Topiramate 100 film-coated tablets 100 mg blister No. 30

Instructions Topiromax 100 film-coated tablets 100 mg blister No. 30

Composition

active ingredient: topiramate;

1 tablet contains topiramate 25 mg or 100 mg;

Excipients: microcrystalline cellulose; lactose monohydrate; pregelatinized starch; sodium starch glycolate (type A); copovidone; talc; colloidal anhydrous silica; magnesium stearate;

coating for applying the Opadry II White shell (Topiromax 25): polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide (E 171);

coating for applying the shell Opadry II Yellow (Topiromax 100): polyvinyl alcohol, polyethylene glycol, quinoline yellow (E 104), talc, titanium dioxide (E 171), iron oxide yellow (E 172), iron oxide red (E 172).

Dosage form

Film-coated tablets.

Main physicochemical properties:

25 mg tablets: white film-coated tablets with a biconvex surface, round in shape;

100 mg tablets: yellow, film-coated tablets with a biconvex surface, round in shape.

Pharmacotherapeutic group

Antiepileptics. Other antiepileptics. Topiramate. ATX code N03A X11.

Pharmacological properties

Pharmacodynamics.

Topiramate belongs to the class of sulfamate-substituted monosaccharides. The exact mechanism of topiramate's anticonvulsant and migraine preventive effects is unknown. Three pharmacological properties of topiramate have been identified that may be related to its antiepileptic efficacy. Topiramate blocks sodium channels and inhibits the generation of repeated action potentials during prolonged depolarization of the neuronal membrane. Topiramate increases the frequency of activation of GABAA receptors by γ-aminobutyrate (GABA) and increases the ability of GABA to induce the flow of chloride ions into neurons, indicating that topiramate potentiates the activity of this inhibitory neurotransmitter. This effect is not blocked by the benzodiazepine antagonist flumazenil. In addition, topiramate does not increase the duration of time that ion channels are open, which distinguishes topiramate from barbiturates that modulate GABAA receptors.

Topiramate may modulate the benzodiazepine-insensitive subtype of GABAA receptors due to significant differences in the antiepileptic properties of topiramate and benzodiazepines. Topiramate inhibits the ability of kainate to activate the kainate/AMPK (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) subtype of glutamate receptors, but has no apparent effect on the activity of N-methyl-D-aspartate (NMDA) among the NMDA receptor subtype. These effects of topiramate are dose-dependent at plasma drug concentrations of 1 μM to 200 μM, with minimal activity in the range of 1 μM to 10 μM. In addition, topiramate inhibits the activity of some carbonic anhydrase isoenzymes. In terms of severity, this pharmacological effect of topiramate is significantly inferior to acetazolamide, a known carbonic anhydrase inhibitor, therefore this activity of topiramate is not considered the main component of its antiepileptic activity.

Pharmacokinetics.

The pharmacokinetic profile of topiramate, compared with other antiepileptic drugs, is characterized by a long plasma half-life, linear pharmacokinetics, predominantly renal clearance, no significant protein binding, and no clinically significant active metabolites. Topiramate is not a potent inducer of drug-metabolizing enzymes, can be administered without regard to food intake, and there is no need to monitor plasma concentrations of topiramate. Clinical studies have shown no significant relationship between plasma concentrations and efficacy or adverse reactions.

Absorption. Topiramate is rapidly and efficiently absorbed. Following oral administration of 100 mg of topiramate to healthy volunteers, mean peak plasma concentrations (Cmax) of 1.5 mcg/mL were achieved within 2 to 3 hours (Tmax). Following oral administration of radiolabeled topiramate and evaluation of urinary radioactivity, the mean extent of absorption of a 100 mg oral dose of 14C-topiramate was found to be at least 81%. Food has no clinically significant effect on the bioavailability of topiramate.

Metabolism. Topiramate is known to be largely unmetabolized in healthy volunteers (20%). However, in patients receiving concomitant therapy with antiepileptic drugs known to induce drug-metabolizing enzymes, the metabolism of topiramate was increased by up to 50%. Six metabolites formed by hydroxylation, hydrolysis, and glucuronidation have been isolated and identified from human plasma, urine, and feces. Each of these metabolites accounted for less than 3% of the total urinary radioactivity following administration of 14C-topiramate. Studies of two metabolites, which retained most of the structure of topiramate, have shown that they exhibit little or no anticonvulsant activity.

Elimination. The major route of elimination of unchanged topiramate (at least 81% of the dose) and its metabolites in humans is the kidney. Approximately 66% of the 14C-topiramate dose is excreted unchanged in the urine within 4 days. When 50 mg and 100 mg of topiramate are administered twice daily, the mean renal clearance is approximately 18 mL/min and 17 mL/min, respectively, indicating tubular reabsorption of topiramate in the kidneys. These data are consistent with the results of studies in rats in which topiramate was administered concomitantly with probenecid and a significant increase in renal clearance of topiramate was observed. After oral administration, plasma clearance of the drug is 20-30 mL/min.

Linearity. Topiramate has low intersubject variability in plasma concentrations, and its pharmacokinetic properties are therefore predictable. Topiramate pharmacokinetics are linear, with plasma clearance remaining constant and the area under the concentration-time curve increasing dose-proportionally over the 100 mg to 400 mg dose range in healthy volunteers. In patients with normal renal function, steady-state plasma concentrations are reached within 4 to 8 days. The Cmax value after multiple oral administration of 100 mg of topiramate twice daily to healthy volunteers is 6.76 μg/mL. After multiple doses of 50 and 100 mg twice daily, the mean plasma elimination half-life of topiramate is approximately 21 hours.

Concomitant use with other antiepileptic drugs: Multiple administration of topiramate in doses of 100 to 400 mg twice daily with phenytoin or carbamazepine demonstrates a dose-proportional increase in plasma concentrations of topiramate.

Renal impairment. In patients with moderate to severe renal impairment, plasma and renal clearance of topiramate are reduced (CLCR ≤ 70 mL/min). As a result, for a given dose of the drug, higher steady-state plasma concentrations of topiramate are expected in patients with renal impairment compared with patients with normal renal function. Patients with known renal impairment may require longer to reach steady-state concentrations after each dose. Half the usual initial and maintenance doses are recommended for patients with moderate to severe renal impairment. Topiramate is effectively removed from plasma by hemodialysis. Prolonged hemodialysis may result in a decrease in topiramate concentrations below the level required to maintain the anticonvulsant effect. A supplemental dose may be required to avoid rapid decreases in topiramate plasma concentrations during hemodialysis. When selecting a dose, the following should be taken into account: 1) the duration of the dialysis period; 2) the clearance rate of the dialysis system used; 3) the value of the renal clearance of topiramate in the patient on dialysis.

Hepatic impairment: In patients with moderate to severe hepatic impairment, the clearance of topiramate is reduced by an average of 26%. Therefore, topiramate should be used with caution in patients with hepatic impairment.

Elderly patients: In elderly patients without renal disease, the plasma clearance of topiramate is not altered.

Pharmacokinetics in children under 12 years of age.

The pharmacokinetics of topiramate in children, as in adults, are linear with dose-independent clearance and steady-state plasma concentrations that increase proportionally with dose. However, children have a higher clearance and a shorter half-life. Therefore, plasma concentrations of topiramate for the same doses in milligrams per kilogram of body weight may be lower in children than in adults. As in adults, antiepileptic drugs that induce hepatic enzymes reduce steady-state plasma concentrations of topiramate.

Indication

Monotherapy for the treatment of adults and children aged 6 years and over with partial seizures with or without secondarily generalized seizures and with primary generalized tonic-clonic seizures.

Adjunctive therapy for the treatment of adults and children aged 2 years and older with partial seizures with or without secondary generalisation, or with primary generalised tonic-clonic seizures and for the treatment of seizures associated with Lennox-Gastaut syndrome.

Prevention of migraine attacks in adults after careful evaluation of alternative treatment options.

Topiramate is not recommended for the treatment of acute conditions.

Contraindication

Hypersensitivity to any component of the drug.

Migraine prevention:

during pregnancy (see sections "Special instructions" and "Use during pregnancy or breastfeeding").

in women of reproductive age who are not using highly effective contraception (see sections "Special instructions for use", "Interaction with other medicinal products and other types of interactions" and "Use during pregnancy or breastfeeding").

Epilepsy:

during pregnancy, if there is no suitable alternative treatment (see sections "Special precautions for use" and "Use during pregnancy or breastfeeding").

in women of childbearing potential not using highly effective contraception. The only exception is women for whom there is no suitable alternative but who are planning a pregnancy and are fully informed about the risks of taking topiramate during pregnancy (see sections “Special instructions”, “Interaction with other medicinal products and other types of interactions” and “Use during pregnancy or breastfeeding”).

Interaction with other medicinal products and other types of interactions

Effect of topiramate on other antiepileptic drugs.

Concomitant administration of topiramate and other antiepileptic drugs (phenytoin, carbamazepine, valproic acid, phenobarbital, primidone) does not affect their steady-state plasma concentrations, except in individual patients in whom concomitant administration of topiramate and phenytoin may result in increased plasma concentrations of phenytoin. This may be due to inhibition of a specific polymorphic isoform of the enzyme (CYP2C19). In any patient taking phenytoin who develops clinical signs or symptoms of intoxication, phenytoin plasma levels should be monitored.

A pharmacokinetic interaction study in patients with epilepsy showed that the addition of topiramate to lamotrigine did not affect the steady-state plasma concentrations of lamotrigine at topiramate doses ranging from 100 to 400 mg/day. In addition, there were no changes in the steady-state plasma concentrations of topiramate during or after discontinuation of lamotrigine treatment (mean dose 327 mg/day).

Topiramate inhibits the CYP2C19 enzyme and may interfere with other substances that are metabolized by this enzyme (e.g. diazepam, imipramine, moclobemide, proguanil, omeprazole).

The effect of other antiepileptic drugs on the drug Topiramate.

Phenytoin and carbamazepine reduce plasma concentrations of topiramate. Addition (or withdrawal) of phenytoin or carbamazepine to topiramate therapy may require dose adjustment of the latter. The dose should be adjusted to achieve the desired therapeutic effect.

The addition (or withdrawal) of valproic acid does not cause therapeutically significant changes in plasma concentrations of topiramate and, accordingly, does not require changes in topiramate doses.

The effect of phenobarbital and primidone on topiramate concentrations has not been studied.

Table 1.

« = no effect (change ≤ 15%);

** = increased concentration in individual patients;

¯ = decrease in plasma concentration;

ND = not studied;

AED = antiepileptic drug.

Other drug interactions.

Digoxin. In single-dose studies, the area under the plasma concentration-time curve (AUC) of digoxin was decreased by 12% when topiramate was co-administered. The clinical significance of this observation is unknown. When topiramate is initiated or discontinued in patients receiving digoxin, special attention should be paid to regular monitoring of serum digoxin concentrations.

Central Nervous System (CNS) Depressants: The effects of co-administration of topiramate with alcohol or other CNS depressants have not been studied. It is not recommended to co-administer topiramate with alcohol or other CNS depressants.

St. John's wort (Hypericum perforatum) preparations. There is a potential risk of reduced plasma concentrations of topiramate and, consequently, reduced efficacy when topiramate is administered concomitantly with St. John's wort preparations. However, clinical studies of this potential interaction have not been conducted.

Lithium preparations. It is known that in healthy volunteers there was a decrease (up to 18%) in the AUC of lithium during concomitant use of topiramate at a dose of 200 mg per day. In patients with bipolar disorder, the pharmacokinetics of lithium remained unchanged during concomitant treatment with topiramate at doses of 200 mg per day, while an increase in the AUC of lithium of up to 26% was observed when topiramate was used at doses of 600 mg per day. It is recommended to monitor the level of lithium during concomitant use with topiramate.

Risperidone. Interaction studies conducted with single doses in healthy volunteers and multiple doses in patients with bipolar disorder are known to have shown similar results. When co-administered with topiramate at increasing doses of 100, 250, and 400 mg/day, there was a decrease in the area under the concentration-time curve (AUC) of risperidone administered at doses of 1-6 mg/day by 16% and 33% for topiramate doses of 250 and 400 mg/day, respectively. However, the differences in AUC for the total active metabolites when risperidone was administered alone or in combination with topiramate were not statistically significant. Minimal changes in the pharmacokinetics of the active metabolites (risperidone + 9-hydroxyrisperidone) were observed, and no changes were observed for 9-hydroxyrisperidone. There were also no clinically significant changes in the pharmacokinetics of the active metabolites of either risperidone or topiramate. After adding topiramate (250-400 mg/day) to risperidone (1-6 mg/day) therapy, an increase in the incidence of adverse reactions was observed compared with the period of treatment before the inclusion of topiramate (90% and 54%, respectively). The most common adverse reactions after the inclusion of topiramate in risperidone treatment were: drowsiness, paresthesia and nausea.

Hydrochlorothiazide. It is known that an interaction study in healthy volunteers evaluated the steady-state pharmacokinetics of hydrochlorothiazide (25 mg every 24 hours) and topiramate (96 mg every 12 hours) when administered alone and concomitantly. The results of the study showed that when topiramate and hydrochlorothiazide were administered simultaneously, the Cmax and AUC of topiramate increased by 27% and 29%, respectively. The clinical significance of these changes is unknown. The administration of hydrochlorothiazide to patients taking topiramate may require an adjustment of the topiramate dose. The pharmacokinetic parameters of hydrochlorothiazide were not significantly altered by concomitant treatment with topiramate. Studies have shown a decrease in serum potassium with topiramate or hydrochlorothiazide, which was more pronounced with topiramate and hydrochlorothiazide in combination.

Metformin.

An interaction study in healthy volunteers evaluated the steady-state pharmacokinetics of metformin and topiramate when metformin was administered alone and when metformin and topiramate were co-administered. The results showed that the mean Cmax and AUC0-12h of metformin increased by 18% and 25%, respectively, while the mean CL/F decreased by 20% when metformin was co-administered with topiramate. Topiramate had no effect on metformin tmax. The clinical significance of the effect of topiramate on the pharmacokinetics of metformin is unknown. The oral clearance of topiramate from plasma is reduced when co-administered with metformin. The extent of the change in clearance is unknown. The clinical significance of the effect of metformin on the pharmacokinetics of topiramate is unknown.

When topiramate is prescribed or discontinued in patients treated with metformin, their diabetic status should be regularly monitored.

Pioglitazone.

In an interaction study in healthy volunteers, the steady-state pharmacokinetics of topiramate and pioglitazone were evaluated during pioglitazone monotherapy and co-administration of pioglitazone and topiramate. A 15% decrease in pioglitazone AUCτ,ss was observed, with no change in Cmax,ss. This result was not statistically significant. In addition, a 13% and 16% decrease in Cmax,ss and AUCτ,ss of the active hydroxy metabolite, and a 60% decrease in Cmax,ss and AUCτ,ss of the active ketometabolite were observed. The clinical significance of these findings is not established. When topiramate and pioglitazone are co-administered, patients should be regularly monitored for their diabetic status.

Glibenclamide. In an interaction study in patients with type 2 diabetes mellitus, the steady-state pharmacokinetics of glibenclamide 5 mg/day were evaluated when administered alone and concomitantly with topiramate 150 mg/day. A 25% decrease in glibenclamide AUC24 was observed when administered concomitantly with topiramate. The systemic exposure of the active metabolites 4-trans-hydroxyglibenclamide (M1) and 3-cis-hydroxyglibenclamide (M2) was reduced by 13% and 15%, respectively. Concomitant treatment with glibenclamide had no effect on the steady-state concentrations of topiramate.

When topiramate and glibenclamide are administered concomitantly, the diabetic status of patients should be regularly monitored.

Other types of interactions.

Medications that contribute to the development of nephrolithiasis.

Valproic acid. Concomitant use of topiramate with valproic acid has caused hyperammonemia with or without encephalopathy in patients who tolerated monotherapy with these drugs well. In most cases, symptoms resolved after discontinuation of one of the drugs. This adverse reaction is not associated with a pharmacokinetic interaction.

Cases of hypothermia, defined as a spontaneous decrease in body temperature to < 35°C, have been reported in association with the concomitant use of valproic acid and topiramate, with or without hyperammonemia. This adverse reaction in patients receiving topiramate and valproic acid concomitantly may occur either at the start of topiramate therapy or after an increase in the daily dose.

Warfarin: Decreases in prothrombin time/international normalized ratio (PT/INR) have been reported in patients receiving topiramate in combination with warfarin. Therefore, INR should be closely monitored in patients receiving topiramate and warfarin concomitantly.

Additional studies of pharmacokinetic drug interactions.

Additional clinical studies were conducted to assess the potential pharmacokinetic interactions of topiramate with other drugs. The changes in Cmax and AUC as a result of the interaction are shown in Table 2. The first column indicates the concomitant drug. The second column describes the changes in the concentration of the concomitant drug when topiramate is added. The third column (topiramate concentration) indicates the effect of the concomitant drug on the concentration of topiramate.

Table 2

Summary of results of additional clinical studies of pharmacokinetic drug interactions

aPercent change in plasma Cmax or AUC compared to monotherapy.

« – no effect on Cmax and AUC (no more than 15% of the initial data).

ND – not studied.

*DEA – desacetyldiltiazem, DEM – N-dimethyldiltiazem.

The bAUC of flunarizine increased by 14% in patients receiving flunarizine alone. The increased exposure may be due to its accumulation during steady-state concentrations.

Application features

Pregnancy prevention program.

Topiramate can cause serious birth defects and fetal growth retardation when used by women during pregnancy.

Some data suggest an increased risk of neurodevelopmental disorders in children exposed to topiramate in utero compared to children not exposed to this drug (see section "Use during pregnancy or lactation").

Women of reproductive age

Before starting treatment with topiramate, women of childbearing potential should be screened for pregnancy. The patient should be fully informed and understand the risks associated with the use of topiramate during pregnancy (see sections “Contraindications” and “Use during pregnancy or lactation”). This includes the need to consult a specialist if the woman is planning a pregnancy to discuss switching to alternative methods of treatment before stopping contraception, and to seek immediate medical attention if she becomes pregnant or thinks she may become pregnant.

Female children.

The prescribing physician should ensure that parents/guardians of female children taking topiramate understand the need to seek medical advice after the child reaches menarche. At this time, the patient and parents/guardians should be fully informed about the risks associated with in utero exposure to topiramate and the need to use highly effective contraception as soon as possible. The need for continued topiramate therapy should be re-evaluated and alternative treatment options should be considered.

Educational materials regarding these measures are available for healthcare professionals and patients (or parents/guardians).

As with other antiepileptic drugs, some patients may experience an increase in seizure frequency or the appearance of new seizure types when taking topiramate. These events may be the result of overdose, decreased plasma concentrations of concomitant antiepileptic drugs, disease progression, or a paradoxical effect.

Adequate hydration is very important when using topiramate to reduce the risk of nephrolithiasis. Drinking adequate fluids before and during exercise or exposure to high temperatures may reduce the risk of temperature-related adverse reactions (see section 4.8).

Oligohydrosis.

Oligohidrosis (decreased sweating) has been reported in association with the use of topiramate. Decreased sweating and hyperthermia (increased body temperature) may occur primarily in young children exposed to high ambient temperatures.

Mood disorders/depression.

An increased incidence of mood disorders and depression has been reported during treatment with topiramate.

Suicide/suicidal thoughts.

Suicidal ideation and behavior have been reported in patients treated with antiepileptic drugs for several indications. A meta-analysis of placebo-controlled trials of antiepileptic drugs has been reported to show a small increased risk of suicidal ideation and behavior. The mechanism of this phenomenon is unknown, but the available data do not exclude the possibility of an increased risk with topiramate.

Therefore, it is recommended that patients be monitored for signs of suicidal ideation and behavior and appropriate treatment should be instituted. Patients (and caregivers) should seek medical advice at the first appearance of suicidal ideation and behavior.

Nephrolithiasis.

Some patients, especially those with a predisposition to nephrolithiasis, may be at increased risk of developing kidney stones and associated symptoms such as renal colic, renal pain, or flank pain. Risk factors for nephrolithiasis include a history of stone formation, a family history of nephrolithiasis, and hypercalciuria. None of these risk factors are sufficiently predictive of stone formation while taking topiramate. In addition, the risk is further increased in patients taking concomitant medications that promote the development of nephrolithiasis.

Kidney dysfunction.

Topiramate should be administered with caution to patients with renal impairment (CLCR ≤ 70 mL/min) as plasma and renal clearance of topiramate are reduced in such patients. Dosage recommendations for patients with known renal impairment are provided in the Dosage and Administration section.

Liver dysfunction.

Topiramate should be administered with caution to patients with impaired hepatic function due to the possibility of decreased clearance of topiramate.

Acute myopia and secondary angle-closure glaucoma.

Cases of acute myopia syndrome associated with secondary angle-closure glaucoma have been reported with topiramate. Symptoms include a sudden decrease in visual acuity and/or eye pain. Ophthalmological examination may reveal myopia, decreased anterior chamber depth, hyperemia (redness of the eyes), and increased intraocular pressure. Mydriasis may also be present. The syndrome described may be associated with supraciliary effusion, causing displacement of the lens and iris and the development of secondary angle-closure glaucoma. Symptoms usually occur within the first month of topiramate treatment. Unlike primary open-angle glaucoma, which is rarely observed in patients under 40 years of age, secondary angle-closure glaucoma associated with topiramate has been observed in both children and adults. Treatment involves early discontinuation of topiramate and appropriate measures to reduce intraocular pressure.

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

It should be determined whether topiramate can be prescribed to patients with a history of visual impairment.

Visual field defects.

Visual field defects, independent of elevated intraocular pressure, have been reported in patients treated with topiramate. In clinical trials, most of these cases were reversible and resolved after discontinuation of treatment. If visual defects occur at any time during therapy, discontinuation of the drug should be considered.

Topiramate may cause hyperchloremic, non-anion gap, metabolic acidosis (i.e., a decrease in plasma bicarbonate concentration below normal in the absence of respiratory alkalosis). The decrease in serum bicarbonate concentration is a consequence of topiramate inhibition of renal carbonic anhydrase. In most cases, the decrease in bicarbonate concentration occurs at the beginning of the drug, although this effect may occur at any time during treatment with topiramate. The level of decrease in concentration is usually small or moderate (an average of 4 mmol/L when used in adult patients at a dose of 100 mg per day and about 6 mg/kg of body weight per day when used in children). In some cases, patients have had a decrease in concentration below 10 mmol/L. Certain diseases or treatments that lead to the development of acidosis (e.g., renal disease, severe respiratory disease, status epilepticus, diarrhea, surgery, ketogenic diet, certain medications) may be additional factors that enhance the bicarbonate-lowering effect of topiramate.

Chronic metabolic acidosis increases the risk of kidney stone formation and can potentially lead to osteopenia.

In children, chronic metabolic acidosis may lead to growth retardation. The effect of topiramate on bone-related complications has not been systematically studied in either children or adult patients.

Depending on the underlying disease, appropriate investigations, including serum bicarbonate levels, are recommended during topiramate treatment. If symptoms or signs (e.g. Kussmaul breathing, dyspnoea, anorexia, nausea, vomiting, fatigue, tachycardia or arrhythmia) suggestive of metabolic acidosis are present, serum bicarbonate levels should be monitored. If metabolic acidosis develops or progresses, it is recommended to reduce the dose or discontinue topiramate (by dose reduction).

Topiramate should be prescribed with caution to patients with risk factors for metabolic acidosis.

Cognitive impairment.

Cognitive impairment in epilepsy is multifactorial and may be related to the underlying cause of the disease, epilepsy itself, or antiepileptic treatment. There have been reports in the literature of cognitive impairment in adults treated with topiramate, requiring dose reduction or discontinuation of the drug. However, the available data on the effects of topiramate on cognitive function in children are insufficient, and the relationship needs further investigation.

Hyperammonemia and encephalopathy.

Hyperammonemia with or without encephalopathy has been reported with topiramate (see section 4.8). The risk of hyperammonemia with topiramate is dose-dependent. Hyperammonemia has been reported more frequently when topiramate is used concomitantly with valproic acid (see section 4.5).

Patients who develop unexplained lethargy or mental status changes related to topiramate monotherapy or adjunctive therapy are advised to consider hyperammonemic encephalopathy and measure blood ammonia levels.

Dietary considerations: If a patient experiences weight loss while taking topiramate, a maintenance diet or nutritional support may be recommended.

The drug contains lactose, therefore it is not recommended for patients with lactase deficiency, galactosemia or glucose or galactose malabsorption syndrome.

Use during pregnancy or breastfeeding

Pregnancy.

The risk is associated with epilepsy and the use of antiepileptic drugs.

Women of childbearing potential, especially women planning pregnancy and pregnant women, should seek specialist advice on the potential risks to the foetus from both seizures and antiepileptic treatment. The need for antiepileptic treatment should be reconsidered when planning pregnancy. Women receiving antiepileptic drugs should avoid abrupt discontinuation of treatment, as this may lead to exacerbation of seizures and serious consequences for both the woman and the foetus. Monotherapy should be preferred whenever possible, as the risk of birth defects is higher with combination therapy with antiepileptic drugs.

Risk related