Topamax, 50 mg capsules 60 pcs

The 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.

The drug increases the activity of GABA (GABA) against some subtypes of GABA receptors (including GABAA-receptors) and modulates the activity of GABAA-receptors themselves, also inhibits kainate/AMPK (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor subtype sensitivity to glutamate, and has no effect on NMDA activity with respect to NMDA-receptor subtype. The efficacy of the drug is 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 considerably inferior to acetazolamide, the known carbonic anhydrase inhibitor, in terms of the severity of this pharmacological effect, so that this activity of topiramate is not the main component of its antiepileptic activity.

Pharmacokinetics

Intake

After oral administration, topiramate is rapidly and effectively absorbed from the GI 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, Cmax 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 Vd is 0.55-0.8 L/kg. The value of Vd 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.

Excretion

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 the drug at 50 mg and 100 mg 2 times/day, the average T1/2 was on average 21 hours.

Pharmacokinetics in special clinical cases

The renal excretion rate 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 and, as a consequence, plasma Css of topiramate may be increased compared to patients with normal renal function. The time to reach plasma Css 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 rate 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 Css in plasma increases in proportion to increasing the dose. Note that in children, topiramate clearance is increased and its T1/2 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

Active substance:

Topiramate 50 mg

Auxiliary substances:

sugar grits [sucrose, starch treacle] 150.00 mg,

povidone 34.733 mg,

cellulose acetate 18.076 mg.

Composition of the hard gelatin capsule:

gelatin 80.6-83.5 mg,

water 12.5-15.4 mg,

sorbitan laurate 0.0397 mg,

sodium lauryl sulfate 0.0397 mg,

titanium dioxide (E171) 0.99 mg,

Opacode Black S-1-17822/23 black ink (ink composition: Shellac glaze solution in ethanol, iron oxide black, n-butyl alcohol, isopropyl alcohol, propylene glycol, ammonium hydroxide) 5-10 mg.

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 begin with a low dose of the drug 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 to start treatment with a low dose followed by a gradual adjustment to an effective dose. The dose is started with 25-50 mg taken at night for 1 week. Thereafter, the dose may be increased by 25-50 mg at 1-2 week intervals and taken in 2 doses. 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 the plasma concentration of Topamax® to achieve the optimal effect of the drug treatment.

The dose recommendations are applicable 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. Subsequently, the dose may be increased at 1- to 2-week intervals by 1 to 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 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, the concentration of topiramate in the blood will increase. In these situations, if clinically indicated, the dose of Topamax® may be reduced.

In monotherapy in adults, Topamax® is given at a dose of 25 mg at bedtime for 1 week. Then the dose is increased at 1-2 week intervals by 25 mg or 50 mg in 2 doses. If a patient cannot tolerate this mode of dose escalation, the intervals between dose escalations may be increased or the dose may be raised more gently. Dose selection 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 administered at a dose of 0.5-1 mg/kg of body weight in the first week of treatment before bedtime. Then the dose is increased at 1- to 2-week intervals by 0.5 to 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 size of the dose and the rate of dose 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, it is prescribed 25 mg before bedtime for 1 week. Then the dose is increased by 25 mg/day at 1 week intervals. If such therapy regimen is intolerable, the dose is increased by a smaller amount or at longer intervals. The dose is adjusted depending on 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 no 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® of approximately half the daily dose should be given on hemodialysis days. The additional dose should be divided into two doses taken at the beginning and after the completion of hemodialysis. 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)

Concomitant administration of Topamax® with other PEDs (phenytoin, carbamazepine, valproic acid, phenobarbital, primidone) does not influence their Css values in plasma, except in individual patients in whom addition of Topamax® to phenytoin may cause increase in phenytoin plasma concentration. 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 doses of topiramate 100-400 mg/day. During and after withdrawal of lamotrigine (mean dose 327 mg/day) the Css of topiramate did not change.

The effect of other PEDs on plasma concentrations of topiramate

Phenytoin and carbamazepine decrease plasma concentrations of topiramate when used concomitantly with Topamax® . 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. Addition or withdrawal of valproic acid does not cause clinically significant changes in plasma concentrations of topiramate and therefore does not require changing the dose of Topamax®.

. PEPK addedPEPK concentrationTopiramate concentrationPhenytoinol no effect (increased plasma concentration in single cases)48% decrease in plasma concentrationCarbamazepine no effectreduction in plasma concentration by 40%Valproic acid no effect no effectphenobarbital no effectnot investigatedPrimidonot no effectnot investigated

Penetopropic acid no effectphenytoinol no effectphenytoinol no effectnot investigatedPrimidonot no effectnot investigated/p>

In the studies, the AUC of digoxin was decreased by 12% when using Topamax® in a single dose at the same time. The clinical significance of this effect has not been established. Serum digoxin concentrations should be monitored when prescribing or discontinuing Topamax® in patients receiving digoxin.

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

When Topamax® is coadministered with preparations based on Hypericum perforatum, plasma concentrations of topiramate may decrease and as a consequence, the drug efficacy may also decrease. Clinical studies of interaction of the drug Topamax® and preparations on the basis of Hypericum perforatum have not been conducted.

When concomitant use of 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 ethinylestradiol efficacy was observed at doses of Topamax® 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 about any changes in the timing and nature of their periods. The effectiveness of contraceptives may be reduced even in the absence of 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 the pharmacokinetics of lithium, 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. When topiramate is administered simultaneously 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 of the active substances (risperidone and 9-hydroxyrisperidone) did not change significantly. 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 when hydrochlorothiazide (25 mg) and topiramate (96 mg) were administered separately and together. The results showed that concomitant administration of topiramate and hydrochlorothiazide increased Cmax of topiramate by 27% and its AUC by 29%. The clinical relevance 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. 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 the Tmax of metformin in plasma. Topiramate clearance is decreased when coadministered with metformin. The extent of the observed changes in clearance has not been studied. The clinical significance of the effect of metformin on topiramate pharmacokinetics is not clear. If Topamax® is added or withdrawn in patients receiving metformin, the condition of diabetic patients should be monitored.

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

Also for the active hydroxymetabolite pioglitazone a decrease in Cmax and AUC of 13% and 16%, respectively, and for the active ketometabolite a decrease in both Cmax and AUC of 60% was detected. The clinical significance of these data has not been clarified. When prescribing Topamax® and pioglitazone together, the patient should be closely monitored to assess the course of diabetes mellitus.

A drug interaction study has been 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 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 carefully monitored to assess the course of diabetes mellitus.

In concomitant administration of Topamax® with other drugs that predispose to the development of nephrolithiasis, the risk of formation of kidney stones may increase. These drugs should be avoided during treatment with Topamax® because 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. An 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 (an 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.

Special Instructions

Topamax® (like other antiepileptic drugs) should be withdrawn gradually to minimize the possibility of increased seizure frequency. In clinical trials the dose of the drug was decreased by 50-100 mg once a week for adults in therapy of epilepsy and by 25-50 mg in adults receiving Topamax® in dose of 100 mg/day for migraine prophylaxis.

In children in clinical trials, Topamax® was gradually withdrawn over 2-8 weeks. If by medical indications rapid discontinuation of Topamax® is necessary, it is recommended to control patient’s condition appropriately.

As with any disease, the dosage regimen should be established 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, 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 exposed to high ambient temperatures. An adequate increase in fluid intake is very important during therapy with topiramate, which helps to 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 suicidal 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 4,045). One case of suicide was reported in a double-blind study of bipolar disorder in a patient receiving topiramate.

Thus, 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 immediate medical attention if they show signs of suicidal ideation or 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 promote nephrolithiasis.

Caution should be exercised when prescribing Topamax® in patients with renal insufficiency.

Patients with hepatic impairment should use Topamax® with caution because of possible decreased clearance of topiramate.

In the use of Topamax®, a syndrome including acute myopia with concomitant secondary closed-angle glaucoma has been described. 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® therapy.

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. When a syndrome involving myopia associated with closed-angle glaucoma occurs, treatment includes discontinuation of Topamax® as soon as the treating physician considers it possible and appropriate measures to lower intraocular pressure. Usually, these measures 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 the drug, although this effect can occur at any time during treatment with topiramate.

The level of reduction 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). Rarely, patients have had decreased 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 increase 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 with Topamax® decreases body weight, the appropriateness of increased nutrition should be considered.

The effect on driving and operating ability

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

Contraindications

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

The use in liver function disorders

With caution should be used in patients with hepatic insufficiency. Plasma clearance is decreased in patients with moderate to severe hepatic impairment.

Perhaps in patients with moderate to severe renal dysfunction

When prescribing the drug in patients with moderate to severe renal dysfunction, it may take 10-15 days to reach equilibrium in this category of patients, as opposed 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 administered in two doses (before and after the procedure) on the days of hemodialysis.

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

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, impaired memory, impaired concentration, tremor, amnesia, hypoesthesia, perversion of taste sensation, impaired thinking, impaired speech, cognitive disorders, apathy, mental impairment, psychomotor disorders, sedative effects; infrequent – loss of taste sensation, akinesia, loss of smell, aphasia, apraxia, aura, burning sensation (mainly on face and extremities), cerebellar syndrome, disruption of circadian rhythm of sleep, 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 fatalities have been reported following overdoses with a mixture of several medications, including topiramate. Severe metabolic acidosis may develop.

A case is known of an overdose in which a patient took a dose of 96 to 110 g of topiramate, resulting 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. If necessary, symptomatic therapy should be carried out. Hemodialysis is an effective way to eliminate topiramate from the body. Patients are advised to increase their fluid intake adequately.

Pregnancy use

There have been no specific controlled studies in which Topamax has been used to treat pregnant women. Topiramate can cause fetal harm when used in pregnant women. Pregnancy records show that infants who have had intrauterine exposure to Topiramate 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.

In comparison with the group of patients not taking antiepileptic drugs, pregnancy records for Topamax monotherapy show an increased likelihood of low birth weight (less than 2500 g). The association of the observed phenomena with taking the drug 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 the drug for the mother exceeds the possible risk to the fetus. When treating and counseling women of childbearing potential, the treating physician should weigh the balance of benefits and risks of treatment and consider alternative treatment options. If Topamax is used during pregnancy or if a patient becomes pregnant while taking this medication, she should be warned of the potential risk to the fetus.

Limited patient observations suggest that topiramate is excreted with breast milk in women, so the physician should decide to withhold breastfeeding or discontinue the drug.

Similarities