Topamax, 25 mg capsules 60 pcs

The antiepileptic drug belongs to the class of sulfamate-substituted monosaccharides.

Topiramate blocks sodium channels and suppresses the occurrence of repetitive action potentials against the background of prolonged depolarization of the neuronal membrane. Topiramate increases GABA (GABA) activity against certain GABA receptor subtypes (including GABA_A receptors), and modulates the activity of GABA_A-receptors, inhibits kainat activation of kainat/AMPK (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor subtype sensitivity to glutamate, does not affect NMDA activity with respect to NMDA receptor subtype.

These effects of the drug are dose-dependent at plasma concentrations of topiramate between 1 μmol and 200 μmol, with minimal activity between 1 μmol and 10 μmol.

In addition, topiramate inhibits the activity of some carboanhydrase isoenzymes. Topiramate is significantly inferior to acetazolamide, a known inhibitor of carbonic anhydrase, in terms of the severity of this pharmacological effect; therefore, this activity of topiramate is not a major component of its antiepileptic activity.

Pharmacokinetics

Intake

After oral administration, topiramate is quickly and effectively absorbed from the gastrointestinal tract. Bioavailability is 81%. Food intake has no clinically significant effect on the bioavailability of the drug.

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

After multiple oral doses of 100 mg twice daily, C_max averages 6.76 mcg/mL.

Distribution

The binding to plasma proteins 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 about 50% of those observed in men, which is associated with a higher content of adipose tissue in women.

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

Metabolism

About 20% of the dose is metabolized after oral administration.

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

Elimation

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

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

After multiple doses of 50 mg and 100 mg 2 times/day, the mean T_1/2 averaged 21 hours.

Pharmacokinetics in Special Clinical Cases

The rate of renal excretion of topiramate is dependent on renal function and is independent of age.

In patients with moderate to severe renal dysfunction (CK ≤ 70 mL/min), renal and plasma clearance of topiramate is decreased, resulting in possible increased plasma C_ss of topiramate compared to patients with normal renal function.

The time to reach plasma C_ss of topiramate in patients with moderate to severe renal impairment is 10 to 15 days. For patients with moderate to severe renal impairment, half the recommended initial and maintenance doses are recommended.

In elderly patients without kidney disease, the plasma clearance of topiramate is not altered.

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

Topiramate is effectively excreted by hemodialysis. Prolonged hemodialysis may cause blood concentrations of topiramate to fall below the amount required to maintain anticonvulsant activity. An additional dose of Topamax® may need to be administered to avoid a rapid drop in plasma concentrations of topiramate during hemodialysis. When adjusting the dose, consideration should be given to:

1) the duration of hemodialysis;

2) the clearance value of the hemodialysis system used;

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

The plasma clearance of topiramate is reduced by an average of 26% in patients with moderate to severe hepatic impairment. Therefore, patients with hepatic impairment 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 adjuvant therapy, are linear, with its clearance independent of the dose, and C_ss in plasma increases in proportion to increasing the dose.

It should be kept in mind that in children, topiramate clearance is increased and its T_1/2 is shorter. Therefore, at the same dose per 1 kg body weight, plasma concentrations of topiramate in children may be lower than in adults. In children, as in adults, antiepileptic drugs that induce hepatic enzymes cause lower plasma concentrations of topiramate.

Indications

Epilepsy:

Migraine:

Active ingredient

Composition

How to take, the dosage

The drug is taken orally, regardless of meals.

The capsules should be opened gently, and the contents mixed with a small amount (about 1 teaspoon) of some soft food. The mixture should be swallowed immediately, without chewing. Do not keep the medicine mixed with food until the next dose. Topamax® capsules may be swallowed whole.

To achieve optimal control of epileptic seizures in adults and children, it is recommended that treatment be initiated with the drug at a low dose followed by titration to an effective dose.

The capsules are for patients who have difficulty swallowing the tablets (e.g., in children and elderly patients).

Partial or generalized tonic-clonic seizures and seizures with Lennox-Gastaud syndrome

Combination anticonvulsant therapy in adults. The minimum effective dose is 200 mg/day. Usually the total daily dose is 200 mg to 400 mg and is taken in 2 doses. Some patients may need to increase the daily dose to a maximum of 1600 mg.

It is recommended that treatment begin with a low dose followed by a gradual adjustment to an effective dose. The dose is started at 25-50 mg, taken at night for 1 week. Thereafter, the dose may be increased by 25-50 mg and taken in 2 doses at 1-2 week intervals.

When selecting a dose, it is necessary to be guided by the clinical effect. In some patients the effect can be achieved by taking the drug once a day. It is not necessary to monitor plasma concentrations of Topamax® to achieve optimal treatment effect.

These dose recommendations apply to all adult patients, including elderly patients, provided they do not have renal disease.

Combination anticonvulsant therapy in children over 2 years of age.The recommended total daily dose of Topamax® as adjunctive therapy is 5 to 9 mg/kg and is taken in 2 doses. The dose should be started at 25 mg (or less, based on an initial dose of 1 to 3 mg/kg per day) at night for 1 week.

Thereafter, the dose may be increased at 1-2 week intervals by 1-3 mg/kg and taken in 2 doses. Dose selection should be guided by clinical effect. A daily dose of up to 30 mg/kg is usually well tolerated.

Epilepsy (including newly diagnosed)

When withdrawing concomitant anticonvulsants for the purpose of topiramate monotherapy, the possible effect of this step on seizure frequency must be considered. Where it is not necessary to abruptly withdraw 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 withdrawn, blood concentrations of topiramate will increase. In these situations, if clinically indicated, the dose of Topamax® may be reduced.

In monotherapy in adults, Topamax® is administered at a dose of 25 mg before bedtime for 1 week. The dose is then increased at 1-2 week intervals by 25 mg or 50 mg in 2 doses. If a patient cannot tolerate this dose escalation regimen, the intervals between dose escalations may be increased, or the dose may be increased more gently.

The dosage should be guided by clinical effect. The starting dose for monotherapy with topiramate in adults is 100 mg/day, and the maximum daily dose should not exceed 500 mg. Some patients with refractory forms of epilepsy tolerate topiramate monotherapy in doses up to 1000 mg/day. These dosing recommendations apply to all adults, including elderly patients without kidney disease.

In monotherapy in children over 2 years of age, Topamax® is given at a dose of 0.5-1 mg/kg body weight before bedtime in the first week of treatment. Then the dose is increased at 1-2 week intervals by 0.5-1 mg/kg/day in 2 doses.

If the child cannot tolerate this mode of dose increase, the dose may be increased more gently or the intervals between dose increases may be increased. The magnitude of the dose and the rate of increase depend on the clinical effect. The recommended dose range for monotherapy with topiramate in children over 2 years of age is 100-400 mg/day. Children with newly diagnosed partial seizures may be prescribed up to 500 mg/day.

Migraine

To prevent migraine attacks, the recommended daily dose of topiramate is 100 mg in 2 doses. At the beginning of treatment, 25 mg before bedtime for 1 week.

Then the dose is increased by 25 mg/day at 1 week intervals. If this regimen is not tolerated, the dose is increased by a smaller amount or at longer intervals.

The dose is adjusted according to the clinical effect. In some cases, positive results are achieved with a daily dose of 50 mg of topiramate. In clinical trials, patients received different doses of topiramate, but not more than 200 mg/day.

Particular patient groups

In patients with moderate to severe renal impairment, dose reduction may be necessary. Half the recommended initial and maintenance dose is recommended.

Hemodialysis: Because topiramate is removed from plasma during hemodialysis, an additional dose of Topamax® equal to approximately half the daily dose should be administered on hemodialysis days.

The additional dose should be divided into two doses given at the beginning and after completion of the hemodialysis procedure. The additional dose may vary depending on the characteristics of the equipment used during hemodialysis.

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

Interaction

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

The concomitant administration of Topamax

sup>® with other PEPs (phenytoin, carbamazepine, valproic acid, phenobarbital, primidone) has no effect on their Csub>ss values in plasma, except in individual patients in whom the addition of Topamax® to phenytoin may cause increased plasma concentrations of phenytoin.

This may be due to inhibition of a specific polymorphic isoform of the cytochrome P450 system enzyme (CYP2Cmeph). Therefore, if symptoms of toxicity develop in patients receiving phenytoin, plasma concentrations of phenytoin should be monitored.

In a study of pharmacokinetics in epileptic patients, the addition of topiramate to lamotrigine had no effect on the plasma Css of the latter at topiramate doses of 100-400 mg/day. There was no change in the Css of topiramate during and after withdrawal of lamotrigine (mean dose 327 mg/day).

The effect of other PEDs on plasma concentrations of topiramate

Phenytoin and carbamazepine when used concomitantly with Topamax® reduce plasma concentrations of topiramate. Addition or withdrawal of phenytoin or carbamazepine during treatment with Topamax® may require changing the dose of the latter. The dose should be adjusted according to the development of the desired clinical effect.

The addition or withdrawal of valproic acid does not cause clinically significant changes in plasma concentrations of topiramate and therefore does not require changes in the dose of Topamax®.

Interaction with other drugs

In the studies conducted, concomitant administration of Topamax® in a single dose decreased the AUC of digoxin by 12%. The clinical significance of this effect has not been established. Serum digoxin concentrations should be monitored when prescribing or withdrawing Topamax® in patients receiving digoxin.

The effects of co-administration of Topamax® with CNS-depressant drugs and with ethanol have not been studied in clinical trials. Co-administration of Topamax® with drugs with CNS depressant effect and with ethanol is not recommended.

When Topamax and preparations based on Hypericum perforatum are taken together, plasma concentrations of topiramate may decrease and as a consequence the effectiveness of the drug may also decrease. No clinical studies of interaction between the drug Topamax® and preparations based on Hypericum perforatum have been conducted.

In concomitant use of an oral contraceptive containing norethisterone (1 mg) and ethinylestradiol (35 mcg), Topamax® at doses of 50-800 mg/day had no significant effect on the effectiveness of norethisterone and at doses of 50-200 mg/day on the effectiveness of ethinylestradiol.

A significant dose-dependent decrease in the efficacy of ethinylestradiol was observed at Topamax® doses of 200-800 mg/day. The clinical significance of the described changes is unclear.

The risk of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking oral contraceptives in combination with Topamax®. Patients taking estrogen-containing contraceptives should inform their physician of any changes in the timing and nature of their periods.

The effectiveness of contraceptives may be reduced even if there is no breakthrough bleeding.

In healthy volunteers, an 18% reduction in the AUC of lithium was observed with concomitant administration of topiramate at a dose of 200 mg/day. In patients with manic-depressive psychosis, the use of topiramate at doses up to 200 mg/day had no effect on lithium pharmacokinetics, but at higher doses (up to 600 mg/day) the AUC of lithium was increased by 26%.

When topiramate and lithium are used concomitantly, plasma concentrations of the latter should be monitored.

Drug interaction studies conducted with single and multiple infusions of topiramate in healthy volunteers and patients with bipolar disorder gave similar results.

The concomitant use of topiramate at daily doses of 250 mg or 400 mg reduced the AUC of risperidone taken at doses of 1-6 mg/day by 16% and 33%, respectively.

The pharmacokinetics of 9-hydroxyrisperidone did not change, and the total pharmacokinetics of the active substances (risperidone and 9-hydroxyrisperidone) did not change significantly.

The change in systemic exposure to risperidone/9-hydroxysperidone and topiramate was not clinically significant, and this interaction is unlikely to be clinically relevant.

Drug interactions have been studied in healthy volunteers when hydrochlorothiazide (25 mg) and topiramate (96 mg) were administered separately and together. Results showed that concomitant administration of topiramate and hydrochlorothiazide increased Cmax of topiramate by 27% and its AUC by 29%.

The clinical significance of these studies has not been identified.

The dose of topiramate may need to be adjusted when hydrochlorothiazide is administered to patients taking topiramate. No significant changes in the pharmacokinetic parameters of hydrochlorothiazide have been observed with concomitant therapy with topiramate.

Drug interactions have been studied in healthy volunteers receiving metformin or a combination of metformin and topiramate.

The results showed that concomitant administration of topiramate and metformin increased Cmax and AUC of metformin by 18% and 25%, respectively, whereas metformin clearance was decreased by 20% when concomitantly administered with topiramate.

Topiramate had no effect on Tmax metformin in plasma. Topiramate clearance is decreased when coadministered with metformin. The extent of identified changes in clearance has not been studied. The clinical significance of the effect of metformin on topiramate pharmacokinetics is unclear.

The addition or withdrawal of Topamax® in patients receiving metformin should be monitored in diabetic patients.

Drug interactions have been studied in healthy volunteers when pioglitazone and topiramate were administered separately and together. A 15% decrease in the AUC of pioglitazone was found, with no change in the Cmax drug. These changes were not statistically significant.

Also for the active hydroxymetabolite pioglitazone, a 13% and 16% decrease in Cmax and AUC, respectively, was found, and for the active ketometabolite, a 60% decrease in both Cmax and AUC was found. The clinical significance of these data has not been clarified.

When Topamax® and pioglitazone are coadministered to patients, the patient should be closely monitored to assess the course of diabetes mellitus.

A drug interaction study was conducted to examine the pharmacokinetics of glibenclamide (5 mg/day) in equilibrium used alone or concomitantly with topiramate (150 mg/day) in patients with type 2 diabetes.

The AUC of glibenclamide was reduced by 25% when topiramate was used. The systemic exposure to the active metabolites, 4-trans-hydroxy-glibenclamide and 3-cis-hydroxy-glibenclamide, was also reduced (by 13% and 15%, respectively).

Glibenclamide had no effect on the pharmacokinetics of topiramate in equilibrium. A statistically non-significant 15% decrease in the AUC of pioglitazone was found with no change in its Cmax.

When prescribing topiramate to patients receiving glibenclamide (or prescribing glibenclamide to patients receiving topiramate), the patient’s condition should be closely monitored to assess the course of diabetes mellitus.

In concomitant administration of Topamax® with other drugs that predispose to nephrolithiasis, the risk of formation of kidney stones may increase. The use of such drugs should be avoided during treatment with Topamax® as they may cause physiological changes that contribute to the development of nephrolithiasis.

The combined use of topiramate and valproic acid in patients who tolerate each drug alone is accompanied by hyperammonemia with or without encephalopathy. In most cases, symptoms and signs disappear after withdrawal of one of the drugs. This adverse event is not caused by pharmacokinetic interaction.

The association between hyperammonemia and the use of topiramate alone or in combination with other drugs has not been established.

The co-administration of topiramate and valproic acid may cause hypothermia (unintentional drop in body temperature below 35°C) in conjunction with hyperammonemia or independently. This phenomenon can occur either after starting valproic acid and topiramate together or when the daily dose of topiramate is increased.

Clinical studies have been conducted to evaluate potential drug interactions between topiramate and other medications. The results of these interactions are summarized in the table.

*expressed as % of Cmax valuesand AUC with monotherapy

**no change in Cmax and AUC (≤ 15% of baseline)br> 1 with repeated flunarizine administration (monotherapy), a 14% increase in AUC was observed, which may be due to accumulation of the drug in the process of reaching equilibrium state

Special Instructions

Topamax® (like other antiepileptic drugs) should be withdrawn gradually to minimize the possibility of increased seizure frequency.

In clinical trials, the drug dose was reduced by 50-100 mg once weekly in adults receiving Topamax® for epilepsy therapy and by 25-50 mg in adults receiving Topamax® at a dose of 100 mg/day for migraine prevention.

In children in clinical trials, Topamax® was gradually withdrawn over 2-8 weeks. If rapid withdrawal of Topamax® is medically necessary, appropriate monitoring of the patient is recommended.

As with any disease, the dosage regimen should be established according to clinical effect (i.e., degree of seizure control, no side effects) and take into account that in patients with impaired renal function, it may take longer for each dose to establish stable plasma concentrations.

In therapy with topiramate, oligohidrosis (decreased sweating) and anhidrosis may occur. Reduced sweating and hyperthermia (increase in body temperature) may occur in children who are exposed to high ambient temperatures.

In therapy with topiramate, an adequate increase in fluid intake is very important to help reduce the risk of nephrolithiasis as well as side effects that may occur with physical activity or elevated temperatures.

There is an increased incidence of mood disorders and depression when treated with topiramate.

The use of antiepileptic drugs, including Topamax®, increases the risk of suicidal ideation 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 receiving topiramate (in 46 of 8,652), about 3 times higher than in patients receiving placebo (0.2%; 8 of 4045). One case of suicide was reported in a double-blind study of bipolar disorder in a patient receiving topiramate.

Hence, patients should be monitored for signs of suicidal ideation and appropriate treatment should be prescribed.

Patients (and their caregivers, if necessary) should be advised to seek medical help immediately if they show signs of suicidal ideation or suicidal behavior.

In some patients, especially those with a predisposition to nephrolithiasis, there may be an increased risk of kidney stone formation and associated symptoms, such as renal colic.

To reduce this risk, an adequate increase in fluid intake is necessary. Risk factors for nephrolithiasis include a history of nephrolithiasis (including family history), hypercalciuria, and concomitant therapy with other drugs that contribute to nephrolithiasis.

Caution should be exercised when prescribing Topamax® in patients with renal impairment (CKD

. In patients with impaired liver function, Topamax® should be used with caution because of possible decreased clearance of topiramate.

In the use of Topamax®, a syndrome has been described that includes acute myopia with concomitant secondary closed-angle glaucoma. Symptoms include acute decrease in visual acuity and/or pain in the eye.

Ophthalmologic examination may reveal myopia, flattening of the anterior chamber of the eye, hyperemia (redness) of the eyeball, and increased intraocular pressure.

Mydriasis may be observed. This syndrome may be accompanied by fluid secretion, resulting in forward displacement of the lens and iris with the development of secondary closed-angle glaucoma. Symptoms usually appear 1 month after initiation of Topamax®.

In contrast to primary open-angle glaucoma, which is rarely seen in patients under 40 years of age, secondary closed-angle glaucoma is seen with topiramate use in both adults and children.

In the event of a syndrome involving myopia associated with closed-angle glaucoma, treatment includes discontinuation of Topamax® as soon as the treating physician considers it possible and appropriate measures to lower intraocular pressure. These measures usually lead to normalization of intraocular pressure.

Elevated intraocular pressure of any etiology can lead to serious complications, including vision loss, if not treated appropriately.

Hyperchloremic, unrelated to anion deficiency, metabolic acidosis may occur with topiramate use (e.g., decreased plasma bicarbonate concentrations below normal levels in the absence of respiratory alkalosis).

This decrease in serum bicarbonate concentration is a consequence of the inhibitory effect of topiramate on renal carboanhydrase.

In most cases, the decrease in bicarbonate concentrations occurs at the beginning of drug administration, although this effect can occur at any time during treatment with topiramate. The level of decrease in concentration is usually mild to moderate (the average is 4 mmol/L when used in adult patients at doses greater than 100 mg/day and about 6 mg/kg/day when used in pediatric practice).

In rare cases, patients have reported concentrations below 10 mmol/L. Certain conditions or treatments that predispose to the development of acidosis (e.g., renal disease, severe respiratory disease, epileptic status, diarrhea, surgery, ketogenic diet, taking certain medications) may be additional factors that enhance the bicarbonate-lowering effect of topiramate.

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

In view of the above, necessary studies, including determination of serum bicarbonate concentrations, are recommended when treating with topiramate. If metabolic acidosis occurs and persists, it is recommended to reduce the dose or discontinue Topamax®.

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

Influence on driving and operating ability

Topamax® acts on the CNS and may cause drowsiness, dizziness, visual disturbances and other symptoms. These adverse effects may pose a risk to patients driving and operating moving machinery, especially while the patient’s response to the drug is pending.

Contraindications

Precaution should be used in patients with renal or hepatic impairment, nephrourolithiasis (including past or family history), and hypercalciuria.

The use in liver function disorders

With caution, use in patients with hepatic insufficiency. Plasma clearance is decreased in patients with moderate to severe hepatic impairment.

Application for renal impairment

When prescribing the drug in patients with moderate to severe renal impairment, it should be noted that it may take 10-15 days to reach equilibrium in this category of patients as compared to 4-8 days in patients with normal renal function.

Because topiramate is removed from plasma during hemodialysis, an additional half daily dose of the drug should be given on the days of hemodialysis in two doses (before and after the procedure).

With caution, use with renal failure, nephrourolithiasis (including past or family history), hypercalciuria.

Pediatric use

The drug is contraindicated 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 common – somnolence, dizziness, paresthesias, in children – apathy, impaired attention; common – nystagmus, lethargy, memory impairment, impaired concentration, tremor, amnesia, hypoesthesia, perversion of taste sensation, thought disorder, speech disorder, cognitive disorders, apathy, mental impairment, psychomotor disorders, sedative effects; infrequent – loss of taste sensation, akinesia, loss of smell, aphasia, apraxia, aura, burning sensation (mainly in the face and extremities), cerebellar syndrome, circadian sleep disturbance, movement coordination disorders, complex partial seizures, seizures, postural vertigo, increased salivation, dysesthesia, dysgraphia, dyskinesia, dysphasia, dystonia, “goose bumps” sensation, grand mal-like tonic-clonic seizures, hyperesthesia, hypoheusia, hypokinesia, hyposmia, peripheral neuropathy, parosmia, preconscious states, recurrent speech, tactile disturbance, stupor, fainting, no response to stimuli, in children – psychomotor hyperactivity.

Mental disorders: frequent – slowed thinking, confusion, depression, insomnia, aggressive reactions, agitation, disorientation, emotional lability, erectile dysfunction, in children – behavioral changes; infrequent – anorgasmia, sexual dysfunction, crying, impaired sexual arousal, dysphemia, early waking in the morning, euphoric mood, auditory and visual hallucinations, hypomanic states, decreased libido, mania, panic states, paranoid states, perseveration in thinking, reading disorder, anxiety, sleep disorders, suicidal ideas or attempts, tearfulness; very rare – feeling of despair.

Digestive system disorders: very often – decreased appetite, anorexia; often – nausea, diarrhea; infrequent – abdominal pain, constipation, dry mouth, oral sensitivity disorder, pancreatitis, increased appetite, gastritis, gastroesophageal reflux, bleeding gums, bad breath, flatulence, glossodynia, oral pain, thirst, dyspeptic symptoms (gastric discomfort, epigastric discomfort, heavy stomach), in children – vomiting.

Muscular system: often – myalgia, muscle cramps, muscle pain in the chest, arthralgia; infrequently – pain in the side, muscle stiffness; very rarely – swollen joints, discomfort in the extremities.

Cardiovascular system: infrequent – bradycardia, palpitations, hot flashes, orthostatic hypotension, Raynaud’s phenomenon.

VIight: often – diplopia, visual impairment, dry eyes; infrequently – accommodation disorder, amblyopia, blepharospasm, transient blindness, unilateral blindness, increased lacrimation, mydriasis, night blindness, photopsia, presbyopia, scotoma (including atrial fibrillation).

In very rare cases – closed-angle glaucoma, involuntary eyeball movements, eyelid edema, myopia, conjunctival edema, maculopathy.

Hearing organ: often – ear pain, tinnitus, in children – vertigo; infrequent – deafness (including sensorineural and unilateral), discomfort in the ears, hearing loss.

Respiratory system: often – difficulty in breathing, nasal bleeding; infrequent – hoarseness, dyspnea on exertion, nasal congestion, hypersecretion in the paranasal sinuses, in children – rhinorrhea; very rare – nasopharyngitis.

Skin and subcutaneous tissue disorders: common – rash, alopecia, itching, decreased facial sensitivity; infrequent – lack of sweating, allergic dermatitis, skin redness, impaired skin pigmentation, bad skin odor, urticaria; very rare – erythema multiforme, para-orbital edema, Stevens-Johnson syndrome, toxic epidermal necrolysis.

As to the urinary system: common – nephrolithiasis, dysuria, semilakiuria; infrequent – exacerbation of urolithiasis, hematuria, urinary incontinence, frequent urge to urinate, renal colic, renal pain; very rare – renal tubular acidosis.

Hematopoietic system: frequently – anemia; infrequently – leukopenia, lymphadenopathy, thrombocytopenia, in children – eosinophilia; very rarely – neutropenia.

Laboratory disorders: infrequent – decrease of bicarbonate in blood (4 mmol/l on average), crystalluria, leukopenia, hypokalemia (decrease of serum potassium level below 3.5 mmol/l).

General disorders: very common – fatigue, irritability, decreased body weight; common – asthenia, anxiety, in children – fever; infrequent – facial edema, allergic reactions, hyperchloremic acidosis, increased appetite, metabolic acidosis, polydipsia, coldness of extremities, fatigue, weakness, calcinosis; very rare – generalized edema, flu-like illness, allergic edema, increased body weight.

Overdose

Symptoms: seizures, somnolence, speech and vision disturbances, diplopia, thinking 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 after overdoses involving a mixture of several medications, including topiramate.

The development of severe metabolic acidosis is possible.

A case of overdose is known when a patient took a dose of 96 to 110 g of topiramate, which resulted in a coma that lasted 20 to 24 hours. The overdose symptoms resolved after 3 to 4 days.

Treatment: if the patient had eaten shortly before taking an overdose of the drug, it is necessary to immediately flush the stomach or induce vomiting. In in vitro studies it has been shown that activated charcoal adsorbs topiramate.

Symptomatic therapy should be given if necessary. Hemodialysis is an effective way to eliminate topiramate from the body. Patients are advised to increase their fluid intake adequately.

Pregnancy use

Topamax® has not been specifically controlled for the treatment of pregnant women. Topiramate may have a damaging effect on the fetus when used in pregnant women.

Pregnancy records show that infants who were exposed to topiramate in utero have an increased risk of birth defects (e.g., craniofacial defects such as cleft lip or palate, hypospadias, and anomalies of various body systems). These malformations have been reported both with topiramate monotherapy and with its use as part of polytherapy.

As compared to the group of patients not taking antiepileptic drugs, pregnancy records for Topamax® monotherapy indicate an increased likelihood of low birth weight (less than 2500 g).

The association of the observed phenomena with drug administration has not been established. In addition, pregnancy records and the results of other studies suggest that the risk of teratogenic effects is higher with combined treatment with antiepileptic drugs than with monotherapy.

The use of Topamax® in pregnancy is justified only when the potential benefit of therapy for the mother exceeds the possible risk to the fetus.

When treating and counseling women of childbearing age, the treating physician should weigh the balance of benefits and risks of treatment and consider alternative treatment options.

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

Limited observations suggest that topiramate is excreted with breast milk in women. If it is necessary to use Topamax® during lactation, discontinuation of breastfeeding or discontinuation of the drug should be considered.

Pediatric use

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

Similarities