Karbagen

Package leaflet: Information for the patient

Karbagen, 150 mg, coated tablets
Karbagen, 300 mg, coated tablets
Karbagen, 600 mg, coated tablets
Oxcarbazepinum
Read the entire 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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you specifically. Do not pass it on to other people. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet:

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

1. What Karbagen is and what it is used for

Karbagen contains the active substance oxcarbazepine.
Karbagen belongs to a group of medicines called antiepileptic or anticonvulsant drugs used in the treatment of epilepsy.
Karbagen helps control seizures or fits in patients with epilepsy.
In people with epilepsy, there are episodes of uncontrolled electrical activity in the brain. These episodes of uncontrolled electrical activity may lead to seizures. Oxcarbazepine helps control the brain's electrical activity. This reduces the likelihood of seizure occurrence.
Karbagen is used in the treatment of partial seizures, with or without secondary generalization to tonic-clonic seizures. Partial seizures affect only a limited area of the brain but may spread to the entire brain and may lead to generalized tonic-clonic seizures. There are two types of partial seizures: simple and complex. In simple partial seizures, the patient remains conscious, whereas in complex partial seizures, the patient's consciousness is altered.
Oxcarbazepine is used in adults and children aged 6 years and older. Usually, the doctor will try to find one medicine that is most suitable for the patient (adult or child). However, in more severe cases of epilepsy, controlling seizures may require treatment with two or more medicines.
Karbagen, coated tablets, may be used as monotherapy or in combination with other antiepileptic medicines.

2. Important information before using Karbagen

You must strictly follow all your doctor's instructions, even if they differ from the information
contained in this leaflet.
When not to use Karbagen:

• if the patient is allergic to oxcarbazepine, eslicarbazepine, or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Karbagen, discuss the following with your doctor or pharmacist:
ƒ if the patient has an allergy (hypersensitivity) (e.g. rash or other allergic reaction) to carbamazepine, a similar
antiepileptic medicine. If the patient is allergic to carbamazepine, there is a probability of 1 in 4 (25%) that they may also be allergic to oxcarbazepine
ƒ if the patient has liver problems, or if such problems develop during treatment (see: Possible adverse effects)
ƒ if the patient has kidney problems, especially those associated with low blood sodium (salt) levels. Oxcarbazepine may further reduce blood sodium levels, which may lead to symptoms of sodium deficiency (see: Possible adverse effects). In case of kidney disease, the doctor may order blood tests before starting therapy and regularly after initiating treatment with Karbagen
ƒ if the patient is taking other medicines that may reduce blood sodium levels (e.g. diuretics, desmopressin, or non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin and ibuprofen). See: Karbagen with other medicines
ƒ if the patient has heart disease, such as heart failure (shortness of breath, ankle swelling). The doctor will perform regular body weight measurements to monitor for fluid retention
ƒ if the patient has heart rhythm disorders
ƒ if the patient is using hormonal contraceptives (see: Karbagen with other medicines)

During treatment
If symptoms of blood disorders occur, such as fatigue, shortness of breath during exertion, paleness, headache, chills, dizziness, infections causing fever, sore throat, mouth ulcers, easier than usual bleeding or bruising, nosebleeds, red or purple spots on the skin, or unexplained skin changes, discuss this with your doctor.
In a small number of people treated with antiepileptic medicines such as oxcarbazepine, thoughts of self-harm or suicidal thoughts have occurred. If such thoughts arise, contact your doctor immediately.
Potentially life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported after oxcarbazepine use, initially appearing as red, target-like spots or patches, often with blisters in the central area.
Other symptoms to watch for include ulcers in the mouth, throat, nose, genital organs, and conjunctivae (red, swollen eyes). These potentially life-threatening skin reactions are often accompanied by flu-like symptoms. The rash may progress to extensive blistering skin lesions or skin peeling.
The highest risk of severe skin reactions occurs during the first weeks of treatment.
There is an increased risk of these reactions in patients of Han Chinese or Thai descent, or other Asian populations (see below, "Patients of Han Chinese and Thai descent").
If the patient develops Stevens-Johnson syndrome or toxic epidermal necrolysis after taking oxcarbazepine, this medicine must not be restarted.
If the patient develops a rash or any of the above-mentioned skin symptoms, they should contact their doctor immediately and inform them about taking this medicine.
This medicine may cause a condition known as hypothyroidism (low thyroid hormone levels). In children, the doctor may order regular blood tests after starting oxcarbazepine treatment.
If seizure frequency increases, contact the doctor, who may decide to discontinue treatment with Karbagen. This is particularly important in children, but may also affect adults.
Before and during oxcarbazepine treatment, the doctor may perform blood tests to determine the individual dose. The doctor will inform the patient when such tests should be performed.

Patients of Han Chinese and Thai descent
The risk of serious skin reactions associated with carbamazepine or its derivatives in patients of Han Chinese or Thai descent can be predicted based on blood test results. The doctor will inform the patient whether a blood test is necessary before starting oxcarbazepine. If the patient belongs to other Asian ethnic groups (e.g. Filipino or Malay), the doctor may also consider the need for blood testing before starting treatment.

Children and adolescents
The doctor may recommend monitoring thyroid function before and during treatment in children.

Karbagen with other medicines
Tell your doctor about all medicines currently used, recently taken, or planned for use, especially those that may interact with oxcarbazepine:
ƒ other antiepileptic medicines, such as phenobarbital, phenytoin, carbamazepine, lamotrigine, and valproic acid. The doctor may wish to adjust the dosage of these medicines if Karbagen is taken concomitantly. When used together with lamotrigine, there is an increased possibility of adverse effects such as nausea, drowsiness, headache, and dizziness
ƒ hormonal contraceptives ("birth control pills"). In the presence of Karbagen, they may become ineffective. Another method of contraception should also be used
ƒ medicines used to treat psychiatric disorders, such as lithium salts and monoamine oxidase inhibitors (MAOIs), such as phenelzine and moclobemide. Concomitant use with lithium salts may increase the frequency of adverse effects
ƒ medicines that may reduce blood sodium levels (e.g. diuretics, desmopressin, and non-steroidal anti-inflammatory drugs, such as indomethacin and ibuprofen). Oxcarbazepine may further reduce blood sodium levels, which may lead to symptoms of deficiency (see: Possible adverse effects). The doctor should order blood tests before starting treatment and regularly after initiating Karbagen therapy
ƒ medicines affecting the body's immune system (immunosuppressants), such as cyclosporine and tacrolimus
ƒ rifampicin (an antibiotic used to treat infections)

Karbagen and alcohol
Exercise particular caution when consuming alcohol during Karbagen treatment, as it may cause excessive drowsiness.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.

Pregnancy
Oxcarbazepine affects the way hormonal contraceptives work, increasing the risk of pregnancy. If the patient is of childbearing age, she should use other contraceptive methods.
Controlling seizures during pregnancy is important, but using antiepileptic medicines at this time may affect the unborn child's development.

Congenital malformations
Studies have not shown an increased risk of congenital malformations associated with oxcarbazepine use during pregnancy, but the risk of fetal malformations cannot be completely ruled out.

Neurodevelopmental disorders
Some studies have shown that exposure to oxcarbazepine in utero negatively affects brain function development (nervous system development) in children, while other studies have not shown such an effect. The possibility of an effect on nervous system development cannot be excluded.

Birth weight
If the mother uses Karbagen during pregnancy, the newborn may be smaller and weigh less than expected [small for gestational age (SGA)]. Among women with epilepsy, in one study, about 15 out of 100 children born to mothers who took oxcarbazepine during pregnancy were smaller and had lower birth weight than expected, compared to about 11 out of 100 children born to women who did not take antiepileptic medicines during pregnancy.
The doctor will discuss the benefits and possible risks associated with using the medicine during pregnancy and help decide whether to use Karbagen.
Do not stop Karbagen treatment during pregnancy without first consulting your doctor.

Breastfeeding
If the patient is using this medicine, she should consult her doctor before starting breastfeeding.
The active substance in Karbagen passes into breast milk. Although available data indicate that the amount of Karbagen transferred to the breastfed infant is small, the risk of adverse effects in the child cannot be excluded. The doctor will discuss the benefits and risks associated with breastfeeding while taking Karbagen. If the patient is breastfeeding while taking Karbagen and suspects that the child is experiencing such adverse effects as excessive drowsiness or poor weight gain, she should inform the doctor immediately.

Driving and operating machinery
Oxcarbazepine has a moderate influence on the ability to drive and operate machinery. Be aware that oxcarbazepine may cause adverse effects such as dizziness, drowsiness, imbalance and coordination problems, vision problems including double or blurred vision, reduced blood sodium levels (which may cause muscle weakness), reduced consciousness—especially at the beginning of treatment or during dose increases—which may affect the ability to drive and operate machinery. If such adverse effects occur, do not drive or operate machinery.

Karbagen contains lactose
If your doctor has informed you that you have intolerance to certain sugars, you should contact your doctor before taking this medicine.

3. How to use Karbagen

This medicine should always be used exactly as directed by the physician. If in doubt, consult your doctor or pharmacist.

If the required dose of the medicine cannot be administered using whole tablets, other formulations containing oxcarbazepine are available.

The doctor will likely start treatment with a low dose and, if necessary, gradually increase it according to the individual needs of the patient.

Recommended dose:

Adults
The initial dose is 300 mg twice daily. If needed, the doctor may gradually increase the dose weekly by up to 600 mg per day. The maintenance dose ranges from 600 mg to 2400 mg per day.

If the patient is taking other antiepileptic medicines, the doctor may reduce their dose or increase the dose of Karbagen more slowly.

When replacing other antiepileptic medicines with Karbagen, the doses of those medicines will be gradually reduced.

Use in children and adolescents aged 6 years and older
The initial dose is 8–10 mg/kg body weight per day, given in two divided doses. If necessary, the doctor may increase the daily dose weekly by approximately 10 mg/kg body weight, up to a maximum dose of 46 mg/kg body weight per day. The usual maintenance dose of oxcarbazepine when used in combination with other antiepileptic medicines is typically 30 mg/kg body weight per day.

For children who cannot swallow tablets or when the required dose cannot be administered using tablets, other pharmaceutical forms containing oxcarbazepine are available.

Use in children under 6 years of age
Karbagen is not recommended for use in children under 6 years of age, as efficacy and safety have not been established in this age group.

Patients with impaired kidney function
In patients with impaired kidney function, the doctor may start treatment with half the usual initial dose and increase the dose of Karbagen more slowly than indicated above.

Patients with severe liver function impairment
In patients with severe liver function impairment, the doctor may adjust the dosing regimen. Always follow the doctor's instructions.

If the required dose of the medicine cannot be administered using whole tablets, other pharmaceutical forms of the medicine containing oxcarbazepine are available.

Method of administration:
The coated tablets should be swallowed whole with a glass of water, with or without food. Do not chew or crush the tablets. The score line on the tablet is intended only to facilitate breaking the tablet if the patient has difficulty swallowing it whole, but does not allow for dividing the tablet into equal doses.

Taking more than the recommended dose of Karbagen
If more than the recommended dose of Karbagen is taken, contact a doctor or pharmacist immediately. Symptoms of overdose include low blood sodium levels, irritability, agitation, confusion, drowsiness or sleepiness, dizziness, nausea, vomiting, fatigue, changes in heart rhythm (fast or irregular heartbeat), tremor, seizures/convulsions, headache, muscle twitching, loss of consciousness, uncontrolled movements (muscle spasms or jerking), double or blurred vision, constricted pupils, low blood pressure, shortness of breath, abnormal level of muscle or body activity, lack of motor coordination, and uncontrolled eye movements.

Missed dose of Karbagen
Take the missed tablet as soon as remembered. However, if it is almost time for the next dose, skip the missed dose and take the next dose at the regular time. Do not take a double dose to make up for a missed dose.

Stopping treatment with Karbagen
Do not stop using Karbagen suddenly without consulting your doctor, as this may lead to a sudden increase in seizures or convulsions. If treatment with Karbagen needs to be discontinued, the doctor will do so gradually.

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

4. Possible side effects

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

Patients should inform their doctor immediately or go to the nearest hospital emergency department if any of the following serious side effects occur; medical intervention may be required:

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

• Increased frequency of infections that may cause fever, severe chills, sore throat, or mouth ulcers (may indicate a low white blood cell count)
• Weight gain, feeling tired, hair loss, muscle weakness, feeling cold (symptoms of hypothyroidism)
• Falls

Rare (may affect up to 1 in 1000 patients):

• Swelling of the face, lips, eyelids, tongue, throat, or inside of the mouth; difficulty speaking or swallowing; sudden hives combined with breathing difficulties, shortness of breath, or wheezing (symptoms of angioedema and anaphylactic reaction)
• Skin rash and/or fever, which may be signs of drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP)
• Feeling tired, shortness of breath during exertion, paleness, chills, dizziness, frequent infections causing fever, sore throat, mouth ulcers, easier than usual bleeding or bruising, nosebleeds, red or purple spots on the skin, or unexplained skin changes (symptoms of reduced platelet count or decreased blood cells)
• Lethargy, disorientation, muscle twitching, or significantly worsened seizures (possible symptoms of hyponatremia due to inappropriate ADH secretion) (see section “Warnings and precautions”)

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

• Potentially life-threatening skin reactions such as severe blistering rash on the skin and/or mucous membranes of the lips, eyes, mouth, nose, and genital organs, and peeling of the skin from large areas of the body (symptoms of severe hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and Lyell’s syndrome) (see section 2: “Warnings and precautions”)
• Red (moist), itchy, irregular rash similar to measles, appearing first on the limbs, sometimes on the face and other parts of the body. The spots may develop into blisters or form raised, red, bright-centered rings. The patient may experience fever, sore throat, headache, and/or diarrhea (erythema multiforme). If such skin reactions occur during treatment with Karbagen, the drug must not be used further. The doctor may decide to discontinue treatment with Karbagen.
• Hypersensitivity reactions may also affect other parts of the body and may cause problems with the lungs (e.g., breathing difficulties or cough with sputum or blood), kidneys (producing little or no urine, or blood in the urine), or liver (liver dysfunction described below, but may also lead to brain swelling causing behavioral changes or drowsiness). Other symptoms include changes in blood tests (described separately in the leaflet), spleen enlargement (causing abdominal swelling and pain/tenderness), or enlarged lymph nodes in the neck, armpits, or groin
• Red, blotchy rash mainly on the face, possibly accompanied by fatigue, fever, nausea, or loss of appetite (systemic lupus erythematosus)
• Much easier than normal bleeding and bruising (thrombocytopenia)
• Symptoms of liver inflammation (nausea, vomiting, loss of appetite, general malaise, fever, itching, yellowing of the skin or whites of the eyes (jaundice), pale stools, dark urine). Liver function should be checked in such cases
• Pancreatitis, which includes the following symptoms: severe pain in the upper abdomen radiating to the back, often with nausea
• Heart disorders, which may cause dizziness, fainting, and irregular heartbeat (atrioventricular block)

If any of the side effects listed below occur, patients should inform their doctor as soon as possible. Medical help may be needed:

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

• Tremor; coordination disturbances; involuntary eye movements; feeling anxious and nervous; depression; mood swings; rash

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

• Irregular heartbeat, or very fast or very slow heart rate

Other possible side effects:

These side effects of Karbagen are usually mild to moderate. Most of them are transient and usually resolve gradually.

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

• Feeling tired, headache, dizziness, fatigue or sluggishness, and/or drowsiness, nausea, vomiting, double vision

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

• Feeling weak; memory loss and/or memory disturbances; difficulty concentrating; lack of emotion or motivation (apathy); restlessness or other mood changes; disorientation; blurred vision; visual disturbances; diarrhea or constipation, stomach (abdominal) pain; acne; hair loss; loss of motor coordination; weight gain; speech disorders

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

• High blood pressure; urticaria (hives)
• Increased liver enzyme activity during treatment with Karbagen

Rare (may affect up to 1 in 1000 patients):

• There have been reports of bone disorders including osteopenia and osteoporosis (reduced bone density) and fractures. Patients should consult their doctor or pharmacist if they have been taking antiepileptic drugs for a long time, have a history of osteoporosis, or have taken steroids.

Reporting of side effects

If any adverse reactions occur, including any not listed in this leaflet, patients should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl

Side effects can also be reported directly to the marketing authorization holder.

Reporting side effects helps provide more information on the safety of the medicine.

5. How to store Karbagen

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the tablet container,
blister pack, or cardboard box. The expiry date refers to the last day of the stated month.
Store below 30°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. Such measures help protect
the environment.

6. Contents of the packaging and other information

What Karbagen contains
The active substance in Karbagen 150 mg, film-coated tablets, is 150 mg of oxcarbazepine per tablet.
The active substance in Karbagen 300 mg, film-coated tablets, is 300 mg of oxcarbazepine per tablet.
The active substance in Karbagen 600 mg, film-coated tablets, is 600 mg of oxcarbazepine per tablet.

The other ingredients are:
Tablet core: crospovidone, hypromellose, microcrystalline cellulose, colloidal anhydrous silica, and magnesium stearate.
Tablet coating: Opadry Buff II OY-LS-37200: titanium dioxide (E171), lactose monohydrate (see section 2 "Karbagen contains lactose"), polyethylene glycol 4000, hypromellose, iron oxide yellow (E172), iron oxide red (E172), iron oxide black (E172); Opadry White II OY-LS-28908: titanium dioxide (E171), lactose monohydrate (see section 2 "Karbagen contains lactose"), polyethylene glycol 4000, hypromellose.

What Karbagen looks like and contents of the pack
Film-coated tablet.
The film-coated tablets are oblong, convex, light yellow in colour and have a division line on both sides. The division line facilitates breaking the tablet for easier swallowing, but not for dividing into two equal doses.
The 150 mg film-coated tablets are marked with ‘OX/150’ on one side and ‘G/G’ on the other.
The 300 mg film-coated tablets are marked with ‘OX/300’ on one side and ‘G/G’ on the other.
The 600 mg film-coated tablets are marked with ‘OX/600’ on one side and ‘G/G’ on the other.
Karbagen film-coated tablets are available in plastic tablet containers containing 100, 200 and 500 tablets, and in blisters containing 10, 20, 30, 50, 60, 100 and 200 tablets.*
* Not all pack sizes may be marketed.
Karbagen film-coated tablets are available as Karbagen 150 mg, 300 mg and 600 mg film-coated tablets.

Marketing Authorisation Holder
Viatris Limited
Damastown Industrial Park
Mulhuddart, Dublin 15
DUBLIN
Ireland

Manufacturer
McDermott Laboratories Ltd. T/A Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange Road, Dublin 13, Ireland
Mylan Hungary Kft., Mylan utca 1., Komárom, 2900, Hungary

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Belgium: Oxcarbazepine Viatris 150 mg, 300 mg, 600 mg filmomhulde tabletten
Denmark: Oxcarbazepin Viatris
France: Oxcarbazepine Viatris 150 mg, 300 mg, 600 mg comprimé pelliculé
Germany: Oxcarbazepin dura 150 mg, 300 mg, 600 mg Filmtabletten
Poland: Karbagen
Slovenia: KARBOX 150 mg, 300 mg, 600 mg filmsko obložene tablete
Spain: Oxcarbazepina VIATRIS 300 mg, 600 mg comprimidos recubiertos con película EFG
Netherlands: Oxcarbazepine Viatris 150 mg, 300 mg, 600 mg filmomhulde tabletten
United Kingdom (Northern Ireland): Oxcarbazepine Mylan 150 mg, 300 mg and 600 mg Film Coated Tablets

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Viatris Healthcare Sp. z o.o.
Tel: +48 22 546 64 00