Treatment-emergent elevated hepatic enzymes were observed during odevixibat clinical trials. Monitor hepatic enzymes and INR at baseline and during treatment. Interrupt treatment if new onset abnormalities occur or symptoms consistent with clinical hepatitis develop. Once hepatic enzymes return to baseline or stabilize at a new baseline, consider restarting odevixibat at 40 mcg/kg/day and increase as tolerated. Consider treatment discontinuation for persistent or recurrent hepatic enzyme abnormalities. Permanently discontinue treatment if a patient progresses to portal hypertension or experiences a hepatic decompensation event (e.g., variceal hemorrhage, ascites, hepatic encephalopathy). During clinical trials, elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 150 units/L or more over baseline were reported in 11% to 37% of patients receiving odevixibat 120 mcg/kg/day (n = 54) compared with 4% to 9% of patients receiving odevixibat 40 mcg/kg/day (n = 23). Hyperbilirubinemia, presenting as total bilirubin elevations (2 mg/dL or more over baseline) and direct bilirubin elevations (1 mg/dL or more over baseline), occurred in 5% to 17% and 11% to 22% of odevixibat-treated patients, respectively. During clinical trials, treatment interruption for elevated hepatic enzymes ranged from 3 to 124 days; no patients permanently discontinued treatment. Splenomegaly (11%), and cholelithiasis (5%) were also reported in patients receiving odevixibat 120 mcg/kg/day in clinical trials (n = 19); no patients receiving odevixibat 40 mcg/kg/day reported these adverse reactions.[66816]

Diarrhea was reported in 21% to 39% of odevixibat-treated patients during clinicals trials. Dehydration was reported in 1 patient. If diarrhea occurs, monitor for dehydration and treat promptly. Interrupt treatment for persistent diarrhea. Once diarrhea has resolved, restart odevixibat at 40 mcg/kg/day and increase the dose as tolerated. Discontinue odevixibat if diarrhea persists and no alternative etiology is identified. During clinical trials, treatment interruption days due to diarrhea ranged from 3 to 7 days. One patient withdrew due to persistent diarrhea. Other gastrointestinal-related adverse reactions reported in odevixibat-treated patients in clinical trials include abdominal pain (13% to 16%), vomiting (16% to 17%), and weight loss (6%).[66816]

Odevixibat may affect the absorption of fat-soluble vitamins (A, D, E, and K) resulting in vitamin A deficiency, vitamin D deficiency, vitamin E deficiency, and vitamin K deficiency. Obtain serum fat-soluble vitamin concentrations and INR (to monitor for vitamin K) at baseline and periodically during treatment. Supplement with fat-soluble vitamins if a deficiency is diagnosed. Discontinue odevixibat if the deficiency persists or worsens despite supplementation. In clinical trials, new onset or worsening fat-soluble vitamin deficiency was reported in 8.6% to 16% of patients receiving odevixibat 120 mcg/kg/day (n = 54); these deficiencies were not observed in those receiving odevixibat 40 mcg/kg/day (n = 23).[66816]

Fracture (bone fractures) was reported in 4% of odevixibat-treated patients in clinical trials (n = 23).[66816]

Hematoma was reported in 9% of odevixibat-treated patients in clinical trials (n = 35).[66816]

Patients with progressive familial intrahepatic cholestasis (PFIC) or Alagille Syndrome (ALGS) may have hepatic impairment at baseline. Establish a baseline pattern of hepatic function variability prior to odevixibat initiation so that potential signs of liver injury can be identified. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, direct bilirubin, and INR during treatment. Interrupt treatment if new onset hepatic function abnormalities occur or symptoms consistent with clinical hepatitis develop. Once hepatic function returns to baseline or stabilizes at a new baseline, consider restarting odevixibat at the recommended indication-specific dose and increase as tolerated. Consider treatment discontinuation for persistent or recurrent hepatic function abnormalities. Permanently discontinue treatment if a patient progresses to portal hypertension or experiences a hepatic decompensation event (e.g., variceal hemorrhage, ascites, hepatic encephalopathy). Safety and efficacy of odevixibat have not been established in patients with clinically significant portal hypertension or decompensated cirrhosis.[66816]

Odevixibat may affect the absorption of fat-soluble vitamins (A, D, E, and K). Obtain serum fat-soluble vitamin concentrations and INR (to monitor for vitamin K) at baseline and periodically during treatment. Supplement with fat-soluble vitamins if vitamin A deficiency, vitamin D deficiency, vitamin E deficiency, or vitamin K deficiency is diagnosed. Discontinue odevixibat if the deficiency persists or worsens despite supplementation.[66816]

There are no data on odevixibat use in human pregnancy to establish a drug-associated risk of major birth defects, miscarriage, or adverse developmental outcomes. Animal reproduction studies suggest odevixibat may cause cardiac malformations in the exposed fetus. In pregnant rabbits receiving odevixibat during organogenesis, an increase in cardiovascular malformations (e.g., 5-chambered heart, small ventricle, large atrium, ventricular septal defect, misshapen aortic valve, dilated aortic arch, right sided and retroesophageal aortic arch, fusion of aortic arch and pulmonary trunk, ductus arteriosus atresia, absence of subclavian artery) occurred at all doses. At the lowest dose, maternal systemic exposure was 2.1 times the maximum recommended human dose (MRHD). There is a pregnancy registry study that monitors pregnancy outcomes in women exposed to odevixibat during pregnancy. Pregnant women exposed to odevixibat, or their health care providers, should report odevixibat exposure by calling 1-855-252-4736.[66816]

Breast-feeding is not expected to result in exposure of the infant to odevixibat at recommended doses; odevixibat has low absorption after oral administration. However, there are no data on the presence of odevixibat in human milk, the effects on the breast-fed infant, or the effects on milk production. Odevixibat may reduce the absorption of fat-soluble vitamins. Monitor fat-soluble vitamin concentrations and increase intake if deficiency is observed during lactation. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.[66816]