Clefirem

Leaflet attached to the packaging: patient information

CLEFIREM, 14 mg, coated tablets

teriflunomide

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

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your 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 Clefirem and what is it used for
• 2. Important information before taking Clefirem
• 3. How to take Clefirem
• 4. Possible side effects
• 5. How to store Clefirem
• 6. Contents of the pack and other information

1. What is Clefirem and what is it used for

What is Clefirem

Clefirem contains the active substance teriflunomide, which is an immunomodulating medicine that regulates the immune system to limit its attack on the nervous system.

What is Clefirem used for

Clefirem is used to treat adults and children and adolescents (aged 10 years and older, weighing over 40 kg) 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) of the nerves in the central nervous system. This process is called demyelination. It disrupts the normal functioning of the nerves. 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 Clefirem works

Clefirem 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 Clefirem

When not to take Clefirem:

• 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 had 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 immune system disorders, such as AIDS;
• if the patient has any severe bone marrow 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 requiring dialysis;
• if the patient has very low blood protein levels (hypoproteinemia). If in doubt, consult your doctor or pharmacist before taking this medicine.

Warnings and precautions

Before starting Clefirem, discuss with your doctor or pharmacist if:

• the patient has liver problems and/or drinks large amounts of alcohol; the doctor may perform blood tests to check if the liver is working properly before and during treatment. If the patient's test results show liver problems, the doctor may stop Clefirem. Refer to section 4.
• 4.
• the patient has high blood pressure, whether or not it is controlled with medication. Clefirem may increase blood pressure. The doctor will check the patient's blood pressure before starting treatment and regularly during treatment. Refer to section 4.
• the patient has an infection. Before taking Clefirem, the doctor will ensure the patient has a sufficient number of white blood cells and platelets in their blood. Since Clefirem 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 suspects they have an infection. During treatment with teriflunomide, viral infections such as herpes simplex 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 viral infection. Refer to section 4.
• the patient has severe skin reactions.
• the patient has respiratory symptoms.
• the patient has weakness, numbness, and pain in their hands and feet.
• the patient is planning to receive a vaccination.
• the patient is taking leflunomide with Clefirem.
• the patient is switching from their current medicine to Clefirem or from Clefirem to another medicine.
• the patient needs to have a specific blood test (calcium level measurement). The results of the calcium level test may be falsely low.

Respiratory reactions

The patient should inform their doctor if they experience unexplained coughing or shortness of breath (difficulty breathing). The doctor may perform additional tests.

Children and adolescents

Clefirem 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 and their caregivers:

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

Clefirem and other medicines

The patient should tell their doctor or pharmacist about all medicines they are taking, have recently taken, or plan to 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., 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 disease;
• activated charcoal, used to reduce the absorption of medicines or other substances.

Pregnancy and breastfeeding

Clefirem should not be taken if the patient is pregnant or thinks they may be pregnant. In pregnant women or those who become pregnant while taking Clefirem, there is an increased risk of birth defects in the child. Women of childbearing age who do not use effective contraception should not take this medicine. If a girl starts menstruating while taking Clefirem, 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 Clefirem, she should inform her doctor, as it is essential to ensure that the medicine is no longer in the body before trying to conceive. 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 Clefirem 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 Clefirem in the blood is low enough for the woman to become pregnant.
More information on laboratory tests can be obtained from the treating doctor.
If a woman suspects she has become pregnant while taking Clefirem or within two years after stopping treatment, she should stop taking Clefirem and immediately contact her doctor to perform a pregnancy test. If the test confirms pregnancy, the doctor may suggest using certain medicines to quickly and sufficiently remove Clefirem from the body.
Contraception
During and after taking Clefirem, women should use effective contraception. Teriflunomide remains in the blood for a long time after stopping treatment. Therefore, effective contraception should still be used after stopping treatment.

• This method should be used until the level of teriflunomide in the blood is low enough (checked by the doctor).
• The patient should discuss with their doctor the best contraceptive method for them and any potential need to change the contraceptive method.

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

Driving and using machines

Clefirem may cause dizziness, which can affect concentration and reaction time. Patients who experience these symptoms should not drive or operate machinery.

Clefirem contains lactose

Clefirem 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.

Clefirem 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 Clefirem

The use of Clefirem 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, consult the doctor.

Adults, children, and adolescents (aged 10 years and older, weighing over 40 kg)

The recommended dose is one 14 mg tablet per day.
Route and method of administration
Clefirem is administered orally. Clefirem is taken once daily at any time of day as a single daily dose.
The tablets should be swallowed whole with water. The tablets should not be divided, crushed, or chewed, as this may alter the amount of medicine absorbed.

Taking a higher dose of Clefirem than recommended

In case of taking a higher dose of Clefirem than recommended, the patient should immediately contact their doctor. Side effects similar to those described in section 4 below may occur.

Missing a dose of Clefirem

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 Clefirem

The patient should not stop taking Clefirem 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, Clefirem 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 the patient experiences any of these symptoms, they should immediately inform their doctor.
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 adults).

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

Common(may affect up to 1 in 10 people)

• 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, and other symptoms such as fever and weakness;
• flu, upper respiratory tract infections, urinary tract infections, bronchitis, sinusitis, sore throat and discomfort when swallowing, cystitis, viral gastroenteritis, tooth infection, laryngitis, fungal foot infection;
• laboratory 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;
• tingling, feeling weak, numbness, 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 of "heart pounding";
• increased blood pressure;
• vomiting, toothache, abdominal pain;
• rash, acne;
• tendon, joint, bone, muscle pain (musculoskeletal pain);
• need to urinate more frequently than usual;
• heavy menstrual bleeding;
• 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 in the arms or legs (peripheral neuropathy);
• changes in the nails, severe skin reactions;
• trauma-related pain;
• psoriasis;
• mouth sores;
• 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 side effects occur, including any side effects not listed in this leaflet, the patient 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.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Clefirem

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack 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 patient should ask their pharmacist how to dispose of medicines they no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Clefirem contains

The active substance of Clefirem is teriflunomide.
Clefirem 14 mg coated tablets

• Each tablet contains 14 mg of teriflunomide.
• The other ingredients are: lactose monohydrate, cornstarch, microcrystalline cellulose (E 460), sodium carboxymethyl cellulose (type A), hydroxypropyl cellulose (E 463), magnesium stearate (E 407B), colloidal silicon dioxide, hypromellose, titanium dioxide (E 171), indigo carmine, aluminum lake (E132), triacetin (E 1518) (see section 2 "Clefirem contains lactose").

What Clefirem looks like and contents of the pack

Clefirem 14 mg coated tablets are light blue, round, biconvex, film-coated tablets with a diameter of approximately 7.1 mm, smooth on both sides.
Clefirem 14 mg coated tablets are available in aluminum blisters packaged in cartons containing 28 or 84 film-coated tablets.
Not all pack sizes may be marketed.

Marketing authorization holder

Bausch Health Ireland Limited
3013 Lake Drive, Citywest Business Campus
Dublin 24, D24PPT3
Ireland
Tel.: +48 17 865 51 00

Importer

Bausch Health Poland Sp. z.o.o.
Ul. Kosztowska 21
41-409 Mysłowice
Poland
Bausch Health Poland Sp. z.o.o.
Ul. Przemysłowa 2
35-959 Rzeszów
Poland
Date of last revision of the leaflet:July 2024