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warnings and cautions
5 WARNINGS AND PRECAUTIONS Hepatotoxicity : Obtain baseline liver transaminase and total bilirubin levels in all patients and monitor yearly and as clinically indicated. Interrupt treatment until the levels have returned to baseline values. For persistent or recurrent liver test abnormalities, consider discontinuing CTEXLI. ( 5.1 ) 5.1 Hepatotoxicity Chenodiol, including CTEXLI, has been associated with hepatotoxicity [see Adverse Reactions ( 6 )] . In Trial 1, one CTEXLI-treated patient (7%) had increased ALT levels > 3 times ULN, which led to treatment interruption. Patients with pre-existing liver disease or bile duct abnormalities may be at higher risk for hepatotoxicity during treatment with CTEXLI. Published reports suggest patients who are poor sulfators of lithocholic acid are more likely to develop chenodiol-induced serum aminotransferase elevations [see Clinical Pharmacology ( 12.3 )] . Obtain baseline liver transaminase (ALT, AST) and total bilirubin levels in all patients prior to treatment initiation with CTEXLI. If liver transaminase levels are elevated > 3 times ULN or total bilirubin level is >2 times ULN, interrupt treatment with CTEXLI until the levels have returned to baseline values. Monitor liver transaminase and total bilirubin levels yearly and as clinically indicated. For persistent or recurrent liver test abnormalities, consider discontinuing CTEXLI. Inform the patient of the symptoms of hepatotoxicity (e.g., abdominal pain, bruising, dark-colored urine, fatigue, bleeding, jaundice, nausea, and pruritus). If clinical signs and symptoms consistent with hepatotoxicity occur, have the patient discontinue CTEXLI immediately.
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adverse reactions
6 ADVERSE REACTIONS The following clinically significant adverse reaction is described elsewhere in the labeling: • Hepatotoxicity [see Warnings and Precautions ( 5.1 )] The most common adverse reactions (incidence > 14%) are diarrhea, headache, abdominal pain, constipation, hypertension, muscular weakness, and upper respiratory tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mirum Pharmaceuticals at 1-855-MRM-4YOU 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 practice. The safety of CTEXLI was evaluated in a randomized, double blind, placebo-controlled, 2-period, 2-treatment crossover trial in 14 patients (16 to 55 years of age) with CTX (Trial 1). CTEXLI is not approved for use in pediatric patients. The dosage of CTEXLI was 250 mg orally three times a day [see Clinical Studies ( 14 )]. The mean (SD) chenodiol exposure during Trial 1 was 139.1 (26.7) days. The most common adverse reactions which occurred in two or more patients ( > 14%) during CTEXLI treatment (including the two 8-week open-label treatment periods) were diarrhea (36%), headache (21%), and abdominal pain (including abdominal pain upper) (14%), constipation (14%), hypertension (14%), muscular weakness (14%), and upper respiratory tract infection (14%). In Trial 1, one CTEXLI-treated patient (7%) had increased ALT levels > 3x ULN, which led to treatment interruption. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of chenodiol. 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. • Hepatobiliary Disorders: Hepatotoxicity [see Warnings and Precautions ( 5.1 )] • Immune System Disorders: Hypersensitivity reactions such as facial swelling, pruritus, rash, urticaria.