IMPORTANT SAFETY INFORMATION
Warnings and Precautions:
Liver Test Abnormalities
Patients enrolled in PFIC and ALGS clinical trials had abnormal liver tests at baseline. In clinical trials,
treatment-emergent elevations of liver tests or worsening of liver tests relative to baseline values were observed
during the clinical trials.
In a clinical trial with PFIC patients, treatment-emergent elevations of liver tests or worsening of liver tests
relative to baseline values were observed during the clinical trial. Most abnormalities included elevations in AST,
ALT, or total and direct bilirubin. Treatment interruption days ranged from 3 days to 124 days; no PFIC patients
permanently discontinued treatment due to liver test abnormalities.
In a clinical trial with ALGS patients, treatment-emergent elevations or worsening in liver tests relative to
baseline values were observed during the trial. Most abnormalities included elevations in ALT or AST. One ALGS
patient interrupted treatment for 40 days; no ALGS patients permanently discontinued treatment due to liver test
Obtain baseline liver tests and monitor during treatment. Dose reduction or treatment interruption may be required
if abnormalities occur. For persistent or recurrent liver test abnormalities, consider treatment discontinuation.
Bylvay was not evaluated in PFIC or ALGS patients with cirrhosis. Closely monitor for liver test abnormalities;
permanently discontinue Bylvay if a patient progresses to portal hypertension or experiences a hepatic
In a PFIC clinical trial, diarrhea was reported in 2 (10%) placebo-treated patients, 9 (39%) Bylvay-treated 40
mcg/kg/day patients, and 4 (21%) Bylvay-treated 120 mcg/kg/day patients. Treatment interruption due to diarrhea
occurred in 2 patients with 3 events during treatment with Bylvay 120 mcg/kg/day. Treatment interruption due to
diarrhea ranged between 3 to 7 days. One patient treated with Bylvay 120 mcg/kg/day withdrew from the pivotal
clinical trial due to persistent diarrhea.
In an ALGS clinical trial, diarrhea in ALGS patients was reported in 1 (6%) placebo-treated patient and in 10 (29%)
Bylvay-treated patients. No patients interrupted or permanently discontinued Bylvay due to diarrhea.
If diarrhea occurs, monitor for dehydration and treat promptly. Interrupt Bylvay dosing if a patient experiences
persistent diarrhea. Restart Bylvay at 40 mcg/kg/day when diarrhea resolves and increase the dose as tolerated if
appropriate. If diarrhea persists and no alternate etiology is identified, stop Bylvay treatment.
Fat-Soluble Vitamin (FSV) Deficiency
Fat-soluble vitamins (FSV) include vitamin A, D, E, and K (measured using INR levels). PFIC patients can have FSV
deficiency at baseline. Bylvay may affect absorption of fat-soluble vitamins. In a clinical trial, new onset or
worsening of existing FSV deficiency was reported in 1 (5%) placebo-treated patient and 3 (16%) Bylvay-treated 120
mcg/kg/day patients; none of the Bylvay-treated 40 mcg/kg/day patients had new onset or worsening of existing FSV
deficiency. In an ALGS clinical trial, new or worsening of existing FSV deficiency was reported in 3 (17.6%)
placebo-treated patients and 3 (8.6%) Bylvay-treated patients.
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.
The most common adverse reactions for Bylvay in patients with PFIC are diarrhea, liver test abnormalities, vomiting,
abdominal pain, and fat-soluble vitamin deficiency.
The most common adverse reactions for Bylvay patients with ALGS are diarrhea, abdominal pain, hematoma, and
For patients taking bile acid binding resins, take Bylvay at least 4 hours before or 4 hours after taking a bile
acid binding resin.
Use in Specific Populations
There are no human data on Bylvay use in pregnant persons to establish a drug-associated risk of major birth
defects, miscarriage, or adverse developmental outcomes. Based on findings from animal reproduction studies, Bylvay
may cause cardiac malformations when a fetus is exposed during pregnancy. There is a pregnancy exposure registry
that monitors pregnancy outcomes in women exposed to Bylvay during pregnancy. For more information, please call
INDICATIONS AND USAGE
Bylvay is an ileal bile acid transporter (IBAT) inhibitor indicated for the treatment of cholestatic pruritus in:
Patients 12 months of age and older with Alagille syndrome (ALGS)
Patients 3 months of age and older with progressive familial
intrahepatic cholestasis (PFIC)
Limitation of Use:
Bylvay may not be
effective in a subgroup of PFIC type 2 patients with specific
ABCB11 variants resulting in non-functional or complete absence
of the bile salt export pump protein
Please see full Prescribing Information.