Boxarid

Leaflet accompanying the packaging: patient information

Boxarid, 14 mg, coated tablets

Teriflunomide

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

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it 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 side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Boxarid and what is it used for
• 2. Important information 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 is Boxarid and what is it used for

What is Boxarid

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

What is Boxarid used for

Boxarid is used to treat adults and children and adolescents (aged 10 years and older) with multiple sclerosis (MS) 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 a relapse, but over time, some problems may persist between relapses. This can lead to physical disability that makes it difficult to perform daily activities.

How Boxarid works

Boxarid 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 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 a severe skin rash or peeling of the skin 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 white blood cell or platelet count,
• if the patient has a severe infection,
• if the patient has severe kidney disease requiring dialysis,
• if the patient has very low blood protein levels (hypoproteinemia).

In case of doubt, the patient should consult a doctor or pharmacist before taking this medicine.

Warnings and precautions

Before starting treatment with Boxarid, the patient should discuss the following with their doctor or pharmacist:

• if the patient has liver function disorders and/or 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 Boxarid. The patient should see section 4.
• if the patient has high blood pressure, whether or not it is controlled with medication. Boxarid may cause an increase in blood pressure. The doctor will check the patient's blood pressure before starting treatment and then regularly during treatment. The patient should see section 4.
• if the patient has an infection. Before taking Boxarid, the doctor will make sure the patient has a sufficient number of white blood cells and platelets in their blood. Because Boxarid 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 white blood cell count 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 patient should immediately inform their doctor if they suspect they have any symptoms of a herpes virus infection. The patient should see section 4.
• if the patient has severe skin reactions.
• if the patient has respiratory symptoms.
• if the patient has weakness, numbness, and pain in their hands and feet.
• if the patient is going to be vaccinated.
• if the patient is taking leflunomide with Boxarid.
• if the patient is switching from their current medicine to Boxarid or from Boxarid to another medicine.
• if the patient has lactose intolerance.
• if the patient is going to have a specific blood test (calcium level measurement). The results of the calcium level measurement may be falsely low.

Respiratory reactions

The patient should inform their doctor if they experience unexplained coughing and shortness of breath. 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 this age group with multiple sclerosis. The warnings and precautions mentioned above also apply to children and adolescents. The following information is important for children, adolescents, and their caregivers:

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

Boxarid and other medicines

The patient should tell their doctor or pharmacist about all medicines they are taking, have recently taken, or might take, including those obtained without a prescription. In particular, the patient should inform their doctor or pharmacist if they are 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, an anticoagulant used to thin the blood (i.e., to make it more fluid) to prevent blood clots;
• oral contraceptives (containing ethinyl estradiol and levonorgestrel);
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin, used to treat infections;
• indomethacin, ketoprofen, used as painkillers or to treat inflammation;
• 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 disease;
• activated charcoal, used to reduce the absorption of medicines or other substances.

Pregnancy, breastfeeding, and fertility

Boxarid must not be taken if the patient is pregnant or thinks they may be pregnant. In pregnant women or those who become pregnant while taking Boxarid, there is an increased risk of birth defects in the baby. Women of childbearing age who are not using effective contraception must not take this medicine. If a girl starts menstruating while taking Boxarid, 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 Boxarid, 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 Boxarid 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 Boxarid in the blood is low enough for the woman to become pregnant. More information on laboratory tests can be obtained from the doctor. If there is a suspicion that the woman has become pregnant while taking Boxarid or within two years after stopping treatment, the patient should stop taking Boxarid and immediately contact their doctor to 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 Boxarid from the body. Contraception During and after treatment with Boxarid, women should use effective contraception. Teriflunomide remains in the blood for a long time after stopping treatment. For this reason, effective contraception should still be used after stopping treatment.

• This method should be used until the level of Boxarid in the blood is low enough - the doctor will check this.
• The patient should discuss with their doctor the best method of contraception for them and any need to change the method of contraception.

Boxarid must not be taken during breastfeeding, as teriflunomide passes into human milk.

Driving and using machines

Boxarid may cause dizziness, which can affect concentration and reaction time. Patients who experience these 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 some sugars, they should contact their doctor before taking this medicine.

Boxarid contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means it is essentially 'sodium-free'.

3. How to take Boxarid

Treatment with Boxarid 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 patient should consult their doctor. AdultsThe recommended dose is one 14 mg tablet per day.

Use in 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. Boxarid 7 mg is not available, so other teriflunomide 7 mg products should be used. Children and adolescents who reach a stable body weight above 40 kg will be informed by their doctor to switch to one 14 mg tablet per day.

Route and method of administration Boxarid is taken orally. Boxarid is taken once daily at any time of day as a single dose. The tablets should be swallowed whole with water. Boxarid can be taken with or without food.

If more Boxarid than recommended is taken

If more Boxarid than recommended is taken, the patient should immediately contact their doctor. Side effects similar to those described in section 4 may occur.

Missing a dose of Boxarid

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

Stopping treatment with Boxarid

The patient should not stop taking Boxarid or change the dose without first consulting their doctor. If the patient has any further doubts about the use of this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Boxarid 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 the following symptoms occur, the patient should immediatelyconsult their doctor. Frequent(may affect up to 1 in 10 people)

• pancreatitis, which may cause symptoms such as abdominal pain, nausea, or vomiting (frequency of occurrence is frequent 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 rash, blisters on the skin, fever, or ulcers in the mouth;
• severe infections or sepsis (a type of infection that can be life-threatening), 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 effects may occur with the following frequency:

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

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

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 on the skin, usually on one side of the upper body or face, as well as other symptoms such as fever and weakness;
• blood test results: reduced 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 of tingling, feeling of weakness, numbness, tingling, or pain in the lower back or leg (sciatica), feeling of numbness, burning, tingling, or pain in the hands and fingers (carpal tunnel syndrome);
• feeling of "heart pounding";
• increased blood pressure;
• vomiting, toothache, abdominal pain;
• rash, acne;
• tendon, joint, bone, muscle pain (musculoskeletal pain);
• need to urinate more often than usual;
• heavy menstrual periods;
• pain;
• lack of energy or feeling weak (asthenia);
• weight loss. Uncommon(may affect up to 1 in 100 people)
• reduced 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 fat (lipid) levels;
• colitis. Rare(may affect up to 1 in 1,000 people)
• liver inflammation or damage. Frequency not known(frequency cannot be estimated from the available data)
• 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:

• pancreatitis.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. 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, 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 to the marketing authorization holder. By reporting side effects, more information can be gathered on the safety of the medicine.

5. How to store Boxarid

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 and blister packaging after "EXP". The expiry date refers to the last day of the month stated. There are no special storage instructions for this medicine. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist 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 Boxarid contains

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

What Boxarid looks like and contents of the pack

Boxarid 14 mg, coated tablets are pentagonal 7.3 mm tablets, coated in a light blue to pale blue color with the marking "14" on one side and smooth on the other side (thickness: 3.5 mm - 4.1 mm). Boxarid is available in cartons containing:

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

Not all pack sizes may be marketed.

Marketing authorization 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 medicine is authorized in the Member States of the European Economic Area 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 more information on this medicine, the patient should 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, lekalert@grodzisk.rgnet.org

Date of last revision of the leaflet: October 2024