odevixibat (Rx)

Brand and Other Names:Bylvay
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsules

  • 400mcg
  • 1200mcg

oral pellets

  • 400mcg
  • 1200mcg

Cholestasis

Indicated for pruritus in patients with progressive familial intrahepatic cholestasis (PFIC) aged ≥3 months

40 mcg/kg PO qAM

If no improvement in pruritus after 3 months, may increase dose in 40 mcg/kg-increments up to 120 mcg/kg/day; not to exceed 6 mg/day

Dosage Modifications

Hepatic impairment

  • Patients with PFIC may have impaired hepatic function at baseline
  • PFIC patients with clinically significant portal hypertension or patients with decompensated cirrhosis: Safety and efficacy not established

Liver abnormalities

  • New onset liver function tests (LFTs) abnormalities or symptoms consistent with clinical hepatitis: Interrupt therapy; once LFTs either return to baseline or stabilize at a new baseline value, consider restarting at lowest dose of 40 mcg/kg, and increase as tolerated if appropriate
  • LFTs abnormalities recur: Consider discontinuing permanently
  • Hepatic decompensation event (eg, variceal hemorrhage, ascites, hepatic encephalopathy) occurs: Permanently discontinue

Dosing Considerations

Limitation of use

  • Not effective in PFIC type 2 patients with ABCB11 variants resulting in nonfunctional or complete absence of bile salt export pump protein

Monitoring parameters

  • Liver function tests (eg, ALT, AST, total bilirubin [TB], and direct bilirubin [DB]) and serum fat-soluble vitamins (FSV) levels: Baseline and during treatment
  • International Normalized Ratio (INR): During treatment

Dosage Forms & Strengths

capsules

  • 400mcg
  • 1200mcg

oral pellets

  • 400mcg
  • 1200mcg

Cholestasis

Indicated for pruritus in patients with progressive familial intrahepatic cholestasis (PFIC) aged ≥3 months

<3 months: Safety and efficacy not established

≥3 months

  • 40 mcg/kg PO qAM
  • Recommended for 40 mcg/kg/day
    • ≤7.4 kg: 200 mcg/day
    • 7.5-12.4 kg: 400 mcg/day
    • 12.5-17.4 kg: 600 mcg/day
    • 17.5-25.4 kg: 800 mcg/day
    • 25.5-35.4 kg: 1200 mcg/day
    • 35.5-45.4 kg: 1600 mcg/day
    • 45.5-55.4 kg: 2000 mcg/day
    • ≥55.5 kg: 2400 mcg/day
  • If no improvement in pruritus after 3 months, may increase dose in 40 mcg/kg-increments up to 120 mcg/kg/day; not to exceed 6 mg/day

Dosage Modifications

Hepatic impairment

  • Patients with PFIC may have impaired hepatic function at baseline
  • PFIC patients with clinically significant portal hypertension or patients with decompensated cirrhosis: Safety and efficacy not established

Liver abnormalities

  • New onset of elevated liver function tests (LFTs) or symptoms consistent with clinical hepatitis: Interrupt therapy; once LFTs either return to baseline or stabilize at a new baseline value, consider restarting at lowest dose of 40 mcg/kg, and increase as tolerated if appropriate
  • Elevated LFTs recur: Consider discontinuing permanently
  • Hepatic decompensation event (eg, variceal hemorrhage, ascites, hepatic encephalopathy) occurs: Permanently discontinue

Dosing Considerations

Select formulation based on patient’s body weight

  • <19.5 kg: Use oral pellets
  • ≥19.5 kg: Use capsules

Limitation of use

  • Not effective in PFIC type 2 patients with ABCB11 variants resulting in nonfunctional or complete absence of bile salt export pump protein

Monitoring parameters

  • Liver function tests (eg, ALT, AST, total bilirubin [TB], and direct bilirubin [DB]) and serum fat-soluble vitamins (FSV) levels: Baseline and during treatment
  • INR: During treatment
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Interactions

Interaction Checker

and odevixibat

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (0)

              Serious - Use Alternative (0)

                Monitor Closely (3)

                • cholestyramine

                  cholestyramine will decrease the level or effect of odevixibat by drug binding in GI tract. Modify Therapy/Monitor Closely. Administer bile acid sequestrants 4 hr before or after odevixibat.

                • colesevelam

                  colesevelam will decrease the level or effect of odevixibat by drug binding in GI tract. Modify Therapy/Monitor Closely. Administer bile acid sequestrants 4 hr before or after odevixibat.

                • colestipol

                  colestipol will decrease the level or effect of odevixibat by drug binding in GI tract. Modify Therapy/Monitor Closely. Administer bile acid sequestrants 4 hr before or after odevixibat.

                Minor (0)

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                  Adverse Effects

                  >10%

                  Diarrhea (21.1-39.1%)

                  AST/ALT increased (12-21.1%)

                  Vomiting (15.8-17.4%)

                  Abdominal pain (13-15.8%)

                  FSV deficiency (7.1-15.8%)

                  Blood bilirubin increased (10.5-13%)

                  Splenomegaly (4.8-10.5%)

                  1-10%

                  Cholelithiasis (2.4-5.3%)

                  Dehydration (2.4-5.3%)

                  Fracture (4.3%)

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                  Warnings

                  Contraindications

                  None

                  Cautions

                  Liver test abnormalities

                  • Patients enrolled in clinical trial had abnormal LFTs at baseline, including elevated AST, ALT, TB, and DB
                  • Treatment interruption days ranged from 3-124 days
                  • Obtain baseline LFTs and monitor during treatment
                  • Not evaluated in PFIC patients with cirrhosis; closely monitor for liver test abnormalities
                  • Permanently discontinue if a patient progresses to portal hypertension or experiences a hepatic decompensation event

                  Diarrhea

                  • Diarrhea reported
                  • If diarrhea occurs, monitor for dehydration, and treat promptly
                  • Interrupt dosing if a patient experiences persistent diarrhea
                  • Restart at 40 mcg/kg/day once resolved; may increase dose as tolerated if appropriate
                  • If diarrhea persists and no alternate etiology is identified, stop treatment

                  FSV deficiency

                  • PFIC patients can have FSV deficiency at baseline
                  • Therapy may affect absorption of fat-soluble vitamins
                  • Obtain serum FSV levels at baseline and monitor during treatment, along with any clinical manifestations
                  • If FSV deficiency is diagnosed, supplement with FSV. Discontinue BYLVAY if FSV deficiency persists or worsens despite adequate FSV supplementation

                  Drug interaction overview

                  • Substrate of P-glycoprotein but not a substrate of breast cancer resistance protein
                  • Bile acid binding resins
                    • Separate bile acid binding resins (eg, cholestyramine, colesevelam, or colestipol) at least 4 hr before or after odevixibat
                    • Bile acid binding resins may bind odevixibat in the gut, which may reduce odevixibat efficacy
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                  Pregnancy & Lactation

                  Pregnancy

                  There are no human data on use in pregnant females to establish a drug-associated risk of major birth defects, miscarriage, or adverse developmental outcomes

                  Animal data

                  • May cause cardiac malformations when a fetus is exposed during pregnancy
                  • In pregnant rabbits treated orally with odevixibat during organogenesis, an increased incidence of malformations in fetal heart, great blood vessels, and other vascular sites occurred at all doses; maternal systemic exposure at the lowest dose was 2.1x the maximum recommended dose

                  Lactation

                  Odevixibat has low absorption following oral administration, and breastfeeding is not expected to result in exposure of infant

                  No data are available on its presence in human milk, effects on the breastfed infants, or effects on milk production

                  Odevixibat may reduce absorption of FSV

                  Monitor FSV levels and increase FSV intake, if FSV deficiency occurs during lactation

                  Pregnancy Categories

                  A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                  B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                  C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                  D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                  X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                  NA: Information not available.

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                  Pharmacology

                  Mechanism of Action

                  Ileal bile acid transport inhibitor (IBATi); acts locally in the distal ileum to decrease reuptake of bile acids and increase clearance of bile acids through the colon, thereby, reducing bile acid serum concentration

                  Although mechanism of action in PFIC 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

                  Absorption

                  Plasma concentration: 0.06-0.72 ng/mL (patients 6 months – 17 years)

                  No accumulation of odevixibat was observed following once-daily dosing

                  Peak plasma concentration: 0.47 ng/mL (single 7.2-mg dose in healthy adults)

                  AUC: 2.19 ng·hr/mL (single 7.2-mg dose in healthy adults)

                  Peak plasma time: 1-5 hr (single 7.2-mg dose in healthy adults)

                  Effect of food

                  • Sprinkle on applesauce (9.6 mg-dose): Decreased peak plasma concentration by 39% and AUC by 35%
                  • High-fat meal (800-100 calories with ~50% of total caloric content of meal from fat): Decreased peak plasma concentration by 72% and AUC by 62%; delayed peak plasma time by 3-4.5 hr
                  • Effect of food on systemic exposures to odevixibat is not clinically significant

                  Distribution

                  Protein bound: >99%

                  Metabolism

                  Metabolized via mono-hydroxylation

                  Elimination

                  Half-life: 2.36 hr

                  Excretion: Feces (97% unchanged); urine (0.002%)

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                  Administration

                  Oral Preparation (oral pellets only)

                  Place a small amount of soft food (up to 30 mL [2 tablespoons] of apple sauce, oatmeal, banana or carrot puree, chocolate, or rice pudding) in a bowl

                  Keep food at or below room temperature

                  Open shell containing oral pellet(s) and empty contents into bowl of soft food

                  Gently tap shell to ensure that all contents have been dispersed

                  If dose requires more than one shell of oral pellets, repeat the steps above

                  Gently mix until well dispersed

                  Oral Administration

                  Administer in the morning with a meal

                  For patients taking bile acid binding resins, take at least 4 hr before or after taking a bile acid binding resin

                  Oral pellets

                  • Administer entire dose immediately after mixture is prepared; follow dose with water
                  • Do not store mixture for future use
                  • Do not use in patients who are exclusively on liquid food

                  Capsules

                  • Do not crush or chew capsules
                  • Unable to swallow capsules
                    • Capsules may be opened, and sprinkled and mixed with a small amount of soft food
                    • Follow directions above for oral pellets to prepare and administer such a mixture

                  Storage H3

                  Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

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                  Images

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                  Patient Handout

                  A Patient Handout is not currently available for this monograph.
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                  Formulary

                  FormularyPatient Discounts

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                  The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                  Tier Description
                  1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                  2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                  3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                  4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                  NC NOT COVERED – Drugs that are not covered by the plan.
                  Code Definition
                  PA Prior Authorization
                  Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                  QL Quantity Limits
                  Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                  ST Step Therapy
                  Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                  OR Other Restrictions
                  Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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                  Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.