CTEXLI

1 INDICATIONS AND USAGE CTEXLI is indicated for the treatment of cerebrotendinous xanthomatosis (CTX) in adults. CTEXLI is a bile acid indicated for treatment of cerebrotendinous xanthomatosis (CTX) in adults. ( 1 )

2 DOSAGE AND ADMINISTRATION • Before initiating CTEXLI, obtain baseline liver transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and total bilirubin levels in all patients. ( 2.1 ) • The recommended dosage is 250 mg orally three times daily. ( 2.2 ) 2.1 Important Recommendation Prior to CTEXLI Treatment Initiation Before initiating CTEXLI, obtain baseline liver transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and total bilirubin levels in all patients [see Warnings and Precautions ( 5.1 )] . 2.2 Recommended Dosage The recommended dosage of CTEXLI is 250 mg administered orally three times daily. Administer CTEXLI with or without food. Swallow tablets whole. Missed Dose If a dose of CTEXLI is missed, advise the patient to skip the missed dose and to resume taking the prescribed dose at the next scheduled time. Patients should not take a double dose. 2.3 Administration Modification and Monitoring If liver transaminase (ALT, AST) levels are elevated > 3 times the upper limit of normal (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 [see Warnings and Precautions ( 5.1 )].

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.

7 DRUG INTERACTIONS • Bile acid sequestering agents and aluminum-based antacids: Avoid concomitant use with CTEXLI. ( 7.1 ) • Coumarin and its derivatives: Monitor prothrombin time and adjust dosage accordingly. ( 7.2 ) 7.1 Effect of Other Drugs on CTEXLI Co-administration of bile acid sequestering agents, such as cholestyramine and colestipol, or aluminum-based antacids may decrease absorption of CTEXLI in the intestine and may result in decreased efficacy of CTEXLI. Avoid concomitant use of bile acid sequestering agents or aluminum-based antacids with CTEXLI. 7.2 Effect of CTEXLI on Other Drugs Due to potential hepatotoxicity, CTEXLI may affect the pharmacodynamics of coumarin and its derivatives, causing unexpected prolongation of the prothrombin time and hemorrhage. If concomitant use of CTEXLI with coumarin or its derivatives is unavoidable, monitor prothrombin time. Adjust the dosage of coumarin or its derivatives in accordance with its approved product labeling.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied CTEXLI (chenodiol) tablets are supplied as 250 mg white film-coated tablets imprinted with “MP” on one side and "250" on the other side. NDC 79378-310-90: 100 count bottle Storage and Handling Store CTEXLI at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].