Bozilos

Leaflet accompanying the packaging: patient information

Bozilos, 14 mg, coated tablets

Teriflunomide

Read the contents of the leaflet carefully before taking the medicine, as it contains important information for the patient.

• This leaflet should be kept in case it needs to be read again.
• In case of any doubts, the doctor or pharmacist should be consulted.
• This medicine has been prescribed specifically for one person. It should not be passed on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Bozilos and what is it 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 is Bozilos and what is it used for

What is Bozilos

Bozilos contains the active substance teriflunomide, which is an immunomodulating agent regulating the immune system to limit its attack on the nervous system.

What is Bozilos used for

Bozilos is used to treat adults and children and adolescents (aged 10 years and older) with multiple sclerosis with a relapsing-remitting course.

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 called demyelination. It prevents the nerves from functioning properly. In people with multiple sclerosis with a relapsing course, there are recurring attacks (relapses) of physical symptoms caused by the abnormal functioning of the nerves. These symptoms vary from person to person but usually include:

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

These symptoms may completely disappear after the relapse has resolved, but over time, some problems may persist between relapses. This can lead to physical disability that makes it difficult to perform daily activities.

How Bozilos works

Bozilos helps protect the central nervous system from the effects of the immune system by limiting the increase in the number of certain white blood cells (lymphocytes). This reduces inflammation, which in people 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 a severe skin rash or peeling, blisters, or mouth sores after taking teriflunomide or leflunomide;
• if the patient has severe liver disease;
• if the patient is pregnant, thinks they may be pregnant, or is breastfeeding;
• if the patient has any severe diseases that affect the immune system, such as acquired immune deficiency syndrome (AIDS);
• if the patient has any severe blood disorders or has a low number of red or white blood cells or platelets;
• if the patient has a severe infection;
• if the patient has severe kidney disease that requires dialysis;
• if the patient has very low protein levels in the blood (hypoproteinemia). In case of doubt, the doctor or pharmacist should be consulted before taking this medicine.

Warnings and precautions

Before starting to take Bozilos, the doctor or pharmacist should be consulted if:

• the patient has liver function disorders and/or the patient drinks large amounts of alcohol; the doctor may perform blood tests to check if liver function is normal before and during treatment. If the patient's test results show liver function disorders, the doctor may stop the use of Bozilos. See section 4.
• the patient has high blood pressure, regardless of whether it is controlled with medication or not. Bozilos may cause an increase in blood pressure. The doctor will check the patient's blood pressure before starting treatment and then regularly during treatment. See section 4.
• the patient has an infection. Before taking Bozilos, the doctor will make sure the patient has a sufficient number of white blood cells and platelets in the blood. Because Bozilos reduces the number of white blood cells in the blood, it may affect the ability to fight infections. The doctor may perform a blood test to check the number of white blood cells if the patient thinks they have an infection. During treatment with teriflunomide, herpes virus infections, including cold sores or shingles, may occur. In some cases, serious complications have occurred. The doctor should be informed immediately if there is any suspicion of herpes virus infection. See section 4.
• the patient has severe skin reactions.
• the patient has respiratory symptoms.
• the patient has weakness, numbness, and pain in the hands and feet.
• the patient is going to be vaccinated.
• the patient is taking leflunomide with Bozilos.
• the patient is switching from their current medicine to Bozilos or from Bozilos to another medicine.
• the patient is going to have a specific blood test (calcium level measurement). The results of the calcium level measurement may be falsely lowered.

Respiratory reactions

The doctor should be informed if the patient experiences a cough of unknown origin and 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 this age group with multiple sclerosis. The warnings and precautions mentioned above also apply to children. The following information is important for children, adolescents, and their caregivers:

• cases of pancreatitis have been observed in patients taking teriflunomide. The doctor may perform blood tests if they suspect pancreatitis.

Bozilos and other medicines

The doctor or pharmacist should be told about all medicines the patient is taking, has recently taken, or might take, including those obtained without a prescription. In particular, the doctor or pharmacist should be informed if the patient is taking any of the following medicines:

• leflunomide, methotrexate, and other medicines that affect the immune system (often called immunosuppressive or immunomodulating medicines);
• rifampicin (used to treat tuberculosis and other infections);
• carbamazepine, phenobarbital, phenytoin, used to treat epilepsy;
• St. John's Wort (a herbal medicine 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 diabetic neuropathy;
• alosetron, used to treat severe diarrhea;
• theophylline, used to treat asthma;
• tizanidine (a muscle relaxant);
• warfarin (a blood thinner) 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 disease;
• cimetidine, used to reduce stomach acid production;
• zidovudine, used to treat HIV infections;
• rosuvastatin, simvastatin, atorvastatin, pravastatin, used to treat high cholesterol;
• sulfasalazine, used to treat inflammatory bowel disease and rheumatoid arthritis;
• cholestyramine, used to treat high cholesterol or itching in liver diseases;
• activated charcoal, used to reduce the absorption of medicines or other substances.

Pregnancy and breastfeeding

Do nottake Bozilos if the patient is pregnantor thinks they may be pregnant. In pregnant women or those who become pregnant while taking Bozilos, there is an increased risk of birth defects in the baby. Women of childbearing age who do not use effective contraception should not take this medicine. If a girl starts menstruating while taking Bozilos, she should inform her doctor, who will provide specialized advice on 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 in the body before trying to become pregnant. The elimination of the active substance may take up to 2 years. This period can be shortened to a few weeks by taking certain medicines that accelerate the removal of Bozilos from the body. In both cases, it should be confirmed by a blood test that the active substance has been sufficiently removed from the body. The doctor should confirm that the level of Bozilos in the blood is low enough for the woman to become pregnant. More information about laboratory tests can be obtained from the doctor. If there is a suspicion that the woman has become pregnant while taking Bozilos or within two years after stopping treatment, Bozilos should be discontinued and the doctor should be contacted immediatelyto perform a pregnancy test. If the test confirms that the woman is pregnant, the doctor may suggest using certain medicines to quickly and sufficiently remove Bozilos from the body. Contraception During and after taking Bozilos, women should use effective contraception. Teriflunomide remains in the blood for a long time after stopping treatment. Therefore, effective contraception should continue to be used after stopping treatment.

• This method should be used until the level of Bozilos in the blood is low enough (the doctor will check this).
• The doctor should be consulted about the best method of contraception for the patient and in case of a need to change the method of contraception.

Bozilos should not be taken during breastfeeding, as teriflunomide passes into human milk.

Driving and using machines

Bozilos may cause dizziness, which can affect concentration and reaction time. Patients who experience these 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 diagnosed with intolerance to some sugars, they should contact their doctor before taking this medicine. This medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means it is considered "sodium-free".

3. How to take Bozilos

The use of Bozilos will be supervised by a doctor experienced in treating multiple sclerosis. This medicine should always be taken exactly as prescribed by the doctor. In case of doubt, the doctor should be consulted.

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 a body weight over 40 kg: one 14 mg tablet per day.
• Children with a body weight of 40 kg or less: one 7 mg tablet per day.

Bozilos is only available in 14 mg strength. If the doctor has prescribed 7 mgof teriflunomide per day, the Bozilos tablet should be divided into two halves along the score line and one half of the tablet taken, which corresponds to 7 mg. In case of doubt, the doctor should be consulted.Children and adolescents who reach a stable body weight above 40 kg will be informed by their doctor about changing the dose to one 14 mg tablet per day. Route and method of administration Bozilos is taken orally. Bozilos is taken once daily at any time of day as a single dose.

Taking a higher dose of Bozilos than recommended

In case of taking a higher dose of Bozilos than recommended, the doctor should be contacted immediately. Side effects similar to those described in section 4 below may occur.

Missing a dose of Bozilos

A double dose should not be taken to make up for a missed tablet. The next dose should be taken as scheduled.

Stopping treatment with Bozilos

Treatment with Bozilos should not be stopped or the dose changed without prior consultation with the doctor. In case of any further doubts about the use of this medicine, the doctor or pharmacist should be consulted.

4. Possible side effects

Like all medicines, Bozilos can cause side effects, although not everybody gets them. The following side effects may occur after taking this medicine.

Severe side effects

Some side effects may be severe or become severe if any of these symptoms occur, the doctor should be informed immediately.

Very common (may affect up to 1 in 10 people)

• pancreatitis, which may cause symptoms such as abdominal pain, nausea, or vomiting (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, hives, swelling of the lips, tongue, or face, or sudden difficulty breathing;
• severe skin reactions, which may cause symptoms, including skin rash, blisters, fever, or mouth sores;
• severe infections or sepsis (a life-threatening infection), which may cause symptoms, including high fever, chills, shivering, reduced urine output, or disorientation;
• pneumonia, which may cause symptoms, including shortness of breath or persistent cough.

Frequency not known(frequency cannot be estimated from the 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 side effectsmay occur with the following frequency:

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

• headache;
• diarrhea, nausea;
• increased ALT activity (increased activity of certain liver enzymes in the blood) shown in tests;
• hair loss.

Common (may affect up to 1 in 10 people)

• flu, upper respiratory tract infection, urinary tract infection, bronchitis, sinusitis, sore throat and discomfort when 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, numbness, or pain of the skin, usually on one side of the upper body or face, and other symptoms such as fever and weakness; laboratory test results: decreased red blood cell count (anemia), changes in liver function and white blood cell count (see section 2), also increased muscle enzyme activity (creatine kinase);
• mild allergic reactions;
• feeling anxious;
• feeling numb, weak, tingling, or pain in the lower back or leg (sciatica), feeling numb, burning, tingling, or pain in the hands and fingers (carpal tunnel syndrome);
• feeling "heart pounding";
• increased blood pressure;
• vomiting, toothache, abdominal pain;
• rash, acne;
• tendon, joint, bone, or muscle pain (musculoskeletal pain);
• need to urinate more often than usual;
• heavy menstrual bleeding;
• pain;
• lack of energy or feeling weak (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, nerve disorders of the arms or legs (peripheral neuropathy);
• changes in the nails, severe skin reactions;
• traumatic pain;
• psoriasis;
• mouth ulcers;
• abnormal blood lipid levels;
• colitis.

Rare (may affect up to 1 in 1000 people)

• liver inflammation or damage.

Frequency not known

• pulmonary hypertension.

Children (aged 10 years and older) and adolescents

The above side effects 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 side effects

If any side effects occur, including any not listed in this leaflet, the doctor or pharmacist should be informed. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Jerozolimskie Avenue 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 to the marketing authorization holder. By reporting side effects, more information can be gathered on the safety of the medicine.

5. How to store Bozilos

The medicine should be stored out of sight and reach of children. This medicine should not be used after the expiry date stated on the carton after "EXP". The expiry date refers to the last day of the month. There are no special storage instructions for this medicine. Medicines should not be disposed of via wastewater or household waste. The pharmacist should be asked how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Bozilos contains

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

What Bozilos looks like and contents of the pack

Bozilos, 14 mg, 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. Blisters of aluminum/PVC/aluminum/OPA containing 14 tablets in a carton. The pack contains 28 or 84 coated tablets. Not all pack sizes may be marketed.

Marketing authorization holder and importer

Marketing authorization holder

Egis Pharmaceuticals PLC, Keresztúri út 30-38, 1106 Budapest, Hungary

Importer

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 medicine is authorized in the Member States of the European Economic Area under the following names:

Iceland (RMS), Bozilos 14 mg film-coated tablets, 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 more detailed information on this medicine, the local representative of the marketing authorization holder should be contacted: EGIS Polska Sp. z o.o., ul. Komitetu Obrony Robotników 45 D, 02-146 Warsaw, Tel.: +48 22 417 92 00, Date of last revision of the leaflet:2.08.2024