Contraindications:Hypersensitivity to topiramate or any other component of the drug; lactose intolerance, lactase deficiency, glucose-galactose malabsorption; period of pregnancy and lactation; age to 18 years for the prevention of migraine; age up to 6 years for use as a monotherapy; age up to 3 years for use in combination therapy.

Carefully:Renal failure, hepatic insufficiency, hypercalciuria, nephrourolythiasis (including in the anamnesis or in a family anamnesis).

Pregnancy and lactation:

Topiramate has a teratogenic effect. The use of topiramate during the first trimester of pregnancy leads to an increase in the frequency of malformations in the fetus (malformations of the limbs, craniofacial defects, heart failure). The use of topiramate in combination with other PEPs further increases the incidence of malformations. Topiramate-Teva is contraindicated for use during pregnancy, including for the prevention of migraine. During the application of Topiramate-Teva, effective contraceptive methods must be used.

Topiramate penetrates into breast milk; the concentration of topiramate in breast milk is equal to its concentration in the blood plasma. For the time of antiepileptic therapy with topiramate-teva, breastfeeding should be discontinued.

Dosing and Administration:

Inside, regardless of food intake, without chewing, squeezed enough water.

For optimal control of seizures, it is recommended to start therapy with low doses with

a gradual incremental increase to an effective dose.

Monotherapy

Adults. The initial dose of 25 mg in the evening for 1 week. Then the dose is gradually increased at intervals of 1-2 weeks by 25-50 mg / day in 2 divided doses. If this mode is intolerant, the dose is increased by a smaller amount or at large intervals time. The dose is selected depending on the clinical effect.

The recommended initial dose is 100 mg / day in 2 divided doses, the maximum

the recommended dose is 500 mg / day in 2 divided doses. In some cases with refractory form

epilepsy patients tolerate monotherapy in doses up to 1000 mg / day.

Children over 6 years.

The drug Topiramat-Teva is designed for children who can swallow the pill.

The initial dose of 0.5-1 mg / kg / day of body weight before bedtime during the first week. Next, you should increase the dose for 1 or 2 weeks by 0.5-1 mg / kg / day in 2 divided doses. When choosing a dose should be guided by the clinical effect.

The recommended daily dose of 100 mg / day (about 2 mg / kg / day) in 2 doses is well tolerated.

As part of combination therapy

Adults. Selection of the dose starts with 25-50 mg once a day in the evening for 1 week. Followed byincrease the dose by 25-50 mg at intervals of 1 or 2 weeks before selecting the effective dose; the frequency of reception is 2 times a day. If this regime is intolerant, the dose is increased by a smaller amount or at longer intervals. The dose is selected depending on the clinical effect.

The minimum effective dose is 200 mg / day. The average daily dose is 200-400 mg / day in 2 doses, in some patients the clinical effect is achieved with a single dose. The maximum daily dose is 800 mg / day.

Children older than 3 years. The recommended daily dose is approximately 5-9 mg / kg / day in 2 divided doses. Begin treatment with a dose of 25 mg or less before going to bed for 1 week. Then the dose is increased by 1-3 mg / kg / day in 2 divided doses at intervals of 1-2 weeks. The daily dose of 30 mg / kg / day in 3 doses is well tolerated.

With cancellation of concomitant PEP with the purpose of transition to monotherapy.

It is necessary to take into account the possible influence of this transition on the frequency of seizures. In cases where there is no need to abruptly abolish associated PEP for safety reasons, it is recommended to reduce their dose gradually, reducing the dose every 2 weeks. With the cancellation of PEP, which are inducers of microsomal liver enzymes, the concentration of topiramate in the blood plasma can increase.In this case, in the presence of clinical indications, the dose of Topiramate-Teva can be reduced.

Prevention of migraine (adults only). The initial dose of 25 mg at bedtime for 1 week. Then the dose is increased by 25 mg at intervals of 1 week. If this regime is intolerant, the dose is increased at large intervals.

The recommended daily dose is 200 mg in 2 divided doses. In some patients, the clinical effect is achieved with the application of 50 mg / day. The dose is selected depending on the clinical effect. With an increase in the daily dose of more than 100 mg, the additional effect of migraine prevention is not observed.

Patients with renal insufficiency. For patients with an average (KC less than 70 ml / min) and severe (KC less than 30 ml / min) degree of renal failure, the recommended initial dose should be reduced 2-fold, and it should be increased by a smaller amount or after long intervals. The dose is selected depending on the clinical effect. It should be borne in mind that reaching the equilibrium concentration will require more time and will be from 10 to 15 days after each increase in the dose of Topiramate-Teva.

Patients in need of hemodialysis. Because the topiramate can be removed by hemodialysis, then the daily dose of topiramate-teva should be increased by 50% on the days of its administration. The additional dose is divided into 2 parts and is administered before and after hemodialysis. The additional dose may differ depending on the characteristics of the dialysis and the equipment used. The dose is selected depending on the clinical effect.

Have patients with hepatic insufficiency Topiramate-Teva should be taken with caution under the supervision of a doctor because of the reduced clearance of topiramate. Have elderly patients correction of the dose is not required.

Side effects:

The frequency of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%: often - not less than 1%, but less than 10%; infrequently - not less than 0.1%, but less than 1%: rarely - not less than 0.01%, but less than 0.1%: very rarely - not less than 0, 01%, including single messages.

Infections: very rarely - nasopharyngitis.

From the side of the blood and lymphatic system: often - anemia, infrequently - leukopenia, thrombocytopenia, lymphadenopathy, thrombocytopenia, eosinophilia; rarely - neutropenia.

From the nervous system: very often - drowsiness, dizziness, paresthesia, depression; often impaired concentration, memory impairment, amnesia, hypoesthesia, headache, nervousness, ataxia, aphasia, dysphemia, perseveration of speech, anorexia, confusion, slowing of psychomotor reactions, anxiety, irritability, insomnia, tremor, impaired coordination, gait disturbance, dysgeusia, apathy (in children), tearfulness (in children), asthenia, lethargy, mood disturbance, euphoria, emotional lability, agitation, cognitive impairment, delayed thinking, confusion, increased aggression, abnormal behavior (in children), psychosis or psychotic symptoms, anorgasmia, sexual dysfunction, decreased libido; infrequently, large and small convulsions, hypokinesia, peripheral neuropathy, clumsiness, dyspnography, stupor, paranoia, mania, psychomotor hyperactivity (in children), visual and auditory hallucinations, agevia, hypogesia, anosmia, parosmia, hyposmia, personality disorientation, suicidal thoughts, suicidal attempts, inability to learn, violation of reading skills, burning sensation (mainly on the face and in the extremities),cerebellar syndrome, awkward movements, postural dizziness, dysesthesia, dyskinesia, goose bumps, pre-fainting conditions, recurring speech, fainting; rarely - panic attacks, a sense of despair, apraxia, hyperesthesia, akinesia, lack of response to stimuli, disturbance of circadian rhythms of sleep (in children).

From the side of the organ of vision: very often - nystagmus; often - blurred vision, diplopia, visual impairment; infrequently - a violation of accommodation, amblyopia, blepharospasm, unilateral blindness, presbyopia, photopsy, visual field defect, scotoma, incl. ciliary, decreased visual acuity; rarely - acute myopia, secondary closed angle glaucoma, accommodation disorder, pain in the eyeball, one-sided blindness, transient blindness, dry eye mucosa, increased lacrimation, mydriasis, night blindness; very rarely - closed-angle glaucoma, violation of eyeballs, maculopathy, edema of the eyelids, conjunctival edema.

From the side of the hearing organ and labyrinthine disorders: often - vertigo, noise in the ears, pain in the ears; infrequent - bilateral deafness, one-sided deafness, neurosensory deafness, discomfort in the ears.

From the cardiovascular system: infrequent - bradycardia, palpitations, marked decrease in blood pressure (BP), orthostatic hypotension; rarely - the phenomenon of Raynaud.

From the respiratory system: often - shortness of breath, nasal congestion, rhinorrhea (in children); infrequently - sinusitis, hoarseness, dyspnea with exercise, hypersecretion in the sinus sinuses.

From the digestive system: very often - nausea, diarrhea; often - vomiting, constipation, abdominal pain, dryness of the oral mucosa, gastritis; infrequently - pancreatitis, flatulence, bloating, gastroesophageal reflux disease, discomfort in epigastrium, gingivitis, bleeding gums, hypersalivation, smell from the mouth, glossalgia, glossodinia, polydipsia, increased appetite.

From the musculoskeletal system and connective tissue: often - arthralgia, muscle spasm, myalgia, muscle twitching, muscle weakness, musculoskeletal pain in the chest; infrequently - swelling of the joint, musculoskeletal stiffness, muscle fatigue, pain in the side.

From the side of the kidneys and urinary system: often - incontinence, nephrolithiasis of dysuria,pollakiuria; infrequent - urolithiasis, hematuria, urinary incontinence, frequent urge to urinate, renal colic, pain in the kidney area; rarely - concrements of ureters, renal tubular acidosis.

From the skin and subcutaneous tissues: infrequently - anhidrosis, vitiligo, oligohydrosis (mainly in children), hypoesthesia of the skin of the face, violation of skin pigmentation; rarely - unpleasant skin odor;

Allergic reactions: often - skin rash, itchy skin; infrequently - generalized pruritus, hives, polymorphic erythema, macular rash, allergic dermatitis; rarely - Stephen-Johnson syndrome, periorbital edema; frequency unknown - toxic epidermal necrolysis.

On the part of the reproductive system: infrequently erectile dysfunction. Laboratory indicators: infrequently - hypokalemia, crystalluria; very rarely - a decrease in the concentration of bicarbonates in the blood plasma, an increase in the activity of "liver" transaminases and alkaline phosphatase

Other: very often - fatigue, weight loss (especially in children); often - fever, weight gain, nosebleeds, fever (in children); infrequently - influenza, epistaxis, blood flushes, metabolic acidosis, cold extremities, hyperchloremic acidosis (in children).

Overdose:

Symptoms: convulsions, drowsiness, headache, speech disorder, accommodation disorder, diplopia, thinking disorder, lethargy, impaired coordination, stupor, marked decrease in blood pressure, abdominal pain, agitation, dizziness, depression and seizures. Possible development of metabolic acidosis. In most cases, the clinical consequences were not severe, but there were deaths after an overdose of PEP combinations that included topiramate.

Treatment: cause vomiting, rinse the stomach, increase the amount of fluid consumed, symptomatic therapy. Enterosorbents are ineffective. Hemodialysis is effective.

Interaction:

Simultaneous reception of topiramate with other PEP (phenytoin, carbamazepine, valproic acid, phenobarbital, primidon and lamotrigine) does not affect their concentration in the blood plasma, except for individual patients in whom the addition of topiramate to phenytoin therapy may cause an increase in the concentration of phenytoin in the blood plasma. This may be due to oppression of the isoenzyme CYP2C_mephsystems of cytochrome P450. Therefore, every patient who takes phenytoin, and in which clinical signs or symptoms of toxicity develop, it is necessary to monitor the concentration of phenytoin in the plasma.

Phenytoin and carbamazepine reduce the concentration of topiramate in blood plasma. Addition or withdrawal of carbamazepine or phenytoin for therapy with topiramate requires a change in the dose of the latter depending on the clinical effect.

The addition or withdrawal of valproic acid or lamotrigine does not cause a clinically significant change in the concentration of topiramate in the blood plasma.

With long-term application of topiramate, the area under the curve "concentration-time" (AUC) for a single dose of digoxin decreased by 12%. The concentration of digoxin in the blood plasma should be carefully monitored both with simultaneous application with topiramate, and after its cancellation.

There is no data on the use of topiramate, together with alcohol and / or other drugs that depress the central nervous system (CNS). Do not use alcohol during the treatment with topiramate and use other medications that depress the central nervous system.

With the simultaneous use of topiramate and St. John's wort, there is a high risk of reducing the concentration of topiramate in the blood plasma and reducing its clinical effectiveness.

With the simultaneous use of topiramate and oral contraceptives (PC) containing 1 mg of norethisterone and 35 μg of ethinylestradiol, topiramate in doses of 50-800 mg / day had no significant effect on the effectiveness of norethisterone and in doses of 50-200 mg / day - on the effectiveness of ethinyl estradiol. A significant dose-dependent decrease in the efficacy of ethinyl estradiol was observed with topiramate at doses of 200-800 mg / day. It should be taken into account the likelihood of reducing contraceptive effect and acyclical bleeding in patients taking PC in combination with topiramate. Patients taking PC should inform the doctor of any changes in the timing and nature of menstrual bleeding. The effectiveness of PC can be reduced even in the absence of acyclic bleeding.

In healthy volunteers, simultaneous intake of lithium salts and topiramate at a dose of 200 mg / day caused a decrease in the area under the concentration-time curve for lithium by 18%, but in patients with manic-depressive syndrome such combination did not change the pharmacokinetics of lithium salts. With an increase in the dose of topiramate to 600 mg / day, the area under the concentration-time curve increased by 26%.In a study of the interaction of drugs in healthy volunteers and in patients with bipolar affective disorder with risperidone, the same results were observed once or repeatedly. When topiramate was used in increasing doses of 250 and 400 mg / day, the systemic effect of risperidone, taken at doses of 1 to 6 mg / day, was reduced by 16% and 33%, respectively. The pharmacokinetics of 9-hydroxyrisperidone did not change, and the total pharmacokinetics of risperidone and 9-hydroxyrisperidone did not change significantly. Minimal changes in the pharmacokinetics of risperidone and 9-hydroxyrisperidone have been noted. When topiramate was added against the background of risperidone (1-6 mg / day), side effects were more frequent (in 90% of patients) than before taking topiramate (250-400 mg / day) (54% of patients). The most frequent adverse reactions were drowsiness, paresthesia and nausea. With simultaneous application of topiramate and metformin, an increase in C_m_Oh and AUC metformin by 18% and by 25%, respectively, whereas the clearance of metformin - is reduced by 20%. The clearance of the topiramate is also reduced.In the case of the addition or withdrawal of topiramate in patients receiving metformin, special attention should be given to a careful study of the glycemic status of these patients.

With simultaneous application of topiramate and glibenclamide, the area under the concentration-time curve for glibenclamide decreases by 25%. The systemic exposure of active metabolites of glibenclamide, 4-trans-hydroxy-glibenclamide and 3-cis-hydroxyglybene clamidum is reduced by 13% and 15%, respectively. Glibenclamide does not affect the pharmacokinetics of topiramate. In the case of the addition or withdrawal of topiramate in patients receiving glibenclamide, special attention should be given to a careful study of the glycemic status of these patients.

Pioglitazone with simultaneous application does not change the pharmacokinetics of topiramate. Topiramate reduces the AUC pioglitazone by 15% without change in C_m_Oh pioglitazone. Reduction of C_m_Ohfor active hydroxymetabolite of pioglitazone is 13%, a AUC - by 16%. FROM_m_Oh and AUC for active ketometabolite pioglitazone reduced by 60%. In the case of the addition or withdrawal of topiramate in patients receiving pioglitazone, special attention should be given to a careful study of the glycemic status of these patients.

Hydrochlorothiazide increases C_m_Oh and AUC topiramate by approximately 30%. The pharmacokinetics of hydrochlorothiazide does not change with topiramate. The dose of topiramate in such a combination should be changed accordingly. The content of potassium in the blood plasma after a single dose of topiramate or hydrochlorothiazide decreases more than after taking these drugs in combination.

Topiramate reduces the action of diltiazem and its metabolite, deacetyl-dithiasem, by 25% and 18%, respectively, but does not affect N-detylldithioasem. With increasing doses, this effect of topiramate is enhanced. Diltiazem increases the effect of topiramate by 20%. This diltiazem effect can be enhanced by simultaneous application of topiramate with other PEPs.

Topiramate, when used concomitantly with drugs that predispose to nephrolithiasis, may increase the risk of nephrolithiasis. Such interaction should be avoided to prevent the creation of a physiological environment that increases the risk of kidney stones.

The simultaneous administration of topiramate and valproic acid is associated with a risk of hyperammonemia and the presence or absence of encephalopathy. This side effect is not associated with pharmacokinetic interaction.

Topiramate does not alter the pharmacokinetics of sumatriptan, propranolol and dihydroergotamine.

Topiramate does not alter the pharmacokinetics of amitriptyline and haloperidol, but enhances the effect of their metabolites.

Topiramate inhibits isoenzyme CYP2C19 and can influence the pharmacokinetics of substances metabolized by this isoenzyme, such as diazepam, imipramine, moclobenide, proguanil, omeprazole.

Special instructions:

Topiramate-Teva, like other PEPs, should be canceled gradually to minimize the possibility of increasing the frequency of seizures, reducing the dose by 100 mg at intervals of 1 week. In some patients, the cancellation of Topiramate-Teva was accelerated and passed without complications. The main way of excretion of topiramate and its metabolites in an unchanged form is excretion by the kidneys. The rate of excretion by the kidneys depends on the function of the kidneys and does not depend on age. In patients with mild to severe renal impairment to achieveequilibrium concentrations in the blood plasma may take 10-15 days compared with 4-8 days in patients with normal renal function.

As with other antiepileptic drugs, dose selection scheme formulation of topiramate-Teva should be guided by the therapeutic efficacy (i.e. the degree of reduction of seizure frequency, lack of side effects), and should take into account the fact that in patients with impaired renal function to establish an equilibrium concentration of topiramate in the blood plasma for each dose may take a longer time.

When therapy with Topiramate Teva-raising is very important to adequate fluid intake volume, thereby reducing the risk of nephrolithiasis, and the side effects that may occur under the influence of physical activity or high temperatures.

Topiramate in the treatment of drug-Teva increased risk of stones in the kidneys and the matching of clinical symptoms, such as renal colic, especially in patients who are predisposed to nephrolithiasis and hypercalciuria.None of these risk factors reliably leads to the formation of concrements during therapy with topiramate, but with simultaneous application with other drugs predisposing to the development of nephrolithiasis (acetazolamide, triamterene, ascorbic acid in a dose of more than 2 g / day), the risk of developing nephrolithiasis rises. It is necessary to avoid the use of Topiramate-Teva against the background of increased formation of ketone bodies in the body due to an increased risk of developing nephrolithiasis.

With the application of Topiramate-Teva, a syndrome can be manifested, which is an acute myopia associated with secondary closed-angle glaucoma. The syndrome is accompanied by a sharp attack of visual acuity and / or eye pain. In ophthalmological examination, myopia, flattening of the anterior chamber, hyperemia (reddening of the eyes) and increased intraocular pressure are detected, and also mydriasis. The described syndrome can be associated with supraciliary ejaculation, which causes a shift in the lens and iris and the development of secondary closed-angle glaucoma. Typically, symptoms occur after a month of primary therapy.Unlike primary open-angle glaucoma, which was rarely detected in patients under 40 years of age, secondary closed angle glaucoma associated with the use of topiramate was observed in both children and adults. Treatment provides for the cancellation of Topiramate-Teva if the doctor deems it appropriate, and taking appropriate measures to reduce intraocular pressure.

With the use of topiramate, hyperchloremic, not associated with an anion deficiency, metabolic acidosis (eg, a decrease in bicarbonate concentration in the blood plasma below the norm in the absence of respiratory alkalosis) may occur. Such a decrease in the concentration of bicarbonate in the blood plasma is a consequence of the inhibition of renal carbonic anhydrase by topiramate. In most cases, the decrease in bicarbonate concentration occurs at the beginning of Topiramat-Teva, although this effect may occur in any period of treatment with Topiramate-Teva. The nature of the decrease in bicarbonate concentration is usually mild or moderate (mean value is 4 mmol / L when administered in adult patients at a dose of more than 100 mg / day and about 6 mg / kg per day when applied in pediatric practice).Reducing the concentration of bicarbonates below 10 mmol / l was noted in rare cases. Some diseases or methods of treatment that predispose to the development of acidosis (e.g., renal disease, severe respiratory disease, status epilepticus, diarrhea, surgery, increased formation of ketone bodies in the body, taking certain medications) may be additional factors enhancing bicarbonate-reducing effect of topiramate. Chronic metabolic acidosis increases the risk of developing nephrolithiasis. In children, chronic metabolic acidosis can cause osteomalacia and lead to a slowdown in growth.

In the treatment with topiramate, it is recommended to carry out the necessary studies, including determining the concentration of bicarbonates in the blood serum. When metabolic acidosis and its persistence occur, it is recommended that the dose of Topiramate-Teva be reduced or discontinued.

When Topiramate-Teva is used, there is an increase in the incidence of behavioral diseases (including increased aggressiveness), psychotic reactions and depression.

During clinical trials in patients with epilepsy with topiramate almost 3 times more often than in the placebo group, there were cases associated with an increase in suicidal activity (suicidal ideation, suicide attempts and completed suicide). When using Topiramate-Teva, patients should be examined for suicidal thoughts and suicidal behavior. If suicidal activity is detected in patients, consideration should be given to the possibility of appropriate treatment. Patients, their relatives, caregivers should be informed about the need to see a doctor if suicidal activity is detected.

Patients with any personality disorders need special control, especially at the beginning of treatment with topiramate.

With prolonged use of Topiramate-Teva, weight loss is possible, especially in children during intensive growth. With a persistent reduction in body weight, the patient should be advised to take an additional meal. If this measure is ineffective, consider changing the dosage regimen. The use of Topiramate-Teva in acute migraine attacks has not been studied.

Effect on the ability to drive transp. cf. and fur:During the treatment with Topiramat-Teva, the patient should refrain from driving and practicing potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions due to the fact that acting on the CNS, Topiramate-Teva can cause drowsiness, dizziness, dizziness vision and other adverse symptoms.

Form release / dosage:

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

Packaging:

Tablets of 25 mg. For 10 tablets in a blister from PA / Al / PVC / Al. 2; 3; 6; or 10 blisters together with instructions for use in a pack of cardboard.

Tablets of 50 mg and 100 mg. For 10 tablets in a blister from PA / Al / PVC / Al. 2, 5; 6 or 10 blisters together with instructions for use in a pack of cardboard.

Tablets of 200 mg. For 10 tablets in a blister from PA / Al / PVC / Al. 3; 6 or 10 blisters together with instructions for use in a pack of cardboard.

Storage conditions:

Store at a temperature of no higher than 30 ° C in a place protected from moisture. 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:LP-001304

Date of registration:29.11.2011

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Industries, Ltd. Israel

Representation: & nbspTeva Teva Israel

Information update date: & nbsp12.09.2015

Illustrated instructions

Instructions

Topiramate-Teva (Topiramate-Teva)