Zonisamide Mylan

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 
 

1. NAME OF THE MEDICINAL PRODUCT 
 

Zonisamide Mylan 25 mg hard capsules 

Zonisamide Mylan 50 mg hard capsules 

Zonisamide Mylan 100 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Zonisamide Mylan 25 mg hard capsules 

 

Each hard capsule contains 25 mg of zonisamide.  

 

Zonisamide Mylan 50 mg hard capsules 

 

Each hard capsule contains 50 mg of zonisamide.  

 

Zonisamide Mylan 100 mg hard capsules 

 

Each hard capsule contains 100 mg of zonisamide. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Hard capsule. 

 

Zonisamide Mylan 25 mg hard capsules 

 

A white opaque body and a white opaque cap, marked ‘Z 25’ in black containing white/almost white 

powder. Each hard capsule is approximately 14.4 mm in length. 

 

Zonisamide Mylan 50 mg hard capsules 

 

A white opaque body and a white opaque cap, marked ‘Z 50’ in red containing white/almost white 

powder. Each hard capsule is approximately 15.8 mm in length. 

 

Zonisamide Mylan 100 mg hard capsules 

 

A white opaque body and a white opaque cap, marked ‘Z 100’ in black containing white/almost white 

powder. Each hard capsule is approximately 19.3 mm in length. 

 
 
4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 
 

Zonisamide Mylan is indicated as: 

• monotherapy in the treatment of partial seizures, with or without secondary generalisation, in 

adults with newly diagnosed epilepsy (see section 5.1); 

• adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in 

adults, adolescents, and children aged 6 years and above. 

 

4.2 Posology and method of administration 
 

Posology - adults 



3 
 

 

Dosage escalation and maintenance 

Zonisamide Mylan may be taken as monotherapy or added to existing therapy in adults. The dose 

should be titrated on the basis of clinical effect. Recommended escalation and maintenance doses are 

given in Table 1. Some patients, especially those not taking CYP3A4-inducing agents, may respond to 

lower doses. 

 

Withdrawal 

When Zonisamide Mylan treatment is to be discontinued, it should be withdrawn gradually (see section 

4.4). In clinical studies of adult patients, dose reductions of 100 mg at weekly intervals have been used 

with concurrent adjustment of other antiepileptic medicine doses (where necessary). 

 

Table 1.  Adults – recommended dosage escalation and maintenance regimen 

Treatment 

Regimen 

Titration Phase Usual Maintenance 

Dose 

Monotherapy - 

Newly diagnosed 

adult patients 

Week 1 + 2 Week 3 + 4 Week 5 + 6  

300 mg per day  

(once a day). 

If a higher dose is 

required: increase at 

two-weekly intervals in 

increments of 100 mg up 

to a maximum of 500 mg. 

100 mg/day 

(once a day) 

200 mg/day  

(once a day) 

300 mg/day  

(once a day) 

Adjunctive therapy 

- with CYP3A4- 

inducing agents (see 

section 4.5) 

Week 1 Week 2 Week 3 to 5  

300 to 500 mg per day 

(once a day or two divided 

doses). 

50 mg/day  

(in two divided 

doses) 

100 mg/day 

(in two divided 

doses) 

Increase at 

weekly intervals 

in increments of 

100 mg 

- without 

CYP3A4-inducing 

agents; or with renal 

or hepatic impairment 

Week 1 + 2 Week 3 + 4 Week 5 to 10  

300 to 500 mg per day 

(once a day or two divided 

doses). 

Some patients may 

respond to lower doses. 

50 mg/day (in 

two divided 

doses) 

100 mg/day (in 

two divided 

doses) 

Increase at two-

weekly intervals 

in increments of 

up to 100 mg 

 

General dosing recommendations for Zonisamide Mylan in special patient populations 
 

Paediatric population (aged 6 years and above) 
 

Dosage escalation and maintenance 

Zonisamide Mylan must be added to existing therapy for paediatric patients aged 6 years and above. 

The dose should be titrated on the basis of clinical effect. Recommended escalation and maintenance 

doses are given in Table 2. Some patients, especially those not taking CYP3A4-inducing agents, may 

respond to lower doses. 

 

Physicians should draw the attention of paediatric patients and their parents/carers to the Patient Alert 

Box (in the package leaflet) on preventing heat stroke (see section 4.4: Paediatric Population). 
 
 



4 
 

Table 2.  Paediatric population (aged 6 years and above) – recommended dosage escalation 
and maintenance regimen 

Treatment 

Regimen 

Titration Phase Usual Maintenance Dose 

Adjunctive therapy 
- with CYP3A4- 

inducing agents 

(see section 4.5) 

Week 1 Weeks 2 to 8 Patients of 

weight 

20 to 55 kg
a 

Patients of 

weight > 55 kg 

1 mg/kg/day 

(once a day) 

Increase at weekly 

intervals in 

increments of 
1 mg/kg 

6 to 8 mg/kg/day 

(once a day) 

300 – 

500 mg/day 

(once a day) 

 
 
- without 

CYP3A4-inducing 

agents 

Week 1 + 2 Weeks ≥ 3 
 
 
6 to 8 mg/kg/day 

(once a day) 

 
 

300 – 

500 mg/day 

(once a day) 

1 mg/kg/day 

(once a day) 

Increase at two-

weekly intervals 

in increments of 
1 mg/kg 

Note: 

a. To ensure a therapeutic dose is maintained the weight of a child should be monitored and the dose 

reviewed as weight changes occur up to a weight of 55 kg.  The dose regime is 6-8 mg/kg/day up 

to a maximum dose of 500 mg/day. 

 

The safety and efficacy of zonisamide in children aged below 6 years or those below 20 kg have not yet 

been established. 

 

There are limited data from clinical studies in patients with a body weight of less than 20 kg. Therefore 

children aged 6 years and above and with a body weight less than 20 kg should be treated with caution. 

 

It is not always possible to precisely achieve the calculated dose with the commercially available 
capsule strengths of zonisamide. In these cases it is therefore recommended that the zonisamide total 
dose should be rounded up or down to the nearest available dose that can be achieved with 
commercially available capsule strengths of zonisamide (25 mg, 50 mg and 100 mg). 

 

Withdrawal 

When zonisamide treatment is to be discontinued, it should be withdrawn gradually (see section 4.4). 

In clinical studies of paediatric patients, down-titration was completed by dose reductions at weekly 

intervals in increments of about 2 mg/kg (i.e. in accordance with the schedule in Table 3). 

 

Table 3.  Paediatric population (aged 6 years and above) – recommended down-titration 

schedule 

Weight Decrease at weekly intervals in increments of: 

20 – 28 kg 25 to 50 mg / day* 

29 – 41 kg 50 to 75 mg / day* 

42 – 55 kg 100 mg / day* 

>55 kg 100 mg / day* 

Note: 

* All doses are once daily. 

 

Elderly 

Caution should be exercised at initiation of treatment in elderly patients as there is limited information 

on the use of zonisamide in these patients. Prescribers should also take account of the safety profile of 

zonisamide (see section 4.8). 

 



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Renal impairment 

Caution must be exercised in treating patients with renal impairment, as there is limited information on 

use in such patients and a slower titration of Zonisamide Mylan might be required. Since zonisamide 

and its metabolites are excreted renally, it should be discontinued in patients who develop acute renal 

failure or where a clinically significant sustained increase in serum creatinine is observed. 

 

In subjects with renal impairment, renal clearance of single doses of zonisamide was positively 

correlated with creatinine clearance. The plasma AUC of zonisamide was increased by 35% in subjects 

with creatinine clearance < 20 ml/min. 

 

Hepatic impairment 

Use in patients with hepatic impairment has not been studied. Therefore use in patients with severe 

hepatic impairment is not recommended. Caution must be exercised in treating patients with mild to 

moderate hepatic impairment, and a slower titration of Zonisamide Mylan may be required. 

 

Method of administration 

Zonisamide Mylan hard capsules are for oral use. 

 

Effect of food 

Zonisamide Mylan may be taken with or without food (see section 5.2). 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to 

sulfonamides. 

 

4.4 Special warnings and precautions for use 
 

Unexplained rash 

 

Serious rashes occur in association with zonisamide therapy, including cases of 

Stevens-Johnson syndrome. 
 

Consideration must be given to discontinuing zonisamide in patients who develop an otherwise 

unexplained rash. All patients who develop a rash while taking zonisamide must be closely supervised, 

with additional levels of caution applied to those patients receiving concomitant antiepileptic agents 

that may independently induce skin rashes. 

 

Withdrawal seizures 

In accordance with current clinical practice, discontinuation of zonisamide in patients with epilepsy 

must be accomplished by gradual dose reduction, to reduce the possibility of seizures on withdrawal. 

There are insufficient data for the withdrawal of concomitant antiepileptic medicines once seizure 
control with zonisamide has been achieved in the add-on situation, in order to reach monotherapy with 
zonisamide. Therefore, withdrawal of concomitant anti-epileptic medicinal products must be 
undertaken with caution. 

 

Sulfonamide reactions 

Zonisamide is a benzisoxazole derivative, which contains a sulfonamide group. Serious immune based 

adverse reactions that are associated with medicinal products containing a sulfonamide group include 

rash, allergic reaction and major haematological disturbances, including aplastic anaemia, which very 

rarely can be fatal. Cases of agranulocytosis, thrombocytopenia, leucopenia, aplastic anaemia, 

pancytopenia and leucocytosis have been reported. There is inadequate information to assess the 

relationship, if any, between dose and duration of treatment and these events. 

 

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 paediatric patients receiving zonisamide. Symptoms include acute onset of 



6 
 

decreased visual acuity and/or ocular pain. Ophthalmologic findings can include myopia, anterior 
chamber shallowing, and ocular hyperaemia (redness) and increased intraocular pressure. This 
syndrome may be associated with supraciliary effusion resulting in anterior displacement of the lens 
and iris, with secondary angle closure glaucoma. Symptoms may occur within hours to weeks of 
initiating therapy. Treatment includes discontinuation of zonisamide, as rapidly as possible in the 
judgment of the treating physician, and appropriate measures to reduce intraocular pressure. Elevated 
intraocular pressure of any aetiology, if left untreated, can lead to serious sequelae including 
permanent vision loss. Caution should be used when treating patients with history of eye disorders 
with zonisamide. 

 

Suicide ideation and behaviour 

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in 

several indications. A meta-analysis of randomised placebo-controlled trials of anti-epileptic medicinal 

products has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of 

this risk is not known and the available data do not exclude the possibility of an increased risk for 

zonisamide. 

 

Therefore, patients should be monitored for signs of suicidal ideation and behaviours and appropriate 

treatment should be considered. Patients (and caregivers of patients) should be advised to seek 

medical advice should signs of suicidal ideation or behaviour emerge. 

 

Kidney stones 

Some patients, especially those with a predisposition to nephrolithiasis, may be at increased risk for 

renal stone formation 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 prior stone 

formation, a family history of nephrolithiasis and hypercalciuria. None of these risk factors can 

reliably predict stone formation during zonisamide treatment. In addition, patients taking other 

medications associated with nephrolithiasis may be at increased risk. Increasing fluid intake and urine 

output may help reduce the risk of stone formation, particularly in those with predisposing risk factors. 

 

Metabolic acidosis 

Hyperchloraemic, non-anion gap, metabolic acidosis (i.e. decreased serum bicarbonate below the 

normal reference range in the absence of chronic respiratory alkalosis) is associated with zonisamide 

treatment. This metabolic acidosis is caused by renal bicarbonate loss due to the inhibitory effect of 

zonisamide on carbonic anhydrase. Such electrolyte imbalance has been observed with the use of 

zonisamide in placebo-controlled clinical trials and in the post-marketing period. Generally, 

zonisamide-induced metabolic acidosis occurs early in treatment although cases can occur at any time 

during treatment. The amounts by which bicarbonate is decreased are usually small – moderate 

(average decrease of approximately 3.5 mEq/l at daily doses of 300 mg in adults); rarely patients can 

experience more severe decreases. Conditions or therapies that predispose to acidosis (such as renal 

disease, severe respiratory disorders, status epilepticus, diarrhoea, surgery, ketogenic diet, or medicinal 

products) may be additive to the bicarbonate lowering effects of zonisamide. 

 

The risk of zonisamide induced metabolic acidosis appears to be more frequent and severe in younger 

patients. Appropriate evaluation and monitoring of serum bicarbonate levels should be carried out in 

patients taking zonisamide who have underlying conditions which might increase the risk of acidosis, 

in patients who are at an increased risk of adverse consequences 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 (by gradual 

discontinuation or reduction of a therapeutic dose) as osteopenia may develop. 

If the decision is made to continue patients on zonisamide in the face of persistent acidosis, alkali 

treatment should be considered. 

 

Zonisamide should be used with caution in adult patients being treated concomitantly with carbonic 

anhydrase inhibitors such as topiramate or acetazolamide, as there are insufficient data to rule out a 

pharmacodynamic interaction (see also section 4.4 Paediatric Population and section 4.5). 

 

Heat stroke 



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Cases of decreased sweating and elevated body temperature have been reported mainly in paediatric 

patients (see section 4.4 Paediatric Population for full warning). Caution should be used in adults when 

zonisamide is prescribed with other medicinal products that predispose patients to heat related 

disorders; these include carbonic anhydrase inhibitors and medicinal products with anticholinergic 

activity (see also section 4.4 Paediatric Population).  

 

Pancreatitis 

In patients taking zonisamide who develop the clinical signs and symptoms of pancreatitis, it is 

recommended that pancreatic lipase and amylase levels are monitored. If pancreatitis is evident, in the 

absence of another obvious cause, it is recommended that discontinuation of zonisamide be considered 

and appropriate treatment initiated. 

 

Rhabdomyolysis 

In patients taking zonisamide, in whom severe muscle pain and/or weakness develop either in the 

presence or absence of a fever, it is recommended that markers of muscle damage be assessed, 

including serum creatine phosphokinase and aldolase levels. If elevated, in the absence of another 

obvious cause such as trauma or grand mal seizures, it is recommended that zonisamide 

discontinuation be considered and appropriate treatment initiated. 

 

Women of childbearing potential 

Women of childbearing potential must use effective contraception during treatment with zonisamide 

and for one month after discontinuation (see section 4.6). Zonisamide must not be used in women of 

childbearing potential not using effective contraception unless clearly necessary and only if the 

potential benefit is considered to justify the risk to the foetus. Specialist advice should be given to 

women who are of childbearing potential regarding the possible effects of zonisamide on the foetus 

and these risks should be discussed with the patient in relation to the benefits before starting treatment. 

Women planning a pregnancy should meet with their specialists to reassess treatment with zonisamide 

and to consider other therapeutic options. Physicians treating patients with zonisamide should ensure 

that patients are fully informed about the need to use appropriate effective contraception and should 

use clinical judgement when assessing whether oral contraceptives (OCs), or the doses of the OC 

components, are adequate based on the individual patient’s clinical situation. 

 

Body weight 

Zonisamide may cause weight loss. A dietary supplement or increased food intake may be considered 

if the patient is losing weight or is underweight whilst on this medication. If substantial undesirable 

weight loss occurs, discontinuation of zonisamide should be considered. Weight loss is potentially 

more serious in children (see section 4.4. Paediatric Population). 

 

Paediatric population 

The warnings and precautions mentioned above are also applicable to adolescent and paediatric 

patients. The warnings and precautions mentioned below are more relevant to paediatric and 

adolescent patients. 

 



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Heat stroke and dehydration 

Preventing overheating and dehydration in children 

 

Zonisamide can cause children to sweat less and overheat and if the child is not treated this can 

lead to brain damage and death. Children are most at risk especially in hot weather. 

 

When a child is taking zonisamide: 

• The child should stay cool especially in hot weather 

• The child must avoid heavy exercise especially when the weather is hot 

• The child must drink plenty of cold water 

• The child must not take any of these medicines: carbonic anhydrase inhibitors (like 

topiramate and acetazolamide), and anticholinergic agents (like clomipramine, hydroxyzine, 

diphenhydramine, haloperidol, imipramine and oxybutynin). 

 

IF ANY OF THE FOLLOWING OCCUR, THE CHILD NEEDS URGENT MEDICAL 

ATTENTION: 
The skin feels very hot with little or no sweating, or the child becomes confused or has muscle 
cramps, or the child’s heartbeat or breathing become rapid. 

 

• Take the child to a cool, shaded place 

• Keep the child's skin cool with water 

• Give the child cold water to drink 

 

Cases of decreased sweating and elevated body temperature have been reported mainly in paediatric 

patients. Heat stroke requiring hospital treatment was diagnosed in some cases. Heat stroke requiring 

hospital treatment and leading to death has been reported. Most reports occurred during periods of 

warm weather. Physicians should discuss with patients and their carers the potential seriousness of heat 

stroke, situations in which it might arise, as well as action to take in the event of any signs or 

symptoms. Patients or their carers must be warned to take care to maintain hydration and avoid 

exposure to excessive temperatures and strenuous physical exercise depending on the condition of the 

patient. Prescribers should draw the attention of paediatric patients and their parent/carers to the advice 

in the Packaging Leaflet on preventing heat stroke and overheating in children as provided. In the 

event of signs or symptoms of dehydration, oligohydrosis, or elevated body temperature, 

discontinuation of zonisamide should be considered. 

 

Zonisamide should not be used as co-medication in paediatric patients with other medicinal products that 

predispose patients to heat related disorders; these include carbonic anhydrase inhibitors and medicinal 

products with anticholinergic activity. 

 

Body weight 

Weight loss leading to deterioration of general condition and failure to take anti-epilepsy medication 

has been related to a fatal outcome (see section 4.8). Zonisamide is not recommended for paediatric 

patients who are underweight (definition in accordance with the WHO age adjusted BMI categories) or 

have a decreased appetite. 

 

The incidence of decreased body weight is consistent across age groups (see section 4.8); however, 

given the potential seriousness of weight loss in children, weight should be monitored in this 

population. A dietary supplement or increased food intake should be considered if the patient is failing 

to gain weight in accordance with growth charts, otherwise zonisamide should be discontinued. 

 

There are limited data from clinical studies in patients with a body weight of less than 20 kg. Therefore 

children aged 6 years and above with a body weight of less than 20 kg should be treated with caution. 

The long term effect of weight loss in the paediatric population on growth and development is 

unknown. 

 



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Metabolic acidosis 

The risk of zonisamide induced metabolic acidosis appears to be more frequent and severe in paediatric 

and adolescent patients. Appropriate evaluation and monitoring of serum bicarbonate levels should be 

carried out in this population (see section 4.4 - Metabolic acidosis for full warning; see section 4.8 for 

incidence of low bicarbonate). The long term effect of low bicarbonate levels on growth and 

development is unknown. 

 

Zonisamide should not be used as co-medication in paediatric patients with other carbonic anhydrase 

inhibitors such as topiramate and acetazolamide (see section 4.5). 

 

Kidney stones 

Kidney stones have occurred in paediatric patients (see section 4.4 Kidney stones for full warning). 

Some patients, especially those with a predisposition to nephrolithiasis, may be at increased risk for 

renal stone formation 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 prior stone 

formation, a family history of nephrolithiasis and hypercalciuria. None of these risk factors can reliably 

predict stone formation during zonisamide treatment. Increasing fluid intake and urine output may help 

reduce the risk of stone formation, particularly in those with predisposing risk factors. Renal 

ultrasound should be performed at the discretion of the physician. In the event kidney stones are 

detected, zonisamide should be discontinued. 

 

Hepatic dysfunction 

Increased levels of hepatobiliary parameters such as alanine aminotransferase (ALT), aspartate 

aminotransferase (AST), gamma-glutamyltransferase (GGT) and bilirubin have occurred in paediatric 

and adolescent patients, without any consistent pattern in the observations of values above the upper 

limit of normal. Nevertheless, if a hepatic event is suspected, liver function should be evaluated and 

discontinuation of zonisamide should be considered. 

 

Cognition 

Cognitive impairment in patients affected by epilepsy has been associated with the underlying 

pathology and/or the administration of anti-epileptic treatment. In a zonisamide placebo-controlled 

study conducted in paediatric and adolescent patients, the proportion of patients with impaired 

cognition was numerically greater in the zonisamide group compared with the placebo group. 

 

This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially 

‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 

Effect of zonisamide on cytochrome P450 enzymes 

In vitro studies using human liver microsomes show no or little (< 25%) inhibition of cytochrome P450 

isozymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 at zonisamide levels approximately 

two-fold or greater than clinically relevant unbound serum concentrations. Therefore, zonisamide is 

not expected to affect the pharmacokinetics of other medicinal products via cytochrome P450-mediated 

mechanisms, as demonstrated for carbamazepine, phenytoin, ethinylestradiol and desipramine in vivo. 

 

Potential for zonisamide to affect other medicinal products 

Anti-epileptic medicinal products 

In epileptic patients, steady-state dosing with zonisamide resulted in no clinically relevant 

pharmacokinetic effects on carbamazepine, lamotrigine, phenytoin, or sodium valproate. 

 

Oral contraceptives 

In clinical studies in healthy subjects, steady-state dosing with zonisamide did not affect serum 

concentrations of ethinylestradiol or norethisterone in a combined oral contraceptive. 
 
Carbonic anhydrase inhibitors 

Zonisamide should be used with caution in adult patients treated concomitantly with carbonic 



10 
 

anhydrase inhibitors such as topiramate and acetazolamide, as there are insufficient data to rule out a 

possible pharmacodynamic interaction (see section 4.4). 

 

Zonisamide should not be used as co-medication in paediatric patients with other carbonic anhydrase 
inhibitors such as topiramate and acetazolamide (see section 4.4: Paediatric population). 

 

P-gp substrate 

An in vitro study shows that zonisamide is a weak inhibitor of P-gp (MDR1) with an IC50 of 

267 µmol/l and there is the theoretical potential for zonisamide to affect the pharmacokinetics of 

substances which are P-gp substrates. Caution is advised when starting or stopping zonisamide 

treatment or changing the zonisamide dose in patients who are also receiving medicinal products which 

are P-gp substrates (e.g. digoxin, quinidine). 

 

Potential medicinal product interactions affecting zonisamide 

In clinical studies co-administration of lamotrigine had no apparent effect on zonisamide 

pharmacokinetics. The combination of zonisamide with other medicinal products that may lead to 

urolithiasis may enhance the risk of developing kidney stones; therefore the concomitant 

administration of such medicinal products should be avoided. 

 

Zonisamide is metabolised partly by CYP3A4 (reductive cleavage), and also by N-acetyl-transferases 

and conjugation with glucuronic acid; therefore, substances that can induce or inhibit these enzymes 

may affect the pharmacokinetics of zonisamide: 

 

- Enzyme induction: Exposure to zonisamide is lower in epileptic patients receiving 

CYP3A4-inducing agents such as phenytoin, carbamazepine, and phenobarbitone. These 

effects are unlikely to be of clinical significance when zonisamide is added to existing therapy; 

however, changes in zonisamide concentrations may occur if concomitant CYP3A4-inducing 

anti-epileptic or other medicinal products are withdrawn, dose adjusted or introduced, an 

adjustment of the zonisamide dose may be required. Rifampicin is a potent CYP3A4 inducer. 

If co-administration is necessary, the patient should be closely monitored and the dose of 

zonisamide and other CYP3A4 substrates adjusted as needed. 

 

- CYP3A4 inhibition: Based upon clinical data, known specific and non-specific CYP3A4 

inhibitors appear to have no clinically relevant effect on zonisamide pharmacokinetic exposure 

parameters. Steady-state dosing of either ketoconazole (400 mg/day) or cimetidine 

(1200 mg/day) had no clinically relevant effects on the single-dose pharmacokinetics of 

zonisamide given to healthy subjects. Therefore, modification of zonisamide dosing should not 

be necessary when co-administered with known CYP3A4 inhibitors. 

 

Paediatric population 

Interaction studies have only been performed in adults. 

 

4.6 Fertility, pregnancy and lactation 
 

Women of childbearing potential 

Women of childbearing potential must use effective contraception during treatment with zonisamide, 

and for one month after discontinuation. 

 

Zonisamide must not be used in women of childbearing potential not using effective contraception 

unless clearly necessary and only if the potential benefit is considered to justify the risk to the foetus.  

 

Specialist advice should be given to women treated with zonisamide who are of childbearing potential. 

Women planning a pregnancy should meet with their specialists to reassess treatment with zonisamide 

and to consider other therapeutic options. As with all antiepileptic medicines, sudden discontinuation 

of zonisamide should be avoided as this may lead to breakthrough seizures that could have serious 

consequences for the woman and the unborn child. The risk of birth defect is increased by factor 2 to 3 

in the offspring of mothers treated with an antiepileptic medicinal product. The most frequently 



11 
 

reported are cleft lip, cardiovascular malformations and neural tube defect. Multiple antiepileptic 

medicinal product therapy may be associated with a higher risk of congenital malformations than 

monotherapy. 

 

Pregnancy 

There are limited data from the use of zonisamide in pregnant women. Studies in animals have shown 

reproductive toxicity (see section 5.3). The potential risk for humans is unknown. 

 

Data from a registry study suggest an increase in the proportion of babies born at a low birth weight 

(LBW), pre-term or small for gestational age (SGA). These increases are from about 5% to 8% for 

LBW, from about 8% to 10% for pre-term birth and from about 7% to 12% for SGA, all compared with 

mothers treated with lamotrigine monotherapy. 

 

Zonisamide must not be used during pregnancy unless clearly necessary and only if the potential benefit 
is considered to justify the risk to the foetus. If zonisamide is prescribed during pregnancy, patients 
should be fully informed of the potential harm to the foetus and use of the minimal effective dose is 
advised along with careful monitoring. 

 

Breast-feeding 

Zonisamide is excreted in human milk; the concentration in breast milk is similar to maternal plasma. 

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from 

zonisamide therapy. Due to the long retention time of zonisamide in the body, breast-feeding must not 

be resumed until one month after zonisamide therapy is completed. 

 

Fertility 

There are no clinical data available on the effects of zonisamide on human fertility. Studies in animals 
have shown changes in fertility parameters (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 
 

No studies on the effects on the ability to drive and use machines have been performed. However, 

given that some patients may experience drowsiness or difficulty with concentration, particularly early 

in treatment or after a dose increase, patients must be advised to exercise caution during activities 

requiring a high degree of alertness, e.g., driving or operating machines. 

 

4.8 Undesirable effects 
 

Summary of the safety profile 

Zonisamide has been administered to over 1,200 patients in clinical studies, more than 400 of whom 

received zonisamide for at least 1 year.  In addition there has been extensive post-marketing experience 

with zonisamide in Japan since 1989 and in the USA since 2000. 

 

It should be noted that zonisamide is a benzisoxazole derivative, which contains a sulfonamide group. 

Serious immune based adverse reactions that are associated with medicinal products containing a 

sulfonamide group include rash, allergic reaction and major haematological disturbances including 

aplastic anaemia, which very rarely can be fatal (see section 4.4). 

 

The most common adverse reactions in controlled adjunctive-therapy studies were somnolence, 

dizziness and anorexia. The most common adverse reactions in a randomised, controlled monotherapy 

trial comparing zonisamide with carbamazepine prolonged release were decreased bicarbonate, 

decreased appetite, and decreased weight. The incidence of markedly abnormally low serum 

bicarbonate (a decrease to less than 17 mEq/l and by more than 5 mEq/l) was 3.8%. The incidence of 

marked decreases in weight of 20% or more was 0.7%. 

 

Tabulated list of adverse reactions 

Adverse reactions associated with zonisamide obtained from clinical studies and post-marketing 

surveillance are tabulated below. The frequencies are arranged according to the following scheme: 



12 
 

 

very common ≥ 1/10 

common ≥ 1/100 to < 1/10 

uncommon ≥ 1/1,000 to < 1/100 

rare ≥ 1/10,000 to < 1/1,000 

very rare < 1/10,000 

not known cannot be estimated from the available data 
 

Table 4.  Adverse reactions associated with zonisamide obtained from adjunctive use 

clinical studies and post-marketing surveillance 

 

System Organ 
Class (MedDRA 
terminology) 

Very 
Common 

Common Uncommon Very Rare 

Infections and 
infestation 

  Pneumonia 

Urinary tract 

infection 

 

Blood and 
lymphatic system 
disorders 

 Ecchymosis  Agranulocytosis 

Aplastic anaemia 

Leucocytosis 

Leucopoenia 

Lymphadenopathy 

Pancytopenia, 

Thrombocytopenia 

Immune system 
disorders 

 Hypersensitivity  Drug-induced 
hypersensitivity 
syndrome  
Drug rash with 
eosinophilia and 
systemic symptoms 

Metabolism and 
nutrition 
disorders 

Anorexia  Hypokalaemia Metabolic acidosis 

Renal tubular acidosis 

Psychiatric 

Disorders 

Agitation 

Irritability 

Confusional 

state 

Depression 

Affect lability 

Anxiety 

Insomnia 

Psychotic 

disorder 

Anger 

Aggression 

Suicidal ideation 

Suicide attempt 

Hallucination 

Nervous system 

disorders 

Ataxia 

Dizziness 

Memory 

impairment 

Somnolence 

Bradyphrenia 

Disturbance in 

attention 

Nystagmus 

Paraesthesia 

Speech disorder 

Tremor 

Convulsion Amnesia 

Coma 

Grand mal seizure 

Myasthenic syndrome 

Neuroleptic malignant 

syndrome 

Status epilepticus 

Eye disorders Diplopia   Angle closure 

glaucoma 

Eye pain 

Myopia 

Vision blurred 

Visual acuity reduced 



13 
 

System Organ 
Class (MedDRA 
terminology) 

Very 
Common 

Common Uncommon Very Rare 

Respiratory, 

thoracic and 

mediastinal 

disorders 

   Dyspnoea 

Pneumonia aspiration 

Respiratory disorder 

Hypersensitivity-type 

Pneumonitis 

Gastrointestinal 

disorders 

 Abdominal pain 

Constipation 

Diarrhoea 

Dyspepsia 

Nausea 

Vomiting Pancreatitis 

Hepatobiliary 

disorders 

  Cholecystitis 

Cholelithiasis 

Hepatocellular damage 

Skin and 

subcutaneous 

tissue disorders 

 Rash 

Pruritus 

Alopecia 

 Anhidrosis 

Erythema multiforme 

Stevens-Johnson 

syndrome 

Toxic epidermal 

necrolysis 

Musculoskeletal 

and connective 

tissue disorders 

   Rhabdomyolysis 

Renal and 

urinary 

disorders 

 Nephrolithiasis Calculus urinary Hydronephrosis 

Renal failure 

Urine abnormality 

General 

disorders and 

administration 

site conditions 

 Fatigue 

Influenza-like 

illness 

Pyrexia 

Oedema 

peripheral 

  

Investigations Decreased 

bicarbonate 

Weight 

decreased 
 Blood creatine 

phosphokinase 

increased 

Blood creatinine 

increased 

Blood urea increased 

Liver function tests 

abnormal 

Injury, 

poisoning and 

procedural 

complications 

   Heat stroke 

 

In addition there have been isolated cases of Sudden Unexplained Death in Epilepsy Patients (SUDEP) 

receiving zonisamide. 

 

Table 5.  Adverse reactions in a randomised, controlled monotherapy trial comparing 

zonisamide with carbamazepine prolonged release 

 

System Organ Class 
(MedDRA terminology†) 

Very Common Common Uncommon 

Infections and 
infestation 

  Urinary tract infection 

Pneumonia 



14 
 

Blood and lymphatic 

disorders 
  Leucopenia 

Thrombocytopenia 

Metabolism and 

nutrition disorders 
 Decreased appetite Hypokalaemia 

Psychiatric Disorders  Agitation 
Depression 

Insomnia 

Mood swings 

Anxiety 

Confusional state 
Acute psychosis 

Aggression 

Suicidal ideation 

Hallucination 

Nervous system 

disorders 
 Ataxia 

Dizziness 

Memory impairment 

Somnolence 

Bradyphrenia 

Disturbance in attention 

Paraesthesia 

Nystagmus 

Speech disorder 

Tremor 

Convulsion 

Eye disorders  Diplopia  

Respiratory, thoracic 

and mediastinal 

disorders 

  Respiratory disorder 

Gastrointestinal 

disorders 
 Constipation 

Diarrhoea 

Dyspepsia  

Nausea  

Vomiting 

Abdominal pain 

Hepatobiliary disorders   Cholecystitis acute 

Skin and subcutaneous 
tissue disorders 

 Rash Pruritus 

Ecchymosis 

General disorders and 

administration site 

conditions 

 Fatigue 

Pyrexia 

Irritability 

 

Investigations Decreased 
bicarbonate 

Weight decreased 

Blood creatinine 

phosphokinase increased 

Alanine aminotransferase 

increased 

Aspartate 

aminotransferase 

increased 

Urine analysis 
abnormal 

† MedDRA version 13.1 
 

Additional information on special populations 
 

Elderly 

A pooled analysis of safety data on 95 elderly subjects has shown a relatively higher reporting 

frequency of oedema peripheral and pruritus compared to the adult population. 

 

Review of post-marketing data suggests that patients aged 65 years or older report a higher frequency 

than the general population of the following events: Stevens-Johnson syndrome (SJS) and Drug 

Induced Hypersensitivity syndrome (DIHS). 

 

Paediatric population 
The adverse event profile of zonisamide in paediatric patients aged 6 to 17 years in placebo-controlled 

clinical studies was consistent with that of adults. Among 465 subjects in the paediatric safety database 

(including a further 67 subjects from the extension phase of the controlled clinical trial) there were 

7 deaths (1.5%; 14.6/1000 person-years): 2 cases of status epilepticus, of which one was related to 



15 
 

severe weight loss (10% within 3 months) in an underweight subject and subsequent failure to take 

medication; 1 case of head injury/haematoma, and 4 deaths in subjects with pre-existing functional 

neurological deficits for various causes (2 cases of pneumonia-induced sepsis/organ failure, 1 SUDEP 

and 1 head injury). A total of 70.4% of paediatric subjects who received ZNS in the controlled study or 

its open label extension had at least one treatment-emergent bicarbonate measurement below 

22 mmol/L. The duration of low bicarbonate measurements was also long (median 188 days). 

A pooled analysis of safety data on 420 paediatric subjects (183 subjects aged 6 to 11 years, and 

237 subjects aged 12 to 16 years with a mean duration of exposure of approximately 12 months) has 

shown a relatively higher reporting frequency of pneumonia, dehydration, decreased sweating, 

abnormal liver function tests, otitis media, pharyngitis, sinusitis and upper respiratory tract infection, 

cough, epistaxis and rhinitis, abdominal pain, vomiting, rash and eczema, and fever compared to the 

adult population (particularly in subjects aged below 12 years) and, at a low incidence, amnesia, 

creatinine increased, lymphadenopathy, and thrombocytopenia. The incidence of a decrease in body 

weight of 10% or more was 10.7% (see section 4.4). In some cases of weight decrease there was a 

delay in transition to the next Tanner stage and in bone maturation. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 

 

Symptoms 

There have been cases of accidental and intentional overdose in adult and paediatric patients. In some 

cases, the overdoses were asymptomatic, particularly where emesis or lavage was prompt. In other 

cases, the overdose was followed by symptoms such as somnolence, nausea, gastritis, nystagmus, 

myoclonus, coma, bradycardia, reduced renal function, hypotension and respiratory depression. A very 

high plasma concentration of 100.1 μg/ml zonisamide was recorded approximately 31 hours after a 

patient took an overdose of zonisamide and clonazepam; the patient became comatose and had 

respiratory depression, but recovered consciousness five days later and had no sequelae. 

 

Management 

No specific antidotes for zonisamide overdose are available. Following a suspected recent overdose, 

emptying the stomach by gastric lavage or by induction of emesis may be indicated with the usual 

precautions to protect the airway. General supportive care is indicated, including frequent monitoring 

of vital signs and close observation. Zonisamide has a long elimination half-life so its effects may be 

persistent. Although not formally studied for the treatment of overdose, haemodialysis reduced plasma 

concentrations of zonisamide in a patient with reduced renal function, and may be considered as 

treatment of overdose if clinically indicated. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antiepileptics, other antiepileptics, ATC code: N03AX15 

 

Zonisamide is a benzisoxazole derivative. It is an anti-epileptic medicine with weak carbonic 

anhydrase activity in-vitro. It is chemically unrelated to other anti-epileptic agents. 

 

Mechanism of action 

The mechanism of action of zonisamide is not fully elucidated, but it appears to act on 

voltage-sensitive sodium and calcium channels, thereby disrupting synchronised neuronal firing, 

reducing the spread of seizure discharges and disrupting subsequent epileptic activity. Zonisamide also 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


16 
 

has a modulatory effect on GABA-mediated neuronal inhibition. 

 

Pharmacodynamic effects 

The anticonvulsant activity of zonisamide has been evaluated in a variety of models, in several species 

with induced or innate seizures, and zonisamide appears to act as a broad-spectrum anti-epileptic in 

these models. Zonisamide prevents maximal electroshock seizures and restricts seizure spread, 

including the propagation of seizures from cortex to sub-cortical structures and suppresses 

epileptogenic focus activity. Unlike phenytoin and carbamazepine however, zonisamide acts 

preferentially on seizures originating in the cortex. 

 

Clinical efficacy and safety 
 

Monotherapy in partial seizures, with or without secondary generalisation 

Efficacy of zonisamide as monotherapy was established in a double-blind, parallel group, 

non-inferiority comparison to carbamazepine prolonged release (PR) in 583 adult subjects with newly 

diagnosed partial seizures with or without secondary generalised tonic-clonic seizures. Subjects were 

randomised to carbamazepine and zonisamide received treatment for a duration of up to 24 months 

depending on response. Subjects were titrated to the initial target dose of 600 mg carbamazepine or 

300 mg of zonisamide. Subjects who experienced a seizure were titrated to the next target dose i.e. 

800 mg carbamazepine or 400 mg of zonisamide. Subjects who experienced a further seizure were 

titrated to the maximal target dose of 1200 mg carbamazepine or 500 mg zonisamide. Subjects who 

were seizure-free for 26 weeks at a target dose level continued on this dose for another 26 weeks. Main 

outcomes of this study are presented in this table: 

 

 

Table 6. Efficacy results for Monotherapy Study 310 

 Zonisamide Carbamazepine  

n (ITT population) 281 300   

Six months seizure freedom   Diff CI95% 

PP-population* 79.4% 83.7% -4.5% -12.2% ; 3.1% 

ITT-population 69.4% 74.7% -6.1% -13.6% ; 1.4% 

< 4 seizures during 3 month 

baseline period 

71.7% 75.7% -4.0% -11.7% ; 3.7% 

> 4 seizures during 3 month 

baseline period 

52.9% 68.9% -15.9% -37.5% ; 5.6% 

     

Twelve months seizure freedom     

PP-population 67.6% 74.7% -7.9% - 17.2% ; 1.5% 

ITT-population 55.9% 62.3% -7.7% - 16.1% ; 0.7% 

< 4 seizures during 3 month 

baseline period 

57.4% 64.7% -7.2% -15.7% ; 1.3% 

> 4 seizures during 3 month 

baseline period 

44.1% 48.9% -4.8% -26.9% ; 17.4% 

     

Seizure Sub-type (6 month 

seizure freedom-PP population) 

    

All partial 76.4% 86.0% -9.6% -19.2% ; 0.0% 

Simple partial 72.3% 75.0% -2.7% -20.0% ; 14.7% 



17 
 

Complex partial 76.9% 93.0% -16.1% -26.3% ; -5.9% 

All generalized Tonic-Clonic 78.9% 81.6% -2.8 -11.5% ; 6.0% 

Secondary Tonic-Clonic 77.4% 80.0% -2.6% -12.4% ; 7.1% 

Generalized Tonic-Clonic 85.7% 92.0% -6.3% -23.1% ; 10.5% 

     

PP = Per Protocol Population; ITT = Intent To Treat Population 

*Primary endpoint 
 

Adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation in 

adults 

In adults, efficacy has been demonstrated with zonisamide in 4 double-blind, placebo-controlled studies 

of periods of up to 24 weeks with either once or twice daily dosing. These studies show that the 

median reduction in partial seizure frequency is related to zonisamide dose with sustained efficacy at 

doses of 300-500 mg per day. 

 
Paediatric population 
 

Adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in 

adolescent and paediatric patients (aged 6 years and above) 

In paediatric patients (aged 6 years and above), efficacy has been demonstrated with zonisamide in a 

double-blind, placebo-controlled study, which included 207 subjects and had a treatment duration of 

up to 24 weeks. A 50% or greater reduction from baseline in seizure frequency during the 12-week 

stable dose period was seen in 50% of the zonisamide-treated subjects and 31% of the patients on 

placebo. 

 

Specific safety issues that were encountered in the paediatric studies were: decreased appetite and 

weight loss, decreased bicarbonate levels, increased risk of kidney stones and dehydration. All these 

effects and specifically weight loss may have deleterious implications for growth and development, 

and may lead to general deterioration of health. Altogether, data on effects on long-term growth and 

development are limited. 

 

5.2 Pharmacokinetic properties 
 

Absorption 

Zonisamide is almost completely absorbed after oral administration, generally reaching peak serum or 

plasma concentrations within 2 to 5 hours of dosing. The first-pass metabolism is believed to be 

negligible. Absolute bioavailability is estimated to be approximately 100%. Oral bioavailability is not 

affected by food, although peak plasma and serum concentrations may be delayed. 

 

Zonisamide AUC and Cmax values increased almost linearly after single dose over the dose range of 

100-800 mg and after multiple doses over the dose range of 100-400 mg once daily. The increase at 

steady state was slightly more than expected on the basis of dose, probably due to the saturable binding 

of zonisamide to erythrocytes. Steady state was achieved within 13 days. Slightly greater than 

expected accumulation occurs relative to single dosing. 

 

Distribution 

Zonisamide is 40 – 50 % bound to human plasma proteins, with in vitro studies showing that this is 

unaffected by the presence of various antiepileptic medicinal products (i.e., phenytoin, phenobarbitone, 

carbamazepine, and sodium valproate). The apparent volume of distribution is about 1.1 – 1.7 l/kg in 

adults indicating that zonisamide is extensively distributed to tissues. Erythrocyte/plasma ratios are 

about 15 at low concentrations and about 3 at higher concentrations. 

 

Biotransformation 

Zonisamide is metabolised primarily through reductive cleavage of the benzisoxazole ring of the parent 



18 
 

drug by CYP3A4 to form 2-sulfamoylacetylphenol (SMAP) and also by N-acetylation. Parent drug and 

SMAP can additionally be glucuronidated. The metabolites, which could not be detected in plasma, are 

devoid of anticonvulsant activity. There is no evidence that zonisamide induces its own metabolism. 

 

Elimination 

Apparent clearance of zonisamide at steady-state after oral administration is about 0.70 l/h and the 

terminal elimination half-life is about 60 hours in the absence of CYP3A4 inducers. The elimination 

half-life was independent of dose and not affected by repeat administration. Fluctuation in serum or 

plasma concentrations over a dosing interval is low (< 30%). The main route of excretion of 

zonisamide metabolites and unchanged drug is via the urine. Renal clearance of unchanged zonisamide 

is relatively low (approximately 3.5 ml/min); about 15 - 30 % of the dose is eliminated unchanged. 

 

Linearity / non-linearity 

Zonisamide exposure increases with time until steady state is achieved by approximately 8 weeks. 

When comparing the same dose level, subjects of higher total body weight appear to have lower 

steady-state serum concentrations, but this effect appears to be relatively modest.  Age (≥ 12 years) 

and gender, after adjustment for body weight effects, have no apparent effect on zonisamide 

exposure in epileptic patients during steady-state dosing.  There is no need for dose adjustment with 

any of the AEDs including CYP3A4 inducers. 

 

Pharmacokinetic/pharmacodynamic relationship 

Zonisamide lowers the 28-day average seizure frequency and the decrease is proportional (log-linear) 

to zonisamide average concentration. 

 

Special patient groups 

 

Renal impairment 

Renal clearance of single doses of zonisamide was positively correlated with creatinine clearance. The 

plasma AUC of zonisamide was increased by 35% in subjects with creatinine clearance < 20 ml/min (see 

also section 4.2.). 

 

Hepatic impairment 

The pharmacokinetics of zonisamide in patients with impaired liver function have not been adequately 

studied. 

 

Elderly 

No clinically significant differences were observed in the pharmacokinetics between young (aged 

21-40 years) and elderly (65-75 years). 

 

Children and adolescents (5-18 years) 

Limited data indicate that pharmacokinetics in children and adolescents dosed to steady state at 1, 7 or 

12 mg/kg daily, in divided doses, are similar to those observed in adults, after adjustment for 

bodyweight. 

 

5.3 Preclinical safety data 
 

Findings not observed in clinical studies, but seen in the dog at exposure levels similar to clinical use, 

were liver changes (enlargement, dark-brown discolouration, mild hepatocyte enlargement with 

concentric lamellar bodies in the cytoplasm and cytoplasmic vacuolation) associated with increased 

metabolism. 

 

Zonisamide was not genotoxic and has no carcinogenic potential. 

 

Zonisamide caused developmental abnormalities in mice, rats, and dogs, and was embryolethal in 

monkeys, when administered during the period of organogenesis at zonisamide dosage and maternal 

plasma levels similar to or lower than therapeutic levels in humans. 

 



19 
 

In a repeated-dose oral toxicity study in juvenile rats, at exposure levels similar to those observed in 

paediatric patients at the maximum recommended dose, decreases in body weight and changes in renal 

histopathology and clinical pathology parameters and behavioural changes were observed.  Changes in 

renal histopathology and clinical pathology parameters were considered to be related to carbonic 

anhydrase inhibition by zonisamide.  The effects at this dose level were reversible during the recovery 

period. At a higher dose level (2-3-fold systemic exposure compared to therapeutic exposure) renal 

histopathological effects were more severe and only partially reversible. Most adverse effects observed 

in the juvenile rats were similar to those seen in the repeated-dose toxicity studies of zonisamide in 

adult rats, but renal tubular hyaline droplets and transitional hyperplasia were observed in the juvenile 

study only.  At this higher dose level, juvenile rats showed a decrease in growth, learning, and 

developmental parameters.  These effects were considered likely related to the decreased body weight 

and exaggerated pharmacologic effects of zonisamide at the maximum tolerated dose. 

 

In rats, decreased numbers of corpora lutea and implantation sites were observed at exposure levels 

equivalent to the maximum therapeutic dose in humans; irregular oestrus cycles and a decreased 

number of live foetuses were observed at exposure levels three times higher. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Zonisamide Mylan 25 mg and 100 mg hard capsules 

 

Capsule contents 

Microcrystalline cellulose 

Sodium laurilsulfate 

Hydrogenated vegetable oil 

 

Capsule shells 

Titanium dioxide (E171) 

Gelatin 

 

Printing ink 

Shellac 

Black iron oxide (E172) 

Potassium hydroxide 

 

Zonisamide Mylan 50 mg hard capsules 

 

Capsule contents 

Microcrystalline cellulose 

Sodium laurilsulfate 

Hydrogenated vegetable oil 

 

Capsule shells 

Titanium dioxide (E171) 

Gelatin 

 

Printing ink 

Shellac 

Iron oxide Red (E172) 

 

 

6.2 Incompatibilities 
 

Not applicable. 



20 
 

 

6.3 Shelf life 
 
36 months 

 

6.4 Special precautions for storage 
 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container 

 

Zonisamide Mylan 25 mg and 50 mg hard capsules 

 

PVC-PVdC/Aluminium foil blisters in cardboard cartons containing 14, 28 and 56 capsules. 

PVC-PVdC/Aluminium foil perforated unit dose blisters in cardboard cartons containing 14 x 1 capsules. 

 

Zonisamide Mylan 100 mg hard capsules 

 

PVC-PVdC/Aluminium foil blisters in cardboard cartons containing 28, 56, 98 and 196 capsules. 

PVC-PVdC/Aluminium foil perforated unit dose blisters in cardboard cartons containing 56 x 1 capsules. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 

No special requirements for disposal. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Mylan S.A.S 
117 allee des Parcs, 
69 800 Saint Priest,  
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 

 

Zonisamide Mylan 25 mg hard capsules 

 

EU/1/16/1093/001 

EU/1/16/1093/002 

EU/1/16/1093/003 

EU/1/16/1093/004 

 

Zonisamide Mylan 50 mg hard capsules 

 

EU/1/16/1093/005 

EU/1/16/1093/006 

EU/1/16/1093/007 

EU/1/16/1093/008 

 

Zonisamide Mylan 100 mg hard capsules 

 

EU/1/16/1093/009 

EU/1/16/1093/010 



21 
 

EU/1/16/1093/011 

EU/1/16/1093/012 

EU/1/16/1093/013 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 31 March 2016 

 

 

10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 

Agency:  http://www.ema.europa.eu 
  

http://www.ema.europa.eu/


22 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE  

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 



23 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

J. Uriach y Compañía, S.A. 

Av. Camí Reial, 51-57 

ES-08184 – Palau-solità i Plegamans 

Barcelona 

Spain 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to medical prescription. 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  

 

• Periodic safety update reports (PSURs) 

 

The requirements for submission of  PSURs for this medicinal product are set out in the list of Union 

reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 

subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk management plan (RMP) 

 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 

and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 

and any agreed subsequent updates of the RMP. 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of an 

important (pharmacovigilance or risk minimisation) milestone being reached. 

 

 

  



24 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



25 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

 



26 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Zonisamide Mylan 25 mg hard capsules 

zonisamide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each hard capsule contains 25 mg zonisamide. 

 

 

3. LIST OF EXCIPIENTS 
 
 
 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsules 

 

Blisters: 

14 hard capsules 

28 hard capsules 

56 hard capsules 

  

Unit Dose Blisters: 

14 x 1 hard capsules 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

Read the package leaflet before use 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 

OUT OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children 

 

 

7. OTHER SPECIAL WARNINGS, IF NECESSARY 
 
 
 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 



27 
 

 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S.  

117 Allee des Parcs,  

69 800 Saint Priest,  

France 

 

 

12. MARKETING AUTHORISATION NUMBER 

 

EU/1/16/1093/001 

EU/1/16/1093/002 

EU/1/16/1093/003 

EU/1/16/1093/004 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 
 
 

15. INSTRUCTIONS FOR USE 
 
 
 

16. INFORMATION IN BRAILLE 

 

Zonisamide Mylan 25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN



28 
 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER PACK 
 
 
 

1. NAME OF THE MEDICINAL PRODUCT 

 

Zonisamide Mylan 25 mg hard capsules 

zonisamide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 



29 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 
 
 

1. NAME OF THE MEDICINAL PRODUCT 

 

Zonisamide Mylan 50 mg hard capsules. 

zonisamide 
 
 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each hard capsule contains 50 mg zonisamide. 
 
 

3. LIST OF EXCIPIENTS 
 
 
 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsules 

 
Blisters: 

14 hard capsules 

28 hard capsules 

56 hard capsules 

  

Unit Dose Blisters: 

14 x 1 hard capsules 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 
Read the package leaflet before use 

Oral use 

 
 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 

OUT OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children 
 
 

7. OTHER SPECIAL WARNINGS, IF NECESSARY 
 
 
 

8. EXPIRY DATE 

 

EXP 
 
 

9. SPECIAL STORAGE CONDITIONS 

 
 
 



30 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 
Mylan S.A.S. 
117 Allee des Parcs, 
69 800 Saint Priest,  
France 
 
 

12. MARKETING AUTHORISATION NUMBER 

 

EU/1/16/1093/005 

EU/1/16/1093/006 

EU/1/16/1093/007 

EU/1/16/1093/008 
 
 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 
 
 

15. INSTRUCTIONS FOR USE 
 
 
 

16. INFORMATION IN BRAILLE 

 

Zonisamide Mylan 50 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN



31 
 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Zonisamide Mylan 50 mg hard capsules 

zonisamide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

 



32 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Zonisamide Mylan 100 mg hard capsules. 

zonisamide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE 

 

Each hard capsule contains 100 mg zonisamide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsules 

 

Blisters: 

28 hard capsules 

56 hard capsules 

98 hard capsules 

196 hard capsules 

 

Unit Dose Blisters: 

56 x 1 hard capsules 

 

 

5. METHOD AND ROUTE OF ADMINISTRATION 

 

Read the package leaflet before use 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 

OUT OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children 

 

 

7. OTHER SPECIAL WARNINGS, IF NECESSARY 

 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



33 
 

9. SPECIAL STORAGE CONDITIONS 

 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

117 Allee des Parcs, 

69 800 Saint Priest,  

France 

 

 

12. MARKETING AUTHORISATION NUMBER 

 

EU/1/16/1093/009 

EU/1/16/1093/010 

EU/1/16/1093/011 

EU/1/16/1093/012 

EU/1/16/1093/013 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

 

15. INSTRUCTIONS FOR USE 

 

 

 

16. INFORMATION IN BRAILLE 

 

Zonisamide Mylan 100 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 



34 
 

NN



34 
 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Zonisamide Mylan 100 mg hard capsules 

zonisamide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

  



35 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



36 
 

Package leaflet: Information for the patient 

 

Zonisamide Mylan 25 mg hard capsules 

Zonisamide Mylan 50 mg hard capsules 

Zonisamide Mylan 100 mg hard capsules 

zonisamide 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or pharmacist. 

- This medicine has been prescribed for you only.  Do not pass it on to others.  It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. See section 4. 

 

What is in this leaflet 

1. What Zonisamide Mylan is and what it is used for 

2. What you need to know before you take Zonisamide Mylan 

3. How to take Zonisamide Mylan 

4. Possible side effects 

5. How to store Zonisamide Mylan 

6. Contents of the pack and other information 

 

 

1. What Zonisamide Mylan is and what it is used for 

Zonisamide Mylan contains the active substance zonisamide, and is used as an antiepileptic medicine. 

 

Zonisamide Mylan is used to treat seizures that affect one part of the brain (partial seizure), which may 

or may not be followed by a seizure affecting all of the brain (secondary generalisation). 

 

Zonisamide Mylan may be used: 

• on its own to treat seizures in adults 

• with other antiepileptic medicines to treat seizures in adults, adolescents, and children aged 6 years 

and above. 

 

 

2. What you need to know before you take Zonisamide Mylan 

 

Do not take Zonisamide Mylan 

- if you are allergic to zonisamide or any of the other ingredients of this medicine (listed in section 6). 
- if you are allergic to other sulfonamide medicines. Examples include: sulfonamide 

antibiotics, thiazide diuretics, and sulfonylurea antidiabetes medicines. 

 

Warnings and precautions 

Zonisamide Mylan belongs to a group of medicines (sulfonamides) which can cause severe allergic 

reactions, severe skin rashes, and blood disorders, which very rarely can be fatal (see section 4. Possible 

Side Effects). 

 

A small number of people being treated with antiepileptics such as zonisamide have had thoughts of 

harming or killing themselves. If at any time you have these thoughts, immediately contact your doctor. 

 

Serious rashes occur in association with zonisamide therapy, including cases of Stevens-Johnson 

syndrome. 

 

Talk to your doctor or pharmacist before taking Zonisamide Mylan if you: 

- are younger than 12 years old, as you may be at greater risk of decreased sweating, heat stroke, 



37 
 

pneumonia and liver problems.  If you are younger than 6 years old, Zonisamide Mylan is not 

recommended for you 

- are elderly, as your dose of Zonisamide Mylan may need adjusting, and you may be more likely to 

develop an allergic reaction, severe skin rash, swelling of the feet and legs, and itchiness when 

taking Zonisamide Mylan (see section 4 Possible Side Effects) 

- suffer from liver problems, as your dose of Zonisamide Mylan may need adjusting 

- have eye problems such as glaucoma 

- suffer from kidney problems as your dose of Zonisamide Mylan may need adjusting 

- have previously suffered from kidney stones, as you may be at increased risk of developing more 

kidney stones. Reduce the risk of kidney stones by drinking sufficient water 

- live in a place or are on holiday in a place where the weather is warm. Zonisamide Mylan can make 

you perspire less, which can cause your body temperature to increase. Reduce the risk of 

overheating by drinking sufficient water and keeping cool 

- are underweight, or have lost a lot of weight as Zonisamide Mylan can cause you to lose more 

weight. Tell your doctor as this may need to be monitored. 

- are pregnant or could become pregnant (see section ‘pregnancy, breast-feeding and fertility’ for 

further information). 

 

If any of these applies to you, tell your doctor before you take Zonisamide Mylan. 

 

Children and adolescents 

Talk to your doctor about the following risks:  

 

Preventing overheating and dehydration in children 

 

Zonisamide Mylan can cause your child to sweat less and overheat and if your child is not treated this 

can lead to brain damage and death. Children are most at risk especially in hot weather. 

 

When your child is taking Zonisamide Mylan: 

- keep your child cool especially in hot weather 

- your child must avoid heavy exercise especially when the weather is hot 

- give your child plenty of cold water to drink 

- your child must not take these medicines: 

carbonic anhydrase inhibitors (like topiramate and acetazolamide), and anticholinergic agents (like 

clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine and oxybutynin). 

 

If your child’s skin feels very hot with little or no sweating, becomes confused, has muscle cramps, or 

your child’s heartbeat or breathing becomes rapid: 

- take your child to a cool, shaded place 

- sponge your child’s skin with cool (not cold) water 

- give your child cold water to drink 

- seek urgent medical assistance. 

 

 

• Body weight: You should monitor your child’s weight every month and see your doctor as soon as 

possible if your child is not gaining enough weight.  Zonisamide Mylan is not recommended for 

children who are underweight or have a small appetite, and should be used with caution in those 

below 20 kg. 

• Increased acid level in the blood and kidney stones: Reduce these risks by ensuring that your child 

drinks enough water and is not taking any other medicine which could cause kidney stones (see 

Other medicines).  Your doctor will monitor your child’s blood bicarbonate levels and kidneys 

(see also section 4). 

 

Do not give this medicine to children below the age of 6 years because it is not known for this age 

group whether the potential benefits are greater than the risks. 

 

Other medicines and Zonisamide Mylan 



38 
 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines, including medicines obtained without a prescription. 

- Zonisamide Mylan should be used carefully in adults when taken with medicines that can cause 

kidney stones, like topiramate or acetazolamide. In children, this combination is not 

recommended. 

- Zonisamide Mylan could possibly increase your blood levels of medicines like digoxin and 

quinidine, and so a reduction in their dose may be required. 

- Other medicines like phenytoin, carbamazepine, phenobarbitone and rifampicin can decrease your 

blood levels of Zonisamide Mylan, which may require an adjustment of your dose of Zonisamide 

Mylan. 

 

Zonisamide Mylan with food and drink 

Zonisamide Mylan can be taken with or without food. 

 

Pregnancy, breast-feeding and fertility 

If you are a woman of childbearing age you must use adequate contraception while taking, and for one 

month after stopping, Zonisamide Mylan. 

 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your 

doctor for advice before taking this medicine. You should not stop your treatment without discussing this 

with your doctor. 

 

You must only take Zonisamide Mylan during your pregnancy if your doctor tells you to. Research has 

shown an increased risk of birth defects in children of women taking anti-epileptic medicines. 

A study showed that babies born to mothers using zonisamide during pregnancy were smaller than 

expected for their age at birth, compared with babies born to mothers treated with lamotrigine 

monotherapy. Make sure you are fully informed about the risks and the benefits of using zonisamide for 

epilepsy during pregnancy. 

 

Do not breast-feed whilst taking, or for one month after stopping Zonisamide Mylan. 

 

There are no clinical data available on the effects of zonisamide on human fertility. Studies in animals 

have shown changes in fertility parameters. 

 

Driving and using machines 

Zonisamide Mylan may affect your concentration, ability to react/respond, and may make you feel sleepy, 

particularly at the beginning of your treatment or after your dose is increased. Be especially careful while 

driving or operating machinery if Zonisamide Mylan affects you in this way. 

 

Zonisamide Mylan contains sodium 

This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-

free’. 

 

3. How to take Zonisamide Mylan 

 

Always take this medicine exactly as your doctor or pharmacist has told you.  Check with your 

doctor or pharmacist if you are not sure. 

 

The recommended adult dose 

 

When you take Zonisamide Mylan on its own: 

- The starting dose is 100 mg taken once a day. 

- This may be increased by up to 100 mg at intervals of two weeks. 

- The recommended dose is 300 mg once a day. 

 

When you take Zonisamide Mylan with other antiepileptic medicines: 

- The starting dose is 50 mg daily taken in two equal doses of 25 mg. 



39 
 

- This may be increased by up to 100 mg at intervals of one to two weeks. 

- The recommended daily dose is between 300 mg and 500 mg. 

- Some people respond to lower doses. The dose may be increased more slowly if you experience 

side effects, are elderly or if you suffer from kidney or liver problems.  

 

Use in children (aged 6 to 11 years) and adolescents (aged 12 to 17 years) weighing at least 

20 kg: 

- The starting dose is 1 mg per kg of body weight taken once a day. 

- This may be increased by 1 mg per kg of body weight at intervals of one to two weeks. 

- The recommended daily dose is 6 to 8 mg per kg for a child with a body weight of up to 55 kg or 

300 to 500 mg for a child with a body weight more than 55 kg (which ever dose is lower) taken 

once a day. 

 

Example: A child who weighs 25 kg should take 25 mg once a day for the first week, and then increase 

the daily dose by 25 mg at the start of each week until a daily dose between 150 to 200 mg is reached. 

 

If you feel that the effect of Zonisamide Mylan is too strong or too weak, talk to your doctor or 

pharmacist. 

 

- Zonisamide Mylan capsules must be swallowed whole with water. 

- Do not chew the capsules. 

- Zonisamide Mylan can be taken once or twice daily, as instructed by your doctor. 

- If you take Zonisamide Mylan twice a day, take half the daily dose in the morning and half in the 

evening. 

 

If you take more Zonisamide Mylan than you should 

If you may have taken more Zonisamide Mylan than you should, tell a carer (relative or friend), your 

doctor or pharmacist immediately, or contact your nearest hospital casualty department, taking your 

medicine with you.  You may become sleepy and could lose consciousness. You might also feel sick, 

have a sore stomach, muscle twitches, eye movement, feel faint, have a slowed heartbeat, and reduced 

breathing and kidney function.  Do not try to drive. 

 

If you forget to take Zonisamide Mylan 

- If you forget to take a dose, don’t worry: take the next dose when it is due. 

- Do not take a double dose to make up for a forgotten dose. 

 

If you stop taking Zonisamide Mylan 

- Zonisamide Mylan is meant to be taken as a long-term medicine. Do not reduce your dose or 

stop your medicine unless your doctor tells you to. 

- If your doctor advises you to stop taking Zonisamide Mylan your dose will be reduced gradually 

to lower the risk of more seizures. 

 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Zonisamide Mylan belongs to a group of medicines (sulfonamides) that can cause severe allergic 

reactions, severe skin rashes, and blood disorders, which very rarely can be fatal. 

 

Contact your doctor immediately if you: 

- have difficulty breathing, a swollen face, lips or tongue, or a severe skin rash as these symptoms 

may indicate that you are having a severe allergic reaction 

- have signs of overheating - high body temperature but little or no sweating, rapid heartbeat and 

breathing, muscle cramps, and confusion 



40 
 

- have thoughts of harming or killing yourself.  A small number of people being treated with anti- 

epileptics such as Zonisamide Mylan have had thoughts of harming or killing themselves 

- have pain in your muscles or a feeling of weakness, as this may be a sign of abnormal muscle 

breakdown which can lead to kidney problems 

- get a sudden pain in your back or stomach, have pain on urinating (passing water) or notice blood in 

your urine, as this may be a sign of kidney stones 

- develop visual problems such as eye pain or blurred vision while taken zonisamide. 

 

Contact your doctor as soon as possible if you: 

- have an unexplained skin rash, as this could develop into a more severe skin rash or skin peeling 

- feel unusually tired or feverish, have a sore throat, swollen glands, or find that you bruise more 

easily, as this may mean you have a blood disorder 

- have signs of increased acid level in the blood- headaches, drowsiness, shortness of breath and 

loss of appetite. Your doctor may need to monitor or treat this. 

 

Your doctor may decide that you should stop using Zonisamide Mylan. 

 

The most common side effects of Zonisamide Mylan are mild. They occur during the first month of 

treatment and usually decrease with continued treatment.  In children ages 6 – 17 years old, side effects 

were consistent with those described below with the following exceptions: pneumonia, dehydration, 

sweating decreased (common), abnormal liver enzymes (uncommon), middle ear infection, sore throat, 

sinus and chest infections, cough, nosebleeds, runny nose, stomach pain, vomiting, rash, eczema and 

fever. 

 

Very common (may affect more than 1 in 10 people): 

- agitation, irritability, confusion, depression 

- poor muscle coordination, dizziness, poor memory, sleepiness, double vision 

- loss of appetite, decreased blood levels of bicarbonate (a substance that prevents your blood from 

becoming acidic). 

 

Common (may affect up to 1 in 10 people): 

- difficulty sleeping, strange or unusual thoughts, feeling anxious or emotional 

- slowed thoughts, loss of concentration, speech abnormalities, abnormal skin sensation (pins and 

needles), tremor, involuntary movement of the eyes 

- kidney stones 

- skin rashes, itching, allergic reactions, fever, tiredness, flu-like symptoms, hair loss 

- ecchymosis (a small bruise caused by blood leaking from broken blood vessels in the skin) 

- loss of weight, nausea, indigestion, stomach pains, diarrhoea (loose stools), constipation 

- swelling of the feet and legs 

- vomiting 

- mood swings 

- increased blood levels of creatinine (a waste product that your kidneys should normally remove) 

- increased levels of liver enzymes in the blood. 

 

Uncommon (may affect up to 1 in 100 people): 

- anger, aggression, thoughts of suicide, suicide attempt 

- gall bladder inflammation, gallstones 

- urinary stones 

- lung infection / inflammation, urinary tract infections 

- low blood potassium levels, convulsions/seizures 

- breathing disorders 

- hallucinations 

- abnormal urine tests. 

 

Very rare (may affect up to 1 in 10,000 people): 

- memory loss, coma, neuroleptic malignant syndrome (inability to move, sweating, fever, 

incontinence), status epilepticus (prolonged or repeated seizures) 



41 
 

- shortness of breath, inflammation of the lungs 

- inflammations of the pancreas (severe pain in the stomach or back) 

- liver problems, kidney failure 

- severe rashes or skin peeling (at the same time you may feel unwell or develop a fever) 

- abnormal muscle breakdown (you may feel pain or weakness in your muscles) which can lead to 

kidney problems 

- swollen glands, blood disorders (reduction in the number of blood cells, which can make infection 

more likely and can make you look pale, feel tired and feverish, and bruise more easily) 

- decreased sweating, overheating 

- problems with your urine 

- increased blood levels of creatine phosphokinase or urea which can be seen in a blood test 

- abnormal results from liver function tests 

- glaucoma, which is a blockage of fluid in the eye causing increased pressure in the eye. Eye pain, 

blurred vision or decreased vision may occur and can be signs of glaucoma. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 

listed in this leaflet.  You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this 

medicine. 

 

 

5. How to store Zonisamide Mylan 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the blister and the carton after EXP. 

The expiry date refers to the last day of that month. 

 

This medicine does not require any special storage conditions. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Zonisamide Mylan contains: 

 

Zonisamide 25 mg hard capsules: 

The active substance is zonisamide. Each capsule contains 25 mg of zonisamide. 

The other ingredients are: 

- capsule contents: microcrystalline cellulose, hydrogenated vegetable oil and sodium 

laurilsulfate 

- capsule shell: gelatin and titanium dioxide (E171) 

- printing ink: shellac, black iron oxide (E172) and potassium hydroxide. 

 

Zonisamide 50 mg hard capsules: 

The active substance is zonisamide. Each capsule contains 50 mg of zonisamide. 

The other ingredients are: 

- capsule contents: microcrystalline cellulose, hydrogenated vegetable oil and sodium 

laurilsulfate 

- capsule shell: gelatin and titanium dioxide (E171) 

- printing ink: shellac and iron oxide red (E172) 

 

Zonisamide 100 mg hard capsules: 

The active substance is zonisamide. Each capsule contains 100 mg of zonisamide. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


42 
 

The other ingredients are: 

- capsule contents: microcrystalline cellulose, hydrogenated vegetable oil and sodium 

laurilsulfate 

- capsule shell: gelatin and titanium dioxide (E171) 

- printing ink: shellac, black iron oxide (E172) and potassium hydroxide. 

 

 

What Zonisamide Mylan looks like and contents of the pack 

 

Zonisamide Mylan 25 mg hard capsules have a white body and a white cap, marked ‘Z 25’ in black and 

contain a white/almost white powder. 

 

Zonisamide Mylan 50 mg hard capsules have a white body and white cap, marked ‘Z 50’ in red and 

contain a white/almost white powder. 

 

Zonisamide Mylan 100 mg hard capsules have a white body and white cap, marked ‘Z 100’ in black and 

contain a white/almost white powder. 

 

Zonisamide Mylan 25 mg and 50 mg are available in blister packs of 14, 28, 56 capsules and perforated 

unit dose blister packs of 14 x 1 capsules. 

 

Zonisamide Mylan 100 mg are available in blister packs of 28, 56, 98 and 196 capsules and perforated 

unit dose blister packs of 56 x 1 capsules. 

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder 

Mylan S.A.S. 

117 Allee des Parcs 

69 800 Saint Priest 

France 

 

Manufacturer 

J. Uriach y Compania S.A. 

Av Cami Reial 51-57 

08184 Palau-Solita i Plegamans – Barcelona 

Spain 

 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 

 

België/Belgique/Belgien 

Mylan bvba/sprl 

Tél/Tel: + 32 (0)2 658 61 00 

Lietuva 

Mylan Healthcare UAB  

Tel: + 370 5 205 1288 

 

България 

Майлан ЕООД 

Тел: + 359 2 44 55 400 

Luxembourg/Luxemburg 

Mylan bvba/sprl 

Tél/Tel: + 32 (0)2 658 61 00 

(Belgique/Belgien) 

 

Česká republika 

Mylan Healthcare CZ s.r.o. 

Tel: + 420 222 004 400 

Magyarország 

Mylan EPD Kft 

Tel: + 36 1 465 2100 

 

Danmark 

Mylan Denmark ApS 

Tlf: + 45 28 11 69 32 

Malta 

V.J. Salomone Pharma Ltd 

Tel: + 356 21 22 01 74 



43 
 

  

Deutschland 

Mylan Healthcare GmbH 

Tel: + 49 800 0700 800 

 

Nederland 

Mylan BV 

Tel: + 31 (0)20 426 3300  

Eesti  

BGP Products Switzerland GmbH Eesti filiaal  

Tel: + 372 6363 052 

 

Norge 

Mylan Healthcare Norge AS 

Tlf: + 47 66 75 33 00 

 

Ελλάδα 

Generics Pharma Hellas ΕΠΕ  

Τηλ:  + 30 210 993 6410 

Österreich 

Arcana Arzneimittel GmbH 

Tel: + 43 1 416 2418 

 

España 

Mylan Pharmaceuticals S.L. 

Tel: + 34 900 102 712 

Polska 

Mylan Healthcare Sp. z o.o. 

Tel: + 48 22 546 64 00 

 

France 

Mylan S.A.S 

Tél: + 33 4 37 25 75 00 

Portugal 

Mylan, Lda. 

Tel: + 351 21 412 72 56 

 

Hrvatska 

Mylan Hrvatska d.o.o.  

Tel: + 385 1 23 50 599 

România  

BGP Products SRL 

Tel: + 40 372 579 000 

 

Ireland 

Mylan Ireland Limited 

Tel: + 353 (0) 87 1694982 

 

Slovenija 

Mylan Healthcare d.o.o. 

Tel: + 386 1 23 63 180 

Ísland 

Icepharma hf 

Sími: + 354 540 8000 

 

Slovenská republika 

Mylan s.r.o. 

Tel: + 421 2 32 199 100 

Italia 

Mylan Italia S.r.l. 

Tel: + 39 02 612 46921 

 

Suomi/Finland 

Mylan Finland OY 

Puh/Tel: + 358 20 720 9555  

Κύπρος 

Varnavas Hadjipanayis Ltd 

Τηλ: + 357 2220 7700 

 

Sverige 

Mylan AB 

Tel: + 46 855 522 750 

 

Latvija 

Mylan Healthcare SIA  

Tel: + 371 676 055 80 

 

United Kingdom 

Generics [UK] Ltd 

Tel: + 44 1707 853000 

 

 

This leaflet was last revised in MM/YYYY 

 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET