Topiramate side effects. Medicinal reference book geotar. Instructions for use

We have selected real reviews about the drug Topiramate, which are published by our users. Most often, the review is written by mothers of small patients, but also describes a personal history of use. medicinal product on myself.

Indications for use

In monotherapy in adults and children from 6 years of age with partial (with or without secondary generalization) or primary generalized tonic-clonic convulsions;
- in the composition complex therapy in adults and children over 3 years of age with partial with or without secondary generalization or generalized tonic-clonic convulsions, as well as for the treatment of convulsions caused by Lennox-Gastaut syndrome;
- prevention of migraine attacks in adults after careful evaluation of all possible alternatives. Topiramate is not intended for the treatment of acute migraine attacks.

Discussion of the drug Topiramate in the records of mothers

Actions. These drugs include phenytoin, barbiturates, carbamazepine, rifampicin, ritonavir (an HIV protease inhibitor), roxcarbazepine, topiramate, felbamate, griseofulvin, and preparations containing St. John's wort. While taking drugs that affect microsomal enzymes and within 28 days after their withdrawal, you should additionally use a barrier method of contraception (condom and spermicidal gels). Drugs that affect the enterohepatic circulation Antibiotics of the penicillin series (ampicillin) and tetracyclines reduce the enterohepatic circulation of estrogens, increase...

B hassle fell every week. I finally got to a good neurologist with the question of what was wrong with me - they examined me with everything they could, finally made a diagnosis and prescribed the drug maxitopir (aka topiramate). And that's it, you know how you describe it - an active life and social activity, nothing in my life has changed - except that seizures and depression have gone (they sometimes accompany epilepsy). The main thing is not to drink alcohol and get enough sleep. Don't overwork. If you plow yourself that you don’t see anything around you and you don’t feel your legs under you, then there may be an attack, I had this once in three years - I worked 15 hours a day, seven days a week and ate at the computer (forced measures). ..

Film-coated actions Clonazepam tablets Lamotrigine tablets Primidone tablets Topiramate capsules; film-coated tablets Phenytoin tablets Phenobarbital tablets Ethosuximide capsules VIII. Drugs for the treatment of parkinsonism Bromocriptine tablets Levodopa + Carbidopa tablets Levodopa + Benserazide capsules; ta...

Diatra, ophthalmologist at the place of residence.2. Send to ITU for m!3. Compliance with the regime of the day.4. Valproic acid of prolonged action 450 mg in the morning + 450 mg in the evening - constantly! Topiramate 25 mg daily in the evening!6. Hopantenic acid 250 mg - 1/2 tab. 2 times a day - 1 month - April - 2 times a year.7. Control of KLA + thrombus. b / x blood (liver tests), ultrasound of organs abdominal cavity, kidneys I time per quarter.8. Hepatoprotectors (ursosan 250 mg - 1 capsule 1 r / s, inside, drinking plenty of water) - May - courses 2 times a year.9. Re-hospitalization in n\o IGODKB in a year. Disability was denied. How and for what can I buy medicines for a child? Ch...

Prolonged action tablets; prolonged-release film-coated tablets Clonazepam tablets Lamotrigine tablets Primidone tablets Topiramate capsules; film-coated tablets Phenytoin tablets Phenobarbital tablets Ethosuximide capsules VIII. Drugs for the treatment of parkinsonism Bromocriptine tablets Levodopa + Carbidopa tablets Levodopa + Benserazide capsules; dispersible tablets; tablets Piribedil film-coated tablets Tolperisone film-coated tablets Cyclodol tablets IX. Anxiolytics...

PA 20 trihexiphenidyl 21 pyribedil b) anti-epileptic drugs 22 benzobarbital 23 Valprooic acid 24 carbamazepine 25 clonazepam 26 lamatrhine 27 levetyracetam 28 Topiramate 29 phenytoin 30 phenobarbital 31 etosuximide 2) sedative and anxiolytic agents a) neuroleptics (antipsychotic) 32 galleapine 33 risperidone 36 Sulpiride 37 Thioridazine 38 Chlorpromazine b) anxiolytics (tranquilizers) 39 Bromdihydro-chlorophenyl-benzodiazepine 40 Diazepam 41 Medazepam 3) drugs for the treatment of manic-depressive (affective) states a) psychoanaleptics (antidepressants) 42 Amitriptyline 43 Pyrlindol...

Vnosti drug Jeanine. These drugs include: phenytoin, barbiturates, primidone, carbamazepine and rifampicin; there are also suggestions for oxcarbazepine, topiramate, felbamate, ritonavir and griseofulvin and products containing St. John's wort. Contraceptive protection is reduced when taking antibiotics (such as ampicillins and tetracyclines), since, according to some reports, some antibiotics can reduce the intrahepatic circulation of estrogens, thereby lowering the concentration of ethinyl estradiol. Oral combined contraceptives can affect the metabolism of other drugs (including cyclosporine), which leads to a change in their concentration in ...

We have a real problem - attacks every month, and by the spring even more often. How often do you have? Seizures with visual aura and numbness of the hand and cheek. The neurologist prescribed topiramate (anticonvulsant), but we did not give it, there are too many side effects. Have you been on cinnarizine alone? Any information is important to us.

Arbamazepine - tablets; prolonged action tablets; film-coated tablets of prolonged action. Clonazepam tablets. Lamotrigine tablets. Primidone tablets. Topiramate capsules; coated tablets. Phenytoin tablets. Phenobarbital tablets. Ethosuximide capsules. VI. Means for the treatment of allergic reactions Diphenhydramine tablets. Ketotifen tablets. Clemastine tablets. Levocetirizine film-coated tablets. Loratadine tablets. Mebhydrolin - dragee. Hifenadine tablets. Chloropyramine tablets. Cetirizine drops for oral administration; coated tablets. V. Other anti-inflammatory drugs Mesa...

One of the most unpleasant diseases of mankind is considered "falling", or epilepsy. Chronic neuropathy known to the human race since time immemorial. The ancient Greeks called it "Hercules disease", the Russians - "falling". Occurs in a person whose body is predisposed to the occurrence sudden attacks convulsive nature. The symptoms are unpleasant. A sudden epileptic seizure is accompanied by a violation of motor functions and uncontrolled response of organs internal secretion. The disease is the result of a sudden excessive excitation of the neurons of the cerebral cortex. Research in the field of searching for a drug that relieves muscle cramps of various etiologies has been going on for more than a century. To date, there are no more than two dozen, but the most effective antiepileptic drug is Topiramate.

Topiramate is an anticonvulsant, aimed at antiepileptic action by stopping muscle cramps. Also, the drug is effective in the treatment of various manifestations of psychosis, as an anti-manic drug in bipolar disorders. nervous system, including manic-depressive forms of psychosis.

Topiramate's spectrum of application includes:

• stresses of various origins, for example, post-traumatic nature
• alcoholism
• headaches of various etiologies
• neuropathy.

The special qualities of the drug include the ability to stabilize the mood, since it belongs to the group of normiotics. Thanks to all the above qualities, Topiramate belongs to the list of important and vital medicines.

Chemical characteristics

Topiramate, having the empirical formula C12H21NO8S, is a fructose derivative and has a complex chemical structure with a large molecular weight of 339.33 units. In pharmacology, it belongs to the group of drugs with antiepileptic properties. In clinical pharmacology, it belongs to the group of anticonvulsants with the ICD-10 nosological classification - G40 Epilepsy.

According to external indicators Chemical substance Topiramate is characterized as a powder consisting of white crystals, bitter in taste. Liquids that dissolve powder without sediment:

1. ethanol
2. acetone
3. dimethylsulfoxide
4. chloroform.

Pharmacological properties

The work of Topiramate as an antiepileptic drug is based on the principle of reducing the firing frequencies of neurons. The drug is characterized by selectivity in relation to the pathology of the manifested activity of neurons and inhibition of their activity. Three main pathways underlie the action of the drug:

• By raising the tone of GABA receptors, it activates inhibitory neurons.
• By reducing the dynamics of NMDA receptors, it inhibits the excitation of neuronal receptors.
• Direct action on receptors leads to the creation electrical impulse, due to which the regulation of ion channels of neurons occurs.

The ability of Topiramate to block sodium channels with the suppression of the possibility of the occurrence of secondary impulses caused by the potential difference on the depolarized membranes of neurons is characteristic of all antiepileptic drugs belonging to the class of sulfate-substituted monosaccharides.

Thanks to these qualities, there is an increase in the tone of GABA (GABA) receptors with modulation of the dynamics of the GABAA subtype, which serves as a barrier to the motility of the kainate (AMPK) subtype - alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid with a decrease in sensitivity to irritants. factors, in particular glutamate.

This form has no dynamic effect on positive NMDA tone, in particular with respect to the NMDA receptor subtype. Pharmacological properties are determined by the amount of the drug accumulated in plasma up to 200 μmol and, in fact, are dose-dependent, since no prolongation effect of the active substance was observed.

When taking Topiramate, a mild inhibition of some forms of carbonic anhydrase isoenzymes occurs, since active substance the drug has a slightly different focus on epileptic seizures.

The effect of the drug on cell mutation

Clinical observations were carried out on laboratory rats and mice, so data on the effect of the drug on human body, as a carcinogen - are absent. By testing the drug in vivo and in vitro in laboratory conditions at the objects of research, Topiramate showed neither genotoxic nor mutagenic effects during all stages of the research.

In studies for pathological carcinogenicity, Topiramate was administered to three experimental groups of mice for 21 months at the rate of 20, 75 and 300 mg per kilogram of body weight. In the group of mice receiving 300 mg/kg of the drug, cases of tumor formation were observed Bladder, both in males and females.

The mouse bladder is a unique smooth muscle excretion system, similar in its histomorphological structure to human organs. In this group of ward mice, the plasma level of the active substance ranged from 50 to 100% of the equilibrium concentration, which corresponds to similar indicators in monotherapeutic treatment with human Topiramate, but data on the effect of the drug on the human body as a carcinogen have not been reported.

In the course of studies, a certain effect of the drug on pregnant rats and mice was recorded.

As a result of experiments during the period of organogenesis, the probability of obtaining offspring with congenital deformities, mainly with craniofascial defects, increased significantly. Deformities were passed on to the next generations in a progressive form. In this group of experimental subjects, the offspring have already observed:

• micromelia
• ectrodactyly
• Amelia.

In the group of experimental rats, where the dose was increased to 500 mg/kg, the results of the observations were:
significant weight loss in the pregnant female ossification and reduction of the skeleton of the embryo.

In the group of experimental rats and mice, at a dosage of the drug up to 20 mg/kg, the offspring showed both a decrease in the weight of the fetal embryo and violations of the structural structure of the skeleton.

In experimental rabbits, the administered dose of Topiramate was 35 mg/kg. During the experiment, there was an increase in mortality at the embryonic level. And in the group with a dosage of more than 120 mg / kg, deformities of the skeletal structure were manifested thoracic curved ribs.

In all experimental groups, at a dosage of 35 mg, the fact of toxicity of the mother's body to the fetus was recorded. When the maternal organism of animals received a dose of 200 mg or more in the last trimester of pregnancy, individuals were born that transmitted to their offspring multiple defects associated with physical, physiological and mental development.

During the experiment, it was also noted that the active substance Topiramate is able to penetrate the placental barrier, slowing down the development of the embryo, and is released to the mother during the feeding period.

Pharmacokinetic properties

Topiramate is taken orally, with or without food. Has the ability to be rapidly absorbed and adsorbed in gastrointestinal tract with bioavailability within 81%.
A single dose of the drug does not affect the plasma clearance, leaving the values ​​​​at the level of constant values, and is linear.

Depending on the dosage, AUC in the range from 100 to 400 mg, there is a proportional increase. Repeated administration leads to an increase in the active substance in plasma to 2 Cmax - 6.76 at a dosage of 100 mg. The proportion of the active substance Topiramate in the human body varies greatly and is directly dependent on the sex of the individual. In women, the Vd value is half the level of male indicators.

This is due to the excess content of adipose tissue in female body. It is on this principle that the entire process of treating obesity for overweight people is built. In this case, it is necessary exact dosage depending on the gender of the patient.

Up to 70% of the active substance Topiramate and its metabolites are excreted from the body with the help of the genitourinary system, reaching a state of equilibrium in plasma in 4-8 days, provided there is no dysfunction from the kidneys.

Only 20% of the dose taken by the patient is subject to metabolism. As studies on the identification of metabolites have shown, it is excreted from the human body in an unchanged state with urine and stool 6 metabolites of an inactive form.

Clinical and pharmacological research

Topitramate is a complex chemical compound

When observed in a clinical setting, Topiramate is prescribed to eliminate tonic-clonic or partial seizures. It is prescribed for monotherapy, as well as in combination with other anticonvulsants as an additional therapy aimed at repaying the symptoms of Lennox-Gastaut syndrome during the initial diagnosis of epilepsy.

The rate of excretion of the drug genitourinary system is not related to the age category and completely depends on the functionality of the renal system.

In case of impaired renal function, there is a decrease in plasma and renal clearance of Topiramate to CC values.< 60 мл/мин с увеличением времени, когда равновесное состояние будет достигнуто. Этот процесс может занять до двух недель, против недельного восстановления пациентов со здоровой почечной системой.

In the elderly, plasma clearance does not change in patients with healthy kidneys. Its decrease is recorded in patients with severe and moderate hepatic impairment.
To effectively remove Topiramate from the body, hemodialysis is used.

During the administration of the drug Topiramate, as an auxiliary course of therapy, in the blood of children under 12 years of age, a reduced concentration of the drug is noted at identical dosages with adult patients.

Indications for use

Indications for the use of the drug are the following factors:

• Newly diagnosed epilepsy
• Lennox-Gastaut syndrome
• alcoholism syndrome
• post-traumatic stress
• neuropathy
• Migraine*.

* Topiramate is prescribed as preventive measure to prevent migraine in adult patients, but the practice of using the drug in acute attacks of the disease has not yet been studied.
Contraindications include hypersensitivity of the patient's body to the active active substance.

Restrictions on the use of Topiramate

To restrictions on use medication Topiramate may include:

• Children under the age of 2 years.
• Pregnancy of any trimester.
• Breastfeeding.

The antiepileptic drug Topiramate is classified as a drug of increased risk category, both for the use of the drug by pregnant women and for the child they are carrying, since the active substance is able to penetrate the placental barrier and directly affect the fetus.

Topiramate is prescribed to pregnant women in exceptional cases, when the threat to the health of the mother significantly outweighs the risk of potential exposure to the fetus.
When prescribing the drug to nursing mothers, breast-feeding irrevocably stops, since the active substance tends to penetrate into breast milk.

Side effects of Topiramate

Topamax - the same Topiramate

The drug causes some side effects from some organs and systems in the human body:

• Nervous system. Concentration disorder and drowsiness. Dizziness, lethargy, fatigue and loss of emotions. Muscle weakness, amnesia, impaired speech function. Depression.
• organs of vision. Nystagmus, conjunctivitis, diplopia.
• Gastrointestinal tract. gingivitis, anorexia, taste perversion.
• Other side effects include pain in the abdomen, a decrease in total body weight, spontaneous nosebleeds, swelling, chills, impotence, decreased libido.

Interaction of Topiramate with dosage forms

Carbamazepine and Phenytoin help to reduce the level of drug concentration in the blood. Topiramate acts depressingly on oral contraceptives. Simultaneous administration of Topiramate with drugs that have a nephrolithiasis significantly increases the proportion of risk associated with the occurrence of urolithiasis.

An overdose of the drug leads to escalation side effects. In cases of overdosing with the drug, it is necessary to urgently wash the stomach and at the same time induce vomiting. The therapy is carried out in a supportive mode. Hemodialysis is prescribed only in emergency cases.

Precautions while using Topiramate

• Patients on hemodialysis are prescribed an additional, equal to half the daily dose of the drug, before and after the procedure.
• Cancel the drug gradually, weekly reducing the dosage by 100 mg. With an increase in the risk of developing nephrolithiasis, it is recommended to increase the amount of fluid consumed per day.
• With a significant weight loss, enhanced nutrition with the use of dietary supplements is recommended.
• Topiramate is not recommended for people whose work is related to concentration, especially professional drivers.
• It is contraindicated to use the drug in conjunction with those agents that lead to depression of the central nervous system.
• The combination of the drug with alcohol is prohibited.

In conclusion, a few special instructions on the use of the drug:

1. The abolition of the drug is carried out gradually, taking into account the reduction to the minimum frequency indicators. possible manifestations seizures. The weekly dose reduction is 100 mg.
2. With a significant decrease in body weight, the diet is adjusted.
3. During treatment, it is necessary to avoid the use of alcoholic beverages and psychotropic drugs.
4. Topiramate strongly affects the ability to drive and drive vehicles.
5. Topiramate is contraindicated in children under 2 years of age.
6. The drug is prescribed with extreme caution to patients

Topamax (topiramate) is an original drug that is used to treat epilepsy. Its effectiveness and safety has been repeatedly confirmed by numerous clinical trials and many years of practice. Guerrini R. et al proved the effectiveness of Topamax as a monotherapy various forms epilepsy in patients of all age groups. The study included patients who had not previously taken antiepileptic drugs, or who did not respond to treatment with these drugs. The dosage was selected individually depending on the clinical situation and the age of the patient. The study lasted 7 months. During regular drug therapy Topamax in 44% of patients did not have a single convulsive episode, in 76% the frequency of convulsive episodes was significantly reduced. Arroyo S. et al. confirmed the effectiveness of Topamax treatment in persons in whom epilepsy was diagnosed for the first time. The study involved 470 patients of different age groups. After six months of regular pharmacotherapy, complete relief of seizures was achieved in 83% of patients, after a year - in 76% of patients. Ramsay RE. proved the effectiveness of Topamax in the treatment of elderly patients in whom epilepsy was diagnosed for the first time. All study participants were over 60 years of age. The monitoring period was six months. Complete relief of epileptic seizures was achieved in 52% of patients taking the drug at a dose of 50 mg per day and in 58% of patients taking the drug at a dose of 200 mg per day.

The results of the study are also particularly relevant from the point of view that, in addition to effective relief of epileptic seizures in elderly patients, Topamax significantly reduces the likelihood of developing somatic complications associated with an attack. Yu.A. Yakovleva and E.V. Pleshkova proved the ability of Topamax to improve cognitive activity in children. The study involved children, the youngest of whom was 6 years old, the oldest - 17 years old. In a clinical trial, the positive effect of the drug on speech function, the intellectual-mnestic sphere, incl. cognitive functions (memory, attention, concentration, mental activity), emotional sphere. Topamax is rapidly and efficiently absorbed from the gastrointestinal tract. The presence of food content in the gastrointestinal tract does not affect the bioavailability of the drug. Elimination from the body is carried out with urine. The abolition of Topiramate should be made gradually to minimize the risk of an increase in epileptic seizures. If, based on the clinical situation, an abrupt withdrawal of the drug is required, the patient should be under constant medical supervision. During the course of medication, there may be an increased incidence of depressive disorders.

Pharmacology

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

Topiramate blocks sodium channels and suppresses the occurrence of repeated action potentials against the background of prolonged depolarization of the neuron membrane. Topiramate increases the activity of GABA (GABA) in relation to some subtypes of GABA receptors (including GABA A receptors), and also modulates the activity of GABA A receptors themselves, prevents the activation of the sensitivity of the kainate / AMPK subtype (alpha-amino-3) by kainate -hydroxy-5-methylisoxazole-4-propionic acid) receptors for glutamate, does not affect the activity of NMDA against the NMDA receptor subtype. These drug effects are dose-dependent at plasma topiramate concentrations of 1 µmol to 200 µmol, with minimal activity ranging from 1 µmol to 10 µmol.

In addition, topiramate inhibits the activity of some carbonic anhydrase isoenzymes. By the expression of this pharmacological effect topiramate is significantly inferior to acetazolamide, a known inhibitor of carbonic anhydrase, so this activity of topiramate is not the main component of its antiepileptic activity.

Pharmacokinetics

Suction

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

The pharmacokinetics of topiramate 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 oral administration at a dose of 100 mg 2 times / day, Cmax averages 6.76 μg / ml.

Distribution

Plasma protein binding is 13-17%.

After a single oral dose of up to 1200 mg, the average V d is 0.55-0.8 l / kg. The value of V d depends on gender. In women, the 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 reach an equilibrium state.

Metabolism

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

Six practically inactive metabolites have been isolated and identified from human plasma, urine and feces.

breeding

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 repeated administration of the drug at 50 mg and 100 mg 2 times / day, the average half-life was 21 hours.

Pharmacokinetics in special clinical situations

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

In patients with moderate to severe renal impairment (CC ≤ 70 ml / min), the renal and plasma clearance of topiramate is reduced, as a result, an increase in C ss of topiramate in blood plasma is possible compared to patients with normal renal function. The time to reach C ss topiramate in plasma in patients with moderate or severe renal impairment is from 10 to 15 days. Patients with kidney failure moderate or severe, half the recommended initial and maintenance dose is recommended.

In elderly people who do not suffer from kidney disease, the 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. To avoid a rapid drop in plasma concentrations of topiramate during hemodialysis, an additional dose of Topamax may be required. When adjusting the dose should take into account:

1) duration of hemodialysis;

2) the clearance value of the hemodialysis system used;

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

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

In children under 12 years of age, the pharmacokinetic parameters of topiramate are the same as in adults receiving the drug as adjuvant therapy, are linear, while its clearance does not depend on the dose, and C ss in plasma increases in proportion to the increase in dose. It should be borne in mind that in children the clearance of topiramate is increased, and its T 1/2 is shorter. Therefore, at the same dose per 1 kg of body weight, plasma concentrations of topiramate in children may 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 the blood plasma.

Release form

Capsules hard gelatin, size No. 2, with a white body with the inscription "15 mg" and a transparent colorless cap with the inscription "TOP"; the contents of the capsules are white or almost white granules.

Excipients: sugar grains (sucrose, starch syrup) - 45 mg, povidone - 10.4199 mg, cellulose acetate - 5.423 mg.

The composition of the capsule shell: gelatin - 50.8-52.7 mg, water - 9.3-11.2 mg, sorbitan laurate - 0.0252 mg, sodium lauryl sulfate - 0.0252 mg, titanium dioxide (E171) - 0.63 mg, Opacode Black S-1-17822/23 black ink (shellac glaze solution in ethanol, black iron oxide, n-butyl alcohol, isopropyl alcohol, propylene glycol, ammonium hydroxide) - 5-10 mcg.

28 pcs. - polyethylene bottles (1) - cardboard packs.
60 pcs. - polyethylene bottles (1) - cardboard packs.

Dosage

The drug is taken orally, regardless of the meal.

Capsules should be carefully opened, mixed 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 the drug at low doses, followed by titration to an effective dose.

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

Partial or generalized tonic-clonic seizures, as well as seizures against the background of Lennox-Gastaut syndrome

Combined anticonvulsant therapy in adults. The minimum effective dose is 200 mg / day. Usually the total daily dose is from 200 mg to 400 mg and is taken in 2 divided doses. Some patients may need an increase daily dose up 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 at night 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 divided 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 Topamax ® treatment, it is not necessary to control its plasma concentration.

Combined anticonvulsant therapy in children older than 2 years. The recommended total daily dose of Topamax ® as an additional therapy is 5 to 9 mg/kg and is taken in 2 divided doses. Dose titration should begin with 25 mg (or less, based on an initial dose of 1 to 3 mg/kg per day) at night for 1 week. In the future, the dose can be increased at intervals 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. Daily doses up to 30 mg/kg are generally well tolerated.

Epilepsy (including newly diagnosed)

When discontinuing concomitant anticonvulsants for the purpose of topiramate monotherapy, the possible impact of this step on the frequency of seizures should be considered. In cases where there is no need to abruptly stop concomitant anticonvulsants for safety reasons, it is recommended to reduce their doses gradually, reducing the dose of concomitant antiepileptic drugs by 1/3 every 2 weeks.

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

In monotherapy for adults at the beginning of treatment, Topamax ® is prescribed at a dose of 25 mg at bedtime for 1 week. Then the dose is increased at intervals of 1-2 weeks by 25 mg or 50 mg in 2 divided doses. If the patient does not tolerate this dose escalation regimen, then the interval between dose increases can be increased or the dose can be increased more gradually. 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 monotherapy with topiramate at doses up to 1000 mg / day. These dosing recommendations apply to all adults, including elderly patients without kidney disease.

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

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. If this regimen is not tolerated, the dose is increased by a smaller amount or at longer intervals. The dose is selected depending on the clinical effect. In some cases positive result achieved with a daily dose of topiramate 50 mg. In clinical studies, patients received various doses of topiramate, but not more than 200 mg / day.

Special patient groups

In patients with moderate or severe renal insufficiency, a dose reduction may be necessary. It is recommended to use half of the recommended initial and maintenance dose.

Hemodialysis: Since topiramate is removed from plasma by hemodialysis, an additional dose of Topamax ® should be administered on the days of hemodialysis, equal to approximately 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 in hemodialysis.

Topiramate should be used with caution in patients with hepatic impairment.

Overdose

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

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

Treatment: if shortly before taking an excessive dose of the drug, the patient has eaten, it is necessary to immediately wash the stomach or induce vomiting. In vitro studies have shown that Activated carbon adsorb topiramate. If necessary, you should symptomatic therapy. Effective way removal of topiramate from the body is hemodialysis. Patients are advised to adequately increase fluid intake.

Interaction

The effect of Topamax ® on the concentrations of other antiepileptic drugs (AEDs)

Simultaneous administration of the drug Topamax ® with other AEDs (phenytoin, carbamazepine, valproic acid, phenobarbital, primidone) does not affect the values ​​of their C ss in plasma, with the exception of individual patients in whom the addition of Topamax ® to phenytoin may cause an increase in the concentration of phenytoin in plasma. This may be due to inhibition of a specific polymorphic isoform of the enzyme of the cytochrome P450 system (CYP2Cmeph). Therefore, with the development of symptoms of toxicity in patients receiving phenytoin, it is necessary to control the concentration of phenytoin in the blood plasma.

In a pharmacokinetic study in patients with epilepsy, the addition of topiramate to lamotrigine did not affect the C ss of the latter in plasma at doses of topiramate 100-400 mg / day. During and after the abolition of lamotrigine (mean dose 327 mg/day), topiramate C ss did not change.

The effect of other AEDs on the concentration of topiramate in plasma

Phenytoin and carbamazepine, when used simultaneously with Topamax ®, reduce the plasma concentration of topiramate. The addition or withdrawal of 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 desired clinical effect. The addition or withdrawal of valproic acid does not cause clinically significant changes in the concentration of topiramate in blood plasma and, therefore, does not require a change in the dose of Topamax ® .

Interaction with others medicines

In studies conducted with the simultaneous use of the drug Topamax ® in a single dose, the AUC of digoxin decreased by 12%. The clinical significance of this effect has not been established. When prescribing or discontinuing Topamax® in patients receiving digoxin, it is necessary to monitor the concentration of digoxin in serum.

As part of clinical studies, the consequences of the combined use of the drug Topamax ® with drugs that depress the functions of the central nervous system, as well as with ethanol, have not been studied. Joint application drug Topamax ® with medicines, which have a depressing effect on the central nervous system, and with ethanol is not recommended.

When Topamax is taken together with preparations based on St. Clinical studies of the interaction of the drug Topamax ® and preparations based on St. John's wort have not been conducted.

With the simultaneous use of an oral contraceptive containing norethisterone (1 mg) and ethinylestradiol (35 μg), Topamax ® at doses of 50-800 mg / day did not significantly affect the effectiveness of norethisterone and at doses of 50-200 mg / day - on the effectiveness of ethinylestradiol. A significant dose-dependent decrease in the effectiveness of ethinylestradiol was observed at doses of Topamax ® 200-800 mg / day. The clinical significance of the described changes is not clear. The risk of reducing the effectiveness of contraceptives and increased 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 may be reduced even in the absence of breakthrough bleeding.

In healthy volunteers, an 18% decrease in lithium AUC was observed while taking 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, however, with more high doses(up to 600 mg/day) AUC of 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.

Research drug interaction conducted with single and multiple injections of topiramate in 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, the AUC of risperidone, taken in doses of 1-6 mg / day, is reduced by 16% and 33%, respectively. At the same time, the pharmacokinetics of 9-hydroxyrisperidone did not change, and the total pharmacokinetics active substances(risperidone and 9-hydroxyrisperidone) changed insignificantly. The change in systemic exposure to risperidone/9-hydroxyrisperidone and topiramate was not clinically significant and this interaction is unlikely to be of clinical significance.

Drug interactions have been studied in healthy volunteers with separate and co-administration of hydrochlorothiazide (25 mg) and topiramate (96 mg). The results of the studies showed that while taking topiramate and hydrochlorothiazide, there is an increase in C max of topiramate by 27% and its AUC by 29%. The clinical significance of these studies has not been identified. When prescribing hydrochlorothiazide to patients taking topiramate, dose adjustment of topiramate may be required. There were no significant changes in the pharmacokinetic parameters of hydrochlorothiazide during concomitant therapy with topiramate.

Drug interactions have been studied in healthy volunteers treated with metformin or a combination of metformin and topiramate. The results of the studies showed that while taking topiramate and metformin, there is an increase in C max and AUC of metformin by 18% and 25%, respectively, while the clearance of metformin when administered simultaneously with topiramate decreased by 20%. Topiramate had no effect on plasma Tmax of metformin. The clearance of topiramate when co-administered with metformin is reduced. The degree of identified changes in clearance has not been studied. The clinical significance of the effect of metformin on the pharmacokinetics of topiramate is not clear. In case of adding or canceling the drug Topamax ® in patients receiving metformin, the condition of patients should be monitored diabetes.

Drug interactions have been studied in healthy volunteers with separate and co-administration of pioglitazone and topiramate. A decrease in the AUC of pioglitazone by 15% was found, without changing the C max of the drug. These changes were not statistically significant. Also, for the active hydroxymetabolite of pioglitazone, a decrease in C max and AUC by 13% and 16%, respectively, was detected, and for the active ketometabolite, a decrease in both C max and AUC by 60% was found. The clinical significance of these data has not been elucidated. When patients are co-administered with Topamax ® and pioglitazone, the patient's condition should be carefully monitored to assess the course of diabetes mellitus.

A drug interaction study was conducted to study the pharmacokinetics of glibenclamide (5 mg/day) at steady state, used alone or simultaneously with topiramate (150 mg/day) in patients with type 2 diabetes mellitus. When topiramate was used, the AUC of glibenclamide was reduced by 25%. The level of systemic exposure to 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 at steady state. A statistically insignificant decrease in the AUC of pioglitazone by 15% was found in the absence of a change in its C max . When prescribing topiramate to patients receiving glibenclamide (or prescribing glibenclamide to patients receiving topiramate), the patient's condition should be carefully monitored to assess the course of diabetes mellitus.

With the simultaneous use of the drug Topamax ® with other drugs that predispose to the development of nephrolithiasis, it is possible to increase the risk of kidney stones. During the period of treatment with Topamax ®, the use of such drugs should be avoided, since they can cause physiological changes that contribute to the development of nephrolithiasis.

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

When topiramate and valproic acid are taken together, hypothermia (unintentional decrease in body temperature below 35 ° C) may occur in combination with hyperammonemia or independently. This phenomenon can occur as after the start joint reception valproic acid and topiramate, and with an increase in the daily dose of topiramate.

Clinical studies have been conducted to evaluate potential drug interactions between topiramate and other medicinal products. The results of this interaction are summarized in the table.

*expressed as % of Cmax and AUC values ​​for monotherapy
** no change in C max and AUC (≤ 15% of baseline)
1 with multiple doses of flunarizine (monotherapy), an increase in AUC of 14% was observed, which may be associated with the accumulation of the drug in the process of reaching an equilibrium state

Side effects

Determination of the frequency of side effects: very often (≥1/10), often (≥1/100,<1/10), нечасто (≥1/1000 и <1/100), редко (≥1/10 000 и <1/1000) и очень редко (<1/10 000).

From the nervous system: very often - drowsiness, dizziness, paresthesia, in children - apathy, impaired attention; often - nystagmus, lethargy, impaired memory, impaired concentration, tremor, amnesia, hypesthesia, perversion of taste sensations, impaired thinking, impaired speech, cognitive disorders, apathy, mental impairment, psychomotor disorders, sedative effect; infrequently - loss of taste sensitivity, akinesia, loss of smell, aphasia, apraxia, aura, burning sensation (mainly on the face and limbs), cerebellar syndrome, circadian sleep disturbance, impaired coordination of movements, complex partial seizures, convulsions, postural dizziness, increased salivation , dysesthesia, dysgraphia, dyskinesia, dysphasia, dystonia, goosebumps, grand mal tonic-clonic seizures, hyperesthesia, hypogeusia, hypokinesia, hyposmia, peripheral neuropathy, parosmia, presyncope, repetitive speech, impaired sense of 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 change; infrequently - anorgasmia, sexual dysfunction, crying, violation of sexual arousal, dysphemia, early awakenings in the morning, euphoric mood, auditory and visual hallucinations, hypomanic states, decreased libido, mania, panic state, paranoid states, perseveration of thinking, impaired reading skills, restlessness , sleep disturbances, suicidal ideation or attempts, tearfulness; very rarely - a feeling of hopelessness.

From the digestive system: very often - a decrease in appetite, anorexia; often - nausea, diarrhea; infrequently - abdominal pain, constipation, dry mouth, impaired sensitivity in the oral cavity, pancreatitis, increased appetite, gastritis, gastroesophageal reflux, bleeding gums, 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 spasms, muscle cramps, muscle pain in the chest, arthralgia; infrequently - pain in the side, muscle stiffness; very rarely - swelling of the joints, discomfort in the limbs.

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

On the part of the organ of vision: often - diplopia, blurred vision, dry eyes; infrequently - accommodation disturbance, amblyopia, blepharospasm, transient blindness, one-sided blindness, increased lacrimation, mydriasis, night blindness, photopsia, presbyopia, scotoma (including atrial fibrillation), decreased visual acuity; very rarely - angle-closure glaucoma, involuntary eye movements, eyelid edema, myopia, conjunctival edema, maculopathy.

On the part of the organ of hearing: often - pain in the ears, 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; very rarely - nasopharyngitis.

From the skin and subcutaneous tissues: often - rash, alopecia, itching, decreased sensitivity of the face; infrequently - lack of 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.

From the urinary system: often - nephrolithiasis, dysuria, pollakiuria; infrequently - exacerbation of urolithiasis, hematuria, urinary incontinence, frequent urge to urinate, renal colic, pain in the kidney area; very rarely - renal tubular acidosis.

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

On the part of laboratory parameters: infrequently - a decrease in the content of bicarbonates in the blood (an average of 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 - swelling of the face, allergic reactions, hyperchloremic acidosis, increased appetite, metabolic acidosis, polydipsia, cold extremities, fatigue, weakness, calcification; very rarely - generalized edema, flu-like illness, allergic edema, weight gain.

Indications

Epilepsy:

• as monotherapy in adults and children over 2 years of age with epilepsy (including in patients with newly diagnosed epilepsy);
• as part of complex therapy in adults and children over 2 years of age with partial or generalized tonic-clonic seizures, as well as for the treatment of seizures against the background of Lennox-Gastaut syndrome.

• prevention of migraine attacks in adults (the use of Topamax ® for the treatment of acute migraine attacks has not been studied).

Contraindications

• children's age up to 2 years;
• hypersensitivity to the components of the drug.

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

Application features

Use during pregnancy and lactation

Special controlled studies in which Topamax ® was used to treat pregnant women have not been conducted. Topiramate may cause fetal harm when used in pregnant women.

Pregnancy records suggest that infants exposed to topiramate in utero have an increased risk of developing congenital malformations (eg, craniofacial defects such as cleft lip or palate, hypospadias, and developmental anomalies of various body systems). These malformations were recorded both in monotherapy with topiramate and in its use as part of polytherapy.

Compared with the group of patients who do not take antiepileptic drugs, data on pregnancies in monotherapy with Topamax ® indicate an increased likelihood of having children with low body weight (less than 2500 g). The relationship of the observed phenomena with taking the drug has not been established. In addition, pregnancy records and other studies suggest that the risk of developing teratogenic effects in combination treatment with antiepileptic drugs is higher than with monotherapy.

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

In the treatment and consultation of women of childbearing age, the attending physician should weigh the balance of benefits and risks of treatment and consider alternative treatment options.

If Topamax is used during pregnancy, or if the patient becomes 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 it is necessary to use Topamax ® during lactation, the issue of stopping breastfeeding or stopping the drug should be decided.

Application for violations of liver function

Caution should be used in liver failure. In patients with moderate to severe hepatic impairment, plasma clearance is reduced.

Application for violations of kidney function

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

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

Use in children

special instructions

Topamax ® (as well as other antiepileptic drugs) should be discontinued gradually to minimize the possibility of an increase in the frequency of seizures. In clinical studies, the dose of the drug was reduced by 50-100 mg 1 time per week for adults in the treatment of epilepsy and by 25-50 mg in adults receiving Topamax ® at a dose of 100 mg / day for the prevention of migraine. In children in clinical studies, Topamax ® was gradually withdrawn over 2-8 weeks. If, for medical reasons, a quick withdrawal of Topamax ® is necessary, it is recommended to carry out appropriate monitoring of the patient's condition.

As with any disease, the dosage regimen should be set according to clinical effect (i.e. degree of seizure control, absence of side effects) and take into account that in patients with impaired renal function, to establish a stable plasma concentration for each dose may need a longer time.

Topiramate therapy may cause oligohidrosis (reduced sweating) and anhidrosis. Reduced sweating and hyperthermia (increased body temperature) may occur in children exposed to high ambient temperatures. When treating with topiramate, it is very important to adequately increase the amount of fluid consumed, which helps to reduce the risk of developing nephrolithiasis, as well as side effects that may occur under the influence of physical exertion or elevated temperatures.

Topiramate has been associated with an increased incidence of mood disorders and depression.

The use of antiepileptic drugs, including Topamax ® , increases the risk of suicidal thoughts and suicidal behavior in patients taking these drugs for any of the indications.

In double-blind clinical trials, the incidence of suicidal events (suicidal ideation, suicide attempts, suicide) was 0.5% in patients treated with topiramate (in 46 out of 8652 patients), which is about 3 times higher than in patients receiving placebo (0.2%; 8 people out of 4045). One case of suicide was recorded in a double-blind study of bipolar disorder in a patient treated with topiramate.

Thus, it is necessary to monitor the condition of patients in order to detect signs of suicidal thoughts and prescribe appropriate treatment. Patients (and, if necessary, caregivers) should be advised to seek immediate medical attention if signs of suicidal thoughts or suicidal behavior appear.

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

Caution should be exercised when prescribing Topamax® to patients with renal insufficiency (QC<70 мл/мин). Это связано с тем, что у таких пациентов клиренс препарата понижен.

In patients with impaired liver function, Topamax ® should be used with caution due to a possible decrease in the clearance of topiramate.

When Topamax® is used, a syndrome has been described that includes acute myopia with concomitant secondary angle-closure glaucoma. Symptoms include an acute decrease in visual acuity and/or pain in the eye. An ophthalmological examination may reveal myopia, flattening of the anterior chamber of the eye, hyperemia (redness) of the eyeball, and increased intraocular pressure. Mydriasis may occur. This syndrome may be accompanied by fluid secretion leading to anterior displacement of the lens and iris with the development of secondary angle-closure glaucoma. Symptoms usually appear 1 month after the start of Topamax ® . Unlike primary open-angle glaucoma, which is rarely observed in patients under 40 years of age, secondary angle-closure glaucoma is observed with topiramate in both adults and children. If a syndrome involving myopia associated with angle-closure glaucoma occurs, treatment includes discontinuation of Topamax ® as soon as the attending physician deems it possible, and appropriate measures aimed at lowering intraocular pressure. Usually these measures lead to the normalization of intraocular pressure.

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

When using topiramate, hyperchloremic, not associated with anion deficiency, metabolic acidosis (for example, a decrease in plasma bicarbonate concentration below normal levels in the absence of respiratory alkalosis) may occur. This decrease in serum bicarbonate concentration is a consequence of the inhibitory effect of topiramate on renal carbonic anhydrase. In most cases, a decrease in the concentration of bicarbonates occurs at the beginning of the drug, although this effect can occur at any time during treatment with topiramate. The level of decrease in concentration is usually weak or moderate (the average value is 4 mmol / l when used in adult patients at a dose of more than 100 mg / day and about 6 mg / kg / day when used in pediatric practice). In rare cases, patients have experienced a decrease in concentration below 10 mmol / l. Certain diseases or treatments that predispose to acidosis (eg, kidney disease, severe respiratory illness, status epilepticus, diarrhoea, surgery, ketogenic diet, certain drugs) may be additional factors that enhance the bicarbonate-lowering effect of topiramate.

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

In connection with the foregoing, in the treatment of topiramate, it is recommended to carry out the necessary studies, including the determination of the concentration of bicarbonates in serum. If metabolic acidosis occurs and persists, it is recommended to reduce the dose or stop taking Topamax ® .

If, while taking Topamax ®, the patient's body weight decreases, then the question of the advisability of increased nutrition should be considered.

Influence on the ability to drive vehicles and control mechanisms

Topamax ® acts on the central nervous system and may cause drowsiness, dizziness, blurred vision and other symptoms. These adverse effects may pose a danger to patients driving a car and moving machinery, especially during the period until the patient's response to the drug is established.

Anticonvulsant drug

Active substance

Topiramate (topiramate)

Release form, composition and packaging

Excipients: microcrystalline cellulose - 31.4 mg, pregelatinized starch - 23.0 mg, colloidal silicon dioxide (aerosil) - 200 mcg, magnesium stearate - 0.4 mg.

The composition of the film shell: Opadry II 3.2 mg, including polyvinyl alcohol 1.28 mg, macrogol 0.65 mg, talc 0.47 mg, titanium dioxide 0.23 mg, quinoline yellow dye aluminum lacquer 0.53 mg, sunset yellow dye aluminum lacquer 0.04 mg.

Excipients: microcrystalline cellulose - 125.6 mg, pregelatinized starch - 92.0 mg, colloidal silicon dioxide (aerosil) - 800 mcg, magnesium stearate - 1.6 mg.

The composition of the film shell: opadry II 12.8 mg, including polyvinyl alcohol 5.12 mg, macrogol 2.58 mg, talc 1.89 mg, titanium dioxide 0.93 mg, quinoline yellow dye aluminum lacquer 2.10 mg, sunset yellow dye aluminum lacquer 0.16 mg.

10 pieces. - cellular contour packings (1) - packs of cardboard.
10 pieces. - cellular contour packings (2) - packs of cardboard.
10 pieces. - cellular contour packings (3) - packs of cardboard.
10 pieces. - cellular contour packings (4) - packs of cardboard.
10 pieces. - cellular contour packings (5) - packs of cardboard.
100 pieces. - polymer cans (1) - packs of cardboard.

pharmachologic effect

Topiramate is an antiepileptic drug, belongs to the class of sulfate-substituted monosaccharides. It blocks sodium channels and suppresses the occurrence of repeated action potentials against the background of prolonged depolarization of the neuron membrane. Increases the activity of gamma-aminobutyric acid (GABA) in relation to some subtypes of GABA receptors (including GABA A receptors), and also modulates the activity of GABA A receptors themselves, prevents the activation of kainate / AMPK (a-amino-3- hydroxy-5-methylisoxazole-4-propionic acid) glutamate receptors does not affect the activity of N-methyl-D-aspartate (NMDA) in relation to the NMDA receptor subtype. These effects of topiramate are dose dependent at topiramate concentrations of 1 to 200 µmol/L, with minimal activity ranging from 1 to 10 µmol/L.

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

Pharmacokinetics

After oral administration, topiramate is rapidly and well absorbed from the gastrointestinal tract. Bioavailability is about 81%. After ingestion of 400 mg of topiramate, C max 1.5 μg / ml is achieved within 2 hours. Food intake does not have a clinically significant effect on the bioavailability of topiramate. The value of C max after repeated oral administration of 100 mg of topiramate twice a day averaged 6.76 µg/ml.

The pharmacokinetics of topiramate is linear, plasma clearance remains constant, and the area under the concentration-time curve (AUC) in the dose range from 100 to 400 mg increases in proportion to the dose.

Communication with plasma proteins for topiramate is 13-17% in the range of plasma concentrations of 0.5-250.0 μg / ml. After a single dose at a dose of up to 1200 mg, the average V d is 0.55–0.8 l / kg.

The value of V d depends on gender: in women it is approximately 50% of the values ​​observed in men, which is associated with a higher content of adipose tissue in the body of women.

Css max when taking topiramate in patients with normal renal function is achieved after 4-8 days. Penetrates into breast milk and through the placental barrier.

After oral administration, about 20% of the dose taken is metabolized. Metabolized by hydroxylation, hydrolysis and glucuronidation. However, in patients receiving concomitant therapy (AED), which are inducers of microsomal enzymes, the metabolism of topiramate increased up to 50%. Six practically inactive metabolites have been isolated and identified from blood plasma, urine and feces. With the simultaneous administration of inducers of cytochrome P450 isoenzymes, the level of metabolism of topiramate is up to 50%.

The main route of excretion of unchanged topiramate (about 70%) and its metabolites is the kidneys. After oral administration, the plasma clearance of topiramate was 20–30 ml/min. After repeated oral administration of 50 and 100 mg twice a day, the half-life (T 1/2) of topiramate from blood plasma averages 21 hours. Removed from plasma by hemodialysis.

Pharmacokinetics in special clinical situations. Renal and plasma clearance of topiramate with mild renal failure (creatinine clearance (CC) more than 70 ml / min) is not changed. With a moderate degree of renal failure (CC 30-69 ml / min), the renal and plasma clearance of topiramate is reduced by 42%, and with severe renal failure (CC less than 30 ml / min), the renal and plasma clearance of topiramate is reduced by 54% or more.

In moderate and severe hepatic insufficiency, plasma clearance of topiramate is reduced by 20-30%.

In elderly patients without renal and hepatic insufficiency, the clearance of topiramate is not changed.

The pharmacokinetics of topiramate in children, as in adults, is linear with a dose-independent clearance; the equilibrium concentration of topiramate in plasma increases in proportion to the increase in dose. In children, the clearance of topiramate is increased, and T 1/2 is reduced, therefore, at the same dose per 1 kg of body weight, the concentration of topiramate in the blood plasma in children will be lower than in adults. In children, as in adults, antiepileptic drugs that induce microsomal liver enzymes cause a decrease in the concentration of topiramate in the blood plasma and increase the degree of its metabolism.

Indications

- in monotherapy in adults and children from 6 years of age with partial (with or without secondary generalization) or primary generalized tonic-clonic convulsions;

- as part of complex therapy in adults and children over 3 years of age with partial with or without secondary generalization or generalized tonic-clonic convulsions, as well as for the treatment of convulsions caused by Lennox-Gastaut syndrome;

Prevention of migraine attacks in adults after careful evaluation of all possible alternatives. Topiramate is not intended for the treatment of acute migraine attacks.

Contraindications

- hypersensitivity to topiramate or any other component of the drug;

- children's age up to 6 years with monotherapy, up to 3 years as part of combination therapy for epilepsy;

- children's age up to 18 years when used for the prevention of migraine;

- prevention of migraine in pregnant women or women of childbearing age who do not use effective contraception.

FROM caution: renal failure, liver failure, hypercalciuria, nephrourolithiasis (including history or family history).

Dosage

Inside, regardless of the meal. Tablets should not be divided.

For optimal control of seizures, it is recommended to start treatment with low doses and then increase to an effective dose. When used as monotherapy, it is necessary to take into account the possible effect of the withdrawal of concomitant antiepileptic drugs (AEDs) on the frequency of seizures. In cases where there is no need to abruptly cancel AEDs, it is recommended to reduce their doses gradually, reducing doses by 1/3 every 2 weeks. With the abolition of drugs that are inducers of microsomal liver enzymes, the concentration of topiramate in the blood plasma will increase, which should be taken into account in ongoing therapy.

Monotherapy

Adults at the beginning of monotherapy - 25 mg once a day at night for 1 week. Then the dose is increased at intervals of 1-2 weeks by 25-50 mg / day (the daily dose is divided into 2 doses). If this regimen is not tolerated, the dose is increased by a smaller amount or at longer intervals. The dose is selected depending on the effectiveness and tolerability of the therapy. The recommended initial target dose is 100-200 mg/day, the maximum daily dose should not exceed 500 mg in monotherapy. Dosing recommendations apply to all adults, including elderly patients without kidney disease.

Children over 6 years old with monotherapy in the first week of treatment - 0.5-1 mg / kg of body weight at bedtime. Then the dose is increased at intervals of 1-2 weeks by 0.5-1 mg / kg per day (the daily dose is divided into two doses). If this regimen is not tolerated, the dose is increased more smoothly or at longer intervals between dose increases. The magnitude of the dose and the rate of its increase are determined by the clinical efficacy and tolerability of therapy. The recommended dose range for monotherapy with topiramate in children is 100 mg/day and depends on clinical efficacy (in children 6-16 years old, it is about 2 mg/kg/day).

As part of combination therapy

adults

When prescribed as part of combination therapy with other anticonvulsant drugs in adults, the initial dose is 25-50 mg once a day at night for 1 week. Further, the dose is increased by 25-50 mg every week until an effective dose is reached. The minimum effective dose is 200 mg / day, the average daily dose is 200-400 mg, the frequency of administration is 2 times a day. Doses greater than 1600 mg per day have not been studied. The criterion for dose selection is the clinical effect and tolerability, in some patients this effect can be achieved when taking the drug 1 time per day.

Children

When prescribed as part of a combination anticonvulsant therapy in children older than 3 years, the recommended total daily dose is 5-9 mg / kg for 2 doses. Dose selection begins with 25 mg / day (at the rate of 1-3 mg / kg / day) at night for 1 week. In the future, the dose can be increased by 1-3 mg / kg for 1-2 weeks and taken in 2 divided doses. The criterion for the correct selection of the dose is a stable clinical effect and good tolerability. Daily doses up to 30 mg/kg are generally well tolerated.

Migraine Prevention

The recommended total daily dose is 100 mg in 2 divided doses. Begin treatment with a dose of 25 mg or less at bedtime for 1 week. Then the dose is increased by 25 mg / day with an interval of 1 week. If this regimen is not tolerated, the dose is increased by a smaller amount or at longer intervals. The dose is selected depending on the clinical effect. In some patients, a positive result is achieved with a daily dose of 50 mg / day. When using a daily dose of more than 100 mg / day, an additional effect as a prophylaxis of migraine is not observed.

Patients with renal insufficiency. For patients with moderate (CC less than 70 ml / min) and severe (CC less than 30 ml / min) degree of renal insufficiency, the recommended initial dose should be reduced by 2 times, and it should be increased by a smaller amount or at longer intervals. The dose is selected depending on the clinical effect. It should be borne in mind that reaching an equilibrium concentration will require more time and will be from 10 to 15 days after each increase in the dose of Topiramate.

Patients requiring hemodialysis. Since topiramate can be removed by hemodialysis, the daily dose of the drug should be increased by 50% on the days of dialysis. The additional dose is divided into 2 parts and administered before and after hemodialysis. The additional dose may vary depending on the characteristics of the dialysis and the equipment used. The dose is selected depending on the clinical effect.

In patients with liver failure Topiramate should be taken with caution under the supervision of a physician due to the reduced clearance of topiramate.

In elderly patients dose adjustment is not required.

Cancellation of the drug

Antiepileptic drugs, including topiramate, should be discontinued gradually to minimize the possibility of an increase in the frequency of seizures, reducing the dose by 50-100 mg at 1-week intervals in the treatment of epilepsy and by 25-50 mg when topiramate is used for migraine prophylaxis. In children, withdrawal within 2-8 weeks. If, for medical reasons, prompt withdrawal of topiramate is necessary, it is recommended to exercise appropriate monitoring of the patient's condition. The main route of excretion of topiramate and its metabolites in unchanged form is excretion by the kidneys. The rate of excretion by the kidneys depends on the function of the kidneys and does not depend on age. In patients with moderately or severely impaired renal function, it may take 10-15 days to achieve equilibrium plasma concentrations compared to 4-8 days in patients with normal renal function.

As with other AEDs, topiramate dose titration should be based on therapeutic efficacy (i.e. degree of reduction in seizure frequency, absence of side effects) and should take into account the fact that in patients with impaired renal function, in order to establish the equilibrium concentration of topiramate in blood plasma for each dose may take longer.

Side effects

The frequency of side effects is classified in accordance with the recommendations of the World Health Organization: very often - at least 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0.1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - not less than 0.01%, including single messages.

The most common adverse reactions (with an incidence of ≥5% compared with the placebo group, observed in at least 1 double-blind controlled study): anorexia, decreased appetite, mental retardation, depression, slurred speech, insomnia, impaired motor coordination, impaired attention, dizziness, dysarthria, impaired taste sensations, hypesthesia, lethargy, memory loss, nystagmus, paresthesia, drowsiness, tremor, diplopia, visual impairment, diarrhea, nausea, fatigue, irritability, weight loss.

Children

Adverse reactions that, according to the results of double-blind clinical studies, were ≥2 times more common in children than in adults: decreased appetite, increased appetite, hyperchloremic acidosis, hypokalemia, behavioral disturbances, aggression, apathy, sleep disturbance, suicidal thoughts, impaired attention, drowsiness, disturbance of the daily rhythm of sleep, poor quality of sleep, increased lacrimation, sinus bradycardia, general unsatisfactory condition, gait disturbance.

Adverse reactions that occurred in clinical studies exclusively in children: eosinophilia, psychomotor agitation, vertigo, vomiting, pyrexia, fever, learning disabilities.

Table number 1. Undesirable reactions of topiramate

* Identified based on the results of spontaneous reports in the post-registration period. The frequency is calculated according to clinical studies.

Overdose

Signs and symptoms of overdose: convulsions, drowsiness, speech and vision disorders, diplopia, thought disorders, coordination disorders, dizziness, lethargy, stupor, arterial hypotension, abdominal pain, dizziness, agitation and depression, metabolic acidosis. In most cases, the clinical consequences were not severe, but deaths have been reported following overdose with a mixture of several drugs, including topiramate. There is a known case of an overdose of topiramate at a dose of up to 110 g, which led to a coma within 20-24 hours, and then complete recovery after 3-4 days.

Treatment: there is no specific antidote, if necessary, symptomatic therapy is carried out. It is necessary to immediately induce vomiting and gastric lavage, increase water intake. In vitro studies have shown that topiramate adsorbs. Hemodialysis is the most effective way to remove topiramate from the body. Patients are advised to adequately increase fluid intake.

drug interaction

Effect of topiramate on concentrations of other antiepileptic drugs (AEDs)

Simultaneous administration of topiramate with other AEDs (phenytoin, carbamazepine, phenobarbital, primidone) does not affect the values ​​of their steady-state plasma concentrations, with the exception of individual patients in whom the addition of topiramate to phenytoin may cause an increase in plasma phenytoin concentration. This may be due to inhibition of a specific polymorphic isoform of the enzyme of the cytochrome P450 system (CYP2Cmeph). Therefore, in every patient who is taking phenytoin and who develops clinical signs or symptoms of toxicity, it is necessary to monitor the plasma concentration of phenytoin.

In a pharmacokinetic study in patients with epilepsy, the addition of topiramate to did not affect the equilibrium concentration of the latter at doses of topiramate 100-400 mg per day. During treatment and after the abolition of lamotrigine (mean dose of topiramate 327 mg/day), the equilibrium concentration of topiramate did not change.

Valproic acid: the combined use of topiramate and valproic acid in patients who tolerate each drug well separately is accompanied by hyperammonemia with or without encephalopathy. In most cases, symptoms and signs disappear after one of the drugs is stopped. This adverse event is not caused by a pharmacokinetic interaction. The relationship between hyperammonemia and the use of topiramate alone or in combination with other drugs has not been established. When topiramate and valproic acid are taken together, hypothermia (unintentional decrease in body temperature below 35 ° C) may occur in combination 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 dose of topiramate.

The results of interaction with antiepileptic drugs are presented in table No. 2.

Table number 2. Interactions of topiramate and other AEDs

↔ - change in plasma concentration less than 10%;

Increased concentration in selected patients;

↓ - decrease in plasma concentration;

NI - not studied.

Other drug interactions

Digoxin: in a study using a single dose of digoxin, the area under the concentration-time curve (AUC) of digoxin in plasma while taking topiramate decreased by 12%. The clinical significance of this observation is not clear. When prescribing or canceling topiramate in patients taking digoxin, special attention should be paid to monitoring the concentration of digoxin in serum.

Hypericum perforatum: when topiramate is taken together with St. John's wort, the concentration of topiramate in the blood plasma may decrease, and, as a result, the effectiveness of the drug may also decrease. Clinical studies of the interaction of the drug Topiramate and preparations based on St. John's wort have not been conducted.

Oral contraceptives: in a drug interaction study with oral contraceptives in which a combined preparation containing norethisterone (1 mg) and ethinylestradiol (35 μg) was used, topiramate at doses of 50-800 mr per day did not have a significant line on the effectiveness of norethisterone and at doses of 50-200 mg per day day - on the effectiveness of ethinylestradiol. A significant dose-dependent decrease in the effectiveness of ethinylestradiol was observed at doses of topiramate 200-800 mg per day. The clinical significance of the described changes is not clear. The risk of reduced contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking oral contraceptives in combination with topiramate. Patients taking estrogen-containing contraceptives should inform their doctor about any changes in the timing and nature of menstruation. The effectiveness of contraceptives may be reduced even in the absence of breakthrough bleeding.

Lithium: in healthy volunteers, an 18% decrease in lithium AUC was observed while taking topiramate at a dose of 200 mg per day. In patients with manic-depressive psychosis, 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), lithium AUC 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: drug interaction studies conducted with single and repeated administration of topiramate in healthy volunteers and patients with manic-depressive psychosis gave the same results. With the simultaneous use of topiratam in doses of 250 or 400 mg per day, the AUC of risperidone, taken in doses of 1-6 mg per day, is 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 slightly. The change in systemic exposure to risperidone/9-hydroxyrisperidone and topiramate was not clinically significant and this interaction is unlikely to be of clinical significance.

Hydrochlorothiazide: drug interactions were evaluated in healthy volunteers with separate and co-administration of hydrochlorothiazide (25 mg) and topiramate (96 mg). The results of the studies showed that while taking topiramate and hydrochlorothiazide, there is an increase in the maximum concentration of topiramate by 27% and the area under the curve of topiramate concentration by 29%. The clinical significance of these studies has not been identified. Administration of hydrochlorothiazide to patients taking topiramate may require dose adjustment of topiramate. The pharmacokinetic parameters of hydrochlorothiazide did not change significantly during concomitant therapy with topiramate.

Concomitant use of topiramate and metformin there was an increase in C max and AUC of metformin by 18 and 25%, respectively, while the clearance of metformin decreased by 20%. Topiramate did not affect the time to reach Cmax of metformin in blood plasma. Clearance of topiramate decreased when used concomitantly with metformin. The degree of identified changes in clearance has not been studied. The clinical significance of the effect of metformin on the pharmacokinetics of topiramate is not clear. In the case of adding or canceling Topiramate in patients receiving metformin, the course of diabetes mellitus should be carefully monitored.

With the simultaneous use pioglitazone and topiramate showed a decrease in the AUC of pioglitazone by 15%, without changing the C max of pioglitazone. These changes were not statistically significant. Also, for the active hydroxymetabolite of pioglitazone, a decrease in C max and AUC by 13 and 16%, respectively, was detected, and for the active ketometabolite, a decrease in both C max and AUC by 60% was found. The clinical significance of these data has not been elucidated. In the case of the joint appointment of Topiramate and pioglitazone, the course of diabetes mellitus should be carefully monitored.

When applied glibenclamide(5 mg per day) alone or simultaneously with topiramate (150 mg per day) in patients with type 2 diabetes, the AUC of glibenclamide was reduced by 25%. The systemic exposure of 4-trans-hydroxyglibenclamide and 3-cis-hydroxyglibenclamide was also reduced by 13 and 15%, respectively. Glibenclamide did not affect the pharmacokinetics of topiramate at steady state. When prescribing glibenclamide and topiramate to patients simultaneously, it is necessary to take into account the possible pharmacokinetic interaction and carefully monitor the condition of patients to assess the course of diabetes mellitus.

Other drugs: the simultaneous use of topiramate with drugs predisposing to nephrolithiasis should be avoided due to an increased risk of kidney stones.

Additional drug interaction studies are presented in table No. 3.

Table number 3. Results of additional interaction studies between topiramate and various medicinal products (MPs).

a - expressed as % of the values ​​of C max in blood plasma and AUC in monotherapy;

↔ - no changes in C max in blood plasma and AUC (up to 15% of the original data);

b - with repeated oral administration of flunarizine, an increase in AUC by 14% was observed, which may be associated with its accumulation in the process of reaching an equilibrium state;

NI - not studied.

special instructions

Antiepileptic drugs, including topiramate, should be discontinued gradually to minimize the possibility of increased seizure frequency. If, for medical reasons, a quick withdrawal of topiramate is necessary, then it is necessary to carry out appropriate monitoring of the patient's condition.

As with any disease, the dose selection scheme should be guided by the clinical effect and take into account the fact that in patients with impaired renal function, it may take a longer time for each dose to establish a stable plasma concentration of topiramate (from 10 to 15 days, in contrast to 4-8 days in patients with normal renal function). The rate of excretion through the kidneys depends on the function of the kidneys and does not depend on age. When treating with topiramate, it is very important to adequately increase the amount of fluid consumed, which can reduce the risk of developing nephrolithiasis, as well as side effects that may occur under the influence of physical exertion or elevated temperatures.

Mood/depression disorders and suicidal attempts.

When using the drug Topiramate, there is an increase in the incidence of mood disorders (including increased aggressiveness), psychotic reactions and depression.

During clinical studies in patients with epilepsy, when using topiramate more often than in the placebo group, there were cases associated with an increase in suicidal activity (suicidal thoughts, suicidal attempts and completed suicide): the frequency was 0.5% in patients treated with topiramate (46 of 8652 patients ) and 0.2% in patients receiving placebo. The mechanism by which this risk occurs is unknown. When using topiramate, patients should be examined for the presence of suicidal thoughts and suicidal behavior. If suicidal activity is detected in patients, appropriate treatment should be considered. Patients, their relatives, patient care staff should be informed of the need to consult a doctor if signs of suicidal tendencies and suicidal behavior are detected.

Patients with any personality disorders need special monitoring, especially at the beginning of treatment with topiramate.

Nephrolithiasis

In patients with a predisposition to nephrolithiasis, the risk of kidney stones is increased, to prevent which an adequate increase in the amount of fluid consumed is necessary. Risk factors for the development of nephrolithiasis are a history of nephrolithiasis (including family history), hypercalciuria, concomitant therapy with drugs that contribute to the development of nephrolithiasis.

Impaired kidney function

Caution should be exercised when prescribing Topiramate to patients with renal insufficiency (creatinine clearance<70 мл/мин). Это связано с тем, что у таких пациентов клиренс препарата понижен.

Impaired liver function

In patients with impaired hepatic function, topiramate should be taken with caution due to a possible decrease in the clearance of this drug.

Myopia and secondary angle-closure glaucoma

When using topiramate, a syndrome has been described that includes acute myopia with concomitant secondary angle-closure glaucoma. Symptoms include an acute decrease in visual acuity and/or pain in the eye. An ophthalmological examination reveals myopia, flattening of the depth of the anterior chamber, hyperemia (redness of the eyes) and increased intraocular pressure, and there may also be mydriasis. The described syndrome may be associated with supraciliary effusion, which causes a shift of the lens and iris and the development of secondary angle-closure glaucoma. As a rule, symptoms occur after a month of primary therapy. In contrast to primary open-angle glaucoma, which has rarely been diagnosed in patients under 40 years of age, topiramate-associated secondary open-angle glaucoma has been observed in both children and adults. Treatment involves the abolition of the drug Topiramate, if the doctor considers it appropriate, and the adoption of appropriate measures to reduce intraocular pressure. Elevated intraocular pressure in the absence of adequate treatment can lead to serious complications, up to loss of vision.

metabolic acidosis

When using topiramate, hyperchloremic, not associated with an anion deficiency, metabolic acidosis may occur. Such a decrease in the concentration of bicarbonates in the blood serum is a consequence of the inhibitory effect of topiramate on renal carbonic anhydrase. In most cases, a decrease in the concentration of bicarbonates in the blood plasma occurs at the beginning of the administration of topiramate, although this effect may occur at any period of treatment with Topiramate. The decrease in the concentration of bicarbonates in the blood plasma is usually weak or moderate (the average concentration in the blood plasma is 4 mmol / l when used in adults at a dose of more than 100 mg / day and in children at a dose of about 6 mg / kg / day). A decrease in the concentration of bicarbonates in the blood plasma of less than 10 mmol / l was observed in rare cases. Certain diseases or treatments that predispose to acidosis (eg, kidney disease, severe respiratory disease, status epilepticus, diarrhoea, surgery, increased body ketone production, certain drugs) may be additional factors that increase bicarbonate-lowering topiramate effect. Chronic metabolic acidosis increases the risk of developing nephrolithiasis. In children, chronic metabolic acidosis can cause osteomalacia and slow growth. The effect of topiramate on growth and possible complications of the skeletal system in children has not been systematically studied in children and adults.

When treating with topiramate, the necessary studies should be carried out, including the determination of the concentration of bicarbonates in the blood serum. If metabolic acidosis occurs and persists, it is recommended to reduce the dose or stop taking the drug.

Enhanced nutrition

If the patient loses weight while taking topiramate, then it is necessary to consider the advisability of enhanced nutrition.

Topiramate therapy may cause oligohidrosis or anhidrosis. Reduced sweating and hyperthermia may occur in children exposed to high ambient temperatures. In this connection, adequate fluid intake is very important, which can reduce the risk of side effects, including nephrolithiasis.

Laboratory indicators

In 0.4% of patients taking topiramate, hypokalemia was observed, defined as a decrease in serum potassium concentration below 3.5 mmol / l.

Influence on the ability to drive vehicles and control mechanisms

Topiramate has a weak or moderate effect on the ability to drive vehicles and work with mechanisms. Topiramate acts on the central nervous system and may cause drowsiness, dizziness, and other symptoms. It can also cause visual disturbances. These adverse reactions may pose a potential threat to patients when driving vehicles and working with mechanisms, especially during the period of establishing individual sensitivity to the drug. During the period of treatment, care must be taken when driving vehicles and working with mechanisms.

Pregnancy and lactation

There are no specific controlled studies in which topiramate has been used in pregnant women. There is evidence of a possible association between the use of topiramate during pregnancy and congenital malformations (eg, craniofacial defects ("cleft lip" / "cleft palate"), hypospadias, underweight fetus and newborn). These malformations were recorded both in monotherapy with topiramate and in its simultaneous use with other antiepileptic drugs (AEDs). . Pregnancy records and the results of topiramate monotherapy studies indicate an increased likelihood of having children with a body weight deficit (less than 2500 g). The relationship of these cases with the use of topiramate has not been established. Data from other studies suggest that the risk of developing teratogenic effects in combination treatment with other antiepileptic drugs may be higher than with monotherapy.

The use of topiramate during pregnancy is contraindicated. At the time of treatment with the drug, it is necessary to use effective methods of contraception.

A limited number of patient observations suggests that topiramate is excreted in breast milk, so breastfeeding should be discontinued during the use of the drug.

Women of childbearing potential are encouraged to use effective contraception and consider alternative treatments. If topiramate is used during pregnancy, or if the patient becomes pregnant while taking this drug, the doctor should warn her of the potential risk to the fetus.

Dose adjustment is not required in elderly patients.

Terms of dispensing from pharmacies

The drug is released by prescription.

Terms and conditions of storage

Store in a place protected from light at a temperature not exceeding 25°C. Keep out of the reach of children. Shelf life - 2 years. Do not use after the expiry date stated on the packaging.

• Tablets are round, biconvex, film-coated orange. On a transverse section, the core is white or almost white. film-coated tablets Tablets, film-coated white or white with a grayish tint, round, biconvex; slight surface roughness is acceptable, the color of the tablets on the break is white or white with a yellowish tinge. Orange film-coated tablets, round, biconvex; slight surface roughness is acceptable, the color of the tablets on the break is white or white with a yellowish tinge.

pharmachologic effect

Pharmacokinetics

Special conditions

Composition

• 1 tab. topiramate 100 mg Excipients: microcrystalline cellulose - 125.6 mg, pregelatinized starch - 92 mg, colloidal silicon dioxide (aerosil) - 800 mcg, magnesium stearate - 1.6 mg. The composition of the film shell: Opadry II 12.8 mg, including polyvinyl alcohol 5.12 mg, macrogol 2.58 mg, talc 1.89 mg, titanium dioxide 0.93 mg, quinoline yellow dye aluminum lacquer 2.1 mg, sunset yellow dye aluminum lacquer 0.16 mg. 1 tab. topiramate 25 mg Excipients: microcrystalline cellulose - 31.4 mg, pregelatinized starch - 23 mg, colloidal silicon dioxide (aerosil) - 200 mcg, magnesium stearate - 0.4 mg. The composition of the film shell: Opadry II 3.2 mg, including polyvinyl alcohol 1.28 mg, macrogol 0.65 mg, talc 0.47 mg, titanium dioxide 0.23 mg, quinoline yellow dye aluminum lacquer 0.53 mg, sunset yellow dye aluminum lacquer 0.04 mg. 1 tab. topiramate 100 mg Excipients: lactose monohydrate - 205.9 mg, microcrystalline cellulose - 58.5 mg, croscarmellose sodium - 3.9 mg, colloidal silicon dioxide - 7.8 mg, magnesium stearate - 3.9 mg. The composition of the film shell: Opadry II orange - 9.875 mg, including polyvinyl alcohol - 40%, titanium dioxide - 22%, macrogol - 20.2%, talc - 14.8%, aluminum varnish based on sunset yellow dye - 3%; emulsion of simethicone 30% - 0.125 mg, including water - 50-69.5%, polydimethylsiloxane - 25.5-33%, polyethylene glycol sorbitan tristearate - 3-7%, methylcellulose - 1-5%, silica gel - 1-5%. 1 tab. topiramate 25 mg Excipients: lactose monohydrate - 89.26 mg, microcrystalline cellulose - 21.45 mg, croscarmellose sodium - 1.43 mg, colloidal silicon dioxide - 1.43 mg, magnesium stearate - 1.43 mg. The composition of the film shell: Opadry II white - 2.962 mg, including polyvinyl alcohol - 40%, titanium dioxide - 25%, macrogol - 20.2%, talc - 14.8%; emulsion of simethicone 30% - 0.038 mg, including water - 50-69.5%, polydimethylsiloxane - 25.5-33%, polyethylene glycol sorbitan tristearate - 3-7%, methylcellulose - 1-5%, silica gel - 1-5%. topiramate 100 mg excipients: calcium hydrogen phosphate dihydrate, pregelatinized starch (starch C * Pharm.), heavy magnesium hydroxycarbonate (magnesium carbonate is heavy, magnesium stearate, povidone; the composition of the film coat is Selecoat AQ-02140 [hypromellose (hydroxypropyl methylcellulose), macrogol (polyethylene glycol 400), macrogol (polyethylene glycol 6000), titanium dioxide, sunset yellow]. Topiramate 25mg; Auxiliary substances: calcium hydrogen phosphate dihydrate, pregelatinized starch, heavy magnesium hydroxycarbonate, magnesium stearate, povidone

Topiramate indications for use

• Epilepsy. As a monotherapy: Topiramate is used in adults and children over 3 years of age with epilepsy (including patients with newly diagnosed epilepsy). As part of complex therapy: Topiramate is used in adults and children over 3 years of age with partial or generalized tonic-clonic seizures, as well as for the treatment of seizures against the background of Lennox-Gastaut syndrome

Topiramate contraindications

• Hypersensitivity, pregnancy, lactation. Topiramate in this dosage form (tablets), due to difficulty in swallowing, is not recommended for use in children under 3 years of age.

Topiramate dosage

• 100 mg 25 mg

Topiramate side effects

• The most common adverse reactions (with an incidence of ?5% compared with the placebo group, observed in at least 1 double-blind controlled study): anorexia, decreased appetite, mental retardation, depression, slurred speech, insomnia, impaired motor coordination, impaired attention, dizziness, dysarthria, impaired taste sensations, hypesthesia, lethargy, memory loss, nystagmus, paresthesia, drowsiness, tremor, diplopia, visual disturbances, diarrhea, nausea, fatigue, irritability, weight loss. Children Adverse reactions that, according to the results of double-blind clinical studies, were ?2 times more common in children than in adults: decreased appetite, increased appetite, hyperchloremic acidosis, hypokalemia, behavioral disturbances, aggression, apathy, sleep disturbances, suicidal thoughts, impaired attention , drowsiness, circadian sleep disturbance, poor sleep quality, increased lacrimation, sinus bradycardia, general unsatisfactory condition, gait disturbance. Adverse reactions that occurred in clinical studies exclusively in children: eosinophilia, psychomotor agitation, vertigo, vomiting, pyrexia, fever, learning disabilities. Undesirable reactions are given with distribution by frequency and organ systems. The frequency of adverse reactions was classified as follows: very frequent (?1/10), frequent (?1/100,

drug interaction

Overdose

Storage conditions

• store in a dry place
• keep away from children
• store in a place protected from light

Synonyms

• topiromax, maxitopyr, topalepsin, epimax, epitol, toreal, topsaver,