Pruritus due to progressive familial intrahepatic cholestasis: Oral: 40 mcg/kg once daily in the morning; if no improvement after 3 months, may titrate in 40 mcg/kg increments as tolerated up to 120 mcg/kg once daily; maximum total daily dose: 6 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely due to low systemic absorption.
Hepatic impairment prior to treatment initiation:
There are no dosage adjustments provided in the manufacturer's labeling; however, patients with progressive familial intrahepatic cholestasis (PFIC) may have baseline hepatic impairment and odevixibat is indicated for use in PFIC; safety and efficacy have not been established in patients with clinically significant portal hypertension or decompensated cirrhosis.
Hepatic impairment during therapy:
New onset LFT abnormalities or symptoms consistent with clinical hepatitis: Interrupt therapy. Once LFTs either return to baseline or stabilize at a new baseline value, may consider resuming therapy at 40 mcg/kg once daily and increase as tolerated, if appropriate. Consider discontinuing permanently if LFT abnormalities recur.
Portal hypertension or decompensation event (eg, variceal hemorrhage, ascites, hepatic encephalopathy): Permanently discontinue therapy.
(For additional information see "Odevixibat: Pediatric drug information")
Pruritus due to progressive familial intrahepatic cholestasis (PFIC): Note: Odevixibat is available in 2 dosage forms (oral pellets and capsules); indication and dosing are the same for both formulations; however, the product strengths differ (oral pellets: 200 mcg, 600 mcg; capsule: 400 mcg, 1,200 mcg). For ease of dose calculation and convenience, patients may switch dosage forms as needed with dose titration; however, a combination of dosage forms should not be used to achieve the daily dose.
Infants ≥3 months, Children, and Adolescents: Oral: Initial: 40 mcg/kg/dose once daily for 3 months; if no improvement in pruritus after 3 months, increase dose gradually in 40 mcg/kg increments up to 120 mcg/kg/dose once daily; maximum daily dose: 6,000 mcg/day.
Fixed dose (weight-band):
|
Body Weight |
Initial Dose ~40 mcg/kg/dose once daily |
Dose Titration ~80 mcg/kg/dose once daily |
Maximum Dose ~120 mcg/kg/dose once daily |
|---|---|---|---|
|
<7.5 kg |
200 mcg |
400 mcg |
600 mcg |
|
7.5 to <12.5 kg |
400 mcg |
800 mcg |
1,200 mcg |
|
12.5 to <17.5 kg |
600 mcg |
1,200 mcg |
1,800 mcg |
|
17.5 to <25.5 kg |
800 mcg |
1,600 mcg |
2,400 mcg |
|
25.5 to <35.5 kg |
1,200 mcg |
2,400 mcg |
3,600 mcg |
|
35.5 to <45.5 kg |
1,600 mcg |
3,200 mcg |
4,800 mcg |
|
45.5 to <55.5 kg |
2,000 mcg |
4,000 mcg |
6,000 mcg |
|
≥55.5 kg |
2,400 mcg |
4,800 mcg |
6,000 mcg |
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity:
Persistent diarrhea: Withhold odevixibat until diarrhea resolves; once resolved, resume odevixibat at 40 mcg/kg/dose once daily and increase as tolerated, if appropriate. If diarrhea persists and no alternate etiology is identified, discontinue odevixibat.
Fat-soluble vitamin deficiency: Supplement with fat-soluble vitamins; if deficiency persists or worsens despite adequate supplementation, discontinue odevixibat.
There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely due to low systemic absorption.
Infants ≥3 months, Children, and Adolescents:
Baseline hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, patients with progressive familial intrahepatic cholestasis (PFIC) may have baseline hepatic impairment and odevixibat is indicated for use in PFIC; safety and efficacy has not been established in patients with clinically significant portal hypertension or decompensated cirrhosis. Closely monitor liver tests (ALT, AST, bilirubin [total and direct], and INR) so potential signs of liver injury can be identified.
Hepatotoxicity during treatment:
New-onset LFT abnormalities or symptoms consistent with clinical hepatitis: Withhold odevixibat until LFTs either return to baseline values or stabilize at a new baseline value; may consider resuming therapy at 40 mcg/kg/dose once daily and increase as tolerated, if appropriate. If LFT abnormalities recur, consider permanently discontinuing odevixibat.
Portal hypertension or hepatic decompensation event (eg, variceal hemorrhage, ascites, hepatic encephalopathy): Permanently discontinue odevixibat.
Diarrhea, persistent: Interrupt therapy. Once resolved, may resume at 40 mcg/kg once daily and increase as tolerated, if appropriate. If diarrhea persists and no alternate etiology is identified, discontinue therapy.
Fat-soluble vitamin deficiency: If fat-soluble vitamin deficiency is diagnosed, initiate fat-soluble vitamin supplementation. Discontinue therapy if fat-soluble vitamin deficiency persists or worsens despite adequate fat-soluble vitamin supplementation.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Bylvay: 400 mcg, 1200 mcg
Capsule Sprinkle, Oral:
Bylvay (Pellets): 200 mcg, 600 mcg
No
Bylvay: FDA approved July 2021; availability anticipated in July or August 2021.
Bylvay is available via a limited distribution plan by select pharmacies. Further information is available at https://bylvay.com/home-hcp.html or 1-855-ALBIREO.
Oral: Administer capsules in the morning with a meal. Swallow whole with a glass of water; do not crush or chew capsules. If unable to swallow whole, capsules may be opened and sprinkled and mixed with a small amount (up to 2 tablespoons) of soft food (eg, applesauce, oatmeal, banana or carrot puree, chocolate or rice pudding); gently mix until well dispersed and consume immediately; do not store mixture for future use. Capsule contents may also be mixed with water. Empty capsule contents into a small cup and add 5 mL of water; allow capsule contents to sit in the water for ~5 minutes and then draw liquid mixture into an oral syringe; administer between the tongue and side of the mouth; follow dose with additional water. If more than 1 capsule is needed for dose, repeat steps to mix capsule contents with soft food or water and administer immediately. Administer odevixibat at least 4 hours before or 4 hours after administering a bile acid binding resin.
Oral: Administer in the morning with a meal. For patients also taking bile acid binding resins, administer odevixibat at least 4 hours before or 4 hours after administering a bile acid binding resin.
Oral pellets: Open shell and mix pellets with soft food or liquid; do not swallow shell containing oral pellets.
Mixing with food: Open shell and sprinkle oral pellets onto a small amount (up to 2 tablespoons) of soft food (applesauce, oatmeal, banana or carrot puree, chocolate or rice pudding) at or below room temperature; tap shell to ensure all oral pellets have been removed. If more than one shell of oral pellets is needed for dose, repeat the above steps to mix oral pellets. Gently stir until well mixed; administer the entire dose immediately and follow with water. Do not save mixture for later use.
Mixing with liquid: Oral pellet contents may also be mixed with an age-appropriate liquid (eg, breast milk, infant formula, water). Empty capsule contents into a small cup and add 5 mL of liquid. If more than one shell of oral pellets is needed for dose, repeat the above described steps to mix oral pellets with liquid. Allow contents to sit in the liquid for ~5 minutes to allow complete wetting (pellets will not dissolve) and then withdraw liquid mixture into an oral syringe; expel and re-withdraw the liquid back into the syringe 2 to 3 times to ensure pellets mixed with the liquid. Administer liquid dose mixture between the tongue and side of the mouth; avoid administering in back of the mouth as it may cause gagging/choking. Follow dose with additional age-appropriate liquid. Repeat withdrawing of liquid mixture from the small cup until entire dose consumed. Do not administer in a sippy cup; pellets will not pass through the opening.
Capsules: Swallow capsule whole with glass of water; do not crush or chew.
Mixing with food: For patients unable to swallow whole capsule, capsules may be opened and contents sprinkled and mixed with a small amount (up to 2 tablespoons) of soft food (eg, applesauce, oatmeal, banana or carrot puree, chocolate or rice pudding); if more than one capsule is needed for dose, repeat the above steps to mix contents of capsule. Gently mix until well dispersed and consume immediately; do not store mixture for future use.
Mixing with liquid: Capsule contents may also be mixed with an age-appropriate liquid (breast milk, infant formula, water). Empty capsule contents into a small cup and add 5 mL of liquid; if more than one capsule is needed for dose, repeat the above steps to mix contents of capsule. Allow capsule contents to sit in the liquid for ~5 minutes and then draw liquid mixture into an oral syringe; expel and re-withdraw the liquid back into the syringe 2 to 3 times to ensure capsule contents mixed with the liquid. Administer between the tongue and side of the mouth; avoid administering in back of the mouth as it may cause gagging/choking; follow dose with additional age-appropriate liquid. Repeat withdrawing of liquid mixture from the small cup until entire dose consumed.
Pruritus due to progressive familial intrahepatic cholestasis: Treatment of pruritus in patients ≥3 months of age with progressive familial intrahepatic cholestasis (PFIC).
Limitations of use: May not be effective in PFIC type 2 patients with ABCB11 variants resulting in non-functional or complete absence of bile salt export pump protein (BSEP-3).
New onset or worsening of existing fat-soluble vitamin deficiency (vitamins A, D, E, and K) may occur with use of odevixibat. May improve following treatment discontinuation and/or vitamin supplementation.
Mechanism: Related to the pharmacologic action; ileal bile acid transporter (IBAT) inhibitors interfere with fat-soluble vitamin absorption.
Risk factors:
• Preexisting fat-soluble vitamin deficiency
Ileal bile acid transporter (IBAT) inhibitors, including odevixibat, commonly cause adverse gastrointestinal effects; effects may include abdominal pain, diarrhea, and vomiting (Ref). Symptoms may resolve with treatment interruption or discontinuation.
Mechanism: Not clearly established; related to the pharmacologic action. IBAT inhibitors interrupt the enterohepatic circulation of bile acids which results in an increase in gastric and colonic motility (Ref).
Ileal bile acid transporter (IBAT) inhibitors, including odevixibat, may cause new or worsening liver enzyme abnormalities (Ref); abnormalities during clinical trials included increased serum alanine aminotransferase, increased serum aspartate aminotransferase, and increased serum bilirubin. Abnormalities are reversible upon treatment interruption or discontinuation.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Vitamin deficiency (≤16%; includes vitamin A deficiency, vitamin D deficiency, and vitamin E deficiency) (table 1)
|
Drug (Odevixibat) |
Placebo |
Population |
Dose |
Number of Patients (Odevixibat) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|
|
16% |
5% |
Infants, children, and adolescents |
120 mcg/kg/day |
19 |
20 |
Fat-soluble vitamin deficiency (A, D, E) |
|
0% |
5% |
Infants, children, and adolescents |
40 mcg/kg/day |
23 |
20 |
Fat-soluble vitamin deficiency (A, D, E) |
Gastrointestinal: Abdominal pain (13% to 16%) (table 2), diarrhea (21% to 39%) (table 3), vomiting (16% to 17%) (table 4)
|
Drug (Odevixibat) |
Placebo |
Population |
Dose |
Number of Patients (Odevixibat) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
16% |
0% |
Infants, children, and adolescents |
120 mcg/kg/day |
19 |
20 |
|
13% |
0% |
Infants, children, and adolescents |
40 mcg/kg/day |
23 |
20 |
|
Drug (Odevixibat) |
Placebo |
Population |
Dose |
Number of Patients (Odevixibat) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
39% |
10% |
Infants, children, and adolescents |
40 mcg/kg/day |
23 |
20 |
|
21% |
10% |
Infants, children, and adolescents |
120 mcg/kg/day |
19 |
20 |
|
Drug (Odevixibat) |
Placebo |
Population |
Dose |
Number of Patients (Odevixibat) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
17% |
0% |
Infants, children, and adolescents |
40 mcg/kg/day |
23 |
20 |
|
16% |
0% |
Infants, children, and adolescents |
120 mcg/kg/day |
19 |
20 |
Hematologic & oncologic: Splenomegaly (11%)
Hepatic: Increased serum alanine aminotransferase (≤21%) (table 5), increased serum aspartate aminotransferase (≤21%) (table 6), increased serum bilirubin (11% to 13%) (table 7)
|
Drug (Odevixibat) |
Placebo |
Population |
Dose |
Number of Patients (Odevixibat) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|
|
21% |
5% |
Infants, children, and adolescents |
120 mcg/kg/day |
19 |
20 |
Includes increased ALT and AST |
|
13% |
5% |
Infants, children, and adolescents |
40 mcg/kg/day |
23 |
20 |
Includes increased ALT and AST |
|
Drug (Odevixibat) |
Placebo |
Population |
Dose |
Number of Patients (Odevixibat) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|
|
21% |
5% |
Infants, children, and adolescents |
120 mcg/kg/day |
19 |
20 |
Includes increased AST and ALT |
|
13% |
5% |
Infants, children, and adolescents |
40 mcg/kg/day |
23 |
20 |
Includes increased AST and ALT |
|
Drug (Odevixibat) |
Placebo |
Population |
Dose |
Number of Patients (Odevixibat) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
13% |
10% |
Infants, children, and adolescents |
40 mcg/kg/day |
23 |
20 |
|
11% |
10% |
Infants, children, and adolescents |
120 mcg/kg/day |
19 |
20 |
1% to 10%:
Endocrine & metabolic: Dehydration (5%)
Gastrointestinal: Cholelithiasis (5%)
Neuromuscular & skeletal: Bone fracture (4%)
There are no contraindications listed in the manufacturer's labeling.
Substrate of P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Bile Acid Sequestrants: May decrease the serum concentration of Odevixibat. Management: Bile acid sequestrants should be administered either at least 4 hours before, or 4 hours after, odevixibat. Risk D: Consider therapy modification
Based on data from animal reproduction studies, in utero exposure to odevixibat may cause fetal harm, including cardiac malformations.
Odevixibat may reduce maternal absorption of fat-soluble vitamins.
It is not known if odevixibat is present in breast milk.
Following oral administration to nonpregnant patients, systemic concentrations of odevixibat are minimal (below the limit of quantification [0.05 ng/mL]), which would limit potential exposure via breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Odevixibat may reduce absorption of fat-soluble vitamins; monitor and adjust fat-soluble vitamin intake or discontinue odevixibat if a maternal deficiency is observed.
Establish baseline pattern of LFT variability prior to therapy (many patients have abnormal LFTs at baseline). Monitor for new onset or worsening of LFTs (AST, ALT, total and direct bilirubin) relative to baseline values.
INR (baseline and periodically during treatment); signs/symptoms of hepatic decompensation or portal hypertension; fat-soluble vitamin levels (at baseline and periodically during treatment) and signs/symptoms of fat-soluble vitamin deficiency; diarrhea (new onset or worsening of existing; signs of dehydration).
Reversible ileal bile acid transporter (IBAT) inhibitor, which decreases the reabsorption of bile acids (primarily salt forms) from the terminal ileum. Exact mechanism by which odevixibat improves pruritus in patients with progressive familial intrahepatic cholestasis is unknown but may involve IBAT inhibition.
Absorption: Minimal.
Protein binding: >99%.
Metabolism: Hepatic via mono-hydroxylation.
Half-life elimination: 2.36 hours.
Time to peak, serum: 1 to 5 hours.
Excretion: Feces (97% unchanged); urine (<0.002%).
Capsule, sprinkles (Bylvay (Pellets) Oral)
200 mcg (per each): $289.60
600 mcg (per each): $868.80
Capsules (Bylvay Oral)
400 mcg (per each): $579.20
1200 mcg (per each): $1,737.60
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