AUBAGIO 7 mg FILM-COATED TABLETS

2. What you need to know before you take AUBAGIO

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 breast-feeding,
• if you have a serious immune system problem, for example, acquired immune deficiency syndrome (AIDS),
• if you have serious bone marrow problems or if you have a low white blood cell count or a low red blood cell count or a low platelet count,
• if you have a serious infection,
• if you have severe kidney problems that require dialysis,
• if you have a low blood protein level (hypoproteinemia),

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

Warnings and precautions

Talk to your doctor or pharmacist before starting AUBAGIO 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 AUBAGIO. See section 4.
• you have high blood pressure (hypertension), whether or not you are being treated for 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.
• you have an infection. Before you start taking AUBAGIO, your doctor will make sure you have enough white blood cells and platelets in your blood. Since AUBAGIO decreases the number of white blood cells in your blood, this may affect your ability to fight infection. Your doctor may perform blood tests to check your white blood cell count if they think you have any infection. With AUBAGIO treatment, viral infections, including oral or genital herpes (shingles), may occur. In some cases, serious complications have occurred. You should inform your doctor immediately 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 AUBAGIO.
• you are being switched from or to AUBAGIO.
• 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

AUBAGIO 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 AUBAGIO

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 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 relief of itching in liver disease
• activated charcoal to reduce the absorption of medicines or other substances.

Pregnancy and breast-feeding

Do nottake AUBAGIO if you are pregnant or think you may be pregnant. If you are pregnant or become pregnant while taking AUBAGIO, 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 AUBAGIO, 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 AUBAGIO, as you will need to make sure that most of this 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 AUBAGIO 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 AUBAGIO or in the 2 years following treatment, you must stop taking AUBAGIO and contact your doctor immediatelyto have a pregnancy test. If the test confirms pregnancy, your doctor may suggest treatment with certain medicines to eliminate AUBAGIO from your body quickly, as this may reduce the risk to your baby.

Contraception

You must use a reliable contraceptive method during and after treatment with AUBAGIO. Teriflunomide remains in the blood for a long time after stopping it. Continue to take contraceptive measures after stopping treatment.

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

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

Driving and using machines

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

AUBAGIO contains lactose

AUBAGIO 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.

AUBAGIO contains sodium

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

3. How to take AUBAGIO

A doctor with experience in the treatment of multiple sclerosis will supervise treatment with AUBAGIO.

Follow the instructions for administration of this medicine exactly as prescribed by your doctor. In case of doubt, consult your doctor again.

Adults

The recommended dose is one 14 mg tablet per day.

Children and adolescents (10 years of age and older)

The dose depends on body weight:

• children with a body weight over 40 kg: 14 mg once daily.
• children with a body weight of 40 kg or less: 7 mg once daily.

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

Form/Route of Administration

AUBAGIO is administered orally. AUBAGIO is taken once daily 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 side 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 forgotten doses.

If you stop taking 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 medicine, ask your doctor or pharmacist.

4. Possible side effects

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

The following side effects may occur with this medicine.

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 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 the mouth
• serious infections or sepsis (a type of infection that can be life-threatening) that could include symptoms such as high fever, chills, shaking, decreased urine flow, or confusion
• inflammation of the lungs that could include symptoms such as shortness of breath or persistent cough

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

• severe liver disease that may include symptoms such as yellowing of the skin or the 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
• hair loss

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, dental infection, laryngitis, fungal infection of the foot
• herpes virus infections, including oral and genital herpes (shingles) 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 liver and white blood cells in blood tests (see section 2), as well as elevations in a muscle enzyme (creatine phosphokinase)
• 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 hands and fingers (carpal tunnel syndrome)
• palpitations
• increased blood pressure
• feeling sick (vomiting), toothache, pain in the upper abdomen
• 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 platelet count (thrombocytopenia)
• increased sensitivity, especially in the skin; stabbing or pulsating pain in one or more nerves; problems in the nerves of the arms and legs (peripheral neuropathy)
• changes in nails, 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 patients)

• inflammation or liver damage

Frequency not known(frequency cannot be estimated from 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, even if it is not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of AUBAGIO

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 and blister after "EXP". The expiry date refers to the last day of the month stated.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Additional Information

AUBAGIO Composition

The active ingredient is teriflunomide.

AUBAGIO 7 mg film-coated tablets

• Each tablet contains 7 mg of teriflunomide.
• The other ingredients are lactose monohydrate, corn starch, microcrystalline cellulose, sodium starch glycolate (type A), hydroxypropylcellulose, magnesium stearate, hypromellose, titanium dioxide (E171), talc, macrogol 8000, aluminum lake carmine indigo (E132), and yellow iron oxide (E172) (see section 2 "AUBAGIO contains lactose").

AUBAGIO 14 mg film-coated tablets

• Each tablet contains 14 mg of teriflunomide.
• The other ingredients are lactose monohydrate, corn starch, microcrystalline cellulose, sodium starch glycolate (type A), hydroxypropylcellulose, magnesium stearate, hypromellose, titanium dioxide (E171), talc, macrogol 8000, aluminum lake carmine indigo (E132) (see section 2 "AUBAGIO contains lactose").

Product Appearance and Package Contents

AUBAGIO 7 mg film-coated tablets

The film-coated tablets are light blue-greenish gray to light greenish blue in color, 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 cardboard boxes containing 28 tablets in a blister pack with integrated blisters.

AUBAGIO 14 mg film-coated tablets

The film-coated tablets are light blue or pastel blue in color, 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 cardboard boxes containing:

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

Only some pack sizes may be marketed.

Marketing Authorization Holder:

Sanofi Winthrop Industrie

82 avenue Raspail

94250 Gentilly

France

Manufacturer:

Opella Healthcare International SAS

56, Route de Choisy

60200

Compiègne

France

Sanofi Winthrop Industrie

30-36, avenue Gustave Eiffel

37100 Tours

France

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of the last revision of this leaflet:

Other sources of information

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

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

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