Topamax, capsules 25mg, 60pcs

Composition

Active ingredient: topiramate 25 mg. Auxiliary substances: granulated sugar [sucrose, starch molasses] 75.00 mg, povidone 17.3665 mg, cellulose acetate 9.038 mg. The composition of the capsule: gelatin 64,7-67,0 mg, the water of 10.0 and 12.3 mg, sorbitan laurat 0,0312 mg, sodium lauryl 0,0312 mg, titanium dioxide (E 171) 0,78 mg, ink Opacode Black S-1-17822/23 black (ink formulation: a solution of shellac glaze in ethanol, iron oxide black, n-butyl alcohol, isopropyl alcohol, propylene glycol, ammonium hydroxide) 5-10 µg.

Pharmacological action

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_Areceptors), and also modulates the activity of GABA_Areceptors themselves, prevents kainate from activating the sensitivity of the kainate subtype/AMPK (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) of glutamate receptors does not affect the activity of NMDA against the NMDA receptor subtype.

These effects of the drug are dose-dependent at plasma concentrations of topiramate from 1 mmol to 200 mmol, with minimal activity ranging from 1 mmol to 10 mmol.

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

Pharmacokinetics

Suction

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

The pharmacokinetics of topiramate are 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 use at a dose of 100 mg 2 times/day_{, cmax} averages 6.76 mcg / ml.

Distribution

Binding to plasma proteins is 13-17%.

After a single oral dose of up to 1200 mg_{, the} average Vd is 0.55-0.8 l / kg. The value_of vd depends on the 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 use, about 20% of the dose is metabolized.

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

Deduction

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

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

After repeated use of the drug at 50 mg and 100 mg 2 times/day, the average T_1/2 averaged 21 hours.

Pharmacokinetics in special clinical cases

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

In patients with moderate to severe renal impairment (creatinine clearance < 70 ml/min), the renal and plasma clearance of topiramate decreases, as a result, it is possible to increase the C_ss of topiramate in blood plasma compared to patients with normal renal function.

The time to reach C_ss of topiramate in blood plasma in patients with moderate or severe renal impairment is from 10 to 15 days. Patients with moderate or severe renal insufficiency are recommended to use half of the recommended initial and maintenance dose.

The plasma clearance of topiramate does not change in elderly patients who do not suffer from kidney disease.

In patients receiving concomitant therapy with antiepileptic drugs that induce enzymes involved in drug metabolism, the metabolism of topiramate increased by 50%.

Topiramate is effectively eliminated by hemodialysis. Prolonged hemodialysis may 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 topiramate concentrations during hemodialysis, an additional dose of Topamax may be required. When adjusting the dose, you should take into account:

1) the duration of hemodialysis;

2) the clearance of the hemodialysis system used;

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

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

In children under 12 years of age, the pharmacokinetic parameters of topiramate, as well as in adults receiving the drug as adjunctive therapy, are linear, while its clearance does not depend on the dose, and the C_ss in plasma increases in proportion to the dose increase.

It should be borne in mind that in children, the clearance of topiramate is increased, and its 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 blood plasma.

Indications

Epilepsy:

• as monotherapy in adults and children over 2 years of age with epilepsy (including 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 on the background of Lennox-Gastaut syndrome.

Migraines:

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

Use during pregnancy and lactation

There have been no specific controlled trials in which Topamax® was used for the treatment of pregnant women. Topiramate may have a damaging effect on the fetus when used in pregnant women.

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

In comparison with the group of patients who do not take antiepileptic drugs, data on pregnancy records for monotherapy with Topamax®indicate an increased probability of having children with a low body weight (less than 2500 g).

The relationship of the observed phenomena with the use of the drug has not been established. In addition, data from pregnancy records and other studies indicate that the risk of teratogenic effects with combined 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 exceeds the possible risk to the fetus.

When treating and consulting women of childbearing age, the attending physician should weigh the benefit-risk ratio 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 about the potential risk to the fetus.

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

Use in children

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

Contraindications

• Children under 2 years of age;
• hypersensitivity to the components of the drug.

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

Use in patients with liver function disorders

It should be used with caution in patients with hepatic insufficiency. In patients with moderate to severe hepatic impairment, plasma clearance decreases.

Use in patients with impaired renal function

When prescribing the drug to patients with moderate or severe renal impairment, it should be borne in mind that it may take 10-15 days to reach an equilibrium state in this category of patients, as opposed 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 should be prescribed in 2 doses (before and after the procedure) on the days of its implementation.

It should be used with caution in patients with renal insufficiency, nephrourolithiasis (including in the past or in the family history), with hypercalciuria.

Use in children

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

Side effects

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

Nervous system disorders: very often – drowsiness, dizziness, paresthesia, in children – apathy, attention disorders; often – nystagmus, lethargy, memory impairment, impaired concentration, tremor, amnesia, hypesthesia, perversion of taste sensations, impaired thinking, speech disorders, cognitive disorders, apathy, mental disability, psychomotor disorders, sedation; infrequently – loss of taste sensitivity, akinesia, loss of smell, aphasia, apraxia, aura, burning sensation (mainly on the face and limbs), cerebellar syndrome, violation of the circadian rhythm of sleep, impaired coordination of movements, complex partial seizures, convulsions, postural dizziness, increased salivation, dysesthesia, dysgraphia, dyskinesia, dysphasia, dystonia, a feeling of “goosebumps” on the body, tonic-clonic seizures of the grand mal type, hyperesthesia, hypogeusia, hypokinesia, hyposmia, peripheral neuropathy, parosmia, pre – fainting states, repetitive speech, impaired touch, stupor, fainting, lack of response to stimuli, in children-psychomotor hyperactivity.

Mental disorders: often – slow thinking, confusion, depression, insomnia, aggressive reactions, agitation, disorientation, emotional lability, erectile dysfunction, behavior changes in children; infrequently – anorgasmia, sexual dysfunction, crying, sexual arousal disorders, dysphemia, early morning awakenings, euphoric mood, auditory and visual hallucinations, hypomanic states, decreased libido, mania, panic states, paranoid states conditions, perseveration of thinking, impaired reading skills, restlessness, sleep disturbances, suicidal ideation or attempts, tearfulness; very rarely, a sense of hopelessness.

From the digestive system: very often – decreased 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, oral pain, thirst, dyspeptic symptoms (stomach discomfort, epigastric discomfort heaviness in the stomach), in children – vomiting.

Musculoskeletal disorders: 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 extremities.

From the cardiovascular system: infrequently – bradycardia, rapid heartbeat, hot flashes, orthostatic hypotension, Raynaud’s phenomenon.

From the side of the visual organ: often – diplopia, visual impairment, dry eyes; infrequently – accommodation disorders, amblyopia, blepharospasm, transient blindness, unilateral blindness, increased lacrimation, mydriasis, night blindness, photopsia, presbyopia, scotoma (including atrial fibrillation), decreased visual acuity; very rarely – angle-closure glaucoma, involuntary movements of the eyeballs, eyelid edema, myopia, conjunctival edema, maculopathy.

From the side of the hearing organ: often-ear pain, ringing in the ears, vertigo in children; infrequently-deafness (including sensorineural and unilateral), ear discomfort, hearing impairment.

Respiratory system disorders: often-difficulty breathing, nosebleeds; infrequently-hoarseness, shortness of breath during physical exertion, nasal congestion, hypersecretion in the paranasal sinuses, in children – rhinorrhea; very rarely-nasopharyngitis.

Skin and subcutaneous tissue disorders: often-rash, alopecia, pruritus, decreased facial sensitivity; infrequently-lack of sweating, allergic dermatitis, redness of the skin, skin pigmentation disorder, 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 hematopoietic system: often-anemia; infrequently-leukopenia, lymphadenopathy, thrombocytopenia, in children-eosinophilia; very rarely-neutropenia.

From the side of laboratory parameters: infrequently-a decrease in the content of bicarbonates in the blood (on average by 4 mmol/l), crystalluria, leukopenia, hypokalemia (a decrease in the level of potassium in the blood serum below 3.5 mmol/l).

General violations: very often-fatigue, irritability, weight loss; often-asthenia, anxiety, fever in children; infrequently-facial edema, allergic reactions, hyperchloremic acidosis, increased appetite, metabolic acidosis, polydipsia, cold extremities, fatigue, weakness, calcification; very rarely – generalized edema, flu-like diseases, allergic edema, weight gain.

Interaction

Effect of Topamax® on the concentration of other antiepileptic drugs (AEDs)

Concomitant use of 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 the inhibition of a specific polymorphic isoform of the cytochrome P450 (CYP2Cmeph) enzyme. Therefore, if symptoms of toxicity develop in patients receiving phenytoin, it is necessary to monitor 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 latter’s C ss in blood plasma at doses of topiramate 100-400 mg/day. During and after discontinuation of lamotrigine (mean dose 327 mg/day), the_ss of topiramate did not change.

Effect of other AEDs on topiramate plasma concentrations

Phenytoin and carbamazepine, when co-administered with Topamax, reduce topiramate plasma concentrations. 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 necessary 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®.

Added PEP	PEP Concentration	Topiramate concentration
Phenytoin	no effect (increased plasma concentrations in isolated cases)	reduced plasma concentrations by 48%
Carbamazepine	no effect	reduced plasma concentrations by 40%
Valproic acid	no effect	no effect
Phenobarbital	no effect	not investigated
Primidone	no effect	studied

Interaction with other medicinal products

In the conducted studies, when Topamax® was co-administered in a single dose, the digoxin AUC decreased by 12%. The clinical significance of this effect has not been established. When prescribing or discontinuing Topamax in patients receiving digoxin, serum digoxin concentrations should be monitored.

In clinical studies, the effects of co-use of Topamax® with drugs that inhibit the function of the central nervous system, as well as with ethanol, have not been studied. Concomitant use of Topamax® with drugs that have a depressing effect on the central nervous system, and with ethanol is not recommended.

When Topamax is co-administered with preparations based on St. John’s wort (Hypericum perforatum), the concentration of topiramate in plasma may decrease and, as a result, the effectiveness of the drug may also decrease. No clinical studies have been conducted on the interaction of Topamax® and preparations based on St. John’s wort.

When used concomitantly with an oral contraceptive containing norethisterone (1 mg) and ethinyl estradiol (35 mcg), 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 ethinyl estradiol.

A significant dose-dependent decrease in the effectiveness of ethinyl estradiol was observed at doses of Topamax® 200-800 mg / day. The clinical significance of these changes is not clear.

The risk of reduced 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 can be reduced even in the absence of breakthrough bleeding.

In healthy volunteers, the lithium AUC decreased by 18% when topiramate was co-administered at a dose of 200 mg / day. In patients with manic-depressive psychosis, the use of topiramate in doses up to 200 mg / day did not affect the pharmacokinetics of lithium, but at higher doses (up to 600 mg / day) The AUC of lithium was increased by 26%.

With simultaneous use of topiramate and lithium, the concentration of the latter in blood plasma should be monitored.

Drug interaction studies conducted with single and repeated use of topiramate to healthy volunteers and patients with bipolar disorder gave the same results.

When topiratam is co-administered in daily doses of 250 mg or 400 mg, the AUC of risperidone, taken in doses of 1-6 mg / day, decreases 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 the level of systemic exposure to risperidone / 9-hydroxyrisperidone and topiramate was not clinically significant, and this interaction is unlikely to be of clinical significance.

Drug interaction was studied in healthy volunteers with separate and joint use of hydrochlorothiazide (25 mg) and topiramate (96 mg). The results of studies showed that with simultaneous use of topiramate and hydrochlorothiazide, the_cmax of topiramate increased by 27% and its AUC by 29%.

The clinical significance of these studies has not been revealed.

When prescribing hydrochlorothiazide to patients taking topiramate, it may be necessary to adjust the dose of topiramate. No significant changes in the pharmacokinetic parameters of hydrochlorothiazide were observed with concomitant topiramate therapy.

Drug interactions were studied in healthy volunteers treated with metformin or a combination of metformin and topiramate.

The results of studies showed that when taking topiramate and metformin simultaneously, the_cmax and AUC of metformin increased by 18% and 25%, respectively, while the clearance of metformin when administered simultaneously with topiramate decreased by 20%.

Topiramate had no effect on the T_max of metformin in blood plasma. Topiramate clearance decreases when co-administered with metformin. The degree of detected changes in clearance has not been studied. The clinical significance of the effect of metformin on the pharmacokinetics of topiramate is unclear.

If Topamax is added or discontinued in patients receiving metformin, the condition of diabetic patients should be monitored.

The drug interaction was studied in healthy volunteers with separate and joint use of pioglitazone and topiramate. The AUC of pioglitazone decreased by 15%, without changing the_Cmax of the drug. These changes were not statistically significant.

Also, for the active hydroxymetabolite pioglitazone, a decrease in_cmax and AUC by 13% and 16%, respectively, was detected, and for the active ketometabolite, a decrease in both_cmax and AUC by 60% was detected. The clinical significance of these data is unclear.

When Topamax® and pioglitazone are co-administered to patients, 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 decreased by 25%. The level of systemic exposure to the 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 unreliable decrease in pioglitazone AUC by 15% was found in the absence of a change in its_cmax.

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.

Concomitant use of Topamax with other drugs predisposing to the development of nephrolithiasis may increase the risk of kidney stones. During 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 discontinuation of one of the drugs. This adverse event is not caused by a pharmacokinetic interaction.

The association 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 (an 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-use of 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.

Added medicinal product	Concentration of the drug being added*	Topiramate concentration *
Amitriptyline	A 20% increase in the cmax and AUC of nortriptyline (an amitriptyline metabolite)	was not investigated
Dihydroergotamine (orally and subcutaneously)	**	**
Haloperidol	A 31% increase in the metabolite AUC	has not been studied
Propranolol	17% increase incmax 4-OH propranolol (topiramate 50 mg)	increasedcmax by 9% and 16%, increased AUC by 9% and 17% (propranolol 40 mg and 80 mg every 12 hours, respectively)
Sumatriptan (orally and subcutaneously)	* *	not studied
Pisotifen	* *	* *
Diltiazem	reduced AUC of diltiazem by 25% and deacetyldylthiazem by 18% and ** for N-demethyldylthiazem	increased AUC by 20%
Venlafaxine	**	**
Flunarizin	increase in AUC by 16% (50 mg every 12 hours)1	**

*expressed in% of the values of C_max and AUC when alone

**the absence of changes in C_max and AUC (≤ 15% of the original data)1 for multiple doses flunarizine (monotherapy), an increase in AUC by 14%, which might be related to accumulation of the drug in the process of achieving equilibrium

How to take, course of use and dosage

The drug is taken orally, regardless of food intake.

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

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

The 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 associated with 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 to increase the daily dose to a maximum of 1600 mg.

It is recommended to start treatment with a low dose, followed by a gradual selection of the 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 selecting the dose, it is necessary to be guided by the clinical effect. In some patients, the effect can be achieved by taking the drug 1 time / day. To achieve the optimal effect of treatment with Topamax®, it is not necessary to monitor its concentration in plasma.

These dose recommendations apply to all adult patients, including the elderly, if they do not have kidney disease.

Combined anticonvulsant therapy in children over 2 years of age. The recommended total daily dose of Topamax® as an adjunct therapy is 5 to 9 mg / kg and is taken in 2 divided doses. Dose selection should start 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 divided doses. When selecting the dose, it is necessary to be guided by the clinical effect. A daily dose of up to 30 mg / kg is usually well tolerated.

Epilepsy (including newly diagnosed ones)

When discontinuing concomitant anticonvulsant medications with topiramate, consideration should be given to the possible impact of this step on the frequency of seizures. In cases where it is not necessary to abruptly cancel 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.

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

With 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 doses. If the patient does not tolerate this mode of increasing the dose, then you can increase the intervals between dose increases, or increase the dose more smoothly.

When selecting the dose, it is necessary to be guided by the clinical effect. The initial dose for topiramate monotherapy 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 dosage 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 before 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 mode of increasing the dose, then you can increase the dose more smoothly or increase the intervals between dose increases. The size of the dose and the rate of its increase depend on the 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 can be prescribed 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 before bedtime for 1 week.

Then the dose is increased by 25 mg / day with an interval of 1 week. If such a treatment regimen is intolerant, the dose is increased by a smaller amount or at longer intervals.

The dose is selected depending on the clinical effect. In some cases, a positive result is achieved with a daily dose of topiramate 50 mg. In clinical trials, patients received various doses of topiramate, but not more than 200 mg / day.

Special patient groups

In patients with moderate or severe renal insufficiency, a dose reduction may be necessary. Half of the recommended starting and maintenance dose is recommended.

Hemodialysis: Since topiramate is removed from the plasma during 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 the end of the hemodialysis procedure. The additional dose may vary depending on the characteristics of the equipment used for hemodialysis.

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

Overdose

Symptoms: seizures, drowsiness, speech and vision disorders, diplopia, thinking disorders, coordination disorders, lethargy, stupor, hypotension, abdominal pain, dizziness, agitation and depression. In most cases, the clinical consequences were not severe, but deaths were reported after overdose using a mixture of several medications, including topiramate.

Severe metabolic acidosis may occur.

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

Treatment: if the patient has taken food shortly before taking an excessive dose of the drug, it is necessary to immediately flush the stomach or induce vomiting. In vitro studies have shown that activated carbon adsorbs topiramate.

If necessary, symptomatic therapy should be performed. Hemodialysis is an effective way to remove topiramate from the body. Patients are advised to increase their fluid intake appropriately.

Special instructions

Discontinuation of Topamax (as with other antiepileptic drugs) should be gradual to minimize the possibility of increased seizure frequency.

In clinical studies, the dose of the drug was reduced by 50-100 mg once a 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 migraines.

In children in clinical trials, Topamax® was gradually discontinued for 2-8 weeks. If rapid withdrawal of Topamax® is medically necessary, appropriate monitoring of the patient’s condition is recommended.

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

With topiramate therapy, oligohydrosis (reduced sweating) and anhidrosis may occur. Decreased sweating and hyperthermia (increased body temperature) can occur in children exposed to high ambient temperatures.

When using topiramate, it is very important to adequately increase the volume of fluid consumed, which helps reduce the risk of developing nephrolithiasis, as well as side effects that may occur under the influence of physical exertion or elevated temperatures.

When treated with topiramate, there is 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 suicide-related events (suicidal thoughts, suicide attempts, suicide) was 0.5% in patients treated with topiramate (46 people out of 8,652), which is approximately 3 times higher than in patients treated with placebo (0.2%; 8 people out of 4,045). One case of suicide was recorded in a double-blind study of bipolar disorder in a patient receiving 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 behavior occur.

Some patients, especially those with a predisposition to nephrolithiasis, may have an increased risk of kidney stones and associated symptoms, such as renal colic.

To reduce this risk, an adequate increase in the volume of liquid consumed is necessary. Risk factors for the development of nephrolithiasis are a history of nephrolithiasis (including in the family), 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 (CC).

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

When using Topamax®, a syndrome has been described that includes acute myopia with concomitant secondary angle-closure glaucoma. Symptoms include acute visual acuity loss and / or eye pain.

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 can be accompanied by fluid secretion, which leads to the displacement of the lens and iris forward with the development of secondary angle-closure glaucoma. Symptoms usually appear 1 month after the start of Topamax treatment.

Unlike primary open-angle glaucoma, which is rarely seen in patients under 40 years of age, secondary closed-angle glaucoma is observed when topiramate is used in both adults and children.

If a syndrome occurs that includes myopia associated with angle-closure glaucoma, treatment includes discontinuing Topamax® as soon as the attending physician deems it possible, and appropriate measures aimed at lowering intraocular pressure. Usually, these measures lead to normalization of intraocular pressure.

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

When using topiramate, hyperchloremic, non-anion-deficient metabolic acidosis may occur (for example, a decrease in the concentration of bicarbonates in plasma below normal levels in the absence of respiratory alkalosis).

Such a decrease in the concentration of serum bicarbonates 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 taking the drug, although this effect may occur during any period of treatment with topiramate. The level of concentration reduction is usually mild 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 showed a decrease in concentration below 10 mmol/l. Certain diseases or treatments that predispose you to acidosis (for example, kidney disease, severe respiratory diseases, status epilepticus, diarrhea, surgery, ketogenic diet, taking certain medications) may be additional factors that enhance the bicarbonate-reducing effect of topiramate.

In children, chronic metabolic acidosis can lead to growth retardation. The effect of topiramate on growth and possible bone-related complications has not been systematically studied in children and adults.

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

If the patient’s body weight decreases while taking Topamax®, then consideration should be given to the feasibility of increased nutrition.

Influence on the ability to drive motor vehicles and manage mechanisms

Topamax ® acts on the central nervous system and can cause drowsiness, dizziness, visual disturbances and other symptoms. These adverse effects can be dangerous for patients driving a car or moving machinery, especially during the period until the patient’s reaction to the drug is established.

Form of production

Capsules

Storage conditions

In a dry place, at a temperature not exceeding 25 °C

Shelf life

2 years

Active ingredient

Topiramate

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

For adults as prescribed by a doctor, for children as prescribed by a doctor

Indications

Epilepsy