Zoresan capsules 100 mg No. 30

Instructions for Zoresan capsules 100 mg No. 30

Composition

active ingredient: zonisamide;

1 hard capsule contains zonisamide 25 mg or 50 mg or 100 mg;

excipients:

microcrystalline cellulose, sodium lauryl sulfate, colloidal anhydrous silicon dioxide, hydrogenated castor oil;

capsule shell:

for hard capsules of 25 mg or 50 mg: gelatin, purified water, yellow iron oxide (E 172), black iron oxide (E 172), titanium dioxide (E 171), sodium lauryl sulfate;

for 100 mg hard capsule: gelatin, purified water, red iron oxide (E 172), titanium dioxide (E 171), sodium lauryl sulfate.

Dosage form

The capsules are hard.

Main physicochemical properties:

25 mg hard capsules: hard gelatin capsule size No. 4 with an opaque gray cap and an opaque white body, containing a white to almost white powder;

50 mg hard capsules: hard gelatin capsule size No. 3 with an opaque gray cap and an opaque white body, containing a white to almost white powder;

100 mg hard capsules: size No. 1 hard gelatin capsule with an opaque red cap and an opaque white body, containing a white to almost white powder.

Pharmacotherapeutic group

Antiepileptics. Other antiepileptics. Zonisamide. ATX code N03 AX15.

Pharmacological properties

Pharmacodynamics.

Zonisamide is a benzisoxazole derivative antiepileptic drug. It is a weak inhibitor of carbonic anhydrase in vitro and is chemically unrelated to other antiepileptic drugs.

Mechanism of action.

The mechanism of action of zonisamide is not fully understood, but it is believed to block voltage-gated sodium and calcium channels, thereby disrupting synchronized neuronal firing, inhibiting the development of seizures, and preventing further spread of epileptic activity. Zonisamide also has a modulatory effect on GABA-mediated neuronal inhibition.

Pharmacodynamic effects.

The anticonvulsant activity of zonisamide has been evaluated in various models of epilepsy, mainly in groups with induced or congenital seizures, and zonisamide has shown itself to be a broad-spectrum antiepileptic agent. Zonisamide prevents the development of seizures induced by maximal electroshock, limits the spread of seizures, including the spread of the focus of excitation from the cerebral cortex to subcortical structures, and also suppresses the activity of the epileptogenic focus. In contrast to phenytoin and carbamazepine, zonisamide has a selective effect on seizures, the foci of which arise in the cerebral cortex.

Pharmacokinetics.

Absorption.

Zonisamide is almost completely absorbed after oral administration, with Cmax in serum or plasma reached within 2–5 hours after administration. First-pass metabolism is thought to be negligible. Absolute bioavailability is estimated to be approximately 100%. The bioavailability of zonisamide when administered orally is not affected by food intake, although the time to reach Cmax in plasma or serum may be delayed.

The AUC and Cmax values of zonisamide increased almost linearly after single-dose administration (in the dose range of 100–800 mg) and after multiple administration (in the dose range of 100–400 mg once daily). The increase in these values at steady state is slightly greater than expected based on the dose administered, possibly due to the saturable binding of zonisamide to erythrocytes. Steady state was achieved within 13 days. There is somewhat greater accumulation than expected compared with a single dose.

Distribution.

Zonisamide is 40–50% bound to plasma proteins. In vitro studies have shown that the presence of various antiepileptic drugs (e.g. phenytoin, phenobarbital, carbamazepine and sodium valproate) does not affect the extent of zonisamide binding to plasma proteins. The apparent volume of distribution in adults is approximately 1.1–1.7 l/kg, indicating extensive tissue distribution of zonisamide. The red blood cell/plasma ratio is approximately 15 at low concentrations and approximately 3 at higher concentrations.

Biotransformation.

Zonisamide is metabolized by CYP3A4, the main metabolic pathway being cleavage of the benzisoxazole ring to form 2-sulfamoyl acetylphenol (SMAP) and N-acetylation. Zonisamide and SMAP can be conjugated with glucuronic acid. Metabolites that are not detected in plasma lack anticonvulsant activity. There is no evidence that zonisamide can induce its own metabolism.

Breeding.

The steady-state clearance of zonisamide after oral administration is approximately 0.7 l/h, with a terminal half-life of approximately 60 hours (in the absence of concomitant CYP3A4 inducers). The half-life is independent of dose and repeated administration. Fluctuations in serum or plasma concentrations of zonisamide over the dosing interval are low (<30%). The main route of excretion of metabolites and unchanged zonisamide is urine. Renal clearance of unchanged zonisamide is relatively low (approximately 3.5 ml/min); approximately 15–30% of the administered dose is excreted unchanged.

Zonisamide exposure increases over time until steady state is reached, which occurs after approximately 8 weeks. In patients with higher body weight, steady-state serum concentrations of zonisamide are lower, but these differences are small. Age (≥ 12 years) and gender have no apparent effect on zonisamide concentrations in patients with epilepsy during the steady-state period. No dose adjustment of zonisamide is required when used with other antiepileptic drugs, including CYP3A4 inducers.

The relationship between pharmacodynamics and pharmacokinetics.

Zonisamide reduces the average seizure frequency over a 28-day period, and this reduction is proportional to (log-linear) the average zonisamide concentration.

Special patient groups.

Kidney failure.

In patients with renal impairment, renal clearance of single doses of zonisamide was positively correlated with creatinine clearance. Plasma zonisamide AUC was increased by 35% in patients with creatinine clearance <20 mL/min.

Patients with liver dysfunction.

The pharmacokinetics of zonisamide in patients with hepatic impairment have not been adequately studied.

Elderly patients.

No clinically significant differences in the pharmacokinetics of zonisamide were found between young (21–40 years) and elderly (65–75 years) patients.

Children (5–18 years old).

Limited data suggest that the pharmacokinetics of zonisamide in children are similar to those observed in adults.

Indication

Zoresan® is indicated as:

monotherapy in adult patients with partial seizures with or without secondary generalization, with newly diagnosed epilepsy;

adjunctive therapy in adults and children aged 6 years and over with partial seizures with or without secondary generalization.

Contraindication

Hypersensitivity to the active substance, to any of the excipients or to sulfonamides.

Interaction with other medicinal products and other types of interactions

Effect of zonisamide on cytochrome P450 enzymes

An in vitro study of the effect of zonisamide on microsomal oxidation in human hepatocytes showed no significant effect (<25%) of the drug on the activities of cytochrome P450 isoenzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 at plasma concentrations 2-fold or greater above therapeutic levels. Therefore, zonisamide is not expected to affect the pharmacokinetics of other drugs through mechanisms associated with cytochrome P450, as has been demonstrated in vivo for carbamazepine, phenytoin, ethinyl estradiol and desipramine.

Potential effects of zonisamide on other medicinal products.

Antiepileptic drugs.

In patients with epilepsy, long-term administration of zonisamide at therapeutic doses has no clinically significant effect on the pharmacokinetics of carbamazepine, lamotrigine, phenytoin and sodium valproate.

Oral contraceptives.

In clinical studies in healthy volunteers, zonisamide at therapeutic doses did not affect the serum concentrations of ethinylestradiol or norethisterone, which are components of combined oral contraceptives.

Carbonic anhydrase inhibitors.

Zonisamide should be used with caution in adult patients concomitantly with carbonic anhydrase inhibitors such as topiramate and acetazolamide, as there is insufficient data to rule out a pharmacodynamic interaction between them (see section 4.4). Zonisamide should not be administered concomitantly with carbonic anhydrase inhibitors such as topiramate and acetazolamide in children, as there is insufficient data to rule out a possible pharmacodynamic interaction between them (see section 4.4).

P-gp substrates.

In vitro studies have shown that zonisamide is a weak inhibitor of P-gp (MDR1) with an IC50 of 267 μM, which suggests that zonisamide could theoretically affect the pharmacokinetics of drugs that are P-gp substrates. Caution is advised when initiating, discontinuing, or changing the dose of zonisamide in patients who are also taking drugs that are P-gp substrates (e.g. digoxin, quinidine).

There is a potential for other drugs to affect the effects of zonisamide.

In clinical studies, it was found that the simultaneous use of lamotrigine with zonisamide has no significant effect on the pharmacokinetics of the latter. The combined use of zonisamide with drugs that can cause urolithiasis increases the risk of kidney stones, and therefore their simultaneous use should be avoided.

Enzyme inducers. The exposure of zonisamide is reduced when co-administered with drugs that induce CYP3A4, such as phenytoin, carbamazepine and phenobarbital, in patients receiving antiepileptic therapy. These effects are not clinically significant when zonisamide is added to existing therapy, but clinically significant changes in drug concentrations may occur when other drugs that induce CYP3A4 are withdrawn, changed in dosage or added. In such situations, a dose adjustment of zonisamide may be necessary. Rifampicin is a potent CYP3A4 inducer. If co-administration with zonisamide is necessary, the patient should be closely monitored and, if necessary, the dose of zonisamide and other drugs that are CYP3A4 substrates should be adjusted.

CYP3A4 inhibitors. Clinical trial data have not shown a significant effect of specific and non-specific CYP3A4 inhibitors on the pharmacokinetics of zonisamide. Ketoconazole (400 mg/day) or cimetidine (1200 mg/day) had no clinically significant effect on the pharmacokinetics of zonisamide administered as a single dose to healthy volunteers. Therefore, no dosage adjustment of zonisamide is required when co-administered with CYP3A4 inhibitors.

Children.

Drug interaction studies have not been conducted in children.

Application features

Rash of unknown origin.

Serious rashes, including cases of Stevens-Johnson syndrome, have occurred with the use of zonisamide.

It is recommended that zonisamide be discontinued in patients who develop a rash that cannot be explained by other causes. All patients who develop a rash while taking zonisamide should be closely monitored, especially if they are receiving other antiepileptic drugs that can cause rash.

Convulsions due to withdrawal of therapy.

In accordance with current clinical practice, discontinuation of zonisamide in patients with epilepsy should be done by gradual dose reduction to reduce the likelihood of seizures. There is insufficient evidence to support discontinuation of concomitant antiepileptic drugs when seizure control is achieved with zonisamide as adjunctive therapy with the aim of transitioning to zonisamide monotherapy. Therefore, discontinuation of concomitant antiepileptic drugs should be undertaken with caution.

Reactions associated with the presence of a sulfonamide group.

Zonisamide is a benzisoxazole derivative containing a sulfonamide group. Serious immune-mediated adverse reactions associated with sulfonamide-containing medicinal products include skin rashes, allergic reactions and severe haematological disorders, including aplastic anaemia, which in very rare cases has been fatal.

Cases of agranulocytosis, thrombocytopenia, leukopenia, aplastic anemia, pancytopenia, and leukocytosis have been reported. There is insufficient information to assess the possible relationship of these events to the dose and duration of treatment with zonisamide.

Acute myopia and secondary angle-closure glaucoma.

A syndrome consisting of acute myopia associated with secondary angle-closure glaucoma has been reported in adult and pediatric patients treated with zonisamide. Symptoms include acute onset of decreased visual acuity and/or eye pain. Ophthalmological examination may reveal myopia, decreased anterior chamber depth, ocular hyperemia (redness), and increased intraocular pressure. This syndrome may be associated with supraciliary effusion, resulting in anterior lens and iris displacement, secondary to angle-closure glaucoma. Symptoms may occur within hours to weeks of initiating therapy. Treatment includes discontinuation of zonisamide as soon as possible, as directed by a physician, and appropriate measures to lower intraocular pressure. Elevated intraocular pressure of any etiology, if left untreated, can have serious consequences, including permanent vision loss. Caution should be exercised when treating patients with a history of eye disease with zonisamide.

Suicidal thinking and behavior.

Suicidal ideation and behavior have been reported in patients taking antiepileptic drugs for some indications. A meta-analysis of randomized placebo-controlled trials of antiepileptic drugs also showed an increased risk of suicidal ideation and behavior. The mechanism of this risk is unknown, and the available data do not exclude the possibility of an increased risk with zonisamide. Therefore, patients should be monitored for suicidal ideation and behavior, and appropriate treatment should be considered. Patients (and caregivers of patients) are advised to seek medical advice if suicidal ideation and behavior develop.

Some patients, particularly those predisposed to nephrolithiasis, may be at increased risk of developing kidney stones and associated signs and symptoms such as renal colic, renal pain or flank pain. Nephrolithiasis may lead to chronic kidney damage. Risk factors for nephrolithiasis include previous kidney stone formation, a family history of nephrolithiasis and hypercalciuria. None of these risk factors are reliable predictors of kidney stone formation during treatment with zonisamide.

Increased fluid intake and increased urine output may help reduce the risk of kidney stones, especially in individuals with risk factors. At the discretion of the physician, renal ultrasound may be performed. If kidney stones are detected, zonisamide should be discontinued.

Metabolic acidosis.

Hyperchloraemic metabolic acidosis without anion gap (i.e., a decrease in bicarbonate levels below the reference range in the absence of chronic gaseous alkalosis) has been associated with zonisamide therapy. The development of metabolic acidosis is due to the loss of bicarbonate in the kidneys due to the inhibitory effect of zonisamide on carbonic anhydrase. Metabolic acidosis caused by zonisamide usually occurs early in treatment, but can occur at any stage of treatment. The decrease in bicarbonate levels is usually mild (mean value is approximately 3.5 mEq/L at a daily dose of 300 mg in adults); in rare cases, patients may experience a more pronounced decrease. Conditions or treatments that lead to the development of acidosis (e.g. renal disease, severe respiratory disorders, status epilepticus, diarrhoea, surgery, ketogenic diet or medicinal products) may lead to an increase in the bicarbonate-suppressive effect of zonisamide.

Younger patients are at higher risk of zonisamide-induced metabolic acidosis and have a more severe course. Appropriate assessment and monitoring of serum bicarbonate levels should be undertaken in patients receiving zonisamide who have conditions that may increase the risk of acidosis; in patients who are at increased risk of adverse effects of metabolic acidosis; and in patients with symptoms suggestive of metabolic acidosis. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing zonisamide (with gradual withdrawal or reduction of the therapeutic dose) as osteopenia may develop.

If a decision is made to continue zonisamide therapy in the presence of persistent acidosis, correction of acid-base balance should be considered.

Zonisamide should be used with caution in adult patients receiving concomitant treatment with carbonic anhydrase inhibitors such as topiramate or acetazolamide, as there are insufficient data to exclude a pharmacodynamic interaction.

Heatstroke.

Cases of decreased sweating and increased body temperature have been reported mainly in children. Caution should be exercised when prescribing zonisamide to adults concomitantly with drugs that contribute to overheating, including carbonic anhydrase inhibitors and drugs with anticholinergic activity.

Pancreatitis.

Monitoring of pancreatic lipase and amylase levels is recommended in patients who develop clinical signs of pancreatitis while taking zonisamide. In the event of confirmed pancreatitis, in the absence of other obvious causes, it is recommended that zonisamide be discontinued and appropriate treatment instituted.

Rhabdomyolysis.

In patients taking zonisamide who develop severe muscle pain and/or weakness, with or without fever, it is recommended that markers of muscle damage, including creatine phosphokinase and aldolase levels, be evaluated. If these are elevated, in the absence of other obvious causes such as trauma or a major seizure, discontinuation of zonisamide and appropriate treatment are recommended.

Women of reproductive age.

Women of childbearing potential should use reliable methods of contraception during zonisamide therapy and for 1 month after discontinuation. The physician should ensure that the patient is using adequate contraception and, taking into account the individual clinical situation, assess the adequacy of the choice of oral contraceptives. Zonisamide should not be used in women of childbearing potential not using effective contraception unless clearly necessary and only if the potential benefit is considered to be justified by the risk to the fetus. Women of childbearing potential should be counseled about the potential risks to the fetus and the benefits of treatment before initiating zonisamide therapy. If women are planning to become pregnant, they should consult their physician about the need to review zonisamide therapy, including consideration of alternative treatment regimens.

Body weight.

Zonisamide therapy may cause weight loss. When treating patients with low body weight or when weight loss occurs as a result of zonisamide therapy, nutritional supplements and increased nutrition are necessary. In case of significant weight loss, discontinuation of zonisamide should be considered. Weight loss may be more pronounced in children.

The above safety precautions also apply to children.

Below are precautions for pediatric patients that require special attention.

Heat stroke and dehydration.

Prevention of overheating and dehydration in children.

In children, zonisamide may cause decreased sweating and overheating, which, if not treated appropriately, can lead to brain damage and death. Children are at high risk, especially in hot weather.

If your child is taking zonisamide, the following rules must be followed:

Overheating should be avoided, especially in hot weather;

significant physical exertion should be avoided, especially in hot weather;

you should consume plenty of cold water;

The following drugs should not be used: carbonic anhydrase inhibitors (such as topiramate and acetazolamide) and anticholinergic drugs (such as clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynin).

If your child experiences any of the following symptoms, seek emergency medical attention immediately and take immediate first aid measures.

Symptoms:

skin is hot to the touch,

sweating is slight or absent,

confusion of consciousness,

muscle spasms,

rapid heartbeat and/or breathing.

Emergency first aid measures:

place the child in a cool, shaded place;

Wet the child's skin with water to cool it down.

give the child cool water to drink.

Cases of decreased sweating and fever have been reported mainly in children. In some cases, heat stroke requiring inpatient treatment has been diagnosed. In a few cases, heat stroke requiring hospitalization and resulting in death have been reported. Most cases have occurred in warm weather. Patients and caregivers should be warned about the potential seriousness of heat stroke, the situations in which it may occur, and the measures to be taken if any signs or symptoms appear. Patients or caregivers should be warned about the need to drink adequate fluids, avoid excessive heat and strenuous exercise. Physicians should draw the attention of children and their parents/guardians to the recommendations for the prevention of heat stroke and overheating in children, as provided in the package leaflet. If signs and symptoms of dehydration, oligohydrosis or fever develop, consideration should be given to discontinuing zonisamide.

Zonisamide should not be used in children who are concurrently receiving other drugs that provoke heat-related disorders, such as carbonic anhydrase inhibitors and anticholinergic drugs.

Body weight.

Deterioration of general condition and discontinuation of antiepileptic drugs have been associated with weight loss and have resulted in death. Zonisamide is not recommended for children with low body weight or for children with poor appetite. Weight loss occurs with similar frequency in children of different age groups. Given the potential seriousness of weight loss in children, it is necessary to monitor their weight during therapy.

If the child's weight gain is delayed, according to the physical development chart, the use of nutritional supplements or an increase in the volume of food in the child's diet is recommended. Otherwise, the use of zonisamide should be discontinued.

There are limited data on the use of zonisamide in patients weighing less than 20 kg. Therefore, caution should be exercised when treating children aged 6 years and older weighing less than 20 kg. The effect of prolonged low body weight on the growth and development of the child is unknown.

Metabolic acidosis.

The risk of metabolic acidosis due to zonisamide therapy is higher in children. Clinically, metabolic acidosis is also more severe in this age group. Appropriate monitoring and monitoring of serum bicarbonate levels are necessary in this group of patients. The long-term effects of low bicarbonate levels on growth and development are unknown.

Zonisamide should not be used in children concomitantly with other carbonic anhydrase inhibitors such as topiramate or acetazolamide.

Nephrolithiasis.

Kidney stones (nephrolithiasis) have been reported in pediatric patients. Some patients, particularly those predisposed to nephrolithiasis, may be at increased risk of developing kidney stones and associated signs and symptoms such as renal colic, renal pain, or flank pain. Nephrolithiasis may lead to chronic kidney damage. Risk factors for nephrolithiasis include previous kidney stone formation, a family history of nephrolithiasis, and hypercalciuria. None of these risk factors are reliable predictors of kidney stone formation during zonisamide treatment.

Increasing fluid intake and urine output may help reduce the risk of kidney stones, especially in individuals with risk factors. At the discretion of the physician, renal ultrasound may be performed. If kidney stones are detected, zonisamide should be discontinued.

Elevations in some liver function tests, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and bilirubin, have been observed in pediatric patients treated with zonisamide. If hepatic adverse events are suspected, liver function should be assessed and a decision should be made to discontinue zonisamide.

Cognitive functions.

Cognitive impairment in patients with epilepsy is associated with the underlying disease and/or the use of antiepileptic drugs. In a placebo-controlled trial of zonisamide in children and adolescents, the proportion of patients with cognitive impairment was quantitatively higher in the zonisamide group compared to the placebo group.

Excipients.

Zoresan® contains hydrogenated castor oil, which may cause stomach upset and diarrhea.

Use during pregnancy or breastfeeding

Pregnancy.

There are limited data from the use of zonisamide in pregnant women. Animal studies have shown reproductive toxicity. The potential risk for humans is unknown.

An increase in the proportion of infants with low birth weight, premature birth, or infants with insufficient body weight for their gestational age has been reported.

Zonisamide should not be used during pregnancy unless the physician considers that the potential benefit justifies the potential risk to the fetus. If zonisamide is prescribed to pregnant women, they should be fully informed of the potential harm to the fetus. If zonisamide therapy is necessary during pregnancy, it is recommended that the lowest effective dose be used and that the patient be closely monitored.

As with other antiepileptic drugs, abrupt withdrawal of zonisamide should be avoided in pregnant women due to the risk of seizures, which can have serious consequences for both the mother and the fetus. The risk of congenital malformations in children born to mothers taking antiepileptic drugs is 2-3 times higher. The most common malformations are cleft lip, cardiovascular anomalies, and neural tube defects. Combination therapy with antiepileptic drugs is associated with an increased risk of congenital malformations compared with monotherapy.

Breastfeeding period.

Zonisamide passes into breast milk in concentrations similar to those in blood plasma. During breastfeeding, the drug can be used only in cases where, in the opinion of the doctor, the benefit of taking zonisamide for the mother outweighs the potential risk of stopping breastfeeding for the child. Breastfeeding should be discontinued during treatment with the drug. Due to the long half-life of zonisamide, breastfeeding can be resumed no earlier than 1 month after its discontinuation.

Fertility.

There are no clinical data available on the effects of zonisamide on human fertility. Animal studies have shown changes in fertility parameters.

Ability to influence reaction speed when driving vehicles or other mechanisms

Zonisamide has not been studied on the effects on the ability to drive and use machines. However, as some patients may experience drowsiness or difficulty concentrating, especially at the beginning of therapy or after increasing the dose, it is necessary to refrain from activities that require increased concentration, such as driving or operating other mechanisms.

Method of administration and doses

The drug Zoresan® should be taken orally, regardless of meals.

Adults.

Dose escalation and maintenance dose.

Zonisamide can be used as monotherapy or as adjunctive therapy. The dose of the drug should be titrated based on clinical response. The recommended dose titration regimen and maintenance dose are shown in Table 1. Some patients, particularly those not taking CYP3A4 inducers, may respond to lower doses.

Table 1.

Recommended dose escalation regimen and maintenance dose in adults

Drug withdrawal.

If it is necessary to discontinue zonisamide therapy, the drug should be withdrawn gradually. The dose reduction by 100 mg per week should be carried out with simultaneous adjustment of the doses of other antiepileptic drugs (if necessary).

Children (ages 6 and up).

Dose escalation and maintenance dose levels.

Zonisamide should be added to previously prescribed therapy in children aged 6 years and older. The dose of the drug should be titrated based on clinical response. The recommended dose titration regimen and maintenance doses are given in Table 2. In some patients, particularly those not taking drugs that induce CYP3A4, it is possible to obtain a clinical response with lower doses.

The attention of children, their parents or caregivers should be drawn to the special instructions for the patient regarding measures to prevent heat stroke (see section "Special instructions for use").

Table 2.

Recommended dose escalation regimen and maintenance dose levels in children aged 6 years and older.

*To ensure maintenance of the therapeutic dose, the child's body weight should be monitored and the dose should be revised if it changes (until the body weight reaches 55 kg). The dosage regimen is 6–8 mg/kg/day up to a maximum dose of 500 mg/day.

The safety and efficacy of zonisamide in children under 6 years of age or weighing less than 20 kg have not been established. There are limited data on the use of zonisamide in patients weighing less than 20 kg. Therefore, children aged 6 years and older and weighing less than 20 kg should be treated with caution.

It is not always possible to achieve the calculated dose exactly by dosing Zoresan®. In such cases, it is recommended to round the calculated dose up or down to the nearest available Zoresan® dose (25, 50 and 100 mg).

Drug withdrawal.

If it is necessary to discontinue zonisamide therapy, the drug should be withdrawn gradually by reducing the dose by 2 mg/kg once a week (Table 3).

Table 3.

A dose reduction regimen for zonisamide is recommended for children aged 6 years and older.

*All doses of the day are single doses.

Elderly patients.

Caution should be exercised when prescribing zonisamide to elderly patients due to the lack of data on its use in this patient group. The safety profile of zonisamide should also be taken into account (see section 4.8).

Patients with renal failure.

Caution should be exercised when treating patients with renal impairment as data on the use of zonisamide in this patient population are limited. It may be necessary