Odevixibat

Odevixibat – Description

• Odevixibat is an ileal bile acid transporter (IBAT) inhibitor indicated for the treatment of pruritus in patients 3 months and older with progressive familial intrahepatic cholestasis (PFIC) and patients 1 year and older with Alagille syndrome (ALGS).⁶⁶⁸¹⁶ 
• PFIC and ALGS are rare, inherited childhood disorders associated with cholestasis, pruritus, and potentially fatal liver disease.
• The most prominent and problematic manifestation of these conditions is pruritis, which can lead to physical abrasions and scarring, as well as functional impacts (e.g., sleep and mood disorders) and deterioration in quality of life.
• Prior to IBAT inhibitors, treatment relied on supportive pharmacologic therapy for symptomatic relief (e.g., ursodeoxycholic acid, cholestyramine, antihistamines) or surgical intervention (e.g., surgical biliary diversion, liver transplantation).⁶⁶⁸²³ 
• In clinical trials for PFIC (n = 62) and ALGS (n = 52), pediatric patients treated with odevixibat demonstrated greater improvement in pruritus compared to placebo, based on caregiver-reported outcome.
• Monitor hepatic function and fat-soluble vitamin concentrations at baseline and periodically throughout treatment.⁶⁶⁸¹⁶

Indications & Dosage

•  Alagille syndrome-associated cholestatic pruritus
•  Progressive familial intrahepatic cholestasis-associated pruritus

For the treatment of progressive familial intrahepatic cholestasis-associated pruritus

NOTE: Odevixibat may not be effective in progressive familial intrahepatic cholestasis (PFIC) type 2 patients with ABCB11 variants resulting in nonfunctional or complete absence of bile salt export pump protein (BSEP-3).⁶⁶⁸¹⁶

Oral dosage (capsules)

Adults:

40 mcg/kg/dose PO once daily in the morning; round to appropriate capsule strength. If no improvement after 3 months, may increase dose in 40 mcg/kg increments up to 120 mcg/kg/day (Max: 6 mg/day).⁶⁶⁸¹⁶

Children and Adolescents weighing 19.5 kg or more:

40 mcg/kg/dose PO once daily in the morning; round to appropriate capsule strength. If no improvement after 3 months, may increase dose in 40 mcg/kg increments up to 120 mcg/kg/day (Max: 6 mg/day).⁶⁶⁸¹⁶

Oral dosage (oral pellets/granules)

Infants 3 to 11 months and Children weighing less than 19.5 kg:

40 mcg/kg/dose PO once daily in the morning; round to appropriate oral pellet strength. If no improvement after 3 months, may increase dose in 40 mcg/kg increments up to 120 mcg/kg/day.⁶⁶⁸¹⁶

For the treatment of Alagille syndrome-associated cholestatic pruritus

Oral dosage (capsules)

Adults:

120 mcg/kg/dose PO once daily in the morning; round to appropriate capsule strength. May decrease dose to 40 mcg/kg/dose PO once daily for adverse reactions; once tolerability issues stabilize, increase to 120 mcg/kg/day (Max: 7.2 mg/day).⁶⁶⁸¹⁶

Children and Adolescents weighing 19.5 kg or more:

120 mcg/kg/dose PO once daily in the morning; round to appropriate capsule strength. May decrease dose to 40 mcg/kg/dose PO once daily for adverse reactions; once tolerability issues stabilize, increase to 120 mcg/kg/day (Max: 7.2 mg/day).⁶⁶⁸¹⁶

Oral dosage (oral pellets/granules)

Children weighing less than 19.5 kg:

120 mcg/kg/dose PO once daily in the morning; round to appropriate oral pellet strength. May decrease dose to 40 mcg/kg/dose PO once daily for adverse reactions; once tolerability issues stabilize, increase to 120 mcg/kg/day.⁶⁶⁸¹⁶

Maximum Dosage Limits:

•Adults

120 mcg/kg/day (Max: 7.2 mg/day) PO.

•Geriatric

Safety and efficacy have not been established. PFIC and ALGS are largely diseases of pediatric and young adults. Clinical studies did not include patients 65 years of age and older.

•Adolescents

120 mcg/kg/day (Max: 7.2 mg/day) PO.

•Children

120 mcg/kg/day (Max: 7.2 mg/day) PO.

•Infants

3 to 11 months: 120 mcg/kg/day PO.

1 to 2 months: Safety and efficacy have not been established.

•Neonates

Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

• Interrupt treatment with odevixibat if new liver test abnormalities occur or symptoms consistent with clinical hepatitis occur.
• 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 permanent discontinuation of odevixibat if liver test abnormalities recur.
• Permanently discontinue odevixibat if a patient experiences persistent or recurrent liver test abnormalities or, upon rechallenge, signs and symptoms consistent with clinical hepatitis, or a hepatic decompensation event (e.g., variceal hemorrhage, ascites, hepatic encephalopathy).⁶⁶⁸¹⁶

Patients with Renal Impairment Dosing

No dosage adjustments are needed; less than 0.002% of a dose is excreted in the urine.⁶⁶⁸¹⁶

•  ascites
•  hepatic decompensation
•  hepatic encephalopathy

Precautions

•  bleeding
•  breast-feeding
•  hepatic cirrhosis
•  hepatitis
•  portal hypertension
•  pregnancy
•  vitamin A deficiency
•  vitamin D deficiency
•  vitamin K deficiency

Interactions

•  Acetaminophen; Codeine
•  Acetaminophen; Hydrocodone
•  Acetaminophen; Oxycodone
•  Alfentanil
•  Aspirin, ASA; Carisoprodol; Codeine
•  Aspirin, ASA; Oxycodone
•  Atogepant
•  Avanafil
•  Benzhydrocodone; Acetaminophen
•  Bile acid sequestrants
•  Buprenorphine
•  Buprenorphine; Naloxone
•  Butalbital; Acetaminophen; Caffeine; Codeine
•  Butalbital; Aspirin; Caffeine; Codeine
•  Carbamazepine
•  Cariprazine
•  Celecoxib; Tramadol
•  Chlorpheniramine; Codeine
•  Chlorpheniramine; Hydrocodone
•  Cholestyramine
•  Clozapine
•  Codeine
•  Codeine; Guaifenesin
•  Codeine; Guaifenesin; Pseudoephedrine
•  Codeine; Phenylephrine; Promethazine
•  Codeine; Promethazine
•  Colesevelam
•  Colestipol
•  Cyclosporine
•  Diazepam
•  Doravirine
•  Doravirine; Lamivudine; Tenofovir disoproxil fumarate
•  Fentanyl
•  Homatropine; Hydrocodone
•  Hydrocodone
•  Hydrocodone; Ibuprofen
•  Isradipine
•  Lopinavir; Ritonavir
•  Lumateperone
•  Mefloquine
•  Meperidine
•  Methadone
•  Nanoparticle Albumin-Bound Paclitaxel
•  Nanoparticle Albumin-Bound Sirolimus
•  Nimodipine
•  Nirmatrelvir; Ritonavir
•  Nisoldipine
•  Oxycodone
•  Paclitaxel
•  Ritonavir
•  Sildenafil
•  Sirolimus
•  Sufentanil
•  Tacrolimus
•  Tramadol
•  Tramadol; Acetaminophen
•  Ubrogepant
•  Warfarin

Adverse Reactions

•  abdominal pain
•  anemia
•  ascites
•  bleeding
•  bone fractures
•  cholelithiasis
•  coagulopathy
•  dehydration
•  diarrhea
•  elevated hepatic enzymes
•  epistaxis
•  hematoma
•  hepatic decompensation
•  hepatic encephalopathy
•  hepatitis
•  hyperbilirubinemia
•  prolonged bleeding time
•  splenomegaly
•  vitamin A deficiency
•  vitamin D deficiency
•  vitamin K deficiency
•  vomiting
•  weight loss

Monitoring Parameters

Monitoring Parameters

•  INR
•  LFTs
•  serum bilirubin (total and direct)

Classifications

• Alimentary Tract and Metabolism
  • Bile and Liver Therapy
    • Bile Therapy
      •  Ileal Bile Acid Transporter (IBAT) Inhibitors

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