Active substanceTopiramateTopiramate
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  • Dosage form: & nbspFilm-coated tablets.
    Composition:

    Tablets of 25 mg: active substance: topiramate 25 mg; Excipients: lactose monohydrate 6 mg, microcrystalline cellulose 20.675 mg, pregelatinized starch 3.75 mg, sodium carboxymethyl starch 3.125 mg, silicon dioxide colloid 0.25 mg, talc 0.6 mg, magnesium stearate 0.6 mg; film sheath: hypromellose 0.89 mg, macrogol 0.09 mg, titanium dioxide 0.22 mg.

    Tablets of 50 mg: active substance: topiramate 50 mg; Excipients: lactose monohydrate 12 mg, microcrystalline cellulose 41.35 mg, pregelatinized starch. 7.5 mg, sodium carboxymethyl starch 6.25 mg, silicon dioxide colloid 0.5 mg, talc 1.2 mg, magnesium stearate 1.2 mg;

    film sheath: hypromellose 1.72 mg, macrogol 0.18 mg, titanium dioxide 0.44 mg, iron oxide dye yellow 0.06 mg.

    Tablets of 100 mg: active substance: topiramate 100 mg; Excipients: lactose monohydrate 24 mg, cellulose microcrystalline 82.7 mg, pregelatinized starch 15 mg, sodium carboxymethyl starch 12.5 mg, silicon dioxide colloid 1 mg, talc 2.4 mg, magnesium stearate 2.4 mg; film sheath: hypromellose 3.52 mg, macrogol 0.36 mg, titanium dioxide 0.89 mg, iron oxide dye yellow 0.03 mg.

    Tablets of 200 mg: active substance: topiramate 200 mg; Excipients: lactose monohydrate 48 mg, microcrystalline cellulose 165.4 mg, pregelatinized starch 30 mg, sodium carboxymethyl starch 25 mg, silicon dioxide colloid 2 mg, talc 4.8 mg, magnesium stearate 4.8 mg; film sheath: hypromellose 7.3 mg, macrogol 0.77 mg, titanium dioxide 1.45 mg, iron oxide dye yellow 0.01 mg, iron oxide dye red 0.07 mg.

    Description:

    Tablets of 25 mg: Round dvuktsuklyuklye tablets white or almost white, covered with a film sheath, with a risk separating the squeezed numbers 10 and 31 on one side, and extruded by the number 25 on the other side. Cross-sectional view: the core of the tablet and the outer ring of the shell are white or almost white in color.

    Tablets of 50 mg: Round, biconvex tablets of yellow color, covered with a film shell, with a risk separating the squashed numbers 10 and 32 on one side, and the risk and squeezed out figure 50 on the other side. Cross-sectional view: the core of the tablet is white or almost white, the outer ring of the shell is yellow.

    Tablets of 100 mg: Round biconvex tablets of light yellow color, film-coated, with a risk separating the squeezed, numbers 10 and 33 on one side, and risky and squeezed out by the number 100 on the other side. Cross-sectional view: the core of the tablet is white or almost white, the outer ring of the shell is light yellow.

    Tablets of 200 mg: Round biconvex tablets of pink color, covered with a film sheath, with a risk separating the squashed numbers 10 and 34 on one side, and the risk and squeezed out figure 200 on the other side. Cross-sectional view: the core of the tablet is white or almost white, the outer ring of the shell is pink.

    Pharmacotherapeutic group:Antiepileptic agent.
    ATX: & nbsp

    N.03.A.X   Other antiepileptic drugs

    N.03.A.X.11   Topiramate

    Pharmacodynamics:Topiramate is a sulfamate-substituted monosaccharide, is used as an antiepileptic agent. The mechanism of action is associated with a decrease in epileptiform discharges and action potentials due to blockade of potential-dependent sodium channels; increased GABA activity against GABA receptors; and antagonism with glutamatergic receptors of the kainate subtype.The drug does not affect the activity of N-methyl-D-acnapatate (NMDA) against NMDA receptors. These effects of topiramate are linearly dependent on the concentration in the plasma in the range of 1-200 μmol / l. Also topiramate inhibits the activity of certain isoenzymes of carbonic anhydrase (II and IV), but this effect is weaker than that of acetazolamide, and is probably not the main one in the anticonvulsant activity of the drug.
    Pharmacokinetics:Topiramate quickly and completely absorbed from the gastrointestinal tract (GIT). Bioavailability - 80%. Time to reach the maximum concentration in the blood plasma. (TCam) - 2 h after oral administration at a dose of 400 mg. The maximum concentration in blood plasma (Crnax) after repeated ingestion of 100 mg twice a day - 6.76 μg / ml. Binding to plasma proteins is 13-17%. After a single dose of 1200 mg, the volume of distribution is 0.55-0.8 l / kg and depends on the sex: in women it is approximately 50% of the values ​​observed in men. Equilibrium concentration in patients with normal kidney function is achieved approximately, after 4-8 days, with renal failure - 10-15 days. 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 oral intake is linear, plasma clearance remains constant - 20-30 ml / min; the area under the concentration-time 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 - 21 hours. In severe hepatic and renal (creatinine clearance less than 60 ml / min), plasma and renal clearance are reduced. It is excreted primarily by the kidneys in unchanged form (70%) and in the form of metabolites. It is removed from the plasma by hemodialysis.
    It should be borne in mind that the half-life of the topiramate in children is about half as long as in adults. Accordingly, when taking the same dose of the drug (in mg / kg) as in adults, the concentration of plasma in children may be lower than in adults. It should be noted that in both adults and children, simultaneous with topiramate intake of antiepileptic drugs that induce liver enzymes, reduces the equilibrium concentration of topiramate in plasma.
    Indications:

    Epilepsy - / -

    As a means of monotherapy: in adults and children older than 3 years (including patients with newly diagnosed epilepsy)

    As part of complex therapy: in adults and children older than 3 years with partial or generalized tonic-clonic seizures, as well as seizures in the background of the Lennox-Gastaut syndrome.

    Migraine

    Prevention of migraine attacks in adults (the use of topiramate for the treatment of acute migraine attacks has not been studied).

    Contraindications:Hypersensitivity to topiramate or other components of the drug; children under 3 years old, lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
    Carefully:Hepatic or renal failure, history of nephrolithiasis (including familial), hypercalciuria.
    Pregnancy and lactation:Special studies in which topiramate would be used to treat pregnant women, was not conducted. However, the possible association between topiramate during pregnancy and congenital malformations (eg, craniofacial defects, hypospadias and abnormalities of various body systems) can not be ruled out. These developmental anomalies were recorded both with monotherapy with topiramate and with its application in the framework of complex therapy.In addition, the results of studies with pregnancy records indicate that the risk of developing teratogenic effects in combination treatment with antiepileptic drugs may be higher than with monotherapy. Thorapimat should not be used during pregnancy, except in cases of extreme necessity, if the potential benefit to the mother justifies the risk to the fetus. A limited number of observations suggest that topiramate excreted in breast milk. If you need to use the drug Thorapimat during lactation should stop breastfeeding or cancel the drug.
    Dosing and Administration:

    Thorapimatum taken internally, independently from eating.

    Epilepsy

    As a monotherapy In adults (including patients with newly diagnosed epilepsy), including in elderly patients with normal renal function, start with low doses - 25-50 mg once a day at night. After 1 week, the daily dose is gradually increased by 25-50 mg. Further gradual increase in the daily dose (by 25-50 mg) is carried out at intervals of 1 -2 weeks, to the effective dose. In the case of signs of intolerance to the proposed titration regime, an increase in the daily dose is carried out in smaller portions and / or at longer intervals.The recommended daily dose is 100 mg. The maximum daily dose of 500 mg. An approximate titration mode (a variant with a successive increase in the dose of 25 mg per week) at the stage of selecting the effective dose is given in Fig. 1. In cases of refractory epilepsy, the daily dose can be increased to 1000 mg. Individual selection of the dose in the range indicated here is performed by the physician on the basis of the clinical effect. Mode of taking the drug: 2 times a day, in equal doses.



    When using the drug Thorapimat as a monotherapy, it is necessary to take into account the possible effect of withdrawal of concomitant anticonvulsant therapy (other antiepileptic drugs) on the frequency of seizures. In cases where it is undesirable to abruptly cancel other antiepileptic drugs, their doses are reduced gradually, reducing the daily dose by 1/3 every 2 weeks. With the abolition of antiepileptic drugs, which are inducers of microsomal liver enzymes, the concentration of topiramate in plasma will increase. In such situations, in the presence of clinical indications, the dose can be reduced Children with body weight not less than 25 kg, in the first pedel of treatment, Thorapimat is prescribed in a dose of 0.5-1 mg / kg of body weight before bedtime. The choice of starting (starting) dose for children weighing from 15 to 40 kg is given on Fig. 2. Then the dose is increased with an interval of 1-2 weeks at 0.5-1 mg / kg per day, the daily dose divided into 2 doses. If this regime is intolerant, the dose can be increased by a smaller amount and / or at longer intervals. The magnitude of the dose and the rate of its increase are determined clinical

    effectiveness of therapy. The recommended dose range for topiramate monotherapy in children older than 3 years is 3-6 mg / kg per day. With newly diagnosed partial seizures, the dose can be brought up to 500 mg per day.

    As part of complex therapy (with other anticonvulsants) with partial or generalized tonic-clonic seizures, as well as seizures in the background of the Lennox-Gasto syndrome

    In adults, including elderly patients with normal renal function, begin with low doses - 25-50 mg once a day at night. After 1 week, the daily dose is gradually increased by 25-50 mg. Further gradual increase in the daily dose (by 25-50 mg) is carried out at intervals of 1-2 weeks, up to the effective dose. The average effective daily dose is 200-400 mg.If necessary, the daily dose is increased further, but not exceeding the maximum daily dose of 1600 mg. Selection of an individual effective dose in the range of 200-1600 mg is based on the clinical effect. Mode of taking the drug: 2 times a day, in equal dosages. In some cases, the required clinical effect is achieved by taking 1 time per day.

    Children with body weight not less than 25 kg, the recommended total daily dose is 5 to 9 mg / kg. Accepted in 2 divided doses. Selection of the dose begins with 25 mg per day (or less, at a rate of 1-3 mg per 1 kg of the body weight of the child per day), while the drug is taken once a night for 1 week. In the future, with weekly or biweekly intervals, the daily dose can be increased by 1-3 mg / kg, taking the drug in 2 divided doses. When choosing a dose should be guided by the clinical effect. The daily dose to 30 mg / kg of body weight, as a rule, is well tolerated.

    In days of hemodialysis, Thorapimat should be prescribed additionally at a dose equal to 1/2 the daily dose, in 2 divided 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).

    Preventing migraine attacks The recommended total daily dose of topiramate for prevention of migraine attacks is 100 mg and is taken in 2 divided doses. At the beginning of treatment appoint 25 mg at bedtime for 1 week. Then the dose is increased by 25 mg / day at intervals of 1 week. If the patient does not tolerate such a dose-increasing regimen, then it is possible to increase the intervals between dose increases, or to increase the dose by a smaller amount. When choosing a dose, it is necessary to be guided by clinical effect. In some patients, a positive result is achieved with a daily dose of topiramate 50 mg. In clinical studies, patients received various daily doses of topiramate, but not more than 200 mg per day.

    Side effects:

    The incidence of adverse events developing with topiramate is classified according to the recommendations of the World Health Organization: very often - at least 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 - less than 0.01%, including individual reports.

    Infections: very rarely - nasopharyngitis.

    Violations from the blood and lymphatic system: often - anemia; infrequently - leukopenia, lymphadenopathy, thrombocytopenia, in children - eosinophilia; very rarely - neutropenia.

    Disorders from the central nervous system (CNS): very often - drowsiness, dizziness, paresthesia, in children - apathy, attention disturbance; often impaired coordination of movements, nystagmus, lethargy, memory impairment (including anemia), impaired concentration, tremor, amnesia, gait disturbance, hypesthesia, perversion of taste sensations, impaired thinking, decreased mental performance, psychomotor disorders, sedation, speech impairment , dysarthria, cognitive disorders, apathy, mental defectiveness; rarely loss of taste sensitivity, hypokinesia, akinesia, decreased sense of smell, aphasia, apraxia, the appearance of an epileptic aura, a burning sensation in the extremities or on the face, cerebellar syndrome, disturbed circadian rhythm of sleep, complex partial seizures, convulsions, postural dizziness, dysesthesia, increased salivation , dysgraphia, dyskinesia, dysphasia, dystonia, sensation of "goosebumps" in the body, tonic-clonic seizures by type "grand mal", hyperaesthesia, hypogeousia, hypokinesia, hyposmia, peripheral neuropathy, parosmia, pre-memory states, repetitive speech, impaired touch, stupor, fainting, lack of reactions to stimuli, in children - psychomotor hyperactivity.

    Mental disorders: often - delayed thinking, pronounced speech disorders, confusion, depression, insomnia, aggressive reactions, agitation, irritability, disorientation, emotional lability, erectile dysfunction, in children - behavioral change, learning disabilities (difficulties with reading, writing, counting); infrequent anorgasmia, sexual dysfunction, tearfulness, early waking up in the morning, euphoric mood, apathy, auditory and visual hallucinations, hypomanic states, decreased libido, mania, panic, paranoid states, perseveration of thinking, impaired reading skills, dyspharmia, increased distraction, sleep disorders, suicidal ideation or attempts, tearfulness; very rarely - a sense of despair.

    Disorders of the gastrointestinal tract and biliary system: very often - a decrease in appetite, anorexia; often - nausea, diarrhea; infrequently - abdominal pain, constipation, stomach discomfort, dyspepsia, dry mouth, gastritis, gastroesophageal reflux, gingival hemorrhage, heaviness in the stomach, in children - vomiting, bad breath, flatulence, glossodynia, pain in the mouth, violation sensitivity in the oral cavity; infrequently - discomfort in the epigastric region, hypersecretion of the salivary glands, thirst.

    Disturbances from the musculoskeletal system and connective tissue: often - myalgia, including in the chest, muscle spasms, muscle cramps, arthralgia; infrequently - pain in the side, muscle fatigue, muscle weakness, stiffness of the muscles; very rarely - swelling of the joints, discomfort in the extremities.

    Disorders from the cardiovascular system: infrequent - bradycardia, palpitations, "hot flashes" of blood, orthostatic hypotension, Raynaud's syndrome.

    Common violations: very often - fatigue, irritability, weight loss; often - asthenia, anxiety; children - fever; infrequently - edema of the face, allergic reactions, hyperchloremic acidosis, hypokalemia,increased appetite, metabolic acidosis, polydipsia, cold extremities; very rarely - generalized edema, flu-like syndrome, allergic edema, conjunctival edema, weight gain.

    Ophthalmic disorders: often - diplopia, impaired vision, dry eyes; infrequent - accommodation disorder, amblyopia, blepharospasm, transient blindness, unilateral blindness, increased lacrimation, mydriasis, nocturnal, blindness, photopsy, presbyopia, scotoma, including ciliary, decreased visual acuity; very rarely - unpleasant sensations in the eyes, angle-closure glaucoma, involuntary movements of the eyeballs, eyelid edema, myopia, maculopathy, conjunctival edema.

    Disorders from the side of the ear: often - pain in the ears, ringing in the ears, children - vertigo; infrequently - deafness, including neurosensory and one-sided, discomfort in the ears, hearing loss.

    Disturbances from the respiratory system: often - shortness of breath, nosebleeds; infrequently - hoarseness, hoarseness, dyspnoea with physical exertion; congestion of the nose, hypersecretion in the paranasal sinuses, in children - rhinorrhea. Disturbances from the skin and subcutaneous tissues: often - a rash, alopecia, itching, a decrease in the sensitivity of the face; infrequent - no sweating, allergic dermatitis, redness of the skin, skin pigmentation disorder, macular rash, edema of the face, unpleasant skin odor, hives; very rarely - polymorphic erythema, paraorbital edema, Stephen-Johnson syndrome, toxic epidermal necrolysis.

    Disorders from the kidneys and urinary tract: often - nephrolithiasis, dysuria, pollakiuria; infrequently - urolithiasis, hematuria, urinary incontinence, frequent urge to urinate, renal colic, kidney pain; very rarely - renal tubular acidosis.

    Change in laboratory indicators: infrequently - decrease in the content of hydrocarbonates in the blood, crystallography, leukopenia, hypokalemia (decrease in serum potassium concentration below 3.5 mmol / l).

    Overdose:Symptoms: cramps, drowsiness, speech and vision impairments, diplopia, thinking disorders, movement coordination disorders, lethargy, stupor, lowering of blood pressure, abdominal pain, dizziness, agitation and depression. In most cases, the known clinical consequences were not severe,However, deaths have been reported after an overdose with a combination of several medicines, including topiramate. Overdose with topiramate can cause severe metabolic acidosis (see section "Special instructions").
    Treatment: In case of acute overdose, immediately wash the stomach or induce vomiting. The use of activated carbon is ineffective, because in experiments in vitro, it was shown that Activated carbon adsorbs topiramate. If necessary, symptomatic therapy should be given. An effective way to remove topiramate from the body is hemodialysis. Patients are advised to adequately increase the amount of fluid consumed.
    Interaction:

    Effect of topiramate on the concentration of other antiepileptic drugs (PEP):

    Simultaneous reception of topiramate with other PEPs (phenytoin, carbamazepine, valproic acid, phenobarbital, primidon) does not affect the values ​​of their equilibrium concentrations in the plasma, except for individual patients, in whom the addition of topiramate to phenytoin may cause an increase in the concentration of phenytoin in the plasma.This may be due to the inhibition of a specific polymorphic isoform of the enzyme of the cytochrome P450 system (CYP2Cmeph)- 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. In the study of pharmacokinetics in patients with epilepsy, the addition of topiramate to lamotrigine did not affect the equilibrium concentration of the latter at doses of topiramate 100-400 mg per day. During and after lamotrigine abolition (average dose of 327 mg per day), the equilibrium concentration of topiramate did not change.

    The effect of other PEP on the concentration of topiramate

    Phenytoin and carbamazepine reduce the concentrations of topiramate in plasma. Adding or abolishing phenytoin or carbamazepine against a background of treatment with topiramate may require a change in the dose of the latter. Dose should be selected, focusing on achieving the desired clinical effect. The addition or withdrawal of valproic acid does not cause clinically significant changes in the plasma topiramate concentration and, therefore, does not require a dose change.The results of these interactions are summarized in the following table:

    Adding PEP Concentration of PEP Concentration of topiramate

    Phenytoin NC or an increase of 25% * A decrease of 48%

    Carbamazepine NC Reduction of 40%

    Valproic Acid Decrease 11% Decrease 14%

    Phenobarbital NC NO

    Primidone NC NO

    * = increased plasma concentration by 25% in individual patients, usually

    host phenytoin 2 times a day

    NC = change in plasma concentration by less than 10%

    NO = not investigated

    Other drug interactions

    Digoxin: in a study using a single dose of digoxin, the area under the concentration-time curve (AUC) digoxin with a simultaneous reception of topiramate is reduced by 12%. The clinical significance of this observation is not clear. When prescribing or canceling topiramate, patients receiving digoxin, special attention should be paid to monitoring the serum digoxin concentration. Medications that depress the central nervous system: the combined use of topiramate with drugs that exert a depressant effect on the central nervous system, as well as with alcohol is not recommended.

    Oral contraceptives: in the study of drug interaction with oral contraceptives, in which a combined preparation containing norethisterone (1 mg) and ethinyl estradiol (35 μg), topiramate in doses of 50-800 mg per day did not have a significant effect on the effectiveness of norethisterone and in doses of 50-200 mg per day - the effectiveness of ethinylestradiol. A significant dose-dependent decrease in the efficacy of ethinylestradiol was observed with doses of topiramate 200-800 mg per day. The clinical significance of the described changes is not clear. The risk of reducing the effectiveness of contraceptives and strengthening breakthrough bleeding should be considered in patients taking oral contraceptives in combination with topiramate. Patients taking estrogen-containing contraceptives should be informed of any changes in the timing and nature of menstruation. The effectiveness of contraceptives can be reduced even in the absence of "breakthrough" bleeding.

    Lithium: in healthy volunteers there was a decrease AUC lithium by 18% with the simultaneous administration of topiramate at a dose of 200 mg per day. In patients with bipolar disorder, the use of topiramate at doses up to 200 mg per day did not affect the pharmacokinetics of lithium, but at higher doses (up to 600 mg per day) AUC lithium was increased by 26%. With the simultaneous use of topiramate and lithium, the concentration of the latter in the blood plasma should be monitored.

    Hydrochlorothiazide: administration of hydrochlorothiazide to patients receiving topiramate, may require correction of the dose of topiramate.

    Metformin, pioglitazone, glibenclamide: when co-administered with topiramate, the patient's condition should be carefully monitored to assess the course of diabetes mellitus.

    Other drugs

    The simultaneous use of topiramate with drugs predisposing to nephrolithiasis may increase the risk of calculus formation in the kidneys. During treatment with topiramate, the use of drugs that predispose to nephrolithiasis should be avoided, as they can cause changes that promote nephrolithiasis.

    Valproic acid

    The combined use of topiramate and valproic acid in patients who tolerate each drug individually is accompanied by hyperammonemia with or without encephalopathy. In most cases, symptoms and symptoms disappear after the withdrawal of one of the drugs. This adverse event is not caused by pharmacokinetic interaction. The relationship between hyperammonemia and the use of topiramate alone or in combination with other drugs has not been established.

    Special instructions:
    Antiepileptic drugs, including topiramate, should be abolished gradually to minimize the possibility of an increase in the frequency of seizures. In clinical studies, doses were reduced by 50-100 mg at weekly intervals: for adults with epilepsy and for 25-50 mg in adults receiving 100 mg of topiramate per day for prevention of migraine. Children in clinical trials topiramate gradually canceled within 2-8 weeks. If, for medical reasons, fast suppression of topiramate is required, it is recommended that appropriate monitoring of the patient's condition be performed.
    The rate of excretion through the kidneys depends on the functions of the kidneys and does not depend on age. In patients with moderate or severe renal dysfunction, stable plasma concentrations may be required from 10 to 15 days, in contrast to 4-8 days in patients with normal renal function.
    As with any disease, the dose selection scheme should focus on the clinical effect (ie, the degree of control of seizures, the absence of side effects) and take into account the fact that in patients with impaired renal function establishing an equilibrium concentration in the plasma for each dose may need a longer time.
    In the treatment with topiramate, an adequate increase in the amount of fluid consumed is very important, which can reduce the risk of developing nephrolithiasis, as well as side effects that can occur under the influence of physical exertion or elevated temperatures.

    Mood / depression

    When treating topiramate, there is an increased incidence of mood disorders and depression.

    Suicide attempts

    When using antiepileptic drugs, including those containing topiramate, the risk of suicidal thoughts and suicidal behavior increases in patients receiving these drugs for any of the indications. The mechanism of increasing this risk is unknown. In this regard, it is necessary to monitor the status of patients in order to identify signs of suicidal thoughts and prescribe appropriate treatment. It is necessary to recommend patients (and if necessary caring for them) immediately seek medical help in case of signs of suicidal thoughts and suicidal behavior.

    Nephrolithiasis

    In some patients, especially those with a predisposition to nephrolithiasis,the risk of calculus formation in the kidneys and the appearance of associated symptoms, such as renal colic, may increase. To reduce this risk, adequate fluid intake is necessary. Risk factors for developing nephrolithiasis are nephrolithiasis in history (including family history), hypercalciuria, concomitant therapy with drugs that contribute to the development of nephrolithiasis.

    Violation of the function of the liver -

    In patients with impaired hepatic function topiramate It should be used with caution because of the possible reduction in the clearance of topiramate.

    Myopia and secondary closed angle glaucoma

    When topiramate is used, a syndrome including acute Myopia with concomitant secondary closed angle glaucoma. Symptoms include acute visual acuity and / or eye pain. Ophthalmic examination can detect myopia, flattening of the anterior chamber of the eye, hyperemia (reddening) of the eyeball, increased intraocular pressure. There may be mydriasis. This syndrome can be accompanied by the secretion of fluid, leading to a shift in the lens and iris forward with the development of secondary closed-angle glaucoma.Symptoms usually appear 1 month after the application of topiramate. Unlike primary open angle glaucoma, which is rarely seen in patients under 40 years of age, secondary occlusive glaucoma is observed with topiramate in both adults and children. In the event of a syndrome involving myopia associated with occlusive glaucoma, treatment includes discontinuing the administration of topiramate as soon as the attending physician deems it possible, and appropriate measures aimed at lowering the intraocular pressure. Usually these measures lead to normalization of intraocular pressure. Increased intraocular pressure of any etiology in the absence of adequate treatment can lead to serious complications, including loss of vision.

    Metabolic acidosis

    When topiramate is used, hyperchloremic, not associated with an anion deficiency, metabolic acidosis (eg, a decrease in the bicarbonate concentration in the plasma below the normal value in the absence of respiratory alkalosis) may occur. Such a decrease in serum bicarbonate concentration is a consequence of the inhibitory effect of topiramate on renal carboanhydrase.In most cases, a decrease in the concentration of bicarbonate occurs at the beginning of the drug, although this effect can occur in any period of treatment with topiramate. The degree of reduction in concentration is usually mild or moderate (mean value is 4 mmol / L when administered in adult patients at a dose above 100 mg per day and about 6 mg per day per kg of body weight when used in children). In rare cases, the patients noted a decrease in the concentration of bicarbonates below 10 mmol / l. Some diseases or methods of treatment predisposing to the development of acidosis (eg, kidney disease, severe respiratory diseases, epileptic status, diarrhea, surgical interventions, ketogenic diet, intake of certain medications) may be additional factors that enhance bicarbonate-reducing effect of topiramate.

    In children, chronic metabolic acidosis can lead to slower growth. The effect of topiramate on growth and possible complications associated with the bone system in children and adults has not been systematically studied.

    In connection with the foregoing, in the treatment with topiramate, it is recommended to carry out the necessary studies, including determination of serum bicarbonate concentration.When there is metabolic acidosis and its persistence, it is recommended to reduce the dose or stop taking topiramate.

    Laboratory indicators

    Hypokalemia, defined as a decrease in serum potassium concentration below 3.5 mmol / l, was observed in 0.4% of patients who received topiramate.

    Enhanced nutrition

    If the patient's weight decreases with treatment with topiramate, then the question of the advisability of enhanced nutrition should be considered.

    Effect on the ability to drive transp. cf. and fur:
    During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

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

    Packaging:
    For 7 or 10 tablets in a blister of aluminum foil. By 1,2,3,4,6, 8,9,10 blisters with instructions for use in a cardboard box.
    Storage conditions:Store at a temperature not exceeding 30 ° C. Keep out of the reach of children.
    Shelf life:3 years. Do not use after the expiry date printed on the package
    Terms of leave from pharmacies:On prescription
    Registration number:LP-001024
    Date of registration:18.10.2011
    Date of cancellation:2016-10-18
    The owner of the registration certificate:Torrent Pharmaceuticals Co., Ltd.Torrent Pharmaceuticals Co., Ltd. India
    Manufacturer: & nbsp
    Representation: & nbspTORRENT PHARMACEUTICALS LTD. TORRENT PHARMACEUTICALS LTD. India
    Information update date: & nbsp01.10.2015
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