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boxed warning
WARNING: HEPATOTOXICITY and EMBRYOFETAL TOXICITY Hepatotoxicity Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with teriflunomide in the postmarketing setting [see Warnings and Precautions ( 5.1 )] . Concomitant use of teriflunomide with other hepatotoxic drugs may increase the risk of severe liver injury. Obtain transaminase and bilirubin levels within 6 months before initiation of teriflunomide tablets therapy. Monitor ALT levels at least monthly for six months after starting teriflunomide tablets [see Warnings and Precautions ( 5.1 )] . If drug induced liver injury is suspected, discontinue teriflunomide tablets and start an accelerated elimination procedure with cholestyramine or charcoal [see Warnings and Precautions ( 5.3 )] . Teriflunomide tablets are contraindicated in patients with severe hepatic impairment [see Contraindications ( 4 )] . Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking teriflunomide tablets . Embryofetal Toxicity Teriflunomide is contraindicated for use in pregnant women and in females of reproductive potential who are not using effective contraception because of the potential for fetal harm. Teratogenicity and embryolethality occurred in animals at plasma teriflunomide exposures lower than that in humans. Exclude pregnancy before the start of treatment with teriflunomide tablets in females of reproductive potential. Advise females of reproductive potential to use effective contraception during teriflunomide tablets treatment and during an accelerated drug elimination procedure after teriflunomide tablets treatment. Stop teriflunomide tablets and use an accelerated drug elimination procedure if the patient becomes pregnant [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 , 5.3 ), Use in Specific Populations ( 8.1 , 8.3 ), and Clinical Pharmacology ( 12.3 )] . WARNING: HEPATOTOXICITY and EMBRYOFETAL TOXICITY See full prescribing information for complete boxed warning. Hepatotoxicity Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with teriflunomide in the postmarketing setting ( 5.1 ). Concomitant use of teriflunomide with oth...
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warnings and cautions
5 WARNINGS AND PRECAUTIONS Elimination of teriflunomide can be accelerated by administration of cholestyramine or activated charcoal for 11 days. ( 5.3 ) Teriflunomide may decrease WBC. A recent CBC should be available before starting teriflunomide. Monitor for signs and symptoms of infection. Consider suspending treatment with teriflunomide in case of serious infection. Do not start teriflunomide in patients with active infections. ( 5.4 ) Stop teriflunomide if patient has anaphylaxis, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms; initiate rapid elimination. ( 5.3 , 5.5 , 5.6 , 5.7 ) Cutaneous or mucocutaneous ulcers/impaired wound healing: If ulcer or impaired wound healing is suspected, consider discontinuation of teriflunomide treatment and an accelerated drug elimination procedure. ( 5.8 ) If patient develops symptoms consistent with peripheral neuropathy, evaluate patient and consider discontinuing teriflunomide. ( 5.9 ) Teriflunomide may increase blood pressure. Measure blood pressure at treatment initiation and monitor blood pressure during treatment. ( 5.10 ) 5.1 Hepatotoxicity Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with teriflunomide in the postmarketing setting. Patients with pre-existing liver disease and patients taking other hepatotoxic drugs may be at increased risk for developing liver injury when taking teriflunomide. Clinically significant liver injury can occur at any time during treatment with teriflunomide. Patients with pre-existing acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) greater than two times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with teriflunomide. Teriflunomide is contraindicated in patients with severe hepatic impairment [see Contraindications ( 4 )] . In placebo-controlled trials in adult patients, ALT greater than three times the ULN occurred in 61/1045 (5.8%) and 62/1002 (6.2%) of patients receiving teriflunomide 7 mg and 14 mg, respectively, and 38/997 (3.8%) of patients receiving placebo, during the treatment period. These elevations occurred mostly within the first year of treatment. Half of the cases returned to normal without drug di...
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adverse reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the prescribing information: Hepatotoxicity [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] Bone Marrow Effects/Immunosuppression Potential/Infections [see Warnings and Precautions ( 5.4 )] Hypersensitivity Reactions [see Contraindications ( 4 ) and Warnings and Precautions ( 5.5 )] Serious Skin Reactions [see Warnings and Precautions ( 5.6 )] Drug Reaction with Eosinophilia and Systemic Symptoms [see Warnings and Precautions ( 5.7 )] Cutaneous or Mucocutaneous Ulcers and Impaired Wound Healing [see Warnings and Precautions ( 5.8 )] Peripheral Neuropathy [see Warnings and Precautions ( 5.9 )] Increased Blood Pressure [see Warnings and Precautions ( 5.10 )] Respiratory Effects [see Warnings and Precautions ( 5.11 )] Pancreatitis in Pediatric Patients [see Warnings and Precautions ( 5.12 )] Most common adverse reactions (≥10% and ≥2% greater than placebo): headache, diarrhea, nausea, alopecia, increase in ALT. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Concord Biotech Limited at Telephone: 1-855-407-0586 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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. A total of 2047 patients receiving teriflunomide tablets (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 multiple sclerosis; of these, 71% were female. The average age was 37 years. Table 1 lists adverse reactions in placebo-controlled trials with rates that were at least 2% for teriflunomide patients and also at least 2% above the rate in placebo patients. The most common were headache, an increase in ALT, diarrhea, alopecia, and nausea. The adverse reaction most commonly associated with discontinuation was an increase in ALT (3.3%, 2.6%, and 2.3% of all patients in the teriflunomide tablets 7 mg, teriflunomide tablets 14 mg, and placebo treatment arms, respectively). Table 1: Adverse Reactions in Pooled Placebo-Controlled Studies in Patients with Relapsing Forms of Multiple Scler...
adverse reactions table
Table 1: Adverse Reactions in Pooled Placebo-Controlled Studies in Patients with Relapsing Forms of Multiple Sclerosis Adverse Reaction Teriflunomide Tablets, 7 mg (N=1045) Teriflunomide Tablets, 14 mg (N=1002) Placebo (N=997) Headache 18% 16% 15% Increase in Alanine aminotransferase 13% 15% 9% Diarrhea 13% 14% 8% Alopecia 10% 13% 5% Nausea 8% 11% 7% Paresthesia 8% 9% 7% Arthralgia 8% 6% 5% Neutropenia 4% 6% 2% Hypertension 3% 4% 2%