Zonegran

Italy
Brand name Zonegran
Form capsules, hard gelatin
Active substance / Dosage
ZONISAMIDE
Prescription type Prescription only
ATC code
N03AX15
Registration number 036959
Manufacturer AMDIPHARM LTD
Zonegran capsules, hard gelatin

Table of Contents

Package leaflet: Information for the user

Zonegran 25 mg, 50 mg and 100 mg hard capsules

zonisamide
Please read this leaflet carefully before using this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
  • If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

  1. What Zonegran is and what it is used for
  2. What you need to know before taking Zonegran
  3. How to take Zonegran
  4. Possible side effects
  5. How to store Zonegran
  6. Contents of the pack and other information

1. What Zonegran is and what it is used for

Zonegran contains the active substance zonisamide and is used as an antiepileptic medicine.
Zonegran is used to treat epileptic seizures affecting one part of the brain (partial seizures), which may or may not be followed by a seizure involving the entire brain (secondary generalisation).
Zonegran can be used:

  • as monotherapy for the treatment of epileptic seizures in adults
  • in combination with other antiepileptic medicines for the treatment of epileptic seizures in adults, adolescents and children from 6 years of age.

2. What you need to know before taking Zonegran

Do not take Zonegran

  • if you are allergic to zonisamide or to any of the other ingredients of this medicine (listed in section 6),
  • if you are allergic to other sulfonamide medicines, for example: sulfonamide antibiotics, thiazide diuretics, or sulfonylurea diabetes medicines,
  • 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, serious skin rashes, and blood disorders, which very rarely may lead to death (see section 4. Possible side effects).
Serious skin rashes (rash), including cases of Stevens-Johnson syndrome, may occur when taking Zonegran.
Use of Zonegran may cause elevated levels of ammonia in the blood, which could lead to changes in brain function, especially if you are also taking other medicines that may increase ammonia levels (e.g., valproate), have a genetic disorder causing excessive accumulation of ammonia in the body (urea cycle disorder), or have liver problems. Inform your doctor immediately if you experience unusual drowsiness or disorientation.
Talk to your doctor or pharmacist before taking Zonegran if:

  • you are under 12 years of age, as you may be at higher risk of reduced sweating, heat stroke, pneumonia, and liver problems. Zonegran is not recommended for children under 6 years of age.
  • you are elderly, because your dose of Zonegran may need to be adjusted and you may have a higher risk of developing an allergic reaction, serious skin rash, swelling of the feet and legs, or itching when taking Zonegran (see section 4 Possible side effects).
  • you have liver problems, because your dose of Zonegran may need to be adjusted.
  • you have eye problems, such as glaucoma.
  • you have kidney problems, because your dose of Zonegran may need to be adjusted.
  • you have previously had kidney stones, as there may be an increased risk of developing them again. To reduce the risk of kidney stones, drink an adequate amount of water.
  • you live in or are visiting a hot climate. Zonegran can cause reduced sweating, which may lead to increased body temperature. To reduce the risk of excessive body temperature rise, drink an adequate amount of water and try to stay cool.
  • you are underweight or have lost a lot of weight, because Zonegran may cause further weight loss. Inform your doctor, as this may need to be monitored.
  • you are pregnant or could become pregnant (see section "Pregnancy, breastfeeding and fertility" for further information).

If any of these apply to you, inform your doctor before taking Zonegran.
Children and adolescents
Talk to your doctor about the following risks:
Preventing overheating and dehydration in children
Zonegran can reduce your child’s sweating and lead to overheating; if not properly treated, this may result in brain damage or death. Children are at higher risk, especially in hot weather.
While your child is taking Zonegran:

  • Keep your child cool, especially in hot weather
  • Your child should avoid intense physical activity, especially in hot weather
  • Give your child plenty of cold water to drink
  • Your child should not take the following medicines:
  • carbonic anhydrase inhibitors (such as topiramate and acetazolamide) and anticholinergic medicines (such as clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynine).

If your child’s skin is very hot but sweating is little or absent, if your child becomes confused, has muscle cramps, or has a rapid heartbeat or breathing:

  • Move your child to a cool, shaded place

  • Sponge your child’s skin with cool (but not cold) water

  • Give your child cold water to drink

  • Seek urgent medical advice.

  • Body weight: Monitor your child’s weight monthly and see your doctor as soon as possible if your child is not gaining weight adequately. Zonegran is not recommended for underweight children or those with poor appetite, and should be used with caution in children weighing less than 20 kg.

  • Increased blood acid levels and kidney stones: Reduce these risks by ensuring your child drinks enough water and is not taking other medicines that may promote kidney stone formation (see Other medicines). Your doctor will monitor your child’s blood bicarbonate levels and kidney function (see also section 4).

Do not give this medicine to children under 6 years of age, as it is not known whether the potential benefits outweigh the risks in this age group.
Other medicines and Zonegran
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.

  • Zonegran should be used with caution in adults when also taking medicines that may cause kidney stones, such as topiramate or acetazolamide. This combination is not recommended in children.
  • Zonegran may increase blood levels of certain medicines, such as digoxin and quinidine; therefore, their dose may need to be reduced.
  • Other medicines, such as phenytoin, carbamazepine, phenobarbital, and rifampicin, may reduce blood levels of Zonegran. This may require adjustment of the Zonegran dose.

Zonegran with food and drink
Zonegran can be taken with or without food.
Pregnancy, breastfeeding and fertility
If you are a woman of childbearing potential, you must use an adequate contraceptive method while taking Zonegran and for one month after stopping it.
If you are planning a pregnancy, talk to your doctor before stopping contraception and before becoming pregnant about the possibility of switching to other suitable treatments. If you are or suspect you may be pregnant, inform your doctor immediately. Do not stop treatment without first discussing it with your doctor.
You should take Zonegran during pregnancy only as directed by your doctor. Research has shown an increased risk of birth defects in children of women treated with antiepileptic medicines. The risk of birth defects or neurodevelopmental disorders (problems with brain development) for your child after taking Zonegran during pregnancy is not known. One study showed that babies born to mothers who used zonisamide during pregnancy were smaller at birth than expected compared to babies born to mothers treated with lamotrigine monotherapy. Make sure you are fully aware of the risks and benefits of using zonisamide for the treatment of epilepsy during pregnancy.
Do not breastfeed while taking Zonegran or for one month after stopping Zonegran.
There are no clinical data available on the effects of zonisamide on male fertility. Animal studies have shown changes in fertility parameters.
Driving and using machines
Zonegran may affect your concentration and ability to react/respond and may make you feel drowsy, especially at the beginning of treatment or after a dose increase. Be especially careful when driving or operating machinery if you experience these effects after taking Zonegran.
Important information about some of the ingredients of Zonegran
Zonegran contains sunset yellow FCF (E110) and allura red AC (E129)
The 100 mg hard capsules of Zonegran contain a yellow dye called sunset yellow FCF (E110) and a red dye called allura red AC (E129), which may cause allergic reactions.
Zonegran contains soybean oil. If you are allergic to peanuts or soy, do not use this medicine.

3. How to take Zonegran

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Recommended dose for adults
When taking Zonegran alone:

  • The starting dose is 100 mg taken once daily.
  • This dose may be increased by up to 100 mg at intervals of one or two weeks.
  • The recommended dose is 300 mg once daily.

When taking Zonegran with other antiepileptic medicines:

  • The starting dose is 50 mg daily, taken as two equal doses of 25 mg.
  • This dose may be increased by up to 100 mg at intervals of one or two weeks.
  • The recommended daily dose ranges between 300 mg and 500 mg.
  • Some individuals respond to lower doses. The dose may be increased more slowly if side effects occur, in elderly patients, or in patients with kidney or liver problems.

Use in children (6 to 11 years old) and adolescents (12 to 17 years old) with body weight of at least 20 kg:

  • The starting dose is 1 mg per kg of body weight, taken once daily.
  • This dose 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 weighing up to 55 kg, or 300 to 500 mg once daily for a child weighing over 55 kg (whichever is the lower dose).

Example: a child weighing 25 kg should take 25 mg once daily during the first week, then increase the daily dose by 25 mg at the beginning of each week, until reaching a daily dose between 150 and 200 mg.
If you think that the effect of Zonegran is too strong or too weak, talk to your doctor or pharmacist.

  • Zonegran capsules must be swallowed whole with water.
  • Do not chew the capsules.
  • Zonegran may be taken once or twice daily, according to your doctor's instructions.
  • If you take Zonegran twice daily, half of the daily dose should be taken in the morning and half in the evening.

If you take more Zonegran than you should
If you have taken more Zonegran than you should, immediately inform your caregiver (relative or friend), your doctor or pharmacist, or contact the emergency department of your nearest hospital, and bring the medicine with you. Taking an excessive dose may cause drowsiness and loss of consciousness. You may also experience nausea, stomach ache, muscle twitching, eye movements, feeling faint, slowed heartbeat, and reduced breathing and kidney function. Do not attempt to drive.
If you forget to take Zonegran

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

If you stop taking Zonegran

  • Zonegran is intended for long-term use. Do not reduce the dose or stop taking it unless instructed by your doctor.
  • If your doctor advises you to stop taking Zonegran, the dose will be gradually reduced to lower the risk of further epileptic seizures.

If you have any questions about how to use 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.
Zonegran belongs to a group of medicines (sulfonamides) that can cause severe allergic reactions, serious skin rashes and blood disorders, which very rarely may lead to death.

Contact your doctor immediately if:

  • you have difficulty breathing, swelling of the face, lips or tongue, or a severe skin rash, as these symptoms could indicate a serious allergic reaction.
  • you have signs of heat stroke – high body temperature but with little or no sweating, rapid heartbeat and breathing, muscle cramps and confusion.
  • you have thoughts of harming yourself or of suicide. A small number of patients treated with antiepileptic medicines such as Zonegran have had thoughts of self-harm or suicide.
  • you have muscle pains or feel weak, as these could be signs of abnormal muscle breakdown which could lead to kidney problems.
  • you experience sudden pain in your back or stomach, have pain when urinating, or notice blood in your urine, as these could be signs of kidney stones.
  • you develop visual problems such as eye pain or blurred vision during treatment with Zonegran.

Contact your doctor as soon as possible if:

  • you develop an unexplained skin rash, as it could progress to a more severe rash or skin peeling.
  • you feel unusually tired or feverish, have a sore throat, swollen glands, or notice that you bruise easily, as these could indicate a blood disorder.
  • you develop signs of increased acid levels in the blood – headache, drowsiness, shortness of breath and loss of appetite. This may require monitoring or treatment by your doctor.

Your doctor may decide to stop treatment with Zonegran.
The most common side effects of Zonegran are mild. They occur during the first month of treatment and usually improve with continued treatment. In children aged 6 to 17 years, side effects were consistent with those described below, with the following exceptions: pneumonia, dehydration, reduced sweating (common), and liver enzyme abnormalities (uncommon).

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

  • agitation, irritability, confusion, depression.
  • poor muscle coordination, dizziness, poor memory, drowsiness, double vision.
  • loss of appetite, reduced levels of bicarbonate in the blood (a substance that prevents blood from becoming too acidic).

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

  • difficulty sleeping, unusual or strange thoughts, anxiety or emotional lability.
  • slowed thinking, difficulty concentrating, speech abnormalities, abnormal sensations on the skin (tingling), tremor, involuntary eye movements.
  • kidney stones.
  • skin rashes, itching, allergic reactions, fever, fatigue, flu-like symptoms, hair loss.
  • bruising (small discolored spots on the skin caused by bleeding from broken blood vessels).
  • weight loss, nausea, indigestion, stomach pain, diarrhoea (loose stools), constipation.
  • swelling of the feet and legs.

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

  • anger, aggression, suicidal thoughts, suicide attempt.
  • vomiting.
  • inflammation of the gallbladder, gallstones.
  • urinary stones.
  • lung infection/inflammation, urinary tract infections.
  • low potassium levels in the blood, seizures/epileptic fits.

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

  • hallucinations, memory loss, coma, neuroleptic malignant syndrome (inability to move, sweating, fever, incontinence), status epilepticus (prolonged or repeated seizures).
  • breathing disorders, breathlessness, lung inflammation.
  • inflammation of the pancreas (severe pain in the stomach or back).
  • liver problems, kidney failure, increased levels of creatinine (a waste product normally removed by the kidneys) in the blood.
  • severe skin rashes or skin peeling (you may also feel unwell or develop a fever).
  • abnormal muscle breakdown (you may feel muscle pain or weakness), which could lead to kidney problems.
  • swollen glands, blood disorders (reduced number of blood cells, which may increase the risk of infections, cause paleness, fatigue and fever, and make bruising more likely).
  • decreased sweating, excessive increase in body temperature.
  • glaucoma, i.e. a blockage of fluid within the eye causing increased intraocular pressure. Symptoms may include eye pain, blurred vision or loss of vision, which may be signs of glaucoma.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Zonegran

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and the outer carton after
Exp/EXP. The expiry date refers to the last day of that month.
Do not store above 30°C.
Do not use this medicine if you notice any damage to the capsules, blister pack or carton, or any visible signs of deterioration in the medicine. Return the pack to your pharmacist.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Zonegran contains
The active substance 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.

  • Other components in the capsule are microcrystalline cellulose, hydrogenated vegetable oil (soybean seed) and sodium lauryl sulfate.
  • The capsule shell contains gelatin, titanium dioxide (E171), shellac, propylene glycol, potassium hydroxide, black iron oxide (E172). Additionally, the shell of the 100 mg capsules contains sunset yellow FCF (E110) and allura red AC (E129).

See section 2 for important information on excipients: sunset yellow FCF (E110) and
allura red AC (E129), and hydrogenated vegetable oil (soybean seed).
Description of the appearance of Zonegran and contents of the pack

  • Zonegran 25 mg hard capsules have an opaque white body and an opaque white cap, printed with “ZONEGRAN 25” in black.
  • Zonegran 50 mg hard capsules have an opaque white body and an opaque grey cap, printed with “ZONEGRAN 50” in black.
  • Zonegran 100 mg hard capsules have an opaque white body and an opaque red cap, printed with “ZONEGRAN 100” in black.

Zonegran hard capsules are packed in blisters, available in pack sizes 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.

Not all pack sizes may be available.
Marketing Authorisation Holder and Manufacturer
Amdipharm Limited
3 Burlington Road,
Dublin 4, D04 RD68,
Ireland
email: [email protected]
Manufacturer
Eisai GmbH
Edmund-Rumpler-Straße 3
60549 Frankfurt am Main
Germany
SKYEPHARMA PRODUCTION S.A.S.
Zone Industrielle Chesnes Ouest,
55 rue du Montmurier,
SAINT QUENTIN FALLAVIER,
38070, FRANCE
For further information about this medicinal product, contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Amdipharm Limited Amdipharm Limited
Tél/Tel: +32 (0)28 088 620 Tel: +44 (0) 208 588 9131
България Luxembourg/Luxemburg
Amdipharm Limited Amdipharm Limited
Teл.: +44 (0) 208 588 9131 Tél/Tel: +44 (0) 208 588 9131
Česká republika Magyarország
Amdipharm Limited Amdipharm Limited
Tel: +44 (0) 208 588 9131 Tel: +44 (0) 208 588 9131
Danmark Malta
Amdipharm Limited Amdipharm Limited
Tlf: +44 (0) 208 588 9131 +44 (0) 208 588 9131
Deutschland Nederland
Amdipharm Limited Amdipharm Limited
Tel: +49 (0) 800 1840 212 Tel: +31 (0) 208 08 3206
Eesti Norge
Amdipharm Limited Amdipharm Limited
Tel: +44 (0) 208 588 9131 Tlf: +44 (0) 208 588 9131
Ελλάδα Österreich
Amdipharm Limited Amdipharm Limited
Τηλ: +44 (0) 208 588 9131 Tel: +43 (0) 800 298 022
España Polska
Ferrer Internacional, S.A. Amdipharm Limited
Tel: +34 93 600 37 00 Tel: +44 (0) 208 588 9131
France Portugal
CENTRE SPECIALITES Amdipharm Limited
PHARMACEUTIQUES Tel: +44 (0) 208 588 9131
Tél: 01.47.04.80.46
Hrvatska România
Amdipharm Limited Amdipharm Limited
Tel: +44 (0) 208 588 9131 Tel: +44 (0) 208 588 9131
Ireland Slovenija
Amdipharm Limited Amdipharm Limited
Tel: +44 (0) 208 588 9131 Tel: +44 (0) 208 588 9131
Ísland Slovenská republika
Amdipharm Limited Amdipharm Limited
Sími: +44 (0) 208 588 9131 Tel.: +44 (0) 208 588 9131
Italia Suomi/Finland
Amdipharm Limited Amdipharm Limited
Tel: +39 02 600 630 37 Puh/Tel: +44 (0) 208 588 9131
Κύπρος Sverige
Amdipharm Limited Amdipharm Limited
Τηλ: +44 (0) 208 588 9131 Tel: +46 (0)8 408 38 440
Latvija United Kingdom (Northern Ireland)
Amdipharm Limited Amdipharm Limited
Tel: +44 (0) 208 588 9131 Tel: +44 (0) 208 588 9131
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.
Annex IV
Scientific conclusions and grounds for the variation of the terms of the marketing authorisation
Scientific conclusions
Taking into account the assessment by the Pharmacovigilance Risk Assessment Committee (PRAC) for zonisamide, the scientific conclusions of the Committee for Medicinal Products for Human Use (CHMP) are as follows:
"Pregnancy use" is an important potential risk for zonisamide. Zonisamide must not be used during pregnancy or in women of childbearing potential who are not using effective contraception unless clearly necessary, and only if the potential benefits are considered to outweigh the risk to the fetus. Clinical data on the potential risks of congenital malformation and neurodevelopmental disorders associated with zonisamide use during pregnancy are very limited, and these risks remain unknown. Current product information indicates that the potential risk of using zonisamide during pregnancy in women is unknown; however, it does not specifically refer to the risks of congenital malformations and neurodevelopmental disorders. It is considered that product information should clearly reflect the currently available scientific knowledge regarding these potential risks, to ensure that healthcare professionals and patients are adequately informed about what is known regarding risks associated with use during pregnancy. Furthermore, risk minimisation measures relating to use in women of childbearing potential and during pregnancy, as described in the product information, require updating. Given the requirement for women of childbearing potential to use effective contraception throughout treatment and the uncertainties regarding fetal risk associated with use during pregnancy, a pregnancy test should be considered before starting treatment to exclude pregnancy, as recommended for other antiepileptic medicines. In addition, the product information must clearly reflect that antiepileptic therapy should be re-evaluated before conception and before discontinuation of contraception, while the need for urgent review by the patient’s physician in case of suspected or confirmed pregnancy must be clearly stated in the product information. The PRAC concluded that the product information for zonisamide-containing medicines should be amended accordingly.
The CHMP agrees with the scientific conclusions of the PRAC.
Grounds for the variation of the terms of the marketing authorisation
Based on the scientific conclusions on zonisamide, the CHMP considers that the benefit-risk balance of zonisamide remains favourable, subject to the proposed amendments to the product information.
The CHMP recommends a variation to the terms of the marketing authorisation.