Active substanceTopiramateTopiramate
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  • Dosage form: & nbspfilm-coated tablets
    Composition:

    1 tablet, film-coated, contains:

    active substance: topiramate 25 mg or 100 mg;

    Excipients: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, sorbitol, silicon dioxide colloid (aerosil), magnesium stearate;

    composition of the shell: Opadrai II (series 85): partially hydrolyzed polyvinyl alcohol, macrogol-3350, titanium dioxide E 171, talc, iron dye oxide yellow E 172.

    Description:

    Tablets covered with a film coat of yellowish-beige color (for a dosage of 25 mg) or light brown in color (for a dosage of 100 mg), round, biconvex. On the fracture is white or almost white.

    Pharmacotherapeutic group:Antiepileptic remedy
    ATX: & nbsp

    N.03.A.X   Other antiepileptic drugs

    N.03.A.X.11   Topiramate

    Pharmacodynamics:

    Antiepileptic activity of the drug is due to a number of its properties. Topiramate reduces the frequency of occurrence of action potentials characteristic of a neuron in a state of persistent depolarization, which indicates the dependence of the blocking effect of topiramate on sodium channels on the state of the neuron.Increases the activity of GABA (gamma-aminobutyric acid) against certain subtypes of GABA receptors (including GABAAreceptors), and also modulates the activity of GABA itselfA- receptors; reduces the activity of kainate / AMPK receptors (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) (subtype of glutamate receptors), does not affect activity NMDAreceptors (N-methyl-O-aspartate). These effects are dose-dependent with a plasma topiramate concentration of 1-200 μmol / L, with a minimum activity of 1-10 μmol / l.

    Inhibits the activity of certain isoenzymes of carbonic anhydrase (II-IV), but this effect is weaker than that of acetazolamide, and is probably not the main one in the anticonvulsant activity of topiramate.

    Pharmacokinetics:

    Topiramate is rapidly and completely absorbed from the gastrointestinal tract (GIT). Bioavailability is 81%. Eating does not have a clinically significant effect on the bioavailability of the drug.

    Time to reach the maximum concentration in the blood plasma (TCmOh) - 2 hours after a single oral intake in a dose of 400 mg. The maximum concentration in the blood plasma (CmOh) after repeated ingestion of 100 mg twice a day - 6.76 μg / ml.

    Binding to plasma proteins is 15-41%.The volume of distribution (after a single dose of 1.2 g) is 0.55-0.8 l / kg and depends on sex (in women the values ​​are approximately 50% of the values ​​observed in men). Equilibrium concentration in blood plasma (Css) in patients with normal renal function is achieved in 4-8 days, with renal failure - after 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.

    Topiramate (70%) and its metabolites are excreted mainly by the kidneys in unchanged form.

    In severe hepatic and renal (less than 60 ml / min creatinine clearance), plasma and renal clearance of topiramate decrease.

    In elderly patients without kidney disease, the plasma clearance of topiramate does not change.

    Topiramate is effectively removed from the plasma by hemodialysis.

    Pharmacokinetics of topiramate in children under 12 years old

    The pharmacokinetic parameters of topiramate in children, as well as in adults, are linear in nature, and its clearance is independent of the dose, and the equilibrium concentrations in the plasma increase in proportion to the increase in the dose. It should be borne in mind that in children the clearance of topiramate is elevated, and the elimination half-life is shorter. Thus, at the same dose per 1 kg of body weight, the concentrations of topiramate in plasma in children may be lower than in adults.

    In children, as in adults, antiepileptic drugs that induce hepatic enzymes cause a decrease in the equilibrium concentration of topiramate in plasma.

    Indications:

    As a monotherapy for epilepsy in adults and children older than 10 years with a body weight of at least 25 kg (including patients with newly diagnosed epilepsy).

    As part of complex therapy in adults and children older than 10 years with a body weight of at least 25 kg with partial or generalized tonic-clonic seizures, as well as seizures associated with the Lennox-Gastaut syndrome.

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

    Contraindications:

    - Hypersensitivity to the components of the drug;

    - childhood.

    Carefully:

    - Renal or hepatic insufficiency;

    - nefrourolitiaz in the anamnesis (including in the family);

    - hypercalciuria.

    Pregnancy and lactation:

    Special controlled studies in which topiramate would be used to treat pregnant women, was not conducted. Nevertheless, the possible association between topiramate during pregnancy and congenital malformations (eg, craniofacial defects, such as "cleft lip" / "wolf mouth", hypospadias and abnormalities of development of various body systems) can not be ruled out. These developmental anomalies were documented both with monotherapy with topiramate and with its use within the framework of polytherapy. In addition, the results of studies with data accounting for pregnancies indicate that the risk of developing teratogenic effects in combination treatment with antiepileptic drugs may be higher than with monotherapy.The use of topiramate in pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

    ABOUTgrenichnumber Mr.Observations suggest that the topIramat is excreted in breast milk. If you need to use the drug during lactation, you should decide whether to stop breastfeeding or stop taking the drug, given the degree of its importance for the mother.

    Dosing and Administration:

    Inside, regardless of food intake. Tablets are not recommended to be divided into parts.

    To achieve optimal control over the effectiveness and tolerability of therapy, it is recommended to start treatment with taking the drug in low doses, followed by titration to an effective dose.

    Monotherapy

    When carrying out monotherapy in adults the initial dose of the drug during the first week is 25 mg 1 time / day before bedtime. Then the dose is increased at intervals of 1-2 weeks by 25-50 mg / day (the daily dose is divided into 2 divided doses). If this mode of treatment is intolerant, the dose is increased by a smaller amount or at large intervals. When choosing a dose should be guided by the clinical effect.The recommended dose is 100 mg / day, the maximum daily dose is 500 mg. In some cases with monotherapy of refractory to the treatment of epilepsy, the dose of topiramate can be 1000 mg / day. Recommendations dosing is applicable to all adults, including elderly patients without kidney disease.

    With monotherapy in children older than 10 years with a body weight of at least 25 kg in the first week of treatment, the initial dose is 0.5-1 mg / kg body weight before bedtime. Then the dose is increased at intervals of 1-2 weeks by 0.5-1 mg / kg / day, the daily dose divided into 2 divided doses. If this mode of treatment is intolerant, the dose is increased by a smaller amount or at large intervals. The magnitude of the dose and the rate of its increase, as well as in adults, is determined by the clinical efficacy and tolerability of therapy. The recommended range of doses is 100-400 mg / day. With newly diagnosed partial seizures, the dose may be up to 500 mg / day.

    It should be borne in mind that in persons taking anticonvulsant drugs, their withdrawal in the transition to monotherapy with topiramate may affect the frequency of seizures. In cases where it is undesirable to abruptly cancel concomitant anticonvulsant therapy, the dose of drugs is reduced gradually, reducing the dose by 1/3 every 2 weeks.

    Abolition of drugs that are inducers of microsomal "hepatic" enzymes, causes an increase in plasma concentrations of topiramate. In such situations, in the presence of clinical indications, the dose of the drug can be reduced.

    Use in combination with other anticonvulsants

    When topiramate is used in combination therapy with other anticonvulsants in adult patients selection of the dose starts with 25-50 mg once a day, the drug is taken for 1 week at night. Further, the dose can be increased at intervals of 1-2 weeks by 25-50 mg and taken in two divided doses. When choosing a dose, it is necessary to be guided by the clinical effect. To achieve the optimal treatment effect, it is not necessary to monitor the concentration of topiramate in plasma. The minimum effective dose is 200 mg / day. Usually the required total daily dose is 200-400 mg, the frequency of reception is 2 times / day. If necessary, an increase in the daily dose to a maximum of 1600 mg is possible. In some patients, the effect is achieved when taking topiramate 1 time / day. These dosage recommendations apply to all adult patients, including the elderly, in the absence of kidney disease (see section "Special instructions").

    With combined anticonvulsant therapy in children older than 10 years with a body weight of at least 25 kg selection of the dose should start with 25 mg (based on an initial dose of 1 to 3 mg / kg per day), taking them at night for 1 week. In the future, the dose is increased with an interval of 1-2 weeks at 1-3 mg / kg (daily dose divided into 2 divided doses). When selecting a dose withleblows RUtheOnetheatbe a clinical effect. The recommended total daily dose is 5 to 9 mg / kg and is taken in 2 divided doses. The daily dose to 30 mg / kg of body weight, as a rule, is well tolerated.

    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 treatment regimen is intolerant, the dose is increased by a smaller amount or at longer intervals. When choosing a dose, it is necessary to be guided by the clinical effect. In some cases, a positive result is achieved with a daily dose of topiramate 50 mg. In clinical trials, patients received various doses of topiramate, but not more than 200 mg / day.

    Side effects:

    Infections: very rarely - nasopharyngitis.

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

    From the central nervous system (CNS): very often - drowsiness, dizziness, paresthesia, in children - apathy, attention disturbance; often - disruption of coordination of movements, nystagmus, lethargy, memory impairment (including amnesia), impaired concentration, tremor, gait disturbance, hypoesthesia, perversion of taste sensations, impaired thinking, decreased mental activity, psychomotor disorders, sedation; rarely loss of taste sensitivity, hypokinesia, akinesia, decreased sense of smell, aphasia, apraxia, the appearance of an epileptic aura, burning sensation in the limbs or face, cerebellar syndrome, disturbed circadian rhythm of sleep, complex partial seizures, seizures, postural dizziness, dysesthesia, dysgraphia, dyskinesia, dysphasia, dystonia, sensation of "goosebumps", tonic-clonic seizures of the type "grand mal", hyperesthesia, peripheral neuropathy, impaired touch, stupor, syncope, in children - psychomotor hyperactivity .

    Mental disorders: often - slow thinking, expressed by speech disturbances, confusion, depression, insomnia, aggressive reaction, agitation, disorientation, emotional lability, erectile dysfunction in children - a change in behavior, learning disability (difficulty with reading, writing, arithmetic); infrequently - anorgasmia, sexual dysfunction, crying, early awakening in the morning, euphoric mood, auditory and visual hallucinations, hypomania, a decrease in libido, mania, a state of panic, paranoid state, perseveration of thought, impaired reading skills, 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; Infrequent - abdominal pain, constipation, stomach discomfort, dyspepsia, dry mouth, gastritis, gastroesophageal reflux disease, bleeding gums, weight in the stomach in children - vomiting, bad breath, flatulence, glossodiniya, pain in the mouth, pancreatitis , hypersecretion of the salivary glands, thirst.

    Disturbances from the musculoskeletal system and connective tissue: often - myalgia, incl. 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, flushing, orthostatic hypotension, Raynaud's syndrome.

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

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

    Hearing impairment: often - pain in the ears, ringing in the ears, children - vertigo; infrequently - deafness, incl. sensory and one-sided, discomfort in the ears, hearing loss.

    Disturbances from the respiratory system: often - shortness of breath, nosebleeds; infrequently - hoarseness, dyspnea with exercise, nasal congestion, hypersecretion in the paranasal sinuses, in children - rhinorrhea.

    Skin disorders: often - a rash, alopecia, itching, a decrease in the sensitivity of the face; infrequent - no sweating, allergic dermatitis, reddening of the skin, impaired skin pigmentation, unpleasant skin odor, urticaria; very rarely - erythema multiforme, paraorbital edema, Stevens-Johnson syndrome, toxic epidermal necrolysis.

    Disorders from the kidneys and urinary tract: often - nefrourolitiaz, dysuria, pollakiuria; infrequent - exacerbation of urolithiasis, hematuria, urinary incontinence, frequent urge to urinate, renal colic, pain in the kidney area; very rarely - renal tubular acidosis.

    Change in laboratory indicators: infrequently, a decrease in the content of hydrocarbonates in the blood (an average of 4 mmol / l), crystalluria, leukopenia, hypokalemia (a decrease in serum potassium in the serum below 3.5 mmol / l).

    Overdose:

    Symptoms: seizures, drowsiness, speech and vision impairments, diplopia, thinking disorders, 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 after an overdose using a combination of several drugs (LS), including topiramate. Overdose of topiramate can cause severe metabolic acidosis (see section "Special instructions"). A case of an overdose is known when the patient took a dose of topiramate from 96 to 110 g, which entailed someone who continued for 20-24 hours. After 3-4 days the patient's condition returned to normal.

    Treatment:

    In case of acute overdose, immediately wash the stomach or induce vomiting. In studies 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:

    The effect of topiramate on the concentration of other antiepileptic drugs (NEP)

    Simultaneous reception of topiramate with other PEP (phenytoin, carbamazepine, valproic acid, phenobarbital, primidon) does not affect the values ​​of their equilibrium concentrateactivities at plasma, with the exception of individual boland, the of which beforeThe 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 the specific polymorphic isoform of the enzyme of the cytochrome P450 system (isoenzyme 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 treatment and after lamotrigine withdrawal (average dose 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. Addition or withdrawal of 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.

    Other drug interactions

    Digoxin:

    In a study using a single dose of digoxin, the area under the concentration-time curve (AUC) of the latter with 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 concentration of digoxin in the serum.

    Medications that depress the central nervous system:

    In clinical trials, the effects of the combined use of topiramate withalcohol or other substances depressing the functions of the central nervous system have not been studied. It is recommended not to take topiramate together with alcohol or other drugs that cause depression of the central nervous system.

    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.

    Risperidone:

    Studies of drug interactions performed with a single and repeated administration of topiramate to healthy volunteers and patients with bipolar disorder gavethe wild results. With the simultaneous use of topiramate in doses of 250 or 400 mg per day AUC risperidone, taken in doses of 1-6 mg per day, is reduced, respectively, by 16 and 33%. In this case, the pharmacokinetics of 9-hydroxyrisperidone did not change, and the total pharmacokinetics of the active substances (risperidone and 9-hydroxyrisperidone) changed insignificantly. The change in the systemic effect of risperidone / 9-hydroxyrisperidone and topiramate was not clinically significant, and this interaction is unlikely to be of clinical significance.

    Hydrochlorothiazide:

    Drug interaction was evaluated in healthy volunteers with separate and combined use of hydrochlorothiazide (25 mg) and topiramate (96 mg). The results of the studies showed that with the simultaneous administration of topiramate and hydrochlorothiazide, an increase in the maximum concentration (CmOh) of topiramate by 27% and AUC of topiramate by 29%. The clinical significance of these studies has not been revealed. The administration of hydrochlorothiazide to patients receiving topiramate, may require correction of the dose of topiramate. The pharmacokinetic parameters of hydrochlorothiazide did not undergo significant changes with concomitant therapy with topiramate.

    Metformin:

    Drug interactions were evaluated in healthy volunteers who received metformin or a combination of metformin and topiramate. The results of the studies showed that with the simultaneous administration of topiramate and metformin, an increase in CmOh and AUC metformin at 18 and 25%, respectively, whereas the clearance of metformin with simultaneous application with topiramate was reduced by 20%. Topiramate did not affect the time to reach CmOh metformin in the blood plasma.The clearance of topiramate when combined with metformin is reduced. The degree of revealed changes in clearance is not studied. The clinical significance of the effects of metformin on the pharmacokinetics of topiramate is not clear. In the case of the addition or withdrawal of topiramate in patients receiving metformin, you should carefully monitor the patient's condition for assessing the course of diabetes.

    Pioglitazone:

    Drug interaction was evaluated in healthy volunteers with separate and combined use of pioglitazone and topiramate. There was a decrease AUC pioglitazone by 15%, without change in CmOh preparation. These changes were not statistically significant. Also for the active hydroxy metabolite of pioglitazone, a decrease in CmOh and AUC at 13 and 16%, respectively, and for the active ketometabolite, a decrease in CmOh, and AUC by 60%. The clinical significance of these data is not clear. When combined with topiramate and pioglitazone, patients should carefully monitor the patient to assess the course of diabetes.

    Glibenclamide:

    A study was made of the drug interaction to study the pharmacokinetics of glibenclamide (5 mg per day) in an equilibrium state,applied alone or simultaneously with topiramate (150 mg per day) in patients with type 2 diabetes mellitus. When topiramate is used AUC Glibenclamide decreased by 25%. The systemic exposure of 4-trans-hydroxyglybeneclamide and 3-cis-hydroxyglybene clamamide was also reduced by 13 and 15%, respectively. Glibenclamide did not affect the pharmacokinetics of topiramate in the equilibrium state. Statistically unreliable decrease was detected AUC pioglitazone by 15% in the absence of a change in CmOh. When prescribing topiramate to patients receiving glibenclamide (or the appointment of glibenclamide to patients receiving topiramate), you should carefully monitor the patient's condition for assessing the course of diabetes.

    Interaction with drugs that predispose to nephrourolythiasis:

    The simultaneous use of topiramate with other drugs predisposing to nephrourolythiasis may increase the risk of kidney stones. During treatment of topiramatem slfoodAvoid using preparats, etcedramalaggingtheir to nefrourolitiazu, because they can cause physiological changes that promote nefrourolitiazu.

    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.

    Amitriptyline:

    Combined use with topiramate is accompanied by an increase in Cmax and AUC metabolite amitriptyline - nortriptyline - by 20%; the pharmacokinetics of topiramate were not investigated.

    Dihydroergotamine:

    The combined use with dihydroergotamine topiramate (oral and oral) is not accompanied by changes in CmOh and AUC (up to 15% of the initial data) of both drugs.

    Haloperidol:

    Combined use with topiramate is accompanied by an increase AUC metabolite of haloperidol by 31%; the pharmacokinetics of topiramate were not investigated.

    Propranolol:

    Combined use with topiramate is accompanied by an increase in CmOh for 4-hydroxypropranolol by 17% (topiramate 50 mg), an increase in CmOh Topiramate by 9% and 16% and by an increase AUC Topiramate by 9% and 17%, respectively, for propranolol in doses of 40 mg and 80 mg every 12 hours.

    Sumatriptan:

    Combined use with sumatriptan topiramate (orally) is not accompanied by changes in CmOh and AUC (up to 15% of baseline data) of sumatriptan (the pharmacokinetics of topiramate has not been studied).

    Pisotifen:

    Combined use with pizotifen topiramate is not accompanied by changes in CmOh and AUC (up to 15% of the initial data) of both drugs.

    Diltiazem:

    The combined use of diltiazem with topiramate is accompanied by a decrease AUC diltiazem by 25% and deacetylldithiasem by 18%, by an increase AUC topiramate by 20%, no changes CmOh and AUC (up to 15% of the initial data) for N-detylldithiazema.

    Venlafaxine:

    Joint application with venlafaxine topiramate is not accompanied by changes in CmOh and AUC (up to 15% of the initial data) of both drugs.

    Flunarizine:

    Combined use with topiramate is accompanied by an increase AUC by 16% (50 mg every 12 hours); changes in CmOh and AUC (up to 15% of the initial data) for topiramate are absent. With multiple administration of a single flunarizine, an increase AUC by 14%, which may be due to the accumulation of the drug in the process of reaching the equilibrium state.

    Special instructions:

    Antiepileptic drugs, including those containing topiramateshould be lifted gradually to minimize the possibility of higherthe frequency of seizures. In clinical trials, doses were reduced by 50-100 mg at weekly intervals for adults with epilepsy and 25-50 mg in adults receiving 100 mg of topiramate per day to prevent migraine. Children in clinical trials topiramate Postepnativelyenwere for 2-8 weeks. Esland copperchinThe rapid discontinuation of topiramate is required, then it is recommended that the patient be monitored accordingly.

    The rate of excretion through the kidneys depends on the function 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 (i.e.the degree of control of seizures, the absence of side effects) and take into account the fact that patients with impaired renal function to establish an equilibrium concentration in the plasma for each dose may need a longer time. In therapy with topiramate, an adequate increase in the amount of fluid consumed is very important, which can reduce the risk of developing nephrourolythiasis, as well as side effects that may 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 taking these drugs for any of the indications. A meta-analysis of randomized, placebo-controlled trials of antiepileptic drugs showed an increased risk of suicidal ideation and suicidal behavior (0.43% with antiepileptic drugs versus 0.24% with placebo). The mechanism of 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 to patients (and if necessary, carers of patients) to seek medical help immediately if signs of suicidal thoughts or suicidal behavior appear.

    Nephrourolithiasis

    In some patients, especially those with a predisposition to nephrourolythiasis, the risk of kidney stones and the appearance of related symptoms, such as renal colic, may increase. To reduce this risk, an adequate increase in the amount of fluid consumed is necessary.

    Risk factors for developing nephrourolythiasis are nephrourolythiasis in the anamnesis (including family history), hypercalciuria, concomitant therapy with drugs that promote the development of nephrourolythiasis.

    Impaired liver function

    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 using topiramate described 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 observed in patients under 40 years of age, secondaryMr.aI amakrotowgaboutglaucoma observesxia when using topiramate in both adults and children. In the event of a syndrome involving myopia associated with occlusive glaucoma, treatment includes stopping the use 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

    With the use of topiramate, hyperchloremic, not associated with an anion deficiency, metabolic acidosis (eg, a decrease in the concentration of hydrogencarbonates 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, the decrease in the concentration of hydrocarbonates occurs at the beginning of the drug, although this effect can occur in any period of treatment with topiramate. The reduction in concentration is usually mild or moderate (mean value is 4 mmol / L when used 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 pediatric practice). In rare cases, patients have a decrease in the concentration of hydrocarbonates below 10 mmol / l. Some diseases or treatments that predispose to the development of acidosis (for example,kidney disease, severe respiratory diseases, status epilepticus, diarrhea, surgical interventions, ketogenic diet, taking 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 the concentration of hydrocarbonates in the serum. 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 loses weight with treatment with topiramate, then it is necessary to consider the feasibility of enhanced nutrition.

    Effect on the ability to drive transp. cf. and fur:

    Topiramate may cause drowsiness, dizziness.The drug should not be used during work for people whose profession is associated with the performance of potentially hazardous activities requiring special attention and quick reactions (driving and other vehicles, working with moving mechanisms, dispatcher and operator work, etc.).

    Form release / dosage:

    Film coated tablets, 25 mg and 100 mg.

    Packaging:

    For 28 tablets in cans of polymer complete with lids.

    Each bank along with the instruction for use is placed in a pack of cardboard.

    Storage conditions:

    In a place protected from light and moisture, at a temperature of no higher than 25 ° C.

    Keep in notavailableohm for children location.

    Shelf life:

    2 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-008276/10
    Date of registration:17.08.2010
    Expiration Date:Unlimited
    The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia
    Manufacturer: & nbsp
    Representation: & nbspVALENTA PHARM, PAO VALENTA PHARM, PAO Russia
    Information update date: & nbsp24.01.2017
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