Overview
11 DESCRIPTION The active ingredient in BYLVAY (odevixibat) capsules and BYLVAY (odevixibat) oral pellets, an ileal bile acid transporter (IBAT) inhibitor, is (2S)-2-{[(2R)-2-(2-{[3,3-dibutyl-7-(methylsulfanyl)-1,1-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1λ 6 ,2,5-benzothiadiazepin-8yl]oxy}acetamido)-2-(4-hydroxyphenyl)acetly]amino}butanoic acid, which is formulated as the sesquihydrate having the...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Odevixibat is a reversible inhibitor of the ileal bile acid transporter (IBAT). It decreases the reabsorption of bile acids (primarily the salt forms) from the terminal ileum . Pruritus is a common symptom in patients with PFIC and ALGS; the pathophysiology of pruritus in patients with PFIC is not completely understood. Although the complete mechanism by which odevixibat improves pruritus in both PFIC and ALGS patients is unknown, it may involve inhibition of the IBAT, which results in decreased reuptake of bile salts, as observed by a decrease in serum bile acids [see Clinical Pharmacology (12.2) ] . 12.2 Pharmacodynamics Odevixibat reduces serum bile acids in patients with PFIC and ALGS .
Indications
- 1 INDICATIONS AND USAGE BYLVAY is an ileal bile acid transporter (IBAT) inhibitor indicated for: Progressive Familial Intrahepatic Cholestasis (PFIC) the treatment of pruritus in patients 3 months of age and older with progressive familial intrahepatic cholestasis (PFIC). ( 1.1 ) Limitation of Use : BYLVAY is not recommended in a subgroup of PFIC type 2 patients with specific ABCB11 variants resulting in non-functional or complete absence of the bile salt export pump protein. ( 12.5 , 14.
Common Doses
- 40 mcg
- 120 mcg
- 6 mg
- 30 mL
Dosage
2 DOSAGE AND ADMINISTRATION Recommended Dosage PFIC: Patients 3 months and older: 40 mcg/kg taken orally once daily. ( 2.1 ) If there is no improvement in pruritus after 3 months, the dosage may be increased in 40 mcg/kg increments up to 120 mcg/kg once daily, not to exceed a daily dosage of 6 mg/day. ( 2.1 ) ALGS: Patients 12 months and older: 120 mcg/kg taken orally once daily. ( 2.2 ) Preparation and Administration Instructions Administer BYLVAY in the morning with a meal. ( 2.4 ) Do not crush or chew capsules. ( 2.
Contraindications
- 4 CONTRAINDICATIONS IBAT inhibitors, including BYLVAY, are contraindicated in patients with prior or active hepatic decompensation events (e.g., variceal hemorrhage, ascites, hepatic encephalopathy) [see Warnings and Precautions (5.1) ] . Patients with prior or active hepatic decompensation events (e.g., variceal hemorrhage, ascites, hepatic encephalopathy). ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Hepatotoxicity [ see Warnings and Precautions (5.1) ] Diarrhea [see Warnings and Precautions (5.2) ] Fat-Soluble Vitamin Deficiency [see Warnings and Precautions (5.3) ] PFIC: Most common adverse reactions (>2%) are liver test abnormalities, diarrhea, abdominal pain, vomiting, and fat-soluble vitamin deficiency. ( 6.1 ) ALGS: Most common adverse reactions (>5%) are diarrhea, abdominal pain, hematoma, and decreased weight. ( 6.
Interactions
- 7 DRUG INTERACTIONS 7.1 Bile Acid Binding Resins Administer bile acid binding resins (e.g., cholestyramine, colesevelam, or colestipol) at least 4 hours before or 4 hours after administration of BYLVAY [see Dosage and Administration (2.3) ] . Bile acid binding resins may bind odevixibat in the gut, which may reduce BYLVAY efficacy.