Clefirem

Package leaflet: Information for the patient

Clefirem 14 mg film-coated tablets

teriflunomide
equivalent medicine
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Clefirem is and what it is used for
2. What you need to know 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 Clefirem is and what it is used for

What Clefirem is
Clefirem contains the active substance teriflunomide, which is an immunomodulatory agent that modulates the immune system to limit its attacks on the nervous system.

What Clefirem is used for
Teriflunomide is used in adults, children, and adolescents (aged 10 years and older, with body weight above 40 kg) for the treatment of relapsing-remitting multiple sclerosis (MS).

What is multiple sclerosis
MS is a long-term disease affecting the central nervous system (CNS), a system composed of the brain and spinal cord. In multiple sclerosis, inflammation destroys the protective covering (called myelin) that surrounds the nerves of the CNS. This loss of myelin is called demyelination. It prevents nerves from functioning properly.

People with the relapsing form of multiple sclerosis experience repeated attacks (relapses) of physical symptoms caused by improper nerve functioning. These symptoms vary from patient to patient but generally include:

• difficulty walking
• vision problems
• balance problems.

Symptoms may completely disappear after each relapse, but over time, some problems may persist between relapses. This can lead to physical disability that may interfere with daily activities.

How Clefirem works
Clefirem helps protect the central nervous system from attacks by the immune system by limiting the increase of certain white blood cells (lymphocytes). This reduces the inflammation that causes nerve damage characteristic of MS. What you should know before taking Clefirem.

2. What you need to know before taking Clefirem

Do not take Clefirem

• if you are allergic to teriflunomide or to any of the other ingredients of this medicine (listed in section 6),
• if you have ever developed a severe skin rash or skin peeling, blistering and/or mouth ulcers after taking teriflunomide or leflunomide,
• if you have severe liver problems,
• if you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding,
• if you have any serious condition affecting the immune system, for example acquired immunodeficiency syndrome (AIDS),
• if you have any serious bone marrow disorder or if you have low numbers of red blood cells or white blood cells in your blood or a reduced number of platelets,
• if you have a severe infection,
• if you have severe kidney problems requiring dialysis,
• if you have very low levels of protein in your blood (hypoproteinemia). If in doubt, consult your doctor or pharmacist before taking this medicine.

Warnings and precautions
Talk to your doctor or pharmacist before taking Clefirem if:

• you have liver problems and/or consume large amounts of alcohol. Your doctor will request blood tests before and during treatment to monitor liver function. If blood test results show liver problems, your doctor may ask you to stop treatment with Clefirem. See section 4.
• you have high blood pressure (hypertension), whether controlled or not by medication. Clefirem may cause an increase in blood pressure. Your doctor will check your blood pressure before starting treatment and regularly thereafter. See section 4.
• you have an infection. Before starting Clefirem, your doctor will check that your white blood cell and platelet counts are adequate. Since Clefirem reduces the number of white blood cells in the blood, this may affect your ability to fight infections. If you suspect you have an infection, your doctor may perform blood tests to monitor white blood cells. See section 4.
• you have severe skin reactions.
• you have respiratory symptoms.
• you experience weakness, numbness, or pain in your hands or feet.
• you are due to receive a vaccination.
• you are taking leflunomide with Clefirem.
• you are switching to or from treatment with Clefirem.
• you need to undergo a specific blood test (calcium level). Falsely low calcium levels may be observed.

Respiratory reactions
Inform your doctor if you develop unexplained cough or shortness of breath (dyspnea). Your doctor may carry out further investigations.

Children and adolescents
Clefirem is not indicated 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 those caring for them:

• pancreatitis (inflammation of the pancreas) has been observed in patients taking teriflunomide. Your child’s doctor may perform blood tests if pancreatitis is suspected.

Other medicines and Clefirem
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.
In particular, inform your doctor or pharmacist if you are taking any of the following medicines:

• leflunomide, methotrexate, and other medicines that affect the immune system (commonly called 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 kidney problems in diabetics,
• alosetron for management of severe diarrhea,
• theophylline for 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 for infections,
• indometacin, ketoprofen for pain or inflammation,
• furosemide for heart conditions,
• cimetidine for reducing gastric acid,
• zidovudine for HIV infection,
• rosuvastatin, simvastatin, atorvastatin, pravastatin for hypercholesterolemia (high cholesterol),
• sulfasalazine for inflammatory bowel disease or rheumatoid arthritis,
• colestyramine for high cholesterol or relief of itching in liver diseases,
• activated charcoal to reduce absorption of medicines or other substances.

Pregnancy and breastfeeding
Do not take Clefirem if you are pregnant or suspect you may be pregnant. If you become pregnant while taking Clefirem, the risk of birth defects in the baby increases. Women of childbearing potential must not take this medicine without using reliable contraceptive measures.
If your daughter starts menstruating while taking Clefirem, you must inform the doctor, who will provide specialist advice regarding contraception and potential risks in case of pregnancy.
Inform your doctor if you intend to start a pregnancy after stopping treatment with Clefirem, because you must ensure that most of the medicine has been eliminated from your body before planning a pregnancy. Elimination of the active substance may take up to 2 years naturally. This period can be reduced to a few weeks by taking certain medicines that accelerate the elimination of Clefirem from the body.
In all cases, blood testing must confirm that the active substance has been sufficiently eliminated from your body, and you must wait for your doctor’s confirmation that the level of Clefirem in your blood is low enough to allow pregnancy to begin.
For further information on laboratory tests, consult your doctor.
If you suspect a pregnancy while taking Clefirem or within two years after stopping treatment, you must stop taking Clefirem and contact your doctor immediately for a pregnancy test. If the test confirms pregnancy, your doctor may recommend treatment with certain medicines to rapidly and sufficiently eliminate Clefirem from your body, as this may reduce the risk to the fetus.

Contraception
You must use an effective method of contraception during and after treatment with Clefirem. Teriflunomide remains in the blood for a long time after stopping treatment. Continue using effective contraception after stopping treatment.

• Continue until blood levels of Clefirem are sufficiently low. Your doctor will monitor them.
• Consult your doctor about the most suitable contraceptive method for you and in case of any need to change contraception. Do not take Clefirem if you are breastfeeding, as teriflunomide passes into breast milk.

Driving and using machines
Clefirem may cause dizziness, which could impair your ability to concentrate and react. Do not drive or operate machinery if you experience this symptom.

Clefirem contains lactose
Clefirem contains lactose (a type of sugar). If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

Clefirem contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially ‘sodium-free’.

3. How to take Clefirem

Treatment with Clefirem must be supervised by a physician experienced in the treatment of multiple sclerosis.
Take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor.

Adults, children and adolescents (aged 10 years and older, with body weight above 40 kg)
The recommended dose is one 14 mg tablet daily.

Route/method of administration
Clefirem is for oral use. Clefirem should be taken every day as a single daily dose at any time of the day.
The tablet must be swallowed whole with some water. Do not divide, crush or chew the tablet before swallowing, as this could alter the amount of medicine that enters your body.

Clefirem can be taken with or without food.

If you take more Clefirem than you should
If you have taken too much Clefirem, contact your doctor immediately. You may experience adverse 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 the forgotten tablet. Take the next dose at the scheduled time.

If you stop taking Clefirem
Do not stop using Clefirem or change the dose without first talking to your doctor. If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them. The following side effects may occur with this medicine.
Serious side effects
Some side effects may be or may become serious. Contact your doctor immediately if you notice any of the following serious side effects.
Common (may affect up to 1 in 10 people)

• Inflammation of the pancreas which may include symptoms of abdominal pain, nausea or vomiting (frequency is common in paediatric patients and uncommon in adult patients).

Uncommon (may affect up to 1 in 100 people)

• Allergic reactions which may include symptoms such as rash, hives, swelling of the lips, tongue or face, or sudden breathing difficulties
• Severe skin reactions which may include symptoms such as rash, blisters, fever, or mouth ulcers
• Severe infections or sepsis (a type of infection with potential life-threatening risk) which may include symptoms such as high fever, shaking, chills, reduced urine output, or confusion
• Inflammation of the lungs which may include symptoms such as shortness of breath or persistent cough

Not known (frequency cannot be estimated from the available data)

• Severe liver diseases which 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 effects may occur with the following frequencies:
Very common (may affect more than 1 in 10 people)

• Headache
• Diarrhoea, nausea
• Increased ALT (elevation in levels of certain liver enzymes in the blood) detected by blood tests
• Hair thinning

Common (may affect up to 1 in 10 people)

• Influenza, upper respiratory tract infection, urinary tract infection, bronchitis, sinusitis, sore throat and discomfort when swallowing, cystitis, viral gastroenteritis, oral herpes, dental infection, laryngitis, fungal foot infection
• Laboratory tests: decreased red blood cell count (anaemia), changes in liver function and white blood cell test results (see section 2), as well as increases in a muscle enzyme (creatine phosphokinase)
• Mild allergic reactions
• Feeling anxious
• Tingling, weakness, numbness, tingling or pain in the lower back or legs (sciatica); numbness, burning, tingling or pain in the hands and fingers (carpal tunnel syndrome)
• Awareness of heartbeat
• Increased blood pressure
• Nausea (vomiting), toothache, upper abdominal pain
• Rash, acne
• Tendon, joint, bone pain, 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)

• Decreased platelet count (mild thrombocytopenia)
• Increased sensitivity, particularly of the skin; stabbing or pulsating pain in one or more nerves, nerve problems in the arms or legs (peripheral neuropathy)
• Nail disorders, severe skin reactions
• Post-traumatic pain
• Psoriasis
• Inflammation of the mouth/lips
• Abnormal levels of fats (lipids) in the blood
• Inflammation of the colon (colitis)

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

• Inflammation or damage to the liver

Not known (frequency cannot be estimated from the available data)

• Increased blood pressure in the lungs

Children (aged 10 years and above) and adolescents
The side effects listed above also apply to children and adolescents. The following additional information is important for children, adolescents and those caring for them:
Common (may affect up to 1 in 10 people)

• Inflammation of the pancreas

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Clefirem

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after “Exp.”. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Clefirem contains
The active substance is teriflunomide.
Clefirem 14 mg film-coated tablets

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

Description of the appearance of Clefirem and the contents of the pack
Clefirem 14 mg film-coated tablet (tablets)
Clefirem 14 mg film-coated tablets are biconvex, blue, round film-coated tablets with a diameter of approximately 7.1 mm, smooth on both sides.
Clefirem 14 mg film-coated tablets are available in aluminium blisters, in packs of 28 or 84 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Bausch Health Ireland Limited
3013 Lake Drive
Citywest Business Campus
Dublin 24 D24PPT3
Ireland

Manufacturer
Flavine Pharma France
3 Voie d'Allemagne, 13127 Vitrolles, France
Interpharma Services Ltd.
43A Cherni Vrach Blvd. Sofia 1407, Bulgaria

Other sources of information