Topamax

Active material: Topiramate
When ATH: N03AX11
CCF: Anticonvulsants
ICD-10 codes (testimony): G40, G43
When CSF: 02.05.11
Manufacturer: JANSSEN PHARMACEUTICA N.V. (Belgium)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Capsules hard gelatin, size №2, with the shell white with inscription “15 mg” transparent colourless Cap with the inscription “THOR”; contents of capsules – granules white or nearly white.

Excipients: sugar nibs (sucrose, starch stream), povidone, cellulose acetate.

Ingredients of the capsule shell: gelatin, Purified water, silicon dioxide, sodium lauryl, Titanium dioxide, ink black Opakod S-1-17822/23 (contain iron oxide (E172)).

28 PC. – plastic bottles (1) – packs cardboard.
60 PC. – plastic bottles (1) – packs cardboard.

Capsules hard gelatin, size №1, with the shell white with inscription “25 mg” transparent colourless Cap with the inscription “THOR”; contents of capsules – granules white or nearly white.

Excipients: sugar nibs (sucrose, starch stream), povidone, cellulose acetate.

Ingredients of the capsule shell: gelatin, Purified water, silicon dioxide, sodium lauryl, Titanium dioxide, ink black Opakod S-1-17822/23 (contain iron oxide (E172)).

28 PC. – plastic bottles (1) – packs cardboard.
60 PC. – plastic bottles (1) – packs cardboard.

Capsules hard gelatin, size №0, with the shell white with inscription in black ink “50 mg” transparent colourless Cap inscribed with black ink “THOR”; contents of capsules – granules white or nearly white.

Excipients: sucrose, povidone, cellulose acetate, gelatin, Purified water, silicon dioxide, sodium lauryl, Titanium dioxide, ink Black Opacode S-1-1788/23 black (shellac glaze solution in ethanol, iron oxide black, n-butanol, isopropanol, propylene glycol, ammonium hydroxide).

28 PC. – plastic bottles (1) – packs cardboard.
60 PC. – plastic bottles (1) – packs cardboard.

Pharmacological action

The antiepileptic drug, belongs to the class of sulfate-substituted monosaccharide.

Topiramate blocks sodium channels and suppresses emergence of repetitive action potentials against the backdrop of a prolonged membrane depolarization of the neuron. Topiramate enhances GABA activity in relation to certain subtypes of GABA-a receptors (incl. GABA_A-receptors), as well as modulating the activity of GABA itself_A-receptors, prevents the activation of the kainatom subtype sensitivity 60/AMPK (Alpha-amino-3-Hydroxy-5-metilizoksazol-4-propionic acid) ^ receptors, does not affect the activity of the NMDA subtype NMDA against receptors. These effects of the drug doses are at concentration in plasma from topiramata 1 micromoles to 200 mmol, with a minimum of activity ranging from 1 micromoles to 10 mmol.

Besides, topiramate inhibits carbonic anhydrase isoenzymes activity by some. On the expressiveness of this pharmacological effect of topiramate significantly inferior to acetazolamidu – the known toxicities carboangidraza, Therefore, this activity is not the main component topiramata its protivojepilepticheskoj activity.

Pharmacokinetics

Absorption

After taking the drug inside topiramate quickly and efficiently absorbed from the digestive tract. Bioavailability is 81%. Food intake has no clinically meaningful actions on the bioavailability of the drug.

After receiving a drug inside pharmacokinetics topiramata whereby the, plasma clearance remains constant, and the AUC in the range of doses from 100 mg 400 mg increases with the dose.

After repeated oral dose 100 mg 2 times / day C_max averages 6.76 ug / ml.

Distribution

Plasma protein binding is 13-17%.

After a single intake of the dose to 1200 mg average V_d is 0.55-0.8 l / kg. The value V_d It depends on gender. Women are approximately 50% from the values, observed in men, that is associated with higher content of fat tissue in the body women.

In patients with normal renal function to achieve the equilibrium condition may need from 4 to 8 days.

Metabolism

After intake of metabolized about 20% dose.

From plasma, human urine and feces were isolated and identified 6 almost inactive metabolites.

Deduction

Topiramate (70%) and its metabolites are excreted mainly kidneys.

Once inside the plasma clearance of the drug is 20-30 ml / min.

After repeated dose on 50 mg 100 mg 2 times per day average T_1/2 averaged 21 no.

Pharmacokinetics in special clinical situations

Speed out topiramata kidneys depends on renal function and does not depend on age.

In patients with impaired renal function (CC ≤ 60 ml / min) Kidney and plasma clearance topiramata dropping.

Time to reach equilibrium in patients (c) mild or acute violations of the kidney is from 10 to 15 days.

In the elderly, not suffering from renal diseases, plasma clearance topiramata does not change.

In patients with moderately severe and severe violations of the liver decreases plasma clearance.

Patients, receiving concomitant antiepileptic drugs therapy, enzymes which induce, involved in the metabolism of drugs, metabolism at increased topiramata 50%.

Topiramate is excreted effectively by hemodialysis.

Children under the age of 12 years topiramata pharmacokinetic parameters as well as in adults, receiving the drug as adjuvant therapy, are linear in nature, the clearance does not depend on the dose, a C_ss in the plasma increases with increasing dose. It should be taken into account, topiramata ground children raised, but his T_1/2 a shorter. Therefore, when the same dose based on 1 kg body weight topiramata concentration in plasma in children may be lower, than in adults. Children, as in adults, antiepileptic drugs, inducing liver enzymes, cause decreased concentration topiramata in plasma.

Testimony

Epilepsy:

-as monotherapy in adults and children older than 2 years (incl. in patients with newly diagnosed epilepsy);

— as part of an integrated therapy in adults and children older than 2 years with parcialnymi or generalized tonic-klonicakimi seizures, as well as to treat seizures on background of Lennox-Gastaut syndrome.

Migraine:

-Prevention of migraine attacks in adults (application of Topamaks^® for the treatment of acute attacks of migraine is not known).

Dosage regimen

The drug is taken orally, regardless of the meal.

Capsule should carefully open, mix the contents with a little (about 1 teaspoon) any soft foods. This mixture must be swallowed, without chewing. Do not store medication, mixed with food, until the next admission. Topamaks Capsules^® can be swallowed whole.

Epilepsy

For optimal control of epileptic seizures in adults and children are advised to start treatment with the drug at low doses with subsequent titration to effective dose.

Capsules are intended for patients, experiencing difficulties with swallowing tablets (eg, children and elderly patients).

During the monotherapy adult, including elderly patients with normal renal function, at the beginning of treatment Topamaks^® appoint 25 mg 1 times per day at bedtime for 1 of the week. Then increase the dose at intervals of 1-2 weeks 25-50 mg / day 2 admission. In rejecting this regime therapy dose increased less or with large intervals. Dose selection criterion is the clinical effect. The initial dose is 100 mg / day, the maximum daily dose – 500 mg. In some cases, when persistent form of epilepsy patients endure interferon drug Topamaks^® at doses up to 1 g / day.

At monotherapy older children 2 years in the first week of treatment Topamaks^® administered at a dose of 0.5-1 mg/kg body weight before bedtime. Then increase the dose at intervals of 1-2 weeks 0.5-1 mg / kg / day, the daily dose is divided into 2 admission. In rejecting such treatment dose can be increased less or with large intervals. The magnitude of the dose and rate of its increase is determined by the clinical effectiveness of therapy. Recommended range dose with monotherapies topiramatom for children older than 2 s is 3-6 mg / kg / day. At newly diagnosed partial seizures pripadkah the dose may be up to 500 mg / day.

In applying the drug Topamaks^® of combination therapy with other anticonvulsants in Adult, including elderly patients with normal renal function, the minimum effective dose of 200 mg / day. The average daily dose is 200-400 mg, the multiplicity of reception – 2 times / day. Selection of doses begin with 25-50 mg 1 time / day at night, take medication for 1 of the week. Next, you should increase the dose to 25-50 mg at intervals of 1 or 2 weeks before the selection of effective dose; the multiplicity of reception – 2 times / day. If necessary, the daily dose can be increased up to a maximum – 1600 mg. Dose selection criterion is the clinical effect. Some patients effect is achieved in the employment drug 1 time / day. To achieve an optimal effect of treatment with Topamaks^® not necessarily to control its concentration in plasma.

In applying the drug Topamaks^® of combination therapy with other anticonvulsants in older children 2 years the recommended total daily dose ranges from 5 to 9 mg / kg, the multiplicity of reception – 2 times / day. Selection of doses begin with 25 mg / day (or less, calculated 1-3 mg / kg body weight / day), take medication at night for 1 of the week. In the future, with weekly or two weeks ' interval dose can be increased to 1-3 mg/kg and taking the drug in 2 admission. When selecting a dose should be guided by clinical effect. The daily dose of up to 30 mg / kg body weight, usually, well tolerated.

At abolition of the accompanying anticonvulsants, with the aim of monotherapy topiramatom it is necessary to take into account the potential impact of this step on the frequency of seizures. Where, When there is no need to abolish the accompanying sharply protivosudorozhny drug for safety reasons, It is recommended that you reduce the dose gradually, reducing the dose of collateral protivojepilepticheskogo drug on one third of every 2 of the week.

When you cancel a drugs, are inducers of liver enzymes, topiramata concentration in the blood will increase. In such situations, when there is clinical evidence dose Topamaks^® You can reduce the.

Migraine

To Prevention of migraines daily dose topiramata is 100 mg 2 admission. Early treatment appoint 25 mg before bedtime during 1 of the week. Then the dose 25 mg/day with an interval of 1 week. In rejecting this regime therapy dose increased less or with large intervals. Dose picked depending on clinical effect. In some cases, a positive result is achieved with a daily dose of topiramata 50 mg. In clinical studies, patients received different doses of topiramata, but not more 200 mg / day.

Side effect

Determining the frequency of side effects: Often (≥1/10), often (≥1/100, <1/10), sometimes (≥1 / 1000 <1/100), rarely (≥1/10 000 and <1/1000) and very rare (<1/10 000).

From the central and peripheral nervous system: Often – drowsiness, dizziness, paresthesia, children – apathy, impaired attention; often – incoordination, nistagmo, slackness, memory impairment, impaired concentration, tremor, amnesia, irregular gait, gipesteziya, perversion of taste sensations, aphronia, speech disorder, dysarthria, cognitive abnormality, apathy, Psychic ills, psychomotor disturbances, sedation; sometimes – loss of taste sensitivity, akinesia, anosmia, afazija, burning sensation (mainly on the face and extremities), Cerebellar syndrome, circadian rhythm sleep, awkward movements, postural dizziness, increased salivation, dysesthesia, Dysgraphia, dyskinesia, disfazija, feeling “formication” on the body, giperesteziya, gipogevzija, gipokineziya, hyposmia, perifericheskaya neuropathy, parosmija, predobmorochnye status, repeating it, paraphia, stupor, swoon, No responses to stimuli, children – psychomotor hyperactivity.

Mental disorders: often – slow thinking, confusion, depression, insomnia, aggressive reactions, excitation, irritability, loss of direction, emotional lability, jerektilnajaja dysfunction, children – behavior change; sometimes – anorgazmija, sexual dysfunction, cry, violation of sexual arousal, disfemija, early awakening in the morning, euphoric mood, auditory and visual hallucinations, gipomaniakalnyoe status, decrease in libido, mania, State of panic, paranoid state, perseveration of thinking, violation of reading skills, restlessness, sleep disorders, suicidal ideation or attempts, tearfulness; rarely – feeling of hopelessness.

From the digestive system: Often – decreased appetite, anorexia; often – nausea, diarrhea; sometimes – abdominal pain, constipation, dry mouth, violation of sensitivity in the oral cavity, gastritis, hastroэzofahealnыy reflux, krovotochivosty right, bad breath, flatulence, glossodiniya, pain in the mouth, thirst, dyspeptic symptoms (stomach discomfort, epigastric discomfort, heaviness in the stomach), children – vomiting.

On the part of the musculoskeletal system: often – myalgia, muscle spasms, muscle cramps, muscle pain in chest area, arthralgia; sometimes – pain in side, stiffness of muscles; rarely – swelling of joints, discomfort in the extremities.

Cardio-vascular system: sometimes – bradycardia, cardiopalmus, hot flushes, orthostatic hypotension, Raynaud's phenomenon.

On the part of the organ of vision: often – diplopia, blurred vision, dry eyes; sometimes – ccomodation, amblyopia, Nictitating spasm, transient blindness, unilateral blindness, increased lacrimation, midriaz, night blindness, photopsia, presbyopia, Atrial scotoma, scotoma, decrease of Visual acuity; rarely – zakrыtougolynaya glaucoma, violation of eye movements, swelling of the eyelids, myopia, conjunctival swelling.

On the part of the organ of hearing: often – ear pain, tinnitus, children – vertigo; sometimes – deafness, sensorineural deafness, single sided deafness, discomfort in the ears, hearing disorder.

The respiratory system: often – labored breathing, nose bleed; sometimes – hripota, shortness of breath on exertion, nasal congestion, hypersecretion in paranasal sinuses, children – rhinorrhea; rarely – nazofaringit.

Dermatological reactions: often – rash, alopecia, itch, decrease the sensitivity of the person; sometimes – the absence of sweating, atopic dermatitis, erythema, violation of skin pigmentation, swelling of the face, the unpleasant smell of leather, hives; rarely – erythema multiforme, paraorbitalnyj edema, Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the urinary system: often – nephrolithiasis, dizurija, thamuria; sometimes – urolithiasis disease, hematuria, urinary incontinence, frequent urination, počečnaâ how, pain in kidneys; rarely – pochechnokanalcevyj acidosis.

From the hematopoietic system: often – anemia; sometimes – leukopenia, lymphadenopathy, thrombocytopenia, children – eozinofilija; rarely – neutropenia.

Laboratory findings: sometimes – loss of bicarbonate in the blood (on average 4 mmol / l), kristallurija, leukopenia, kaliopenia (reduction in the level of potassium in the blood serum of below 3.5 mmol / l).

General disorders: Often – fatigue, irritability, weight loss; often – asthenia, anxiety, children – elevated temperature; infrequently – swelling of the face, allergic reactions, cold extremities; rarely – generalized edema, flu-like illness, Allergic swelling, weight gain.

Contraindications

- Children up to age 2 years;

- Hypersensitivity to the drug.

FROM caution should be used in renal or hepatic insufficiency, nefrourolitiaze (incl. in the past or family history), when hypercalciuria.

Pregnancy and lactation

Safety studies of the drug Topamaks^® in pregnant women were not conducted. Nonetheless, use Topamaks^® when pregnancy is possible only in cases, when the intended benefits to the mother outweighs the potential risk to the fetus.

A limited number of observations suggests, that topiramate is excreted in breast milk. If necessary, the use of the drug Topamaks^® lactation should decide the issue of termination of breastfeeding.

Cautions

Cancel Topamaks^® should gradually, to minimize the possibility of increasing the frequency of seizures. When conducting clinical trials drug dose reduced to 50-100 mg 1 once a week – for adults in the treatment of epilepsy and on 25-50 mg – adult, receiving Topamaks^® dose 100 mg/day for migraine prevention. Children in clinical research Topamaks^® gradually terminated during 2-8 weeks. If for medical reasons you need fast lifting preparation Topamaks^®, It is recommended that you monitor the patient's condition. Cancel the drug in some patients has been accelerated and passed without complications.

As with any disease dose selection scheme must be installed in accordance with clinical effect (that is, the degree of control of seizures, no side effects) and take into account the, patients with impaired kidney to establish a stable plasma concentration for each dose may need more time.

Topiramatom therapy is very important an adequate increase in fluids, that helps reduce the risk of nefrolitiaza, and side effects, which may occur under the influence of physical activity or elevated temperatures.

In the treatment of topiramate observed increased incidence of mood disorders and depression.

During the double-blind clinical studies using topiramate on approved and investigational indications, suicide attempts occurred at a frequency 0.003 while taking topiramate (13 cases among 3999 patsentov), placebo – a frequency 0 (0 cases among 430 patients). Was awarded one completed suicide attempt during a clinical study on the application of drugs in bipolar disorders.

In applying the drug Topamaks^® may increase the risk of Kidney stone formation and occurrence of related symptoms, such as renal colic, especially in patients with a predisposition to nefrolitiazu. Risk factors for nefrolitiaza are stone in history (incl. in the family), hypercalciuria, concomitant therapy with other drugs, contributing to the development of nefrolitiaza.

In applying the drug Topamaks^® Describes the syndrome, includes acute myopia with accompanying secondary zakratougolna glaucoma. Symptoms include acute decrease of Visual acuity and/or pain in the eye. In a survey of patients can be detected myopia, flattening the anterior Chamber of the eye, hyperemia (redness) eyeball, increased intraocular pressure. Mydriasis may occur. This syndrome may be accompanied by fluid secretion, resulting in the displacement of the lens and the iris forward with the development of secondary angle closure glaucoma. Symptoms usually begin 1 a month after the beginning of drug Topamaks^®. Unlike primary open angle glaucoma, which is rarely observed in patients up to 40 years, secondary angle-closure glaucoma occurs when applying topiramata as adults, and children. If you experience a syndrome, includes myopia, associated with zakratougolna glaucoma, treatment includes discontinuations Topamaks^®, as soon as your doctor deems this possible, and the corresponding measures, aimed at lowering intraocular pressure. Typically, these measures lead to the normalization of intraocular pressure.

Increased intraocular pressure of any etiology in the absence of adequate treatment can lead to serious complications, until vision loss.

When applying topiramata may occur giperhloremicheskij, not associated with deficiency of anions, metabolic acidosis (eg, reduction of the concentration of plasma bicarbonate below the normal level in the absence of respiratory alkalosis). Such a drop in serum bicarbonate concentration is a consequence of inhibiting effect on kidney topiramata carbonic anhydrase. In most cases, reduction of the concentration of bicarbonate occurs at the beginning of taking the drug, Although this effect can appear in any period of treatment topiramatom. Reduce the concentration level is typically weak or moderate (the average value is 4 mmol/l in the application in adult patients at a dose more 100 mg/day and about 6 mg/kg/day when used in pediatric practice). In rare cases, patients noted decreased concentration below 10 mmol / l. Some diseases or treatments, predisposing to the development of acidosis (eg, kidney disease, severe respiratory diseases, status epilepticus, diarrhea, surgery, ketogenic diet, taking certain medications) There may be additional factors, Add bicarbonate-reducing effect topiramata.

Children chronic metabolic acidosis can lead to stunted growth. Influence of topiramata on growth and possible complications, associated with skeletal system, not been studied systematically in children and adults.

In connection with the above,, When treating topiramatom is recommended to undertake the necessary research, including determination of the concentration of serum bicarbonate. If you experience a metabolic acidosis and its persistirovanii, It is recommended that you reduce the dose or stop taking the drug Topamaks^®.

If a dose Topamaks^® the patient decreases body weight, You should consider the appropriateness of nutritional.

In patients with liver Topamaks^® should be used with caution because of possible reduction topiramata ground clearance.

Effects on ability to drive vehicles and management mechanisms

Topamax^® acts on the central nervous system and may cause drowsiness, dizziness, blurred vision and other symptoms. These adverse effects can be dangerous for patients, Governors of the car and the traffic arrangements, especially at a time, until a patient's response to drug.

Overdose

Symptoms: convulsions, drowsiness, speech and vision, diplopia, thought disorders, incoordination, lethargy, stupor, hypotension, abdominal pain, dizziness, agitation and depression. In most cases, the clinical effects were not severe, but the deaths were noted after an overdose using a mixture of several drugs, including topiramate. May develop severe metabolic acidosis.

Treatment: If shortly before receiving excessive doses of medication a patient has food, You must immediately rinse the stomach or cause vomiting. In in vitro studies have shown, that activated charcoal to adsorb topiramate. If necessary, symptomatic therapy should be undertaken. Effective way of deducing from an organism topiramata is hemodialysis. Patients are advised to adequately increase in fluids.

Drug Interactions

The influence of the drug Topamaks^® the concentrations of other antiepileptic drugs (PEP)

Admission drug Topamaks^® with other PROBES (phenytoin, Carbamazepine, valproic acid, phenobarbital, prymydon) has no effect on the values of their sustained plasma concentrations. Simultaneous application of Topamaks^® led in some cases to increased concentrations fenitoina, due, apparently, oppression izofermenta (CYP2C_Map). Therefore, when developing symptoms of toxicity in patients, receiving phenytoin, There is a need to monitor fenitoina concentration in the blood plasma.

The study of pharmacokinetics in patients with epilepsy to add to lamotridzhinu topiramata will not affect C_ss the latest in plasma at doses topiramata 100-400 mg / day. During and after the abolition of lamotrigine (the average dose 327 mg / day) equilibrium concentration topiramata hasn't changed.

The influence of other PROBES on the concentration of plasma topiramata

Phenytoin and carbamazepine while applying the drug Topamaks^® lower topiramata concentration in plasma. Adding or canceling fenitoin or carbamazepine on background of drug treatment Topamaks^® may require dose changes last. Dose picked depending on the development of the necessary clinical effect. Add or cancel valproeva acid does not cause clinically significant changes of concentration of plasma and topiramata, Consequently, does not require changing the dosage Topamaks^®.

Interaction with other drugs

Studies, while applying the drug Topamaks^® in a single dose of Digoxin AUC was decreased to 12%. The clinical significance of this effect is not installed. In appointing or revoking the drug Topamaks^® patients, receiving digoxin, You must monitor the concentration of Digoxin in serum.

As part of clinical studies the effects of combined application of drug Topamaks^® with drugs, depressing the central nervous system, as well as with ethanol, We have not been studied. Joint application of Topamaks^® medicine, have a depressing effect on the central nervous system, and with ethanol is not recommended.

Together with the use of oral contraceptive, containing norethisterone (1 mg) and ethinyl estradiol (35 g), Topamax^® doses 50-800 mg/day had no significant impact on the effectiveness of norethisterone and doses 50-200 mg / day – on the effectiveness of ethinyl estradiol. Clinical significance of the described changes is not clear. Significant dose-related decrease in the effectiveness of ethinyl estradiol were observed at doses of the drug Topamaks^® 200-800 mg / day. The risk of reducing the effectiveness of contraceptives and the strengthening of breakthrough bleeding should be considered in patients, taking oral contraceptives, combined with the drug Topamaks^®. Sick, estrogensoderzhaschie taking contraceptives, You should tell your doctor about any changes the timing and nature of menstruation. Contraceptive effectiveness can be reduced even in the absence of breakthrough bleeding.

In healthy volunteers, there was a reduction in the AUC of lithium 18% while receiving topiramate at a dose 200 mg / day. In patients with manic-depressive psychosis application of topiramate at dosages up to 200 mg / day had no effect on the pharmacokinetics of lithium, However, at higher doses (to 600 mg / day) AUC was increased by Lithium 26%. While applying topiramata and lithium should monitor the concentration of plasma of blood.

Drug interaction studies, made with single and multiple introduction topiramata healthy volunteers and patients with manic-depressive, gave the same results. While applying topiratama in daily doses 250 mg or 400 mg AUC risperidone, received doses 1-6 mg / day, reduced accordingly on the 16% and 33%. When the pharmacokinetics 9-gidroksirisperidona has not changed, and total pharmacokinetics of active substances (risperidone and 9-gidroksirisperidona) changed slightly. Change the level of systemic effects of risperidone/9-gidroksirisperidona and topiramata was not clinically significant, and this interaction is unlikely to be of clinical significance.

Prescribed drug interaction has been studied in healthy volunteers in the separate and joint appointment hydrochlorothiazide (25 mg) and topiramata (96 mg). Research has shown, that while admission topiramata and hydrochlorothiazide, increase C_max topiramata on 27% and his AUC on 29%. The clinical significance of these studies not found. In appointing the hydrochlorothiazide patients, receiving topiramate, may require dose adjustment topiramata. There were no significant changes farmakokineticeskih parameters of hydrochlorothiazide in related therapy topiramatom.

Prescribed drug interaction has been studied in healthy volunteers, treated with metformin or a combination of metformin and topiramata. Research has shown, that while admission topiramata and metformin increases (C)_max and AUC of metformin on 18% and 25% respectively, whereas the clearance of metformin together with the appointment of topiramatom fell 20%. Topiramate does not affect t_max metformin in plasma. Topiramata ground clearance with a joint appointment with metformin decreases. The degree of change identified clearance has not been studied. Clinical significance of the impact of metformin on farmakokinetiku topiramata not clear. If you are adding or withdrawal of the drug Topamaks^® patients, receiving metformin, Special attention should be paid to careful study of diabetic status of these patients.

Prescribed drug interaction has been studied in healthy volunteers in the separate and joint appointment pioglitazon and topiramata. Reduction in AUC was detected pioglitazon on 15%, without changing C_max product. These changes were not statistically significant. Also for active gidroksimetabolita pioglitazon revealed reduced C_max and AUC of 13% and 16% respectively, and for active ketometabolita reduction were identified and C_max and AUC of 60%. The clinical significance of these data is not clear. The joint appointment patients drug Topamaks^® and pioglitazon, Special attention should be paid to careful study of diabetic status of these patients.

A study was conducted to examine drug interactions pharmacokinetics glibenklamida (5 mg / day) at equilibrium, used in isolation or in conjunction with topiramatom (150 mg / day) patients with diabetes 2 type. When applying the declining glibenklamida AUC topiramata 25%. Was also lowered the level of systemic effects of active metabolites – 4-TRANS-2-hydroxy-CIS 3 and glibenklamida-hydroxy-glibenklamida (respectively 13% and 15%). Glibenclamide does not affect the farmakokinetiku topiramata in equilibrium. Detected statistically unreliable reduction AUC pioglitazon on 15% If there is no change in its C_max. When assigning topiramata sick, receiving glibenclamide (or destination glibenklamida sick, receiving topiramate), the patient should be closely monitored to assess the flow of diabetes.

While applying the drug Topamaks^® with other drugs, conducive to the development of nefrolitiaza, may increase the risk of Kidney stone formation. During drug treatment Topamaks^® These drugs should be avoided, because they can cause physiological changes, conducive to the development of nefrolitiaza.

Combined application of topiramata and valproeva acid in patients, good tolerate each medication individually, accompanied by giperammoniemiei with or without encephalopathy. In most cases, symptoms and signs disappear after the cancellation of one of the drugs. This unfortunate phenomenon is not due to farmakokineticski interactions. The relationship between giperammoniemiei and application topiramata in isolation or in combination with other drugs is not installed.

To assess potential options for the drug interaction between topiramatom and other drugs in clinical trials have been conducted. The results of this interaction are summarized in table.

*expressed in % the values of C_max and AUC when alone
**no change (C)_max и AUC (≤ 15% from the source data)
¹ After repeated admission flunarizina (monotherapy) There was an increase in AUC on 14%, that may be due to accumulation of the drug in the process of achieving equilibrium

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children, dry place at temperatures no higher than 25 ° C. Shelf life – 2 year.