Label Changes for:
Changes have been made to the CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
- (addition) Patients with a history of a hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in AUBAGIO. Reactions have included anaphylaxis, angioedema, and serious skin reactions.
WARNINGS AND PRECAUTIONS
Bone Marrow Effects/Immunosuppression Potential/Infections
Bone Marrow Effects (this heading replaces White Blood Cell (WBC) count decrease)
- Cases of thrombocytopenia with AUBAGIO, including rare cases with platelet counts less than 50,000/mm3, have been reported in the postmarketing setting. (addition of sentence to paragraph)
Hypersensitivity and Serious Skin Reactions
- AUBAGIO can cause anaphylaxis and severe allergic reactions. Signs and symptoms have included dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue.
- Cases of serious skin reactions, including cases of Stevens-Johnson syndrome (SJS) and a fatal case of toxic epidermal necrolysis (TEN), have been reported with AUBAGIO.
- In patients treated with leflunomide, the parent compound, very rare cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have also been reported.
- Inform patients of the signs and symptoms of anaphylaxis and angioedema and signs and symptoms that may signal a serious skin reaction. Inform patients that a fever associated with signs of other organ system involvement (e.g., rash, lymphadenopathy, or hepatic dysfunction) may be drug-related. Instruct patients to discontinue AUBAGIO and seek immediate medical care should these signs and symptoms occur. Discontinue AUBAGIO, unless the reactions are clearly not drug-related, and begin an accelerated elimination procedure immediately. In such cases, patients should not be re-exposed to teriflunomide.
- (addition of sentence) Interstitial lung disease, including acute interstitial pneumonitis, has been reported with AUBAGIO in the postmarketing setting.
Hypersensitivity and Serious Skin Reactions (replaces Skin Reactions bullet)
Post-Marketing Experience (new subsection added)
The following adverse reactions have been identified during post approval use of AUBAGIO.
- Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Hypersensitivity reactions, some of which were severe, such as anaphylaxis and angioedema
- Severe skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome
- Interstitial lung disease
PATIENT COUNSELING INFORMATION
Serious Allergic Reactions (new section added)
- Advise patients to discontinue AUBAGIO and seek immediate medical attention if any signs or symptoms of a hypersensitivity reaction occur. Signs and symptoms include dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue or skin rash.
Who should not take AUBAGIO?
Do not take AUBAGIO if you:
- you have had an allergic reaction to AUBAGIO or a medicine called leflunomide (addition)
What are possible side effects of AUBAGIO?
AUBAGIO may cause serious side effects, including:
- Allergic reactions, including serious skin problems. Tell your doctor if you have difficulty breathing, itching, swelling on any part of your body including in your lips, eyes, throat or tongue, or any skin problems such as rash or redness and peeling. (update of prior bullet serious skin problems)
5 WARNINGS AND PRECAUTIONS
- Updated study data...In placebo-controlled trials, ALT greater than three times the ULN occurred in 61/1045 (5.8%) and 62/1002 (6.2%) of patients receiving AUBAGIO 7 mg and 14 mg, respectively, and 38/997 (3.8%) of patients receiving placebo, during the treatment period.
5.4 Bone Marrow Effects/Immunosuppression Potential/Infections
Updated study data in the following sections
- White Blood Cell (WBC) count decrease
- Risk of Infection / Tuberculosis Screening
5.5 Peripheral Neuropathy
- Updated study data ... The incidence of peripheral neuropathy confirmed by nerve conduction studies was 1.4% (13 patients) and 1.9% (17 patients) of patients receiving 7 mg and 14 mg of AUBAGIO, respectively, compared with 0.4% receiving placebo (4 patients). Treatment was discontinued in 0.7% (8 patients) with confirmed peripheral neuropathy (3 patients receiving AUBAGIO 7 mg and 5 patients receiving AUBAGIO 14 mg). Five of them recovered following treatment discontinuation. Not all cases of peripheral neuropathy resolved with continued treatment. Peripheral neuropathy also occurred in patients receiving leflunomide.
5.7 Increased Blood Pressure
- Updated study data ... In placebo-controlled studies, the mean change from baseline to the end of study in systolic blood pressure was +2.3 mmHg and +2.7 mmHg for AUBAGIO 7 mg and 14 mg, respectively, and -0.6 mmHg for placebo. The change from baseline in diastolic blood pressure was +1.4 mmHg and +1.9 mmHg for AUBAGIO 7 mg and 14 mg, respectively, and -0.3 mmHg for placebo. Hypertension was an adverse reaction in 3.1% and 4.3% of patients treated with 7 mg or 14 mg of AUBAGIO compared with 1.8% for placebo.