Prescribing Information for the Patient

AUBAGIO 7Film-Coated Tablets

AUBAGIO 14Film-Coated Tablets

teriflunomida

Read this entire prescribing information carefully before starting to take this medication, as it contains important information for you.

• Keep this prescribing information, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you and should not be given to others

even if they have the same symptoms as you, as it may harm them.

• If you experience any adverse effects, consult your doctor or pharmacist,even if they are

not listed in this prescribing information. See section 4.

Contents of the pack and additional information

AUBAGIO contains the active ingredient teriflunomida, which is an immunomodulator agent that adjusts the immune system to limit its attack on the nervous system.

What is AUBAGIO used for

AUBAGIO is used in adults and in children and adolescents (10 years of age and older) 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 formed by the brain and spinal cord. In MS, 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 functioning correctly.

People who suffer from the relapsing form of MS will have repeated attacks (recurrences) of the physical symptoms caused by the inadequate functioning of the nerves. These symptoms vary from patient to patient, but usually include:

•difficulty walking

•vision problems

•balance problems.

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

How AUBAGIO works

AUBAGIO helps to 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.

Do not take AUBAGIO:

• 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 breastfeeding,
• if you have a severe condition that affects the immune system, for example, acquired immunodeficiency syndrome (AIDS),
• if you have severe bone marrow problems or if you have a low number of white blood cells, red blood cells or platelets in your blood or a reduced number of platelets,
• if you have a severe infection,
• if you have severe kidney problems that require dialysis,
• if you have a very low level of proteins in your blood (hypoproteinemia),

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take AUBAGIO if:

• suffer from liver problems and/or if you drink large quantities of alcohol. Your doctor may perform blood tests to check the functioning of your liver before treatment and during treatment. If the test results indicate a liver problem, your doctor may interrupt the treatment with AUBAGIO. See section 4.
• have high blood pressure (hypertension), whether or not you are being treated to control it. AUBAGIO may cause an increase in blood pressure. Your doctor will check your blood pressure before starting treatment and regularly during treatment. See section 4.
• have an infection. Before you start taking AUBAGIO, your doctor will ensure that you have enough white blood cells and platelets in your blood. Since AUBAGIO reduces the number of white blood cells in your blood, this may affect your ability to fight off the infection. Your doctor may perform blood tests to check your white blood cells if they suspect that you have any infection.With teriflunomide treatment, you may get viral infections, including oral herpes or herpes zoster (shingles). In some cases, serious complications have occurred. You must inform your doctor immediately if you suspect that you have any symptoms of viral herpes infection.See section 4.
• have severe skin reactions.
• have respiratory symptoms.
• have weakness, numbness and pain in your hands and feet.
• are going to be vaccinated.
• are taking leflunomide with AUBAGIO.
• are changing your medication from or to AUBAGIO.
• are scheduled to have a specific blood test (calcium level). A false decrease in calcium levels may be detected.

Respiratory reactions

Inform your doctor if you have cough and shortness of breath without explanation. Your doctor may perform additional tests.

Children and adolescents

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

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

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

Other medicines and AUBAGIO

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine. This includes over-the-counter medicines.

Especially, inform 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
• hypericum (a plant-based medicine for depression)
• repaglinide, pioglitazone, nateglinide or rosiglitazone for diabetes
• daunorubicin, doxorubicin, paclitaxel or topotecan for cancer
• duloxetine for depression, urinary incontinence or kidney disease in diabetics
• 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 itching in liver disease
• activated charcoal to reduce the absorption of medicines or other substances.

Pregnancy and breastfeeding

Do not take AUBAGIO if you are pregnant or think you may be pregnant.If you are pregnant or become pregnant while taking AUBAGIO, you will have a higher risk of having a baby with birth defects. Women of childbearing age should not take this medicine unless they are using reliable contraceptive methods.

If your daughter starts menstruating while taking AUBAGIO, she must inform her doctor, who will give her specialized advice on contraceptive methods and the possible risks in case of pregnancy.

Inform your doctor if you plan to become pregnant after stopping treatment with AUBAGIO, as you need to ensure that most of this medicine has been eliminated from your body before trying to become pregnant. The natural elimination of the active ingredient may take up to 2 years. This time period can be reduced to a few weeks by taking certain medicines to accelerate the elimination of AUBAGIO from your body.

You need your doctor to confirm, from a blood test, that the level of active ingredient in your blood is low enough for you to become pregnant.

For more information on laboratory tests, contact your doctor.

If you suspect that you are pregnant while taking AUBAGIO or in the two years after stopping treatment, you must interrupt AUBAGIO and contact your doctor immediately to perform a pregnancy test. If the test confirms pregnancy, your doctor may suggest a treatment with certain medicines to eliminate AUBAGIO from your body quickly and sufficiently, as this may reduce the risk to your baby.

Contraception

You must use an effective contraceptive method during and after treatment with AUBAGIO. Teriflunomide remains in your blood for a long time after you stop taking it. Continue to use contraceptive methods after stopping treatment.

Do not take AUBAGIO during breastfeeding as teriflunomide passes into breast milk.

Driving and operating machines

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

AUBAGIO contains lactose

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

AUBAGIO contains sodium

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

A healthcare professional experienced in treating multiple sclerosis will oversee treatment with AUBAGIO.

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again.

Adults

The recommended dose is one 14 mg tablet per day.

Children and adolescents (10 years of age and above)

The dose depends on body weight:

• children with a body weight greater than 40 kg: 14 mg once a day.
• children with a body weight less than or equal to 40 kg: 7 mg once a day.

Your doctor will instruct children and adolescents who reach a stable body weight above 40 kg to switch to one 14 mg tablet per day.

Form/administration route

AUBAGIO is administered orally. AUBAGIO is taken once a day in a single daily dose at any time of day.

The tablet should be swallowed whole with water.

AUBAGIO can be taken with or without food.

If you take more AUBAGIO than you should

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

If you forget to take AUBAGIO

Do not take a double dose to make up for missed doses.

If you interrupt treatment with AUBAGIO

Do not stop treatment or change the dose of AUBAGIO without consulting your doctor first.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

This medicine may cause the following side effects.

Severe side effects

Some side effects may be or may become severe,if you experience any of these,inform your doctor immediately.

Frequent(may affect up to 1 in 10 people)

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

Uncommon(may affect up to 1 in 100 people)

• Allergic reactions that could include symptoms of rash, hives, swelling of lips, tongue, or face, or sudden difficulty breathing
• Severe skin reactions that could include symptoms of skin rash, blisters, fever, or ulcers in your mouth
• Severe infections or sepsis (a type of infection that can be potentially fatal) that could include symptoms such as high fever, chills, decreased urine flow, or confusion
• Pneumonia that could include symptoms such as shortness of breath or persistent cough

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

• Severe liver disease that may include symptoms such as yellowing of the skin or eyes, darker urine than normal, nausea, and vomiting without explanation, or abdominal pain.

Other side effectsmay occur with the following frequencies:

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

• Headache
• Diarrhea, feeling of illness
• IncreasedALT (increase in certain liver enzymes in the blood) in tests
• Thinner hair

Frequent(may affect up to 1 in 10 people)

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

Uncommon(may affect up to 1 in 100 people)

• Decrease in the number of platelets (mild thrombocytopenia)
• Increased sensitivity, especially in the skin; stabbing or pulsating pain in one or more nerves; nerve problems in arms and legs (peripheral neuropathy)
• Changes in nails, severe skin reactions
• Post-traumatic pain
• Poriasis
• Inflammation of the mouth/lips
• Abnormal levels of fats (lipids) in the blood
• Colitis (inflammation of the colon)

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

• Liver inflammation or damage

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

• Pulmonary hypertension

Children (10 years of age and older) and adolescents

The previously listed side effects also apply to children and adolescents. The following additional information is important for children, adolescents, and their caregivers:

Frequent(may affect up to 1 in 10 people)

• Pancreatitis

Reporting side effects

If you experience side effects, consult your doctor or pharmacist, even if they are side effects that do not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box, and the case after "CAD". The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. By doing so, you will help protect the environment.

Composition of AUBAGIO

The active ingredient is teriflunomida.

AUBAGIO 7 mg film-coated tablets

• Each tablet contains7mg of teriflunomida.
• The other components are lactose monohydrate, maize starch, microcrystalline cellulose, sodium starch glycolate (type A), hydroxypropylcellulose, magnesium stearate, hypromellose, titanium dioxide (E171), talc, macrogol 8000, aluminium lake carmine (E132) and iron oxide yellow (E172) (see section 2 “AUBAGIO contains lactose”).

AUBAGIO 14 mg film-coated tablets

• Each tablet contains14mg of teriflunomida.
• The other components are lactose monohydrate, maize starch, microcrystalline cellulose, sodium starch glycolate (type A), hydroxypropylcellulose, magnesium stearate, hypromellose, titanium dioxide (E171), talc, macrogol 8000, aluminium lake carmine (E132) (see section 2 “AUBAGIO contains lactose”).

Appearance of the product and contents of the pack

AUBAGIO 7 mg film-coated tablets

The film-coated tablets are of a very pale blue-green to pale blue colour, hexagonal in shape, engraved with ('7') on one side and a corporate logo on the other side.

AUBAGIO 7 mg film-coated tablets are available in cartons containing 28 tablets in a blister pack.

AUBAGIO 14 mg film-coated tablets

The film-coated tablets are of a pale blue or pale blue pastel colour, pentagonal in shape, engraved with ('14') on one side and a corporate logo on the other side.

AUBAGIO 14 mg film-coated tablets are available in cartons containing:

• 14, 28, 84 and 98 tablets in blister packs;
• 10x1 tablet in perforated unit dose blisters.

Only some pack sizes may be marketed.

Marketing authorisation holder:

Sanofi Winthrop Industrie

82 avenue Raspail

94250 Gentilly

France

Manufacturer responsible:

Opella Healthcare International SAS

56, Route de Choisy

60200

Compiègne

France

Sanofi Winthrop Industrie

30-36, avenue Gustave Eiffel

37100 Tours

France

Further information on this medicinal product can be obtained by contacting the local representative of the marketing authorisation holder:

Last update of this leaflet:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

You can also find a copy of the leaflet and patient card with safety information in the QR code mentioned below.

Inclusion of the QR code +www.qr-aubagio-sanofi.eu