Topyramat | Topamax capsules 50 mg, 60 pcs.

packaging 60 pcs - polyethylene bottles (1) - packs of cardboard

Pharmacological action

Antiepileptic drug, belongs to the class of sulfamate-substituted monosaccharides.

Topiramate blocks sodium channels and inhibits the occurrence of repeated action potentials against the background of prolonged depolarization of the neuron membrane. Topiramate increases the activity of GABA (GABA) against certain subtypes of GABA receptors (including GABAA receptors), it also modulates the activity of the GABAA receptors themselves, prevents the kainate from activating the sensitivity of the kainate / AMPK (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) subtype of glutamate receptors, does not affect the activity of NMDA with respect to the NMDA receptor subtype . These drug effects are dose-dependent at a plasma topiramate concentration of from 1 μmol to 200 μmol, with a minimum activity ranging from 1 μmol to 10 μmol.

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

Pharmacokinetics

Absorption

After oral administration, topiramate is rapidly and effectively absorbed from the digestive tract. Bioavailability is 81%. Eating does not have a clinically significant effect on the bioavailability of the drug.

The pharmacokinetics of topiramate is linear, the plasma clearance remains constant, and the AUC in the dose range from 100 mg to 400 mg increases in proportion to the dose.

After repeated oral administration at a dose of 100 mg 2 times / day, Cmax averages 6.76 μg / ml.

Distribution of

Plasma protein binding is 13-17%.

After a single oral dose of up to 1200 mg, the average Vd is 0.55-0.8 l / kg. Vd is sex dependent. In women, values ​​are approximately 50% of those observed in men, which is associated with a higher content of adipose tissue in the body of women.

In patients with normal renal function, it may take 4 to 8 days to reach equilibrium.

Metabolism

After oral administration, about 20% of the dose is metabolized.

6 practically inactive metabolites were isolated and identified from human plasma, urine and feces.

Excretion

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

After oral administration, the plasma clearance of the drug is 20-30 ml / min.

After multiple doses of 50 mg and 100 mg 2 times / day, the average T1 / 2 averaged 21 hours.

Pharmacokinetics in special clinical cases

The rate of topiramate excretion by the kidneys depends on renal function and does not depend on age.

In patients with moderate and severe renal impairment (CK 70 ml / min), renal and plasma clearance of topiramate is reduced, as a result, an increase in Css of topiramate in blood plasma is possible compared with patients with normal renal function. The time to reach Css of topiramate in plasma in patients with moderate or severe impaired renal function is 10 to 15 days. Patients with moderate or severe renal insufficiency are recommended to use half of the recommended initial and maintenance doses.

In the elderly, not suffering from kidney disease, the plasma clearance of topiramate does not change.

In patients receiving concomitant antiepileptic drug therapy that induces enzymes involved in drug metabolism, topiramate metabolism increased by 50%.

Topiramate is effectively eliminated by hemodialysis. Prolonged hemodialysis can lead to a decrease in the concentration of topiramate in the blood below the amount required to maintain anticonvulsant activity. In order to avoid a rapid drop in the concentration of topiramate in plasma during hemodialysis, an additional dose of Topamax® may be required. When adjusting the dose, one should take into account:

1) the duration of hemodialysis

2) the clearance of the used hemodialysis system

3) the effective renal clearance of topiramate in a patient undergoing dialysis.

Plasma clearance of topiramate is reduced by an average of 26% in patients with moderate or severe liver failure. Therefore, patients with hepatic insufficiency should use topiramate with caution.

In children under the age of 12, the pharmacokinetic parameters of topiramate, as well as in adults receiving the drug as adjuvant therapy, are linear in nature, while its clearance is dose-independent, and plasma Css increases in proportion to the dose increase. It should be noted that in children, the clearance of topiramate is increased, and its T1 / 2 is shorter. Therefore, at the same dose per 1 kg of body weight, plasma concentrations of topiramate in children can be lower than in adults. In children, as in adults, antiepileptic drugs that induce liver enzymes cause a decrease in the concentration of topiramate in blood plasma.

Indications

Epilepsy: as monotherapy in adults and children over 2 years old with epilepsy (including in patients with newly diagnosed epilepsy)

as part of complex therapy in adults and children over 2 years old with partial or generalized tonic-clonic seizures, as well as for treatment seizures on the background of Lennox-Gastaut syndrome.

Migraine: prevention of migraine attacks in adults (the use of TopamaxВ® for the treatment of acute migraine attacks has not been studied).

Contraindications

children under 2 years of age

hypersensitivity to the components of the drug.

Caution should be used for renal or hepatic insufficiency, nephrourolithiasis (including in the past or in a family history), and with hypercalciuria.

Use in cases of impaired liver function

Caution should be used in case of liver failure. In patients with moderate to severe impaired liver function, plasma clearance is reduced.

Application for impaired renal function

When prescribing the drug to patients with moderate or severely impaired renal function, it should be borne in mind that in order to achieve an equilibrium state in this category of patients, it may take 10-15 days, in contrast to 4-8 days in patients with normal function the kidneys. Since topiramate is removed from plasma during hemodialysis, an additional dose of the drug equal to half the daily dose should be prescribed in 2 days (before and after the procedure) on its days.

Caution should be used for renal failure, nephrourolithiasis (including in the past or in a family history), Since topiramate is removed from plasma during hemodialysis, an additional dose of the drug equal to half the daily dose should be prescribed in 2 days (before and after the procedure) on its days.

Caution should be used for renal failure, nephrourolithiasis (including in the past or in a family history), Since topiramate is removed from plasma during hemodialysis, an additional dose of the drug equal to half the daily dose should be prescribed in 2 days (before and after the procedure) on its days.

Caution should be used for renal failure, nephrourolithiasis (including in the past or in a family history),with hypercalciuria.

Use in children

The drug is contraindicated for use in children under 2 years of age.

Use during pregnancy and lactation

There have been no special controlled studies in which TopamaxВ® has been used to treat pregnant women. Topiramate can have a damaging effect on the fetus when used in pregnant women.

Pregnancy records indicate that infants exposed to intrauterine topiramate have an increased risk of developing congenital malformations (for example, craniofacial defects such as cleft lip or palate, hypospadias, and abnormalities in the development of various body systems). These malformations were recorded both with topiramate monotherapy and with its use as part of polytherapy.

Compared with the group of patients who are not taking antiepileptic drugs, pregnancy records with monotherapy with TopamaxВ® testify to an increased likelihood of giving birth to children with low body weight (less than 2500 g). The relationship of the observed phenomena with the drug has not been established. In addition, pregnancy counting data and the results of other studies indicate that the risk of teratogenic effects in combination treatment with antiepileptic drugs is higher than in monotherapy.

The use of TopamaxВ® during pregnancy is justified only if the potential benefit of the therapy to the mother outweighs the potential risk to the fetus.

When treating and consulting women of childbearing age, the attending physician should weigh the ratio of benefit and risk of treatment and consider alternative treatment options.

If TopamaxВ® is used during pregnancy, or if the patient became pregnant while taking the drug, she should be warned of the potential risk to the fetus.

A limited number of observations suggest that topiramate is excreted in breast milk in women. If you need to use the drug TopamaxВ® during lactation, you should decide whether to stop breastfeeding or to stop taking the drug.

Composition

1 caps.

topiramate 50 mg

Excipients: sugar grains (sucrose, starch syrup) - 150 mg, povidone - 34.733 mg, cellulose acetate - 18.076 mg.

Capsule shell composition: gelatin - 80.6-83.5 mg, water - 12.5-15.4 mg, sorbitan laurate - 0.0397 mg, sodium lauryl sulfate - 0.0397 mg, titanium dioxide (E171) - 0.99 mg, Opacode Black S-1-17822 / 23 ink black (a solution of shellac glaze in ethanol, black iron oxide, n-butyl alcohol, isopropyl alcohol, propylene glycol, ammonium hydroxide) - 5-10 μg.

Dosage and administration of

The drug is taken orally, regardless of food intake.

Capsules should be carefully opened, mix their contents with a small amount (about 1 teaspoon) of any soft food. This mixture should be swallowed immediately without chewing. Do not store the drug mixed with food until the next dose. Topamax® Capsules can be swallowed whole.

To achieve optimal control of epileptic seizures in adults and children, it is recommended to start treatment with taking the drug in low doses, followed by titration to an effective dose.

Capsules are intended for patients who have difficulty swallowing tablets (e.g., children and elderly patients).

Partial or generalized tonic-clonic seizures, as well as seizures associated with Lennox-Gastaut syndrome

Combination anticonvulsant therapy in adults. The minimum effective dose is 200 mg / day. Typically, the total daily dose is from 200 mg to 400 mg and is taken in 2 divided doses. Some patients may need to increase the daily dose to a maximum of 1600 mg. It is recommended to start treatment with a low dose followed by a gradual selection of an effective dose. Dose selection begins with 25-50 mg, taking them overnight for 1 week. In the future, at intervals of 1-2 weeks, the dose can be increased by 25-50 mg and taken in 2 doses. When choosing a dose, it is necessary to be guided by the clinical effect. In some patients, the effect can be achieved when taking the drug 1 time / day. To achieve the optimal effect of treatment with Topamax®, it is not necessary to control its plasma concentration.

These dose recommendations apply to all adult patients, including elderly patients, in the absence of kidney disease.

Combined anticonvulsant therapy in children over 2 years of age. The recommended total daily dose of Topamax® as an adjuvant is 5 to 9 mg / kg and is taken in 2 divided doses. Dose selection should begin with 25 mg (or less, based on an initial dose of 1 to 3 mg / kg per day) overnight for 1 week. In the future, the dose can be increased with an interval of 1-2 weeks by 1-3 mg / kg and taken in 2 doses. When choosing a dose, it is necessary to be guided by the clinical effect. A daily dose of up to 30 mg / kg is usually well tolerated.

Epilepsy (including first diagnosed)

When canceling concomitant anticonvulsants with topiramate monotherapy is necessary to take into account the possible effect of this step on the frequency of seizures. In those cases when there is no need to abruptly cancel concomitant anticonvulsants for safety reasons, it is recommended that their doses be reduced gradually, reducing the dose of concomitant antiepileptic drugs by 1/3 every 2 weeks.

With the cancellation of drugs that are inducers of microsomal liver enzymes, the concentration of topiramate in the blood will increase. In such situations, in the presence of clinical indications, the dose of Topamax® can be reduced.

With monotherapy, adults at the beginning of treatment with Topamax® are prescribed a dose of 25 mg at bedtime for 1 week. Then the dose is increased with an interval of 1-2 weeks by 25 mg or 50 mg in 2 divided doses. If the patient does not tolerate such a mode of increasing the dose, then you can increase the intervals between dose increases, or increase the dose more smoothly. When choosing a dose, it is necessary to be guided by the clinical effect. The initial dose for monotherapy with topiramate in adults is 100 mg / day, and the maximum daily dose should not exceed 500 mg. Some patients with refractory forms of epilepsy tolerate topiramate monotherapy in doses up to 1000 mg / day. These dosage recommendations apply to all adults, including elderly patients without kidney disease.

With monotherapy, children over 2 years of age in the first week of treatment are prescribed Topamax® at a dose of 0.5-1 mg / kg body weight at bedtime. Then the dose is increased with an interval of 1-2 weeks by 0.5-1 mg / kg / day in 2 divided doses. If the child does not tolerate such a dose increase regimen, then it is possible to increase the dose more smoothly or increase the intervals between dose increases. The magnitude of the dose and the rate of its increase depend on the clinical effect. The recommended dose range for topiramate monotherapy in children over the age of 2 years is 100-400 mg / day. Children with newly diagnosed partial seizures can be prescribed up to 500 mg / day.

Migraine

For the prevention of migraine attacks, the recommended daily dose of topiramate is 100 mg in 2 divided doses. At the beginning of treatment, 25 mg is prescribed at bedtime for 1 week. Then the dose is increased by 25 mg / day with an interval of 1 week. In case of intolerance to such a regimen of therapy, the dose is increased by a smaller amount or at large intervals. The dose is selected depending on the clinical effect. In some cases, a positive result is achieved with a daily dose of 50 mg topiramate. In clinical studies, patients received various doses of topiramate, but not more than 200 mg / day.

Special patient groups

Dose reduction may be necessary in patients with moderate or severe renal failure. It is recommended to use half of the recommended initial and maintenance dose.

Hemodialysis: since topiramate is removed from plasma during hemodialysis, an additional dose of Topamax® equal to about half the daily dose should be administered on the days of hemodialysis. The additional dose should be divided into two doses taken at the beginning and after completion of the hemodialysis procedure. The additional dose may vary depending on the characteristics of the equipment used during hemodialysis.

In patients with hepatic impairment, topiramate should be used with caution.

Side effects

Determination of the frequency of side effects: very often ( 1/10), often ( 1/100,

From the nervous system: very often - drowsiness, dizziness, paresthesia, in children - apathy, impaired attention often - nystagmus, lethargy, impaired concentration, attention loss, tremor, amnesia, hypesthesia, perversion of taste, impaired thinking, speech impairment, cognitive impairment, apathy, mental impairment, psychomotor disturbances , sedative infrequently - loss of taste sensitivity, akinesia, loss of smell, aphasia, apraxia, aura, burning sensation (mainly on the face and limbs), cerebellar syndrome, circadian sleep rhythm disturbance, arushenie coordination, complex partial seizures, convulsions, postural dizziness, increased salivation, dysesthesia, dysgraphia, dyskinesia, dysphasia, dystonia, tingling sensation throughout the body, tonic-clonic seizures of grand mal type hypersensitivity, gipogevziya, hypokinesia, hyposphresia, peripheral neuropathy, parosmia, fainting conditions, repeated speech, impaired touch, stupor, fainting, lack of response to stimuli, in children - psychomotor hyperactivity.

Mental disorders: often - slow thinking, confusion, depression, insomnia, aggressive reactions, agitation, disorientation, emotional lability, erectile dysfunction, in children - behavior changes infrequently - anorgasmia, sexual dysfunction, crying, sexual arousal, dyspemia, early morning awakenings, euphoric mood, auditory and visual hallucinations, hypomanic states, decreased libido, mania, panic state, paranoid states, perseveration of thinking, naru reading skills, restlessness, sleep disturbances, suicidal ideas or attempts, tearfulness is very rare - a feeling of hopelessness.

From the digestive system: very often - decreased appetite, anorexia often - nausea, diarrhea infrequently - abdominal pain, constipation, dry mouth, impaired sensation in the oral cavity, pancreatitis, increased appetite, gastritis, gastroesophageal reflux, gum bleeding, unpleasant bad breath, flatulence, glossodynia, pain in the oral cavity, thirst, dyspeptic symptoms (discomfort in the stomach, discomfort in the epigastric region, heaviness in the stomach), in children - vomiting.

From the musculoskeletal system: often - myalgia, muscle cramps, muscle cramps, muscle pain in the chest, arthralgia infrequently - side pain, muscle stiffness very rarely - swelling of the joints, discomfort in the limbs.

From the cardiovascular system: infrequently - bradycardia, palpitations, flushing, orthostatic hypotension, Raynaud's phenomenon.

From the side of the organ of vision: often - diplopia, impaired vision, dry eyes infrequently - impaired accommodation, amblyopia, blepharospasm, transient blindness, unilateral blindness, increased lacrimation, mydriasis, night blindness, photopsy, presbyopia, scotoma (including atrial ), decreased visual acuity is very rare - angle-closure glaucoma, involuntary movements of the eyeballs, eyelid edema, myopia, conjunctival edema, maculopathy.

On the part of the hearing organ: often - ear pain, ringing in the ears, in children - vertigo infrequently - deafness (including neurosensory and one-sided), discomfort in the ears, hearing impairment.

From the respiratory system: often - shortness of breath, nosebleeds infrequently - hoarseness, shortness of breath during physical exertion, nasal congestion, hypersecretion in the paranasal sinuses, in children - rhinorrhea is very rare - nasopharyngitis.

From the skin and subcutaneous tissues: often - rash, alopecia, itching, decreased sensitivity of the face infrequently - lack of perspiration, allergic dermatitis, redness of the skin, impaired skin pigmentation, unpleasant skin odor, urticaria very rarely - erythema multiforme, paraorbital edema, Stevens syndrome Johnson's toxic epidermal necrolysis.

From the urinary system: often - nephrolithiasis, dysuria, pollakiuria infrequently - exacerbation of urolithiasis, hematuria, urinary incontinence, frequent urination, renal colic, pain in the kidney area is very rare - renal tubular acidosis.

From the hemopoietic system: often - anemia infrequently - leukopenia, lymphadenopathy, thrombocytopenia, in children - eosinophilia is very rare - neutropenia.

On the part of laboratory indicators: infrequently - a decrease in the content of bicarbonates in the blood (on average by 4 mmol / L), crystalluria, leukopenia, hypokalemia (a decrease in the level of potassium in the blood serum below 3.5 mmol / L).

General disorders: very often - fatigue, irritability, weight loss often - asthenia, anxiety, in children - fever infrequently - facial swelling, allergic reactions, hyperchloremic acidosis, increased appetite, metabolic acidosis, polydipsia, cold limbs, fatigue, weakness , calcification is very rare - generalized edema, flu-like diseases, allergic edema, weight gain.

Drug Interaction

Effect of Topamax® on the Concentration of Other Antiepileptic Drugs (PEPs)

Co-administration of Topamax® with Other PETs (Phenytoin, Carbamazepine, Valproic Acid, Phenobarbita except in some patients whose addition of Topamax® to phenytoin may cause an increase in plasma phenytoin concentration. This may be due to the inhibition of the specific polymorphic isoform of the cytochrome P450 enzyme (CYP2Cmeph). Therefore, when developing symptoms of toxicity in patients receiving phenytoin, it is necessary to control the concentration of phenytoin in blood plasma.

In the study of pharmacokinetics in patients with epilepsy, the addition of topiramate to lamotrigine did not affect the latter's Css in blood plasma at doses of topiramate 100-400 mg / day. During and after discontinuation of lamotrigine (average dose of 327 mg / day), Css topiramate did not change.

Effects of other PEPs on plasma concentrations of topiramate in plasma

Phenytoin and carbamazepine when co-administered with Topamax® reduce plasma concentrations of topiramate. Addition or cancellation of phenytoin or carbamazepine on the background of treatment with Topamax® may require a change in dose of the latter. The dose is selected depending on the development of the desired clinical effect. The addition or cancellation of valproic acid does not cause clinically relevant changes in the plasma concentrations of topiramate and therefore does not require a change in the dose of Topamax®.

Dobavlyaem y PЭPKontsentratsyya PЭPKontsentratsyya topyramata

Fenytoynotsutstvye the effect (Increase concentrations in plasma in edynychn h cases) Reduction concentrations in plasma by 48%

Karbamazepynotsutstvye эffektasnyzhenye concentrations in plasma by 40%

Valproevaya kyslotaotsutstvye эffektaotsutstvye the effect

Fenobarbytalotsutstvye эffektane of research

Prymydonotsutstvye эffektane of research

Interaction with second drugs

In the studies with the simultaneous use of the drug that of Topamax® in a single dose of digoxin AUC decreased by 12%. The clinical significance of this effect has not been established. Serum digoxin concentrations should be monitored when prescribing or canceling Topamax® in patients receiving digoxin.

In clinical studies, the effects of co-administration of Topamax® with CNS depressants and with ethanol have not been studied. Co-administration of Topamax® with CNS depressant drugs and ethanol is not recommended.

When co-administered with Topamax and Hypericum perforatum, the concentration of topiramate in plasma may decrease and, as a consequence, the effectiveness of the drug may also decrease. Clinical studies of the interaction of the drug Topamax® and preparations based on St. John's wort have not been conducted.

With oral contraceptive containing norethisterone (1 mg) and ethinyl estradiol (35 μg), Topamax® at doses of 50-800 mg / day had no significant effect on the efficacy of norethisterone and at doses of 50-200 mg / day on the efficacy of ethinyl estradiol. A significant dose-dependent decrease in the efficacy of ethinylestradiol was observed at doses of the drug Topamax® 200-800 mg / day. The clinical significance of the described changes is not clear. The risk of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking oral contraceptives in combination with Topamax®. Patients taking estrogen-containing contraceptives should tell their doctor about any changes in the timing and nature of their periods. The effectiveness of contraceptives can be reduced even in the absence of breakthrough bleeding.

Healthy volunteers experienced a 18% decrease in lithium AUC with concomitant administration of topiramate at a dose of 200 mg / day. In patients with manic-depressive psychosis, the use of topiramate at doses up to 200 mg / day did not affect the pharmacokinetics of lithium, but at higher doses (up to 600 mg / day) AUC of lithium was increased by 26%. When co-administered with topiramate and lithium, the latter should be monitored for blood plasma.

Drug interaction studies conducted with single and multiple topiramate administration to healthy volunteers and patients with bipolar disorder have yielded similar results. Co-administration of topiramate with daily doses of 250 mg or 400 mg AUC of risperidone taken at 1-6 mg / day decreases by 16% and 33%, respectively. However, the pharmacokinetics of 9-hydroxyrisperidone did not change, and the total pharmacokinetics of the active substances (risperidone and 9-hydroxyrisperidone) did not change significantly. The change in the level of systemic exposure of risperidone / 9-hydroxyrisperidone and topiramate was not clinically relevant, and this interaction is unlikely to be clinically relevant.

Drug interactions have been studied in healthy volunteers with the separate and co-administration of hydrochlorothiazide (25 mg) and topiramate (96 mg). The results of the studies showed that when topiramate and hydrochlorothiazide were taken concomitantly, topiramate Cmax increased by 27% and its AUC by 29%. The clinical significance of these studies has not been identified. Patients receiving topiramate may require dose adjustment of topiramate when administering hydrochlorothiazide. No significant changes in the pharmacokinetic parameters of hydrochlorothiazide were observed with concomitant topiramate therapy.

Drug interaction has been studied in healthy volunteers receiving metformin or a combination of metformin and topiramate. The results of the studies showed that when topiramate and metformin were taken concomitantly, Cmax and AUC of metformin increased by 18% and 25%, respectively, whereas metformin clearance when administered with topiramate decreased by 20%. Topiramate had no effect on Tmax of metformin in blood plasma. Topiramate clearance decreases when co-administered with metformin. The extent of detected changes in clearance has not been studied. The clinical relevance of the effects of metformin on the pharmacokinetics of topiramate is unclear. If Topamax® is added or canceled in patients, receiving metformin, the condition of patients with diabetes mellitus should be monitored.

Drug interaction has been studied in healthy volunteers with separate and co-administration of pioglitazone and topiramate. Pioglitazone AUC was decreased by 15%, with no change in Cmax. These changes were not statistically significant. Also, for the active hydroxymetabolite of pioglitazone, a decrease of Cmax and AUC by 13% and 16%, respectively, was found, and for the active ketometabolite a decrease in both Cmax and AUC by 60% was detected. The clinical relevance of these data has not been elucidated. When co-prescribing patients with Topamax® and pioglitazone, the patient's condition should be carefully monitored to evaluate diabetes.

A drug interaction study was conducted to study the pharmacokinetics of glibenclamide (5 mg / day) in an equilibrium condition, used alone or concomitantly with topiramate (150 mg / day) in patients with type 2 diabetes. When using topiramate, the AUC of glibenclamide was reduced by 25%. The level of systemic exposure of active metabolites, 4-trans-hydroxy-glibenclamide and 3-cis-hydroxy-glibenclamide, was also reduced (by 13% and 15%, respectively). Glibenclamide did not affect the pharmacokinetics of topiramate in equilibrium. A statistically unreliable decrease in AUC of pioglitazone by 15% was detected in the absence of a change in its Cmax. When administering topiramate to patients receiving glibenclamide (or appointing glibenclamide to patients receiving topiramate), the patient's condition should be carefully monitored to evaluate the course of diabetes.

With the use of Topamax® with other drugs that predispose to nephrolithiasis, the risk of kidney stones may increase. The use of such drugs should be avoided during treatment with Topamax®, since they can cause physiological changes that promote nephrolithiasis.

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

Hypothermia (unintentional decrease in body temperature below 35 ° C) may occur with topiramate and valproic acid when combined with hyperammonemia or independently. This phenomenon can occur both after the start of co-administration of valproic acid and topiramate, and with an increase in the daily dose of topiramate.

Clinical studies have been conducted to evaluate potentially possible drug interactions between topiramate and other drugs. The results of this interaction are summarized in the table. what may be related to the accumulation of the drug in the process of achieving equilibrium

Overdose

Symptoms: convulsions, drowsiness, impaired speech and vision, diplopia, impaired thinking, impaired coordination, lethargy, stupor, arterial hypotension, abdominal pain, dizziness, agitation and depression. In most cases, the clinical consequences were not severe, but overdose deaths were reported using a mixture of several drugs, including topiramate. Severe metabolic acidosis may develop.

A case of overdose is known, when the patient took a dose of topiramate from 96 to 110 g, which resulted in a coma lasting 20-24 hours. After 3-4 days, the symptoms of overdose resolved.

Treatment: if shortly before taking an overdose, the patient has been taking food, it is necessary to immediately wash the stomach or cause vomiting. In vitro studies have shown that activated carbon adsorbs topiramate. If necessary, symptomatic therapy should be performed. Hemodialysis is an effective way of removing topiramate from the body. Patients are advised to adequately increase the volume of fluid consumed.

Storage conditions

The drug should be stored out of the reach of children, in a dry place at a temperature not exceeding 25 РC.

Expiration

2 years.

Deystvuyuschee substances

Topyramat

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Dosage form

Dosage form

capsules

Janssen Pharmaceutical N.V., Belgium