Bylvay (odevixibat)

Dosage of odevixibat sesquihydrate is expressed in terms of odevixibat.

Administer odevixibat orally once daily in the morning with a meal.

Odevixibat is commercially available as capsules and pellets for oral administration. The oral pellets are intended for use by patients weighing <19.5 kg and the capsules are intended for use by patients weighing >=19.5 kg.

The drug should be taken with food.

Odevixibat should be administered at least 4 hours before or after administration of bile acid sequestrants.

No dosing information is available for this tab.

No dosing information is available for this tab.

In vitro, odevixibat does not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, or 2D6, or induce CYP isoenzymes 1A2, 2B6, or 3A4.

Odevixibat is a substrate of P-glycoprotein (P-gp), but is not a substrate of breast cancer resistance protein (BCRP).

In vitro, odevixibat did not inhibit P-gp, BCRP, organic anion transporter polypeptide (OATP) 1B1 or OATP1B3, organic anion transporter (OAT)1, OAT3, organic cation transporter 2 (OCT2), or multidrug and toxin extrusion exporter 1 (MATE1) and MATE2K.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Ileal Bile Acid Transporter Inhibitors/Bile Acid Sequestrant

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Bile acid sequestrants may bind to linerixibat, maralixibat and odevixibat in the gut, resulting in decreased absorption of the IBAT inhibitor.(1-3)

CLINICAL EFFECTS: Coadministration of bile acid sequestrants with IBAT inhibitors may cause reduced efficacy of IBAT inhibitors.(1-3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturers state to administer bile acid sequestrants (cholestyramine, colesevelam, and colestipol) at least 4 hours before or 4 hours after administration of IBAT inhibitors.(1-3)

DISCUSSION: Bile acid sequestrants are known to bind to drugs when given concurrently. Administration with IBAT inhibitors may result in decreased systemic absorption.(1-3)

*Prior or active hepatic decompensation events (e.g., variceal hemorrhage, ascites, hepatic encephalopathy).

There are no contraindication contraindications for this drug.

• Bleeding esophageal varices
• Diarrhea
• Hepatic encephalopathy
• Pregnancy

• Disease of liver
• Vitamin A deficiency
• Vitamin D deficiency
• Vitamin E deficiency
• Vitamin K deficiency

Most common adverse reactions (>2%) reported in patients with PFIC receiving odevixibat include liver test abnormalities, diarrhea, abdominal pain, vomiting, and fat-soluble vitamin deficiency.

Most common adverse reactions (>5%) reported in patients with ALGS receiving odevixibat include diarrhea, abdominal pain, hematoma, and weight loss.

More Frequent

• Abnormal hepatic function tests
• Diarrhea
• Increased alanine transaminase
• Increased aspartate transaminase

Rare or Very Rare

• Bloody stools
• Dehydration
• Drug-induced hepatitis
• Rectal bleeding
• Subdural intracranial hemorrhage

More Frequent

• Acute abdominal pain
• Vitamin A deficiency
• Vitamin D deficiency
• Vitamin E deficiency
• Vitamin K deficiency

Less Frequent

• Constipation
• Gastroesophageal reflux disease
• Headache disorder
• Hematoma
• Hyperbilirubinemia
• Nausea
• Skin rash
• Splenomegaly
• Vomiting
• Weight loss

Rare or Very Rare

• Anemia
• Biliary calculus
• Epistaxis
• Fracture
• Gastrointestinal hemorrhage
• Gingival bleeding
• Irritability

No enhanced messaging available.

Safety and efficacy of odevixibat have been established in pediatric patients 3 months to 17 years of age for the treatment of pruritus due to PFIC. Use of odevixibat in this age group is supported by data from a 24-week, randomized, double-blind, placebo-controlled trial conducted in 62 patients with a confirmed diagnosis of PFIC type 1 or type 2 (Trial 1) and an open-label, 72-week, extension trial in patients with PFIC (Trial 2).

Safety and efficacy of odevixibat have been established in pediatric patients 12 months to 17 years of age for the treatment of pruritus due to ALGS. Use of odevixibat in this age group is supported by data from a randomized, double-blind, placebo-controlled trial conducted in 52 patients with a confirmed diagnosis of ALGS and one open-label extension trial in ALGS patients.

Safety and efficacy of odevixibat for the treatment of pruritus in pediatric patients <3 months of age with PFIC have not been established. Safety and efficacy of odevixibat for the treatment of pruritus in pediatric patients <12 months of age with ALGS have not been established.

There are insufficient human data on use of odevixibat in pregnant women to establish a drug-associated risk of major birth defects, miscarriage, or adverse developmental outcomes. In animal studies, increased incidence of malformations in fetal heart, great blood vessels, and other vascular sites were reported in pregnant rabbits receiving odevixibat at all dosages during organogenesis; maternal systemic exposure at the lowest dose was 2.1 times the maximum recommended human dosage. Since odevixibat may inhibit the absorption of fat-soluble vitamins, which are necessary for normal fetal growth and development, clinicians should monitor pregnant patients for a deficiency and supplement as needed. Pregnancy may require increased fat-soluble vitamin supplementation.

A pregnancy safety study that monitors outcomes in women exposed to odevixibat during pregnancy is available. Pregnant women exposed to odevixibat, or their healthcare providers, should report odevixibat exposure by calling 1-855-463-5127.

Odevixibat is minimally absorbed following oral administration; therefore, breast-feeding is not expected to result in exposure to the infant at the recommended dosage. It is not known whether odevixibat is distributed into human milk. The effects of the drug on breast-fed infants or on milk production are unknown. Consider the developmental and health benefits of breast-feeding along with the mother's need for odevixibat and any potential adverse effects on the breast-fed child from the drug or underlying maternal condition.

Patients with PFIC or ALGS may also have concomitant fat-soluble vitamin deficiency. Because odevixibat may further reduce absorption of fat-soluble vitamins, monitor fat-soluble vitamin levels and provide supplementation if a deficiency is diagnosed during lactation.

The manufacturer makes no specific dosage recommendations for geriatric patients.

The manufacturer states that PFIC and ALGS are largely diseases of pediatric and young adult patients. Clinical studies with odevixibat did not include patients >=65 years of age.