CLEFIREM 14 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Clefirem 14 mgfilm-coated tablets

teriflunomide

Read all of this leaflet carefully before you start 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 you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Clefirem and what is it used for
2. What you need to know before you take Clefirem
3. How to take Clefirem
4. Possible side effects
5. Storage of 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 immunomodulatory agent that adjusts the immune system to limit its attack on the nervous system.

What Clefirem is used for

Teriflunomide is used in adults and in children and adolescents (10 years of age and older, weighing over 40 kg) to treat relapsing-remitting multiple sclerosis (MS).

What is multiple sclerosis

MS is a long-term disease that affects the central nervous system (CNS). The CNS is made up of the brain and spinal cord. In multiple sclerosis, inflammation destroys the protective sheath (myelin) that surrounds the nerves of the CNS. This loss of myelin is called demyelination. This makes the nerves stop working properly.

People with the relapsing form of multiple sclerosis will have repeated attacks (relapses) of physical symptoms caused by the poor functioning of the nerves. These symptoms vary from person to person but usually include:

• difficulty walking
• vision problems
• balance problems

The symptoms can disappear completely after a relapse, but over time, some problems may remain. This can cause physical disabilities that can interfere with daily activities.

How Clefirem works

Teriflunomide helps protect against attacks on the central nervous system by the immune system, limiting the growth of some white blood cells (lymphocytes). This limits the inflammation that causes nerve damage in MS.

2. What you need to know before you take Clefirem

Do not takeClefirem

• if you are allergic to teriflunomide or any of the other ingredients of this medicine (listed in section 6)
• if you have ever developed a severe skin rash or peeling of the skin, blisters, and/or ulcers in the mouth after taking teriflunomide or leflunomide
• if you have severe liver problems
• if you are pregnant, think you may be pregnant, or are breast-feeding
• if you have a serious immune system problem, such as acquired immune deficiency syndrome (AIDS)
• if you have serious bone marrow problems or a low number of white blood cells, red blood cells, or platelets in your blood
• if you have a serious infection
• if you have severe kidney problems that require dialysis
• if you have a low level of proteins in your blood (hypoproteinemia)

In case of doubt, ask your doctor or pharmacist before taking this medicine.

Warnings and precautions

Tell your doctor or pharmacist before starting teriflunomide if:

• you have liver problems and/or if you drink large amounts of alcohol. Your doctor may perform blood tests to check your liver function before and during treatment. If the test results indicate a liver problem, your doctor may stop treatment with teriflunomide. See section 4.
• you have high blood pressure (hypertension), whether or not you are being treated for it. Teriflunomide may cause an increase in blood pressure. Your doctor will check your blood pressure before starting treatment and regularly during treatment. See section 4.
• you have an infection. Before you start taking teriflunomide, your doctor will make sure you have enough white blood cells and platelets in your blood. Since teriflunomide decreases the number of white blood cells in the blood, this may affect your ability to fight infection. Your doctor may perform blood tests to check your white blood cells if they think you have any infection. With teriflunomide treatment, viral infections such as oral or genital herpes (shingles) may occur. In some cases, serious complications have occurred. You should immediately inform your doctor if you suspect you have any symptoms of viral infection. See section 4.
• you have severe skin reactions.
• you have respiratory symptoms.
• you have weakness, numbness, and pain in hands and feet.
• you are going to be vaccinated.
• you are taking leflunomide with teriflunomide.
• you are being switched from or to teriflunomide.
• a specific blood test (calcium level) is scheduled. A false decrease in calcium levels may be detected.

Respiratory reactions

Tell your doctor if you have unexplained cough and shortness of breath. Your doctor may perform additional tests.

Children and adolescents

Teriflunomide is not indicated for use in children under 10 years of age, as it has not been studied in patients with MS in this age group.

The warnings and precautions listed above also apply to children. The following information is important for children and their caregivers:

• pancreatitis has been observed in patients receiving teriflunomide. Your child's doctor may perform blood tests if they suspect pancreatitis.

Other medicines and Clefirem

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines without a prescription.

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

• leflunomide, methotrexate, and other medicines that affect the immune system (often referred to as immunosuppressants or immunomodulators)
• rifampicin (a medicine used to treat tuberculosis and other infections)
• carbamazepine, phenobarbital, phenytoin for epilepsy
• St. John's Wort (a herbal medicine for depression)
• repaglinide, pioglitazone, nateglinide, or rosiglitazone for diabetes
• daunorubicin, doxorubicin, paclitaxel, or topotecan for cancer
• duloxetine for depression, urinary incontinence, or diabetic neuropathy
• alosetron for severe diarrhea
• theophylline for asthma
• tizanidine, a muscle relaxant
• warfarin, an anticoagulant to thin the blood (make it more fluid) and prevent clots
• oral contraceptives (ethinylestradiol, levonorgestrel)
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin for infections
• indomethacin, ketoprofen for pain or inflammation
• furosemide for heart disease
• cimetidine to reduce stomach acid
• zidovudine for AIDS
• rosuvastatin, simvastatin, atorvastatin, pravastatin for high cholesterol
• sulfasalazine for inflammatory bowel disease or rheumatoid arthritis
• cholestyramine for high cholesterol or relief of itching in liver disease
• activated charcoal to reduce the absorption of medicines or other substances

Pregnancy and breast-feeding

Do not take teriflunomide if you are pregnant or think you may be pregnant. If you are pregnant or become pregnant while taking teriflunomide, there is an increased risk of having a baby with birth defects. Women of childbearing age must not take this medicine if they are not using reliable contraceptive methods.

If your daughter has her first period while taking teriflunomide, she must inform her doctor, who will provide specialized advice on contraceptive methods and potential risks in case of pregnancy.

Tell your doctor if you plan to become pregnant after stopping treatment with this medicine, as you need to make sure that most of the medicine has been eliminated from your body before trying to become pregnant. The natural elimination of the active substance may take up to 2 years. This period can be reduced to a few weeks by taking certain medicines to accelerate the elimination of teriflunomide from the body. In any case, you need your doctor to confirm, based on a blood test, that the level of active substance in your blood is low enough for you to become pregnant.

For more information on laboratory tests, contact your doctor.

If you suspect you are pregnant while taking teriflunomide or in the 2 years following treatment, you must stop taking teriflunomide and contact your doctor immediately for a pregnancy test. If the test confirms pregnancy, your doctor may suggest treatment with certain medicines to eliminate teriflunomide from your body quickly, as this may reduce the risk to your baby.

Contraception

You must use an effective contraceptive method during and after treatment with this medicine. Teriflunomide remains in the blood for a long time after stopping treatment. Continue to take contraceptive measures after stopping treatment.

• Continue to do so until the levels of teriflunomide in your blood are low enough (your doctor will check this).
• Ask your doctor about the best contraceptive method for you and in case you need to change methods.

Do not take this medicine during breast-feeding, as teriflunomide passes into breast milk.

Driving and using machines

Teriflunomide may cause dizziness, which may affect your ability to concentrate and react. If you are affected, do not drive or use machines.

Clefirem contains lactose

This medicine contains lactose (a type of sugar). If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

Clefirem contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially "sodium-free".

3. How to take Clefirem

A doctor with experience in treating multiple sclerosis will supervise treatment with teriflunomide.

Follow the instructions for administration of this medicine exactly as prescribed by your doctor. If you are unsure, consult your doctor again.

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

The recommended dose is one 14 mg tablet per day.

Form/Route of Administration

Teriflunomide is administered orally. This medicine is taken once daily, at any time of day.

Swallow the tablet whole with a little water. Do not break, crush, or chew the tablet before swallowing, as this may change the amount of medicine that enters your body.

Teriflunomide can be taken with or without food.

If you take more Clefiremthan you should

If you have taken too much teriflunomide, call your doctor immediately. You may experience side effects similar to those described in section 4 (below).

If you forget to take Clefirem

Do not take a double dose to make up for forgotten doses. Take your next dose at the scheduled time.

If you stop taking Clefirem

Do not stop treatment or change the dose of this medicine without consulting your doctor first. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

Some side effects may be serious, if you experience any of these, tell your doctor immediately.

Common(may affect up to 1 in 10 people)

• Pancreatitis that may include symptoms of abdominal pain, nausea, or vomiting (common in pediatric patients and uncommon in adult patients).

Uncommon(may affect up to 1 in 100 people)

• Allergic reactions that may include symptoms of rash, hives, swelling of lips, tongue, or face, or sudden difficulty breathing.
• Severe skin reactions that may include symptoms of skin rash, blisters, fever, or ulcers in the mouth.
• Severe infections or sepsis (a type of infection that can be life-threatening) that may include symptoms such as high fever, chills, shaking, decreased urine flow, or confusion.
• Lung inflammation that may include symptoms such as shortness of breath or persistent cough.

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

• Liver disease that may include symptoms such as yellowing of the skin or whites of the eyes, darker than normal urine, unexplained nausea and vomiting, or abdominal pain.

Other side effectsmay occur with the following frequencies:

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

• Headache
• Diarrhea, feeling sick
• Increased ALT (increase in certain liver enzymes in the blood) in blood tests
• Thinning hair

Common(may affect up to 1 in 10 people)

• Herpes virus infections, including oral herpes and shingles (herpes zoster) 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 weakness.
• Flu, upper respiratory tract infection, urinary tract infection, bronchitis, sinusitis, sore throat and difficulty swallowing, cystitis, viral gastroenteritis, tooth infection, laryngitis, fungal infection of the foot
• Laboratory values: a decrease in the number of red blood cells (anemia), changes in liver and white blood cells in tests (see section 2), as well as elevations in a muscle enzyme (creatine phosphokinase).
• Mild allergic reactions
• Feeling anxious
• Pins and needles, feeling weak, numbness, tingling, or pain in the lower back or leg (sciatica); feeling numb, burning, tingling, or pain in hands and fingers (carpal tunnel syndrome)
• Palpitations
• Increased blood pressure
• Feeling sick (vomiting), toothache, pain in the upper abdominal region
• Rash, acne
• Pain in tendons, joints, bones, muscle pain (musculoskeletal pain)
• Need to urinate more often than usual
• Heavy periods
• Pain
• Lack of energy or weakness (asthenia)
• Weight loss

Uncommon(may affect up to 1 in 100 people)

• Mild decrease in the number of platelets (thrombocytopenia)
• Increased sensitivity, especially in the skin; stabbing or pulsating pain in one or more nerves; problems with the nerves in the arms and legs (peripheral neuropathy)
• Abnormalities in the nails, severe skin reactions
• Post-traumatic pain
• Psoriasis
• Mouth/lip inflammation
• Abnormal levels of fats (lipids) in the blood
• Colon inflammation (colitis)

Rare(may affect up to 1 in 1,000 patients)

• Liver inflammation or damage

Frequency not known(frequency cannot be estimated with the available data)

• Pulmonary hypertension

Children (10 years of age and older) and adolescents

The side effects 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 side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Clefirem

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after "EXP". The expiry date refers to the last day of the month shown.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Return any unused medicine to your pharmacist. In case of doubt, ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Packaging Content and Additional Information

Composition ofClefirem

The active ingredient is teriflunomide.

Clefirem 14 mg film-coated tablets EFG

• Each tablet contains 14 mg of teriflunomide.
• The other components are: lactose monohydrate, corn starch, microcrystalline cellulose (E460), sodium carboxymethyl starch (type A), hydroxypropyl cellulose (E463), magnesium stearate (E407B), anhydrous colloidal silica E551, titanium dioxide (E171), hypromellose (E641), aluminum lake indigo carmine (E132), triacetin (E1518) (see section 2 "Clefirem contains lactose").

Appearance of the Product and Packaging Content

Clefirem 14 mg film-coated tablet EFG (tablets)

Clefirem is a film-coated tablet of pale blue color, round, approximately 7.1 mm in diameter, biconvex and smooth on both sides.

Clefirem 14 mg film-coated tablets EFG are presented in aluminum blisters in boxes of 28 or 84 film-coated tablets.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Bausch Health Ireland Limited

Lake Drive 3013

Citywest Business Campus

Dublin 24 D24PPT3

Ireland

Manufacturer

Bausch Health Poland Sp. z.o.o.

Ul. Przemyslowa 2

35-959 Rzeszów

Poland

Bausch Health Poland Sp. z.o.o.

Ul. Kosztowska 21

41-409 Myslowice

Poland

Date of the Last Revision of this Leaflet: September 2024

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/