Boxarid

Patient Information Leaflet

Boxarid, 14 mg, film-coated tablets
Teriflunomide
Please read this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. 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, please tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Boxarid is and what it is used for

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

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

What is multiple sclerosis
Multiple sclerosis is a chronic disease that attacks the central nervous system. The central nervous system consists of the brain and spinal cord. In multiple sclerosis, inflammatory processes destroy the protective covering (called myelin) around the nerves in the central nervous system. This process is known as demyelination. As a result, nerves are unable to function properly.

In people with relapsing-remitting multiple sclerosis, there are repeated attacks (relapses) of physical symptoms caused by improper nerve function. 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 symptoms may persist between relapses. This may lead to physical disability, making it difficult to perform daily activities.

How Boxarid works
Boxarid 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 Boxarid

When not to take Boxarid

• 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 mucosal 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 Boxarid, discuss with your doctor or pharmacist:

• if the patient has liver function disorders and/or consumes large amounts of alcohol. The doctor may perform blood tests to check liver function before and during treatment. If test results indicate impaired liver function, the doctor may discontinue treatment with Boxarid. Refer to section 4.
• if the patient has high blood pressure (hypertension), regardless of whether it is controlled with medication or not. Boxarid may increase blood pressure. The doctor will check the patient's blood pressure before starting treatment and regularly thereafter. Refer to section 4.
• if the patient has an infection. Before administering Boxarid, the doctor will ensure the patient has adequate levels of white blood cells and platelets in the blood. Since Boxarid reduces the number of white blood cells, it may impair the ability to fight infections. The doctor may perform blood tests if the patient suspects an infection. Viral infections such as herpes virus, including cold sores or shingles, may occur during treatment with teriflunomide. Serious complications have occurred in some cases. Immediately inform the doctor if any symptoms suggestive of herpes virus infection develop. Refer to section 4.
• if the patient experiences severe skin reactions.
• if the patient has respiratory symptoms.
• if the patient experiences weakness, numbness, or pain in the hands and feet.
• if the patient intends to receive vaccination.
• if the patient is taking leflunomide together with Boxarid.
• if the patient is switching from another medication to Boxarid or from Boxarid to another medication.
• if the patient has lactose intolerance.
• if the patient is scheduled for a specific blood test (calcium level measurement). Calcium test results 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
Boxarid is not intended for use in children under 10 years of age, as it has not been studied in pediatric patients with multiple sclerosis.
The warnings and precautions listed above also apply to children and adolescents.
The following information is important for children and their caregivers:

• cases of pancreatitis have been observed in patients receiving teriflunomide. The treating physician may perform blood tests if pancreatitis is suspected.

Boxarid and other medicines
Inform the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, including over-the-counter medicines, as well as any medicines the patient plans to take.
In particular, 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 immunosuppressants or immunomodulators);
• rifampicin (used to treat tuberculosis and other infections);
• carbamazepine, phenobarbital, phenytoin, used to treat epilepsy;
• St. John's wort (an 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. to 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 for pain relief or to treat inflammatory conditions;
• 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 for inflammatory bowel disease and rheumatoid arthritis;
• cholestyramine, used in cases of elevated blood cholesterol or itching in liver disease;
• activated charcoal, used to reduce the absorption of medicines or other substances.

Pregnancy, breastfeeding, and fertility
Do not take Boxarid if the patient is pregnant or suspects she may be pregnant. Pregnant women or those who become pregnant while taking Boxarid have an increased risk of congenital malformations in the child. Women of childbearing potential who do not use effective contraception must not take this medicine.
If a girl starts menstruating while taking Boxarid, 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 Boxarid, she should inform her doctor, as it is essential to ensure 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 Boxarid from the body.
In both cases, blood testing must confirm that the active substance has been sufficiently eliminated from the body. The doctor should confirm that the blood concentration of Boxarid is low enough for the woman to become pregnant.
More information about laboratory tests can be obtained from the doctor.
If pregnancy is suspected during treatment with Boxarid or within two years after stopping treatment, discontinue Boxarid immediately and contact the doctor immediately to perform a pregnancy test. If the test confirms pregnancy, the doctor may recommend appropriate treatment to rapidly and adequately eliminate Boxarid from the body to reduce the risk to the unborn child.
Contraception
Women must use effective contraception during treatment with Boxarid and after stopping treatment. Teriflunomide remains in the blood for a long time after discontinuation.
For this reason, effective contraception must continue after stopping treatment.

• Contraception should be continued until blood levels of Boxarid are sufficiently low – this will be confirmed by the doctor.
• Discuss with the doctor the most suitable contraceptive method for the patient, and in case a change in contraceptive method is needed.

Do not take Boxarid while breastfeeding, as teriflunomide passes into human milk.
Driving and operating machinery
Boxarid may cause dizziness, which may impair the ability to concentrate and react. Patients experiencing such symptoms should not drive or operate machinery.
Boxarid contains lactose
Boxarid contains lactose (a type of sugar). If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking this medicine.
Boxarid contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to take Boxarid

Treatment with Boxarid will be supervised by a physician experienced in the treatment of multiple sclerosis.
This medicine should always be taken exactly as prescribed by the physician. In case of doubt, consult your doctor.

Adults
The recommended dose is one 14 mg tablet daily.

Use in 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 daily.
• Children with body weight less than or equal to 40 kg: one 7 mg tablet daily. The 7 mg strength of Boxarid is not available; therefore, other medicinal products containing 7 mg of teriflunomide should be used. Children and adolescents who reach a stable body weight above 40 kg will be informed by the physician to change the dose to one 14 mg tablet daily.

Route and method of administration
Boxarid is administered orally. Boxarid is taken once daily at any time of day as a single daily dose. Tablets should be swallowed whole with water.
Boxarid may be taken with food or independently of meals.

Taking more Boxarid than prescribed
If more Boxarid than prescribed has been taken, contact your doctor immediately. Adverse reactions similar to those described in section 4 below may occur.

Missed dose of Boxarid
Do not take a double dose to make up for a missed tablet. Take the next dose according to the prescribed dosing schedule.

Stopping Boxarid treatment
Do not stop taking Boxarid 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 using this medicine.
Severe adverse reactions
Some adverse reactions may be severe or may become severe. If any of the following symptoms occur, seek medical advice immediately.

Common (may occur in 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 occur in 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 potentially life-threatening infection), which may cause symptoms including high fever, convulsions, chills, reduced urine output or confusion;
• Pneumonitis, 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 normal urine, unexplained nausea and vomiting, or abdominal pain.

Other adverse reactions may occur with the following frequency:

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

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

Common (may occur in 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, dental infection, laryngitis, fungal foot infection;
• Herpes virus infections, including cold sores and shingles, with symptoms such as blisters, burning, itching, numbness or pain in the skin, usually on one side of the upper body or face, and other symptoms such as fever and fatigue;
• Laboratory test results: decreased number of red blood cells (anaemia), changes in the liver and white blood cell counts (see section 2), increased activity of muscle enzymes (creatine kinase) has also been observed;
• Mild allergic reactions;
• Feeling anxious;
• Tingling sensation, feeling of weakness, numbness, tingling or pain in the lower back or leg (sciatica), sensation of numbness, burning, tingling or pain in the hands and fingers (carpal tunnel syndrome);
• Palpitations;
• Increased blood pressure;
• Vomiting, toothache, epigastric pain;
• Rash, acne;
• Pain in tendons, joints, bones, muscle pain (musculoskeletal pain);
• Need to urinate more often than usual;
• Heavy menstrual periods;
• Pain;
• Lack of energy or feeling weak (asthenia);
• Decreased body weight.

Uncommon (may occur in up to 1 in 100 people)

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

Rare (may occur in up to 1 in 1000 people)

• Inflammation or damage to the liver.

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 occur in 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 a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products, 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 authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Boxarid

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box and folding carton after: "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 will help protect the environment.

6. Contents of the packaging and other information

What Boxarid contains

• The active substance is teriflunomide. Each tablet contains 14 mg of teriflunomide.
• The other ingredients are: hydroxypropylcellulose, monohydrate lactose, maize starch, microcrystalline cellulose, sodium carboxymethyl starch (type A), magnesium stearate, hypromellose, titanium dioxide (E 171), macrogol 8000, colloidal anhydrous silica, indigo carmine, aluminium lake (E 132).

What Boxarid looks like and contents of the pack
Boxarid 14 mg film-coated tablets are pale blue to pastel blue, pentagonal 7.3 mm coated tablets, embossed with the code "14" on one side and smooth on the other (thickness: 3.5 mm – 4.1 mm).
Boxarid is available in cardboard boxes containing:

• 14 or 28 film-coated tablets in blisters;
• 14, 28, 84 and 98 film-coated tablets in blisters, placed in folding cartons;
• 10x1 film-coated tablet in perforated single-dose blisters.

Not all pack sizes may be marketed.
Marketing Authorisation Holder
Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest
Hungary
Manufacturer/Importer
Pharmascience International Ltd.
1st floor Iacovides Tower
81-83 Griva Digeni Avenue
1090 Nicosia
Cyprus
GE Pharmaceuticals Ltd.
Industrial Zone
Chekanitza South area
2140 Botevgrad
Bulgaria
Gedeon Richter Plc.
Gyömrői út 19-21.
H-1103 Budapest
Hungary
This medicinal product is authorised in the European Economic Area countries under the following names:
Bulgaria Boxarid 14 mg film-coated tablets
Czech Republic Boxarid
Estonia BOXARID
Lithuania BOXARID 14 mg plėvele dengtos tabletės
Latvia Boxarid 14 mg apvalkotās tabletes
Poland Boxarid
Romania BOXARID 14 mg comprimate filmate
Slovakia BOXARID 14 mg Filmom obalená tableta
Hungary BOXARID 14 mg filmtabletta
For further information about this medicinal product, please contact:
Gedeon Richter Polska Sp. z o.o.
Medical Department
ul. Ks. J. Poniatowskiego 5
05-825 Grodzisk Mazowiecki
tel.: +48 (22) 755 96 48
[email protected]