"The U.S. Food and Drug Administration today approved Tecfidera (dimethyl fumarate) capsules to treat adults with relapsing forms of multiple sclerosis (MS).
MS is a chronic, inflammatory, autoimmune disease of the central nervous system"...
The following serious adverse reactions are described elsewhere in the prescribing information:
- Hepatotoxicity [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]
- Bone Marrow Effects/Immunosuppression Potential/Infections [see WARNINGS AND PRECAUTIONS]
- Peripheral Neuropathy [see WARNINGS AND PRECAUTIONS]
- Acute Renal Failure [see WARNINGS AND PRECAUTIONS]
- Hyperkalemia [see WARNINGS AND PRECAUTIONS]
- Serious Skin Reactions [see WARNINGS AND PRECAUTIONS]
- Blood Pressure Effects [see WARNINGS AND PRECAUTIONS]
- Respiratory Effects [see WARNINGS AND PRECAUTIONS]
The most frequent adverse reactions for AUBAGIO (incidence ≥ 10% and ≥ 2% greater than placebo) in the placebo-controlled studies were ALT increased, alopecia, diarrhea, influenza, nausea, and paresthesia. Alopecia was the most common cause of discontinuation because of adverse events in controlled clinical studies as compared to placebo (0.5% and 1.4% of patients on AUBAGIO 7 mg and 14 mg, respectively, and 0% on placebo).
If desired, teriflunomide can be rapidly cleared from the body by the use of an accelerated elimination procedure [see WARNINGS AND PRECAUTIONS].
Clinical Trial Experience
A total of 844 patients on teriflunomide (7 mg or 14 mg once daily) constituted the safety population in the pooled analysis of placebo controlled studies in patients with relapsing forms of MS (RMS). Approximately 72% of patients were female and the mean age was 38 years.
Study 1 was a 108-week placebo-controlled clinical study in 1086 RMS patients treated with teriflunomide 7 mg (n=368), teriflunomide 14 mg (n=358), or placebo (n=360).
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Table 1 : Adverse Reactions in Study 1 (occurring in
≥ 2% of patients, and reported for teriflunomide 7 mg or 14 mg at ≥
2% higher rate than for placebo)
|PRIMARY SYSTEM ORGAN CLASS Preferred Term (%)||Teriflunomide|
|INFECTIONS AND INFESTATIONS|
|Upper respiratory tract infection||9%||9%||7%|
|BLOOD AND LYMPHATIC SYSTEM DISORDERS|
|IMMUNE SYSTEM DISORDERS|
|NERVOUS SYSTEM DISORDERS|
|Carpal tunnel syndrome||3%||1%||0.3%|
|Abdominal pain upper||6%||5%||4%|
|SKIN AND SUBCUTANEOUS TISSUE DISORDERS|
|MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS|
|Alanine aminotransferase increased||14%||12%||7%|
|Aspartate aminotransferase increased||3%||2%||1%|
|Neutrophil count decreased||2%||3%||0.3%|
|White blood cell count decreased||1%||3%||0%|
Four cardiovascular deaths, including three sudden deaths, and one myocardial infarction in a patient with a history of hyperlipidemia and hypertension were reported among approximately 2600 patients exposed to AUBAGIO in the premarketing database. These cardiovascular deaths occurred during uncontrolled extension studies, one to nine years after initiation of treatment. A relationship between teriflunomide and cardiovascular death has not been established.
In clinical trials, 18% of teriflunomide-treated subjects had mild hypophosphatemia ( ≥ 0.6 mmol/L and < lower limit of normal), compared to 9% of placebo-treated subjects; 5% of teriflunomide-treated subjects had moderate hypophosphatemia ( ≥ 0.3 mmol/L and < 0.6 mmol/L), compared to 1% of placebo-treated subjects. No subject in either treatment group had a serum phosphorus < 0.3 mmol/L.
Read the Aubagio (teriflunomide tablets) Side Effects Center for a complete guide to possible side effects
Effect of teriflunomide on CYP2C8 substrates
There was an increase in mean repaglinide Cmax and AUC (1.7- and 2.4-fold, respectively), following repeated doses of teriflunomide and a single dose of 0.25 mg repaglinide, suggesting that teriflunomide is an inhibitor of CYP2C8 in vivo. The magnitude of interaction could be higher at the recommended repaglinide dose. Therefore, monitoring patients with concomitant use of drugs metabolized by CYP2C8, such as repaglinide, paclitaxel, pioglitazone, or rosiglitazone is recommended as they may have higher exposure.
Effect of teriflunomide on warfarin
A 25% decrease in peak international normalized ratio (INR) was observed when teriflunomide was coadministered with warfarin as compared with warfarin alone. Therefore, when warfarin is coadministered with teriflunomide, close INR follow-up and monitoring is recommended.
Effect of teriflunomide on oral contraceptives
There was an increase in mean ethinylestradiol Cmax and AUC0-24 (1.58- and 1.54-fold, respectively) and levonorgestrel Cmax and AUC0-24 (1.33- and 1.41-fold, respectively) following repeated doses of teriflunomide. Consideration should be given to the type or dose of oral contraceptives used in combination with teriflunomide.
Effect of teriflunomide on CYP1A2 substrates
Repeated doses of teriflunomide decreased mean Cmax and AUC of caffeine (CYP1A2 substrate) by 18% and 55% respectively, suggesting that teriflunomide may be in vivo a weak inducer of CYP1A2. Therefore, patients should be monitored when teriflunomide is coadministered with drugs metabolized by CYP1A2 (such as duloxetine, alosetron, theophylline, and tizanidine), as the efficacy of such drugs could be reduced.
Read the Aubagio Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 9/21/2012
This monograph has been modified to include the generic and brand name in many instances.
Additional Aubagio Information
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