Package Insert: Information for the User

Zonegran 25 mg, 50 mg and 100 mg Hard Capsules

(zonisamide)

Read this package insert carefully before you start taking this medicine because it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

Zonegran contains the active ingredient zonisamide, and is used as an antiepileptic.

Zonegran is used to treat seizures that affect a part of the brain (partial seizures), which may or may not be followed by a seizure that affects the entire brain (secondary generalization).

Zonegran may be used:

• Alone to treat seizures in adults.
• With other antiepileptics to treat seizures in adults, adolescents, and children 6 years and older.

Do not take Zonegran:

• if you are allergic to zonisamide or any of the other ingredients in this medicine (listed in section 6);
• if you are allergic to other sulfonamides, for example: sulfonamide antibiotics, thiazide diuretics, and sulfonylurea antidiabetic drugs;
• if you are allergic to peanuts or soy, do not use this medicine.

Warnings and precautions

Zonegran belongs to a group of medicines (sulfonamides) that can cause severe allergic reactions, severe rashes, and blood disorders, which very rarely can cause death (see section 4. Possible side effects).

The use of Zonegran may cause high levels of ammonia in the blood, which could change brain function, especially if you are also taking other medicines that can increase ammonia levels (e.g., valproate), if you have a genetic disorder that causes too much ammonia in the body (urea cycle disorder), or if you have liver disorders. Inform your doctor immediately if you feel drowsy or confused in an unusual way.

Consult your doctor or pharmacist before starting to take Zonegran:

• if you are under 12 years old, as you may have a higher risk of developing decreased sweating, heatstroke, pneumonia, and liver problems. Zonegran is not recommended for children under 6 years old.
• if you are elderly, as you may need to adjust your Zonegran dose, and you may have a higher risk of developing an allergic reaction, severe rash, swelling of the legs and feet, and itching when taking Zonegran (see section 4. Possible side effects).
• if you have liver problems, as you may need to adjust your Zonegran dose.
• if you have eye problems such as glaucoma.
• if you have kidney problems, as you may need to adjust your Zonegran dose.
• if you have previously had kidney stones, as you may be at a higher risk of developing more kidney stones.Reduce the risk of kidney stones by drinking enough water.
• if you live in a hot place or are going on vacation to a hot place. Zonegran may make you sweat less, which can cause your body temperature to rise.Reduce the risk of overheating by drinking enough water and staying cool.
• if you are underweight or have lost a lot of weight, as Zonegran may cause you to lose more weight. Inform your doctor, as you may need to be monitored.
• if you are pregnant or could become pregnant (for more information, see the section “Pregnancy, breastfeeding, and fertility).

If any of these statements apply to you, inform your doctor before taking Zonegran.

Children and adolescents

Consult your doctor about the following risks:

• Weight:you should monitor your child's weight monthly and see your doctor as soon as possible if they are not gaining enough weight.Zonegran is not recommended for children who are underweight or have a poor appetite, and should be used with caution in children with a weight under 20 kg.

• Increased blood acidity and kidney stones: reduce these risks by making sure your child drinks enough water and does not take any other medicine that can cause kidney stones (see Other medicines). Your doctor will monitor your child's blood bicarbonate levels and kidneys (see also section 4).

Do not administer this medicine to children under 6 years old as there is no information on the safety and efficacy of Zonegran in this age group.

Other medicines and Zonegran

Inform your doctor or pharmacist if you are using or have recently used any other medicine, including those purchased without a prescription.

• Zonegran should be used with caution in adults if taken with medicines that can cause kidney stones, such as topiramate or acetazolamide. In children, this combination is not recommended.
• Zonegran may increase the levels of medicines such as digoxin and quinidine in the blood, and therefore may require a reduction in the dose of these medicines.
• Other medicines such as phenytoin, carbamazepine, phenobarbital, and rifampicin may decrease the levels of Zonegran in the blood, which may require an adjustment in the dose of Zonegran.

Taking Zonegran with food and drinks

Zonegran can be taken with or without food.

Pregnancy, breastfeeding, and fertility

Women of childbearing age should use effective contraceptive measures during treatment with Zonegran and for one month after stopping Zonegran.

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medicine. Do not stop treatment without consulting your doctor.

You should only take Zonegran during pregnancy if your doctor advises it. Research has shown a higher risk of birth defects in children of women taking antiepileptic drugs. A study showed that children whose mothers took zonisamide during pregnancy were smaller than expected for their age at birth, compared to children whose mothers were treated with lamotrigine monotherapy. Make sure you are informed in detail about the risks and benefits of using zonisamide for epilepsy during pregnancy.

Do not breastfeed while taking Zonegran or for one month after stopping Zonegran.

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

Driving and operating machinery

Zonegran may affect concentration, reaction time, and may cause drowsiness, especially at the start of treatment or after increasing the dose. If Zonegran affects you in this way, be extra careful when driving or operating machinery.

Important information about some of the components of Zonegran

Zonegran contains yellow orange S (E110) and red allura AC (E129)

Zonegran 100 mg hard capsules contain a yellow dye called yellow orange S (E110) and a red dye called red allura AC (E129), which may cause allergic reactions.

Zonegran contains soy oil. Do not use the medicine if you are allergic to peanuts or soy.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Recommended dose in adults

When taking Zonegran alone:

• The initial dose is 100 mg once a day.
• It can be increased up to 100 mg in two-week intervals.
• The recommended dose is 300 mg once a day.

When taking Zonegran with other antiepileptic medications:

• The initial dose is 50 mg per day, divided into two equal doses of 25 mg.
• It can be increased up to 100 mg in one- to two-week intervals.
• 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 have kidney or liver problems.

Use in children (6 to 11 years old) and adolescents (12 to 17 years old) weighing at least 20 kg:

• The initial dose is 1 mg per kg of body weight once a day.
• It can be increased by 1 mg per kg of body weight in one- to two-week intervals.
• The recommended daily dose is between 6 mg and 8 mg per kg for a child weighing up to 55 kg or between 300 mg and 500 mg for a child weighing more than 55 kg (the lower dose) once a day.

Example: a child weighing 25 kg should take 25 mg once a day during the first week, and then the daily dose should be increased by 25 mg at the beginning of each week until the daily dose of 150 to 200 mg is reached.

If you estimate that the action of Zonegran is too strong or too weak, inform your doctor or pharmacist.

Pharmacist.

• Zonegran capsules should be swallowed whole with water.
• Do not chew the capsules.
• Zonegran can be taken once or twice a day, as instructed by your doctor.
• If you take Zonegran twice a day, take half the daily dose in the morning and the other half at night.

When taking more Zonegran than you should

If you have taken more Zonegran than you should, inform the person taking care of you (family member or friend), your doctor or pharmacist, or contact the nearest hospital emergency service and bring the medication with you. You may feel drowsy and may lose consciousness. You may also feel like vomiting, have stomach pain, muscle spasms, eye movement, feel like fainting, have a slow heart rate, and decreased respiratory and renal function. Do not drive.

When you forget to take Zonegran

• If you forget to take a dose, do not worry; take the next dose at the usual time.
• Do not take a double dose to compensate for the missed doses.

When interrupting treatment with Zonegran

• Zonegran is intended to be taken as long-term medication. Do not reduce the dose or stop taking the medication unless your doctor tells you to.
• If your doctor advises you to stop treatment, the dose will be gradually reduced to minimize the risk of having more seizures.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Zonegran belongs to a group of medicines (sulfonamides) that can cause severe allergic reactions, severe rashes, and blood disorders, which very rarely can cause death.

Get in touch with your doctor immediately if:

• You have difficulty breathing, swelling of the face, lips, or tongue, or a severe rash, as these symptoms may indicate a severe allergic reaction.
• You have signs of excessive heat: high body temperature with little or no sweating, rapid heartbeat and breathing, muscle cramps, and confusion.
• You have had thoughts of self-harm or suicide. A small number of people taking antiepileptic medicines such as Zonegran have had thoughts of self-harm or suicide.
• You have muscle pain or feel weak, as this may be a sign of abnormal muscle breakdown that can lead to kidney problems.
• You have sudden back or stomach pain, pain while urinating, or notice blood in your urine, as this may be a sign of kidney stones.
• You experience visual problems such as eye pain or blurred vision while taking Zonegran.

Get in touch with your doctor as soon as possible if:

• You have an unexplained rash, as it may become a more severe rash or skin peeling.
• You feel extremely tired or feverish, have a sore throat, swollen glands, or notice that you bruise easily, as this may indicate a blood disorder.
• You have signs of increased acid levels in the blood: headaches, drowsiness, difficulty breathing, and loss of appetite. Medical control or treatment may be necessary.

Your doctor may decide that you should stop taking Zonegran.

The most frequently reported side effects of Zonegran are all mild in nature. They occur during the first month of treatment and often decrease as treatment continues. In children aged 6 to 17 years, the side effects were consistent with the following, except for the following exceptions: pneumonia, dehydration, decreased sweating (frequent), and abnormal liver enzymes (infrequent).

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

• Restlessness, irritability, confusion, depression
• Coordination problems, dizziness, poor memory, drowsiness, double vision
• Loss of appetite, decreased bicarbonate levels in the blood

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

• Difficulty sleeping, unusual or strange thoughts, feeling anxious or emotionally unstable.
• Slow thinking, loss of concentration, speech abnormalities, abnormal skin sensations (tingling), tremors, involuntary eye movements.
• Kidney stones.
• Rashes, itching, allergic reactions, fever, fatigue, flu-like symptoms, hair loss.
• Ecchymosis (a small bruise caused by blood from a broken skin blood vessel).
• Weight loss.
• Nausea, indigestion, stomach pain, diarrhea (loose stools), constipation.
• Swelling of the legs and feet.

Rare side effects(may affect up to 1 in 100 people):

• Anger, aggression, suicidal thoughts, suicide attempt.
• Vomiting.
• Inflammation of the gallbladder or gallstones.
• Urinary stones.
• Pulmonary infection/inflammation, urinary tract infections.
• Low potassium levels in the blood and convulsions/epileptic seizures.

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

• Hallucinations, memory loss, coma, malignant neuroleptic syndrome (inability to move, sweating, fever, incontinence), status epilepticus (prolonged or repeated convulsions).
• Respiratory disorders, difficulty breathing, lung inflammation.
• Pancreatitis (severe stomach or back pain)
• Liver problems, kidney failure, increased creatinine levels in the blood.
• Severe rashes or skin peeling (may also feel unwell and have a fever).
• Abnormal muscle breakdown (may have muscle pain or weakness) that can lead to kidney problems.
• Swollen glands, blood disorders (reduced number of blood cells, which may make you more prone to infections and feel pale, tired, and feverish, and may bruise easily).
• Decreased sweating, excessive body temperature.
• Glaucoma, which is a blockage of the eye's drainage that causes increased internal eye pressure. Eye pain, blurred vision, or decreased vision may be signs of glaucoma.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSpanish System for the Pharmacovigilance of Medicines for Human Usewww.notificaRAM.esBy reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the blister pack and on the box after EXP. The expiration date is the last day of the month indicated.

Do not store above 86°F (30°C).

Do not use this medication if you observe any sign of deterioration in the capsules, blister pack, or box, or any visible sign of deterioration in the medication. Return the packaging to your pharmacist.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medication that you no longer need. This will help protect the environment.

Composition of Zonegran

The active ingredient in Zonegran is zonisamide.

Zonegran 25 mg hard capsules contain 25 mg of zonisamide. Zonegran 50 mg hard capsules contain 50 mg of zonisamide. Zonegran 100 mg hard capsules contain 100 mg of zonisamide.

• The other components present in the capsule content are: microcrystalline cellulose, hydrogenated vegetable oil (soybean) and sodium lauryl sulfate.
• The capsule coating contains: gelatin, titanium dioxide (E171), shellac, propylene glycol, potassium hydroxide, iron oxide black (E172). Additionally, the capsule coating of 100 mg contains Yellow Iron Oxide (E110) and Red Allura (E129).

See section 2 for important information about the components: Yellow Iron Oxide (E110), Red Allura (E129) and hydrogenated vegetable oil (soybean).

Appearance of the product and contents of the package

• Zonegran 25 mg hard capsules have a white opaque body and a white opaque closure and carry a logo and "ZONEGRAN 25" in black.
• Zonegran 50 mg hard capsules have a white opaque body and a grey opaque closure and carry a logo and "ZONEGRAN 50" in black.
• Zonegran 100 mg hard capsules have a white opaque body and a red opaque closure and carry a logo and "ZONEGRAN 100" in black.

Zonegran capsules are packaged in blisters that are in turn packaged in boxes containing:

• 25 mg: 14, 28, 56 and 84 capsules
• 50 mg: 14, 28, 56 and 84 capsules
• 100 mg: 28, 56, 84, 98 and 196 capsules.

Only some package sizes may be marketed.

Marketing Authorization Holder

Amdipharm Limited

3 Burlington Road,

Dublin 4, D04 RD68,

Ireland

e-mail: [email protected]

Responsible for manufacturing

Eisai GmbH,

Edmund-Rumpler-Straße 3,

60549 Frankfurt am Main,,

Germany

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agency:

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