Bozilos

Package leaflet: Information for the patient

Bozilos, 14 mg, coated tablets
Teriflunomide
Please read all of this leaflet carefully before 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 a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Bozilos is and what it is used for

What Bozilos is
Bozilos contains the active substance teriflunomide, which is an immunomodulatory medicine that regulates the immune system in order to reduce its attack on the nervous system.

What Bozilos is used for
Bozilos is used in the treatment of adults, children, and adolescents (aged 10 years and older) with relapsing-remitting multiple sclerosis.

What is multiple sclerosis
Multiple sclerosis is a chronic disease that affects the central nervous system. The central nervous system consists of the brain and spinal cord. In multiple sclerosis, inflammation damages the protective covering (called myelin) around the nerves in the central nervous system. This process is known as demyelination. This damage prevents nerves from functioning properly.

In people with relapsing forms of multiple sclerosis, there are repeated attacks (relapses) of physical symptoms caused by improper nerve function. These symptoms vary between patients but usually include:

• difficulty walking,
• vision problems,
• problems with balance.

These symptoms may completely disappear after a relapse ends, but over time some problems may persist between relapses. This may lead to physical disability, making it difficult to perform daily activities.

How Bozilos works
Bozilos helps protect the central nervous system from the immune system by reducing the increase in number of certain white blood cells (lymphocytes). This reduces the inflammation that, in patients with multiple sclerosis, leads to nerve damage.

2. Important information before taking Bozilos

When not to take Bozilos:

• if the patient is allergic to teriflunomide or any of the other ingredients of this medicine (listed in section 6);
• if the patient has ever experienced severe skin rash, skin peeling, blisters, and/or oral ulceration after taking teriflunomide or leflunomide;
• if the patient has severe liver disease;
• if the patient is pregnant, suspects she may be pregnant, or is breastfeeding;
• if the patient has any severe diseases affecting the immune system, e.g. acquired immunodeficiency syndrome (AIDS);
• if the patient has any severe bone marrow disorders or has low numbers of red or white blood cells or reduced platelet count;
• if the patient has a severe infection;
• if the patient has severe kidney disease requiring dialysis;
• if the patient has very low levels of proteins in the blood (hypoproteinemia).
  If in doubt, consult a doctor or pharmacist before taking this medicine.

Warnings and precautions
Before starting treatment with Bozilos, discuss with your doctor or pharmacist if:

• the patient has impaired liver function and/or drinks large amounts of alcohol; the doctor may perform blood tests to check liver function before and during treatment. If test results indicate liver dysfunction, the doctor may discontinue Bozilos. Refer to section 4 for further information.
• the patient has high blood pressure (hypertension), regardless of whether it is controlled with medication or not. Bozilos may increase blood pressure. The doctor will monitor the patient's blood pressure before starting treatment and regularly thereafter. Refer to section 4 for further information.
• the patient has an infection. Before administering Bozilos, the doctor will ensure the patient has adequate levels of white blood cells and platelets in the blood. Since Bozilos reduces the number of white blood cells, it may impair the ability to fight infections. The doctor may perform a blood test if the patient suspects an infection. Viral infections such as herpes virus (including cold sores or shingles) may occur during treatment with teriflunomide. In some cases, serious complications have occurred. Inform the doctor immediately if any symptoms suggestive of herpes virus infection occur. Refer to section 4 for further information.
• the patient experiences severe skin reactions.
• the patient has respiratory symptoms.
• the patient experiences weakness, numbness, or pain in the hands and feet.
• the patient plans to receive vaccination.
• the patient is taking leflunomide together with Bozilos.
• the patient is switching from another medicine to Bozilos or from Bozilos to another medicine.
• the patient is scheduled for a specific blood test (calcium level measurement). Test results for calcium levels may be falsely low.

Respiratory system reactions
Inform the doctor if the patient develops unexplained cough or shortness of breath (difficulty breathing). The doctor may perform additional tests.

Children and adolescents
Bozilos is not intended for use in children under 10 years of age, as it has not been studied in patients with multiple sclerosis in this age group.
The warnings and precautions listed above also apply to children. The following information is important for children and their caregivers:

• cases of pancreatitis have been observed in patients receiving teriflunomide. The child's doctor may perform blood tests if pancreatitis is suspected.

Bozilos and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take, including over-the-counter medicines.

Specifically, inform the doctor or pharmacist if the patient is taking any of the following medicines:

• leflunomide, methotrexate, and other medicines affecting the immune system (often called immunosuppressive or immunomodulatory drugs);
• rifampicin (used to treat tuberculosis and other infections);
• carbamazepine, phenobarbital, phenytoin, used to treat epilepsy;
• St. John's wort (herbal remedy for depression);
• repaglinide, pioglitazone, nateglinide, or rosiglitazone, used to treat diabetes;
• daunorubicin, doxorubicin, paclitaxel, or topotecan, used to treat cancer;
• duloxetine, used to treat depression, urinary incontinence, or kidney disease in diabetic patients;
• alosetron, used to treat severe diarrhea;
• theophylline, used to treat asthma;
• tizanidine (a muscle relaxant);
• warfarin (an anticoagulant) used to thin the blood (i.e. make it more fluid) to prevent blood clots;
• oral contraceptives (containing ethinylestradiol and levonorgestrel);
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin, used to treat infections;
• indomethacin, ketoprofen, used to treat inflammation or pain;
• furosemide, used to treat heart conditions;
• cimetidine, used to reduce gastric acid secretion;
• zidovudine, used to treat HIV infection;
• rosuvastatin, simvastatin, atorvastatin, pravastatin, medicines used to treat hypercholesterolemia (elevated blood cholesterol levels);
• sulfasalazine, used in inflammatory bowel disease and rheumatoid arthritis;
• cholestyramine, used in cases of elevated blood cholesterol or itching in liver disease;
• activated charcoal, used to reduce absorption of medicines or other substances.

Pregnancy and breastfeeding
Do not take Bozilos if the patient is pregnant or suspects she may be pregnant. There is an increased risk of congenital malformations in the unborn child if the patient becomes pregnant while taking Bozilos or within two years after stopping treatment. Women of childbearing potential who are not using effective contraception must not take this medicine.
If a girl starts menstruating while taking Bozilos, inform the doctor, who will provide specialist advice regarding contraception and potential risks in case of pregnancy.
If a woman plans to become pregnant after stopping Bozilos, she should inform her doctor, as it is essential to ensure that the medicine is no longer present in the body before attempting pregnancy. Elimination of the active substance may take up to 2 years. This period can be shortened to several weeks by taking specific medicines that accelerate the removal of Bozilos from the body. In both cases, blood testing must confirm that the active substance has been sufficiently eliminated from the body. The doctor must confirm that the blood concentration of Bozilos is low enough to allow pregnancy.
More information about laboratory tests can be obtained from the doctor.
If pregnancy is suspected during treatment with Bozilos or within two years after stopping treatment, stop taking Bozilos and immediately contact a doctor to perform a pregnancy test. If the test confirms pregnancy, the doctor may recommend appropriate treatment to rapidly and adequately eliminate Bozilos from the body to reduce the risk to the unborn child.

Contraception
Women must use effective contraception during treatment with Bozilos and after stopping treatment. Teriflunomide remains in the blood for a long time after discontinuation. Therefore, effective contraception must continue after stopping treatment.

• Contraception should be continued until blood levels of Bozilos are sufficiently low (confirmed by the doctor).
• Discuss with the doctor the most suitable method of contraception for the patient and any potential need to change contraceptive methods.

Do not take Bozilos while breastfeeding, as teriflunomide passes into human milk.

Driving and operating machinery
Bozilos may cause dizziness, which may impair concentration and reaction ability. Patients experiencing such symptoms should not drive or operate machinery.

Bozilos contains lactose and sodium
This medicine contains lactose (a type of sugar). If the patient has been previously diagnosed with intolerance to certain sugars, consult a doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. the medicine is considered "sodium-free".

3. How to take Bozilos

Treatment with Bozilos will be supervised by a physician experienced in the management of multiple sclerosis.
This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor.
Adults
The recommended dose is one 14 mg tablet per day.
Children and adolescents (aged 10 years and older)
The dose depends on body weight:

• Children with body weight greater than 40 kg: one 14 mg tablet per day.
• Children with body weight less than or equal to 40 kg: one 7 mg tablet per day.

Bozilos is available only in the 14 mg strength. If your doctor has prescribed 7 mg of teriflunomide per day, divide the Bozilos tablet in half along the break line and take one half, which corresponds to 7 mg. If in doubt, consult your doctor.
Children and adolescents who achieve a stable body weight above 40 kg will be informed by their doctor to change the dose to one 14 mg tablet per day.
Route and method of administration
Bozilos is administered orally. Bozilos is taken daily at any time of day as a single daily dose.
The tablets should be swallowed whole with water.
Bozilos may be taken with food or independently of meals.
Taking more Bozilos than prescribed
If more Bozilos than prescribed has been taken, contact your doctor immediately. Adverse reactions similar to those described in section 4 below may occur.
Missed dose of Bozilos
Do not take a double dose to make up for a missed tablet. Take the next dose according to the prescribed dosing schedule.
Stopping Bozilos treatment
Do not stop taking Bozilos or change the dose without first consulting your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following adverse reactions may occur after taking this medicine.
Serious adverse reactions
Some adverse reactions may be serious or may become serious. If any of the following symptoms occur, contact your doctor immediately.
Common (may affect up to 1 in 10 people)

• Pancreatitis, which may cause symptoms such as abdominal pain, nausea or vomiting (frequency is common in children and adolescents and uncommon in adult patients).

Uncommon (may affect up to 1 in 100 people)

• Allergic reactions, which may cause symptoms including rash, urticaria, swelling of the lips, tongue or face, or sudden breathing difficulties;
• Severe skin reactions, which may cause symptoms including skin rash, blisters on the skin, fever or mouth ulcers;
• Severe infections or sepsis (a type of infection potentially life-threatening), which may cause symptoms including high fever, seizures, chills, reduced urine output or confusion;
• Lung inflammation, which may cause symptoms including shortness of breath or persistent cough.

Frequency not known (frequency cannot be estimated from available data):

• Severe liver disease, which may cause symptoms including yellowing of the skin or whites of the eyes, darker than usual urine, unexplained nausea and vomiting, or abdominal pain.

Other adverse reactions may occur with the following frequency:
Very common (may affect more than 1 in 10 people)

• Headache;
• Diarrhoea, nausea;
• Increased AlAT activity (elevated levels of certain liver enzymes in blood tests);
• Hair thinning.

Common (may affect up to 1 in 10 people)

• Influenza, upper respiratory tract infection, urinary tract infection, bronchitis, sinusitis, sore throat and discomfort during swallowing, cystitis, viral gastroenteritis, tooth infection, laryngitis, fungal foot infection;
• Herpes virus infections, including cold sores and shingles, with symptoms such as blisters, burning, itching, tingling or pain in the skin, usually on one side of the upper body or face, and other symptoms such as fever and fatigue; laboratory findings: decreased number of red blood cells (anaemia), changes in liver function and white blood cell counts (see section 2), increased activity of muscle enzymes (creatine kinase) has also been observed;
• Mild allergic reactions;
• Feeling of restlessness;
• Tingling sensation, feeling of weakness, numbness, tingling or pain in the lower back or leg (sciatica), tingling, burning, numbness, tingling or pain in the hands and fingers (carpal tunnel syndrome);
• Palpitations;
• Increased blood pressure;
• Vomiting, toothache, upper abdominal pain;
• Rash, acne;
• Tendon, joint, bone pain, muscle pain (musculoskeletal pain);
• Need to urinate more often than usual;
• Heavy menstrual periods;
• Pain;
• Lack of energy or feeling of weakness (asthenia);
• Weight loss.

Uncommon (may affect up to 1 in 100 people)

• Decreased platelet count (mild thrombocytopenia);
• Increased sensitivity (especially of the skin), stabbing or pulsating pain along one or more nerves, disorders of nerves in arms or legs (peripheral neuropathy);
• Changes in nails, severe skin reactions;
• Injury-related pain;
• Psoriasis;
• Inflammation of the mouth/lips;
• Abnormal levels of fats (lipids) in the blood;
• Inflammation of the large intestine.

Rare (may affect up to 1 in 1000 people)

• Liver inflammation or damage.

Frequency not known (frequency cannot be estimated from available data)

• Pulmonary hypertension.

Children (aged 10 years and older) and adolescents
The adverse reactions listed above also apply to children and adolescents. The following additional information is important for children, adolescents and their caregivers:
Common (may affect up to 1 in 10 people)

• Pancreatitis.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department for Monitoring Adverse Drug Reactions of the 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Bozilos

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard package following: "EXP". The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
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 package and other information

What Bozilos contains

• The active substance is teriflunomide. Each tablet contains 14 mg of teriflunomide.
• The other ingredients are:
  • Tablet core: monohydrate lactose (see section 2 "Bozilos contains lactose"), corn starch, microcrystalline cellulose, hydroxypropyl cellulose, sodium carboxymethyl starch, talc, calcium stearate.
  • Tablet coating: hypromellose 2910 (6 mP), titanium dioxide (E 171), polyethylene glycol 8000, indigo carmine, aluminium lake (E 132).

What Bozilos looks like and contents of the pack
Bozilos 14 mg film-coated tablets are light blue, round, coated tablets with a score line, approximately 7 mm in diameter. The tablet can be divided into equal doses.
Aluminium/PVC/Aluminium/OPA blisters containing 14 tablets in a cardboard carton.
Pack sizes contain 28 or 84 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Importer
Marketing Authorisation Holder
Egis Pharmaceuticals PLC
Keresztúri út 30-38
1106 Budapest
Hungary

Importers
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola PLA 3000
Malta
Adalvo Ltd.
Malta Life Sciences Park
Building 1, Level 4
Sir Temi Zammit Buildings
San Ġwann SĠN 3000
Malta
KeVaRo GROUP Ltd
9 Tzaritza Elenora Str.,
Office 23,
Sofia 1618,
Bulgaria

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Iceland (RMS) Bozilos 14 mg filmuhúðaðar töflur
Bulgaria Бозилос 14 mg филмирани таблетки
Bozilos 14 mg film-coated tablets
Czech Republic Bozilos
Hungary Bozilos 14 mg filmtabletta
Latvia Bozilos 14 mg apvalkotās tabletes
Lithuania Bozilos 14 mg plėvele dengtos tabletės
Poland Bozilos
Romania Bozilos 14 mg comprimate filmate
Slovakia Bozilos 14 mg filmom obalené tablety

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
EGIS Polska Sp. z o.o.
ul. Komitetu Obrony Robotników 45 D
02-146 Warsaw
Tel.: +48 22 417 92 00