Usual Adult Dose for Pruritus

Initial dose: 40 mcg/kg orally once a day (in the morning)
Maintenance dose: 40 to 120 mcg/kg orally once a day (in the morning)
Maximum dose: 6 mg/day

Comments:

• Patients should be given oral pellet formulations if they weigh less than 19.5 kg; those who weigh 19.5 kg or more should be given capsule formulations.
• The dose may be increased in 40 mg/kg increments after 3 months if pruritus does not improve.

Use: Treatment of pruritus in patients with progressive familial intrahepatic cholestasis (PFIC)

Usual Adult Dose for Pruritus of Partial Biliary Obstruction

Initial dose: 40 mcg/kg orally once a day (in the morning)
Maintenance dose: 40 to 120 mcg/kg orally once a day (in the morning)
Maximum dose: 6 mg/day

Comments:

• Patients should be given oral pellet formulations if they weigh less than 19.5 kg; those who weigh 19.5 kg or more should be given capsule formulations.
• The dose may be increased in 40 mg/kg increments after 3 months if pruritus does not improve.

Use: Treatment of pruritus in patients with progressive familial intrahepatic cholestasis (PFIC)

Usual Pediatric Dose for Pruritus

3 months and older:

• Initial dose: 40 mcg/kg orally once a day (in the morning)
• Maintenance dose: 40 to 120 mcg/kg orally once a day (in the morning)
• Maximum dose: 6 mg/day

Comments:

• Patients should be given oral pellet formulations if they weigh less than 19.5 kg; those who weigh 19.5 kg or more should be given capsule formulations.
• The dose may be increased in 40 mg/kg increments after 3 months if pruritus does not improve.

Use: Treatment of pruritus in patients with PFIC

Usual Pediatric Dose for Pruritus of Partial Biliary Obstruction

3 months and older:

• Initial dose: 40 mcg/kg orally once a day (in the morning)
• Maintenance dose: 40 to 120 mcg/kg orally once a day (in the morning)
• Maximum dose: 6 mg/day

Comments:

• Patients should be given oral pellet formulations if they weigh less than 19.5 kg; those who weigh 19.5 kg or more should be given capsule formulations.
• The dose may be increased in 40 mg/kg increments after 3 months if pruritus does not improve.

Use: Treatment of pruritus in patients with PFIC

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Patients with PFIC and clinically significant portal hypertension or with decompensated cirrhosis: Data not available; frequent monitoring recommended.

Prior to treatment: Liver function tests (e.g., ALT, AST, direct bilirubin, total bilirubin, INR) should be taken

During treatment:

• Treatment should be interrupted if new onset liver function test abnormalities occur OR clinical hepatitis symptoms are observed.
• If abnormalities return to baseline OR stabilized at a new baseline value, providers may consider restarting this drug at 40 mcg/kg orally once a day, and increasing the dose if needed; patients who develop recurring liver test abnormalities should permanently discontinue treatment.
• Patients who develop portal hypertension or hepatic decompensation events (e.g., ascites, hepatic encephalopathy, variceal hemorrhage) should permanently discontinue treatment.

Dose Adjustments

Diarrhea:

• Patients should be monitored for dehydration and should be treated promptly.
• Treatment should be interrupted if persistent diarrhea occurs.
• This drug should be restarted at 40 mcg/kg orally once a day once diarrhea resolves, and the dose may be increased if needed.
• Patients who develop persistent diarrhea without an identifiable alternative etiology should discontinue treatment.

Fat-Soluble Vitamin (FSV) Deficiency:

• Treatment should be discontinued if FSV deficiencies persist or worsen despite appropriate supplementation.

Precautions

CONTRAINDICATIONS:

• None.

Safety and efficacy have not been established in patients younger than 3 months.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug should be taken with a meal.
• Capsules should not be crushed or chewed.
• This drug should be taken at least 4 hours before or after taking bile acid binding resins (if needed).

Reconstitution/preparation techniques: The manufacturer product information should be consulted.

General:

• LIMITATION OF USE: This drug may not be effective in patients with PFIC type 2 with ABCB11 gene variants that result in the functional/complete absence of bile salt export pump protein (BSEP-3).

Monitoring:

• HEMATOLOGIC: INR at baseline and then throughout treatment
• HEPATIC: Liver function tests prior to starting and then throughout treatment
• METABOLIC: FSV levels at baseline and then throughout treatment

Patient advice:

• Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.