Topamax capsules 25 mg 60 pcs
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Active ingredients
Release form
Composition
Active ingredient: Topiramate
Concentration of active ingredient (mg): 25 mg
Pharmacological effect
Antiepileptic drug belongs to the class of sulphamate-substituted monosaccharides. Topiramate blocks sodium channels and suppresses the occurrence of repeated action potentials against the background of long-term depolarization of the neuron membrane. Topiramate increases the activity of gaba (gamk) in relation to certain subtypes of gaba receptors (including gabaa receptors), and also modulates the activity of the gabaa receptors themselves, and prevents the kainate / ampk sensitivity (alpha-amino-3-hydroxy -5-methylisoxazole-4-propionic acid) glutamate receptors, does not affect the activity of nmda in relation to the nmda receptor subtype. These effects of the drug are dose-dependent when plasma topiramate concentration is 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 isoenzymes of carbonic anhydrase. In terms of the severity of this pharmacological effect, topiramate is significantly inferior to acetazolamide, a known inhibitor of carbonic anhydrase, therefore this activity of topiramate is not the main component of its antiepileptic activity.
Pharmacokinetics
Absorption after taking the drug inside topiramate is quickly and effectively absorbed from the gastrointestinal tract. Bioavailability is 81%. Eating does not have a clinically significant effect on the bioavailability of the drug. Topramata pharmacokinetics is linear, plasma clearance remains constant, and AUC in the dose range from 100 mg to 400 mg increases in proportion to the dose. After repeated ingestion in a dose of 100 mg 2 times / day, Cmax averages 6.76 mcg / ml. DistributionPlasma 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 value depends on gender. In women, values are approximately 50% of the values 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 achieve an equilibrium.Metabolism after ingestion is metabolized to about 20% of the dose. 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 ingestion of plasma clearance of the drug is 20-30 ml / min. After repeated administration of the drug in 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 the kidney function and does not depend on age. In patients with impaired renal function of moderate and severe (CK ≤ 70 ml / min), the renal and plasma clearance of topiramate decreases, resulting in an increase in plasma Css of topiramate in blood plasma compared with patients with normal renal function. The time to Css topiramate in blood plasma in patients with moderate or severe renal impairment is from 10 to 15 days. Patients with moderate to severe renal insufficiency are recommended to use half of the recommended initial and maintenance dose. In the elderly, not suffering from kidney disease, plasma clearance of topiramate does not change. In patients receiving concomitant therapy with antiepileptic drugs that induce enzymes involved in the metabolism of drugs, the metabolism of topiramate 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 plasma topiramate concentration during hemodialysis, it may be necessary to prescribe an additional dose of Topamax. Dose adjustment should take into account: 1) the duration of hemodialysis; 2) the amount of clearance of the used hemodialysis system; 3) effective renal clearance of topiramate in a patient on dialysis. Plasma clearance of topiramate is reduced by an average of 26% in patients with moderate to severe liver failure. Therefore, patients with hepatic impairment 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 an adjunct therapy are linear, while its clearance does not depend on the dose, and Css in plasma increases in proportion to the dose increase. It should be borne in mind that in children the clearance of topiramate is increased, and its T1 / 2 is shorter. Therefore, with the same dose per 1 kg of body weight, plasma topiramate concentrations in children may be lower than in adults. In children, as in adults, antiepileptic drugs that induce hepatic enzymes, cause a decrease in the concentration of topiramate in the blood plasma.
Indications
Epilepsy. As a means of monotherapy: in adults and children older than 2 years with epilepsy (including patients with newly diagnosed epilepsy). As part of complex therapy: in adults and children older than 2 years with partial or generalized tonic-clonic seizures, as well as for the treatment of seizures against the background of Lennox-Gastaut syndrome. Migraine. Prevention of migraine attacks in adults. The use of Topamax for the treatment of acute migraine attacks has not been studied.
Contraindications
Precautionary measures
Use during pregnancy and lactation
Special controlled studies in which Topamax was used to treat pregnant women have not been conducted. Topiramate can have a damaging effect on the fetus when used in pregnant women. Pregnancy records show that infants exposed to intrauterine topiramate have an increased risk of congenital malformations (for example, craniofacial defects such as cleft lip or palate, hypospadias, and developmental abnormalities of various body systems). These malformations were recorded both in monotherapy with topiramate and in its use in the framework of polytherapy.Compared with the group of patients not taking antiepileptic drugs, the record of pregnancies with monotherapy with Topamax indicates an increase in the likelihood of having children with low body weight (less than 2500 g). The relationship of the observed phenomena with the drug is not installed. In addition, the records of pregnancies and the results of other studies suggest that the risk of teratogenic effects in the combined treatment with antiepileptic drugs is higher than in monotherapy. Use of the drug Topamax during pregnancy is justified only in the case when the potential benefits of therapy for the mother outweigh the possible risk to the fetus. When treating and consulting women of childbearing age, the attending physician should weigh the ratio of benefits and risks of treatment and consider alternative treatment options. If Topamax 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 necessary, the use of the drug Topamax during lactation should decide on the termination of breastfeeding or discontinuation of the drug.
Dosage and administration
Inside, regardless of the meal. To achieve optimal control of epileptic seizures in children and adult patients, it is recommended to begin treatment with the administration of low doses of the drug, followed by gradual titration to an effective dose. Capsules are intended for patients who have difficulty swallowing pills (for example, children and elderly patients). Topamax capsules should be carefully opened, mix the contents of the capsules 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. Capsules Topamax can be swallowed whole. Partial or generalized tonic-clonic seizures, as well as seizures against the background of the syndrome Lennox-Gastopplication in combination with other anticonvulsants in adult patients. The minimum effective dose is 200 mg per day.Usually, the total daily dose ranges from 200 mg to 400 mg and is taken in two doses. Some patients may need to increase the daily dose to the maximum - 1600 mg. It is recommended to start treatment with a low dose, followed by gradual selection of an effective dose. The selection of the dose begins with 25-50 mg, taking them overnight for 1 week. In the future, with weekly or two-week intervals, the dose can be increased by 25-50 mg and taken in two doses. The selection of the dose should be guided by the clinical effect. In some patients, the effect can be achieved when taking the drug 1 time per 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 the elderly, in the absence of kidney disease (see section “Special Instructions”). Combined anticonvulsant therapy in children older than 2 years: The recommended total daily dose of Topamax as an additional therapy is from 5 to 9 mg / kg and is taken in two doses. The selection of the dose should be started with 25 mg (or less, based on the initial dose of 1 to 3 mg / kg per day), taking them overnight for 1 week. In the future, with weekly or two-week intervals, the dose can be increased by 1–3 mg / kg and taken in two doses. The selection of the dose should be guided by the clinical effect. Daily dosages up to 30 mg / kg are usually well tolerated. Epilepsy (including first diagnosed) Monotherapy: general provisions:
When canceling concomitant anticonvulsant drugs for the purpose of monotherapy with topiramate, it is necessary to consider the possible influence of this step on the frequency of seizures. In cases where there is no need to abruptly cancel concomitant anticonvulsants for safety reasons, it is recommended to reduce their doses gradually, reducing the dose of concomitant anti-epileptic drugs by one third every 2 weeks. With the abolition of drugs that are inducers of liver microsomal enzymes, concentrations of topiramate in the blood will increase. In such situations, in the presence of clinical indications, the dose of Topamax can be reduced. Monotherapy: adults:
At the beginning of treatment, the patient should take 25 mg of Topamax at bedtime for 1 week. Then the dose is increased with an interval of 1 to 2 weeks for 25 or 50 mg (the daily dose is divided into two doses). If the patient does not tolerate such a mode of increasing the dose, it is possible to increase the intervals between dose increases, or to increase the dose more smoothly. The selection of the dose should be guided by the clinical effect. The initial dose for monotherapy with topiramate in adults is 100 mg per day, and the maximum daily dose should not exceed 500 mg. Some patients with refractory forms of epilepsy tolerate monotherapy with topiramate in doses up to 1000 mg per day. These dosing recommendations apply to all adults, including elderly patients without kidney disease. Monotherapy: children:
Children over the age of 2 years in the first week of treatment should be given topiramate at a dose of 0.5-1 mg / kg body weight before bedtime. Then the dose is increased at intervals of 1-2 weeks at 0.5-1 mg / kg per day (the daily dose is divided into two doses). If the child does not tolerate such a mode of increasing the dose, 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 should be determined by the clinical result. The recommended dose range for monotherapy with topiramate in children over the age of 2 years is 100-400 mg / day. Children with newly diagnosed partial seizures can be given up to 500 mg per day. Migraine: The recommended total daily dose of topiramate for the prevention of migraine attacks is 100 mg, taken in 2 divided doses. At the beginning of treatment, the patient should take 25 mg of Topamax at bedtime for 1 week. Then the dose is increased with an interval of 1 week at 25 mg per day. If the patient does not tolerate such a mode of dose increase, then it is possible to increase the intervals between dose increases, or to increase the dose more smoothly. The selection of the dose should be guided by the clinical effect. In some patients, a positive result is achieved with a daily dose of topiramate 50 mg. In clinical studies, patients received various daily doses of topiramate, but not more than 200 mg per day. Special patient groups: Renal failure: Patients with moderate or severe renal insufficiency may need a dose reduction. The use of half the recommended initial and maintenance dose is recommended.Hemodialysis: Since topiramate is removed from plasma during hemodialysis, on the days of hemodialysis, an additional dose of Topamax should be administered, equal to about half the daily dose. 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. Hepatic insufficiency In patients with hepatic insufficiency, topiramate should be used with caution.
Side effects
Undesirable reactions are given with distribution by frequencies and organ systems. The frequency of adverse reactions was classified as follows: very often (≥1 / 10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000 and <1/100), rarely (≥1 / 10000 and < 1/1000) and the frequency is unknown (the frequency cannot be estimated from the available data). The most frequent adverse reactions (the frequency of which was more than 5% and exceeded that in the placebo group for at least one of the indications in controlled clinical studies of topiramate) are: anorexia, loss of appetite, delayed thinking, depression, impaired speech, insomnia, disorders motor coordination, concentration disorder, dizziness, dysarthria, dysgeusia, hypoesthesia, inhibition, memory impairment, nystagmus, paresthesia, drowsiness, tremor, diplopia, blurred vision, iareya, nausea, fatigue, irritability and a decrease in body weight. Infections and invasions: very often: nasopharyngitis *. Disorders of the blood and lymphatic system: often: anemia; infrequently: leukopenia, lymphadenopathy, thrombocytopenia, eosinophilia; rarely: neutropenia *. Immune system disorders: often: hypersensitivity; frequency unknown: allergic edema *, conjunctival edema *. Metabolic and nutritional disorders: often: anorexia, loss of appetite; infrequently: metabolic acidosis, hypokalemia, increased appetite, polydipsia; rarely: hyperchloremic acidosis. Mental disorders: very often: depression; often: delayed thinking, insomnia, disturbed speech, anxiety, confusion, disorientation, aggressive reactions, mood disorders, agitation, emotional lability, depressive mood,anger, behavior disorder; infrequently: suicidal thoughts, attempted suicide, hallucinations, psychotic disorders, auditory hallucinations, visual hallucinations, apathy, difficulty speaking, sleep disorders, affective lability, decreased libido, agitated state, crying, dysfemia, euphoric mood, paranoia, persever. , tearfulness, impaired reading skills, impaired sleep, flattening of emotions, abnormal thinking, loss of libido, lethargy, intrasomnic disorder, confusion, early wake up in the morning, pan cal reaction, elevated mood; seldom: mania, panic disorder, feeling of hopelessness *, hypomania. Violations of the central nervous system: very often: paresthesias, drowsiness, dizziness; often: impaired concentration, impaired memory, amnesia, cognitive disorders, impaired thinking, psychomotor disturbances, convulsions, impaired motor coordination, tremor, lethargy, hypoesthesia, nystagmus, dysgeusia, impaired sense of balance, dysarthria, intentional tremor, sedation; infrequently: depression, tonic-clonic seizures of the “grand mal” type, visual field disturbance, complex partial seizures, speech disorder, psychomotor hyperactivity, syncope, sensory disturbances, drooling, hypersomnia, aphasia, repetitive speech, hypokinesia, dyskinesia, postural dizziness , poor quality of sleep, burning sensation, loss of sensitivity, parosmia, cerebral syndrome, dysesthesia, hypogemia, stupor, clumsiness, aura, agevziya, dysgraphia, dysphasia, peripheral neuropathy, pre-fainting, dystonia, tingling sensation in the body; rarely: apraxia, disturbance of the circadian rhythm of sleep, hyperesthesia, hyposmia, anosmia, essential tremor, akinesia, lack of response to stimuli. Violations of the organ of vision: often: blurred vision, diplopia, visual disturbances; infrequently: reduction of visual acuity, scotoma, myopia *, strange sensations in the eyes *, dry eyes, photophobia, blepharospasm, increased tearing, photopsia, mydriasis, presbyopia; rarely: unilateral blindness, transient blindness, glaucoma, disturbance of accommodation, disturbance of visual spatial perception, atrial scotoma, eyelid edema *, night blindness, amblyopia; frequency unknown: angle-closure glaucoma *, maculopathy *, impaired mobility of the eye *.Disturbances of the organ of hearing and balance: often: vertigo, tinnitus, earache; infrequently: deafness, unilateral deafness, neurosensory deafness, discomfort in the ear, hearing impairment. Cardiovascular disorders: Infrequent: bradycardia, sinus bradycardia, palpitations. Violations of the vascular system: infrequent: hypotension, orthostatic hypotension, hot flashes, hot flushes; rarely: Raynaud's phenomenon. Disturbances of the respiratory system, organs of the chest and mediastinum: often: shortness of breath, nosebleeds, nasal congestion, rhinorrhea, cough *; infrequently: dyspnea on exertion, hypersecretion in the paranasal sinuses, dysphonia. Disorders of the gastrointestinal tract: very often: nausea, diarrhea; often: vomiting, constipation, pain in the epigastric region, dyspepsia, abdominal pain, dry mouth, stomach discomfort, impaired sensitivity in the mouth, gastritis, abdominal discomfort; infrequently: pancreatitis, flatulence, gastroesophageal reflux, pain in the lower abdomen, decreased sensitivity in the mouth, bleeding gums, abdominal distention, discomfort in the epigastric region, sensitivity in the abdomen, hypersalivation, oral pain, unpleasant smell, glosses, unpleasant smell, glosses, gloom . Disorders of the hepatobiliary system: rarely: hepatitis, liver failure. Violations of the skin and subcutaneous tissues: often: alopecia, rash, itching; infrequently: anhidrosis, a violation of sensitivity in the face, urticaria, erythema, generalized itching, macular rash, a violation of skin pigmentation, allergic dermatitis, swelling of the face; infrequently: Stevens-Johnson syndrome *, polymorphic erythema *, change in skin odor, paraorbital edema *, localized urticaria; frequency unknown: toxic epidermal necrolysis *. Disorders of the musculoskeletal system and connective tissue: often: arthralgia, muscle spasms, myalgia, muscle cramps, muscle weakness, musculoskeletal pain in the chest cell; infrequently: swelling of the joints *, stiffness of the muscles, pain in the side, fatigue in the muscles; rarely: limb discomfort *. Kidney and urinary tract disorders: often: nephrolithiasis, pollakiuria, dysuria; infrequently: exacerbation of urolithiasis (kidney stones), stress urinary incontinence, hematuria, urinary incontinence, frequent urination, renal colic, pain in the kidneys; seldom: exacerbation of urolithiasis (stones in the urethra) renal tubular acidosis *.Disorders of the genital organs and breast: infrequently: erectile dysfunction, sexual dysfunction. General disorders and disorders caused by the method of application: very often: fatigue; often: increased body temperature, asthenia, irritability, gait disturbances, feeling unwell, anxiety; infrequently: hyperthermia, thirst, flu-like syndrome *, sluggishness, cold extremities, intoxication, anxiety; seldom: swelling of the face, calcification. Changes in laboratory parameters: very often: weight loss; often: weight gain *; infrequently: crystalluria, abnormal tandem-gait test, leukopenia, increased serum hepatic enzyme activity, rarely: decrease in blood bicarbonate content. Violations of social functioning: infrequently: impaired learning ability. * - undesirable reaction is registered in the post-registration period from spontaneous messages. The frequency is calculated on the basis of clinical research data. Special groups: Children: The following is a list of adverse reactions that were recorded in children 2 and more times more often in controlled clinical trials than in adults: loss of appetite, increased appetite, hyperchloraemic acidosis, hypokalemia, behavioral disorders, aggressive reactions, apathy, violation of sleep, suicidal thoughts, impaired concentration, lethargy, disturbance of the circadian rhythm of sleep, poor quality of sleep, increased lacrimation, sinus bradycardia, poor health, impaired walking ki The following is a list of adverse reactions that were registered in children only during controlled clinical trials: eosinophilia, psychomotor hyperactivity, vertigo, vomiting, hyperthermia, pyrexia, impaired ability to learn.
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 deaths were noted after an overdose using a mixture of several drugs, including topiramate. May develop severe metabolic acidosis.A case of overdose is known when the patient took a dose of topiramate from 96 to 110 g, which caused a coma lasting for 20-24 hours. After 3-4 days, the symptoms of overdose resolved. Treatment: if shortly before taking an excessive dose of the drug, the patient took food, immediately flush the stomach or induce vomiting. In vitro studies have shown that activated carbon adsorbs topiramate. If necessary, symptomatic therapy should be carried out. An effective way to remove topiramate from the body is hemodialysis. Patients are recommended an adequate increase in fluid intake.
Interaction with other drugs
The effect of Topamax on the concentrations of other antiepileptic drugs (AEP):
Simultaneous administration of Topamax with other AEDs (phenytoin, carbamazepine, valproic acid, phenobarbital, primidone) does not affect plasma Css values, except for certain patients in whom the addition of Topamax to phenytoin may cause an increase in plasma phenytoin concentration. This may be due to the inhibition of a specific polymorphic isoform of the cytochrome P450 enzyme system (CYP2Cmeph). Therefore, when symptoms of toxicity develop in patients receiving phenytoin, it is necessary to control the concentration of phenytoin in the blood plasma. In the pharmacokinetic study of patients with epilepsy, the addition of topiramate to lamotrigine did not affect the Css of the latter in plasma at doses of topiramate 100-400 mg / day. During and after the abolition of lamotrigine (the average dose of 327 mg / day), Css topiramate did not change. The effect of other AEDs on plasma plasma topiramate concentration Phenytoin and carbamazepine, while using Topamax, reduced the plasma concentration of topiramate. Adding or removing phenytoin or carbamazepine during treatment with Topamax may require a change in the dose of the latter. The dose is selected depending on the development of the required clinical effect. Addition or removal of valproic acid does not cause clinically significant changes in the concentration of topiramate in the blood plasma and, therefore, does not require a change in the dose of Topamax. Added PEP Concentration of PEP Concentration of Topiramate Phenytoin no effect (increase in plasma concentration in isolated cases) decreaseplasma concentrations by 48% Carbamazepine no effect plasma concentration decreased by 40% Valproic acid no effect no effect Phenobarbital no effect not studied Primidone no effect not investigated Interaction with other drugs In conducted studies with simultaneous use of the drug Topamax in a single dose of digestive AUC digoxin 12% . The clinical significance of this effect has not been established. When prescribing or canceling Topamax in patients receiving digoxin, it is necessary to monitor the concentration of digoxin in the serum. As part of clinical studies, the effects of the combined use of Topamax with drugs that depress the central nervous system, as well as with ethanol, have not been studied. The combined use of Topamax with drugs that have a depressant effect on the central nervous system and ethanol is not recommended. When Topamax and Hypericum perforatum preparations are taken together, Topiramate concentration in the plasma may decrease and, as a result, the effectiveness of the drug may also decrease . Clinical studies of the interaction of the drug Topamax and preparations based on Hypericum perforatum have not been conducted. With simultaneous use of an oral contraceptive containing norethisterone (1 mg) and ethinyl estradiol (35 μg), Topamax at doses of 50-800 mg / day did not significantly affect the effectiveness of norethisterone in doses of 50-200 mg / day - on the effectiveness of ethinyl estradiol. A significant dose-dependent decrease in the efficacy of ethinyl estradiol was observed at doses of the drug Topamax 200-800 mg / day. The clinical significance of the described changes is not clear. The risk of reducing the effectiveness of contraceptives and enhancing breakthrough bleeding should be considered in patients taking oral contraceptives in combination with Topamax. Patients taking estrogen-containing contraceptives should inform the doctor about any changes in the timing and nature of menstruation. The effectiveness of contraceptives can be reduced even in the absence of breakthrough bleeding. In healthy volunteers, lithium AUC decreased by 18% while taking topiramate at a dose of 200 mg / day.In patients with manic-depressive psychosis, the use of topiramate in doses up to 200 mg / day did not affect the pharmacokinetics of lithium, but at higher doses (up to 600 mg / day), lithium AUC was increased by 26%. With the simultaneous use of topiramate and lithium should monitor the concentration of the latter in the blood plasma. Studies of drug interactions conducted with a single and multiple administration of topiramate to healthy volunteers and patients with bipolar disorder, gave the same results. With the simultaneous use of topiratam in daily doses of 250 mg or 400 mg of AUC of risperidone, taken in doses of 1-6 mg / day, reduced by 16% and 33%, respectively. At the same time, the pharmacokinetics of 9-hydroxyrisperidone did not change, and the total pharmacokinetics of the active substances (risperidone and 9-hydroxyrisperidone) changed insignificantly. Changes in the level of systemic exposure to risperidone / 9-hydroxyrisperidone and topiramate were not clinically significant, and this interaction is unlikely to have clinical significance. Drug interaction was studied in healthy volunteers with separate and co-administration of hydrochlorothiazide (25 mg) and topiramate (96 mg). The research results showed that while taking topiramate and hydrochlorothiazide, there is an increase in Cmax of topiramate by 27% and its AUC by 29%. The clinical significance of these studies has not been identified. When administering hydrochlorothiazide to patients taking topiramate, dose adjustment of topiramate may be required. No significant changes in the pharmacokinetic parameters of hydrochlorothiazide were observed with concomitant therapy with topiramate. Drug interactions were studied in healthy volunteers who received metformin or a combination of metformin and topiramate. Research results showed that while taking topiramate and metformin, Cmax and AUC of metformin increased by 18% and 25%, respectively, while clearance of metformin while being administered simultaneously with topiramate decreased by 20%. Topiramate had no effect on Tmax of metformin in the blood plasma. The clearance of a topiramat at joint appointment with metformin decreases. The degree of clearance changes have not been 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 Topamax in patients receiving metformin, the state of patients with diabetes should be monitored. Drug interactions have been studied in healthy volunteers with separate and co-administration of pioglitazone and topiramate. It was revealed a decrease in the AUC of pioglitazone by 15%, without changing the Cmax of the drug. These changes were not statistically significant. Also for the active hydroxymetabolite pioglitazone, a decrease in Cmax and AUC was detected by 13% and 16%, respectively, and for active ketometabolite, a decrease in both Cmax and AUC by 60% was detected. The clinical significance of this data has not been elucidated. When patients are jointly prescribed Topamax and pioglitazone, the patient’s condition should be carefully monitored to assess the course of diabetes. A drug interaction study was conducted to study the pharmacokinetics of glibenclamide (5 mg / day) in an equilibrium state, used alone or simultaneously 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 to active metabolites, 4-trans-hydroxy-glibenclamide and 3-cis-hydroxide, was also reduced.