AUBAGIO 14 mg film-coated tablets

Each film-coated tablet contains 14 mg of teriflunomide.

Excipient with known effect: Each tablet contains 72 mg of lactose (as monohydrate).

For the full list of excipients, see section 6.1.

Film-coated tablet (tablet).

Pale blue to pastel blue, pentagonal film-coated tablets with imprint on one side ('14') and engraved with a corporate logo on the other side.

AUBAGIO is indicated for the treatment of adult patients with relapsing remitting multiple sclerosis (MS).

(please refer to section 5.1 for important information on the population for which efficacy has been established).

The treatment should be initiated and supervised by a physician experienced in the management of multiple sclerosis.

Posology

The recommended dose of AUBAGIO is 14 mg once daily.

Special populations

Elderly population

AUBAGIO should be used with caution in patients aged 65 years and over due to insufficient data on safety and efficacy.

Renal impairment

No dosage adjustment is necessary for patients with mild, moderate or severe renal impairment not undergoing dialysis.

Patients with severe renal impairment undergoing dialysis were not eva luated. Teriflunomide is contraindicated in this population (see section 4.3).

Hepatic impairment

No dosage adjustment is necessary for patients with mild and moderate hepatic impairment. Teriflunomide is contraindicated in patients with severe hepatic impairment (see section 4.3).

Paediatric population

The safety and efficacy of AUBAGIO in children aged from 10 to less than 18 years has not yet been established. There is no relevant use of teriflunomide in children aged from birth to less than 10 years for the treatment of multiple sclerosis.

No data are available.

Method of administration

The film-coated tablets are for oral use. The tablets should be swallowed whole with some water. AUBAGIO can be taken with or without food.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Patients with severe hepatic impairment (Child-Pugh class C).

Pregnant women, or women of childbearing potential who are not using reliable contraception during treatment with teriflunomide and thereafter as long as its plasma levels are above 0.02 mg/l (see section 4.6). Pregnancy must be excluded before start of treatment (see section 4.6).

Breast-feeding women (see section 4.6).

Patients with severe immunodeficiency states, e.g. AIDS.

Patients with significantly impaired bone marrow function or significant anaemia, leucopenia, neutropenia or thrombocytopenia.

Patients with severe active infection until resolution (see section 4.4).

Patients with severe renal impairment undergoing dialysis, because insufficient clinical experience is available in this patient group.

Patients with severe hypoproteinaemia, e.g. in nephrotic syndrome.

Monitoring

Before treatment

Before starting treatment with teriflunomide the following should be assessed:

• Blood pressure

• Alanine aminotransferase (ALT/SGPT)

• Complete blood cell count including differential white blood cell and platelet count.

During treatment

During treatment with teriflunomide the following should be monitored:

• Blood pressure

• Alanine aminotransferase (ALT/SGPT)

• Complete blood cell counts should be performed based on signs and symptoms (e.g. infections) during treatment.

Accelerated elimination procedure

Teriflunomide is eliminated slowly from the plasma. Without an accelerated elimination procedure, it takes an average of 8 months to reach plasma concentrations less than 0.02 mg/l, although due to individual variation in substance clearance it may take up to 2 years. An accelerated elimination procedure can be used at any time after discontinuation of teriflunomide (see section 4.6 and 5.2 for procedural details).

Hepatic effects

Elevations of liver enzymes have been observed in patients receiving teriflunomide (see section 4.8). These elevations occurred mostly within the first 6 months of treatment.

Liver enzymes should be assessed before initiation of teriflunomide therapy - every two weeks during the first 6 months of treatment, and every 8 weeks thereafter or as indicated by clinical signs and symptoms such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine. For ALT (SGPT) elevations between 2- and 3-fold the upper limit of normal, monitoring must be performed weekly. Teriflunomide therapy should be discontinued if liver injury is suspected; consider discontinuing teriflunomide therapy if elevated liver enzymes (greater than 3-fold ULN) are confirmed. Patients with pre-existing liver disease may be at increased risk of developing elevated liver enzymes when taking teriflunomide and should be closely monitored for signals of liver disease.

The medicinal product should be used with caution in patients who consume substantial quantities of alcohol.

Since teriflunomide is highly protein bound and as the bindi