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warnings and cautions
5 WARNINGS AND PRECAUTIONS Hepatotoxicity: Elevations of one or more hepatic function enzymes and bilirubin may occur with Zileuton Extended-Release Tablets. Assess hepatic function enzymes prior to initiation of Zileuton Extended-Release Tablets, monthly for the first 3 months, every 2-3 months for the remainder of the first year, and periodically thereafter. Use Zileuton Extended-Release Tablets with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. ( 5.1 ) Neuropsychiatric Events: Neuropsychiatric events, including sleep disorders and behavior changes, may occur with Zileuton Extended-Release Tablets. Instruct patients to be alert for neuropsychiatric events. Evaluate the risks and benefits of continuing treatment with Zileuton Extended-Release Tablets if such events occur. ( 5.2 ) 5.1 Hepatotoxicity Elevations of one or more hepatic function enzymes and bilirubin may occur during Zileuton Extended-Release Tablets therapy. These laboratory abnormalities may progress to clinically significant liver injury, remain unchanged, or resolve with continued treatment, usually within three weeks. The ALT (SGPT) test is considered the most sensitive indicator of liver injury for Zileuton Extended-Release Tablets. Assess hepatic function enzymes prior to initiation of, and during therapy with, Zileuton Extended-Release Tablets. Assess serum ALT before treatment begins, once a month for the first 3 months, every 2-3 months for the remainder of the first year, and periodically thereafter for patients receiving long-term Zileuton Extended-Release Tablets therapy. If clinical signs and/or symptoms of liver dysfunction develop (e.g., right upper quadrant pain, nausea, fatigue, lethargy, pruritus, jaundice, or “flu-like” symptoms) or transaminase elevations ≥5×ULN occur, discontinue Zileuton Extended-Release Tablets and follow hepatic function enzymes until normal. In controlled and open-label clinical studies involving more than 5000 patients treated with zileuton immediate-release tablets, the overall rate of ALT elevation ≥3×ULN was 3.2%. In these trials, one patient developed symptomatic hepatitis with jaundice, which resolved upon discontinuation of therapy. An additional 3 patients with transaminase elevations developed mild hyperbilirubinemia that was less than 3×ULN. There was no evidence of hypersensitivit...
warnings and cautions
5.1 Hepatotoxicity Elevations of one or more hepatic function enzymes and bilirubin may occur during Zileuton Extended-Release Tablets therapy. These laboratory abnormalities may progress to clinically significant liver injury, remain unchanged, or resolve with continued treatment, usually within three weeks. The ALT (SGPT) test is considered the most sensitive indicator of liver injury for Zileuton Extended-Release Tablets. Assess hepatic function enzymes prior to initiation of, and during therapy with, Zileuton Extended-Release Tablets. Assess serum ALT before treatment begins, once a month for the first 3 months, every 2-3 months for the remainder of the first year, and periodically thereafter for patients receiving long-term Zileuton Extended-Release Tablets therapy. If clinical signs and/or symptoms of liver dysfunction develop (e.g., right upper quadrant pain, nausea, fatigue, lethargy, pruritus, jaundice, or “flu-like” symptoms) or transaminase elevations ≥5×ULN occur, discontinue Zileuton Extended-Release Tablets and follow hepatic function enzymes until normal. In controlled and open-label clinical studies involving more than 5000 patients treated with zileuton immediate-release tablets, the overall rate of ALT elevation ≥3×ULN was 3.2%. In these trials, one patient developed symptomatic hepatitis with jaundice, which resolved upon discontinuation of therapy. An additional 3 patients with transaminase elevations developed mild hyperbilirubinemia that was less than 3×ULN. There was no evidence of hypersensitivity or other alternative etiologies for these findings. Since treatment with Zileuton Extended-Release Tablets may result in increased hepatic function enzymes and liver injury, Zileuton Extended-Release Tablets should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease.
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adverse reactions
6 ADVERSE REACTIONS Hepatotoxicity: Elevations of one or more hepatic function enzymes and bilirubin may occur during Zileuton Extended-Release Tablets therapy [see Warnings and Precautions (5) ]. The most commonly occurring adverse reactions (≥5%) with Zileuton Extended-Release Tablets are sinusitis, nausea, and pharyngolaryngeal pain. Most common adverse reactions (≥5%) included: sinusitis, nausea, and pharyngolaryngeal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Short-Term Clinical Studies Experience The safety data described below reflect exposure to Zileuton Extended-Release Tablets in 199 patients for 12 weeks duration. In a 12-week, randomized, double-blind, placebo-controlled trial in adults and adolescents 12 years of age and older with asthma, patients received Zileuton Extended-Release Tablets two 600 mg tablets (n=199) or placebo (n=198) twice daily by mouth. Eighty-three percent of patients were white, 48% were male, and the mean age was 34 years. Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The most commonly reported adverse reactions (occurring at a frequency of ≥5%) in Zileuton Extended-Release Tablets-treated patients and at a frequency greater than placebo-treated patients are reflected in Table 1. Table 1: Adverse Reactions with ≥5% incidence in a 12-Week Placebo-Controlled Trial in Patients with Asthma. Adverse Reaction Zileuton extended- release tablets 2 Tablets Twice Daily N=199 n (%) Placebo 2 Tablets Twice Daily N = 198 n (%) Sinusitis 13 (6.5) 8 (4.0) Nausea 10 (5.0) 3 (1.5) Pharyngolaryngeal Pain 10 (5.0) 8 (4.0) Less common adverse reactions occurring at a frequency ≥1% and more often in the Zileuton Extended-Release Tablets group than in the placebo group included gastrointestinal disorders (upper abdominal pain, diarrhea, dyspepsia, vomiting), rash, hypersensitivity, and hepatotoxicity. There were no differences in the incidence of adverse reactions based upon gender. The clinical trials did not include sufficient numbers of patients
adverse reactions
6.1 Short-Term Clinical Studies Experience The safety data described below reflect exposure to Zileuton Extended-Release Tablets in 199 patients for 12 weeks duration. In a 12-week, randomized, double-blind, placebo-controlled trial in adults and adolescents 12 years of age and older with asthma, patients received Zileuton Extended-Release Tablets two 600 mg tablets (n=199) or placebo (n=198) twice daily by mouth. Eighty-three percent of patients were white, 48% were male, and the mean age was 34 years. Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The most commonly reported adverse reactions (occurring at a frequency of ≥5%) in Zileuton Extended-Release Tablets-treated patients and at a frequency greater than placebo-treated patients are reflected in Table 1. Table 1: Adverse Reactions with ≥5% incidence in a 12-Week Placebo-Controlled Trial in Patients with Asthma. Adverse Reaction Zileuton extended- release tablets 2 Tablets Twice Daily N=199 n (%) Placebo 2 Tablets Twice Daily N = 198 n (%) Sinusitis 13 (6.5) 8 (4.0) Nausea 10 (5.0) 3 (1.5) Pharyngolaryngeal Pain 10 (5.0) 8 (4.0) Less common adverse reactions occurring at a frequency ≥1% and more often in the Zileuton Extended-Release Tablets group than in the placebo group included gastrointestinal disorders (upper abdominal pain, diarrhea, dyspepsia, vomiting), rash, hypersensitivity, and hepatotoxicity. There were no differences in the incidence of adverse reactions based upon gender. The clinical trials did not include sufficient numbers of patients