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Bylvay Safety
Safety and Tolerability Established in the Largest Clinical Trial Program in PFIC
Bylvay is selective, with minimal systemic exposure. Its starting dose is 40 mcg/kg/day, and it is approved for patients as young as 3 months old.
- Most common adverse reactions (>2%) are liver test abnormalities, diarrhea, abdominal pain, vomiting, and fat-soluble vitamin deficiency
- Diarrhea was the most common adverse event, reported in 39% of patients at 40 mcg/kg/day, and 10% on placebo
Clinical Adverse Reactions in PEDFIC 1
| Preferred Term | Placebo N=20 n(%) | Bylvay 40 mcg/kg/day N=23 n(%) | Bylvay 120 mcg/kg/day N=19 n(%) | Total Bylvay N=42 n(%) |
|---|---|---|---|---|
| Any AE | 17 (85.0) | 19 (82.6) | 16 (84.2) | 35 (83.3) |
| Diarrhea | 2 (10.0) | 9 (39.1) | 4 (21.1) | 13 (31.0) |
| Transaminases increased (ALT,AST) | 1 (5.0) | 3 (13.0) | 4 (21.1) | 7 (16.7) |
| Vomiting | 0 | 4 (17.4) | 3 (15.8) | 7 (16.7) |
| Abdominal pain | 0 | 3 (13.0) | 3 (15.8) | 6 (14.3) |
| Blood bilirubin increased | 2 (10.0) | 3 (13.0) | 2 (10.5) | 5 (11.9) |
| Fat-Soluble Vitamin deficiency (A, D, E) | 1 (5.0) | 0 | 3 (15.8) | 3 (7.1) |
| Splenomegaly | 0 | 0 | 2 (10.5) | 2 (4.8) |
| Cholelithiasis | 0 | 0 | 1 (5.3) | 1 (2.4) |
| Dehydration | 0 | 0 | 1 (5.3) | 1 (2.4) |
| Fracture | 0 | 1 (4.3) | 0 | 1 (2.4) |
IMPORTANT SAFETY INFORMATION AND INDICATION
IMPORTANT SAFETY INFORMATION
Warnings and Precautions:
Liver Test Abnormalities
Patients enrolled in a clinical trial had abnormal liver tests at
baseline. In a clinical trial, treatment-emergent elevations of
liver tests or worsening of liver tests relative to baseline values
were observed during the clinical trial. Most abnormalities included
elevation in AST, ALT, or total and direct bilirubin. Treatment
interruption days ranged from 3 days to 124 days; none of the
patients in the pivotal clinical trial permanently discontinued
treatment due to liver test abnormalities.
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 patients with cirrhosis. Closely monitor for liver test abnormalities; permanently discontinue Bylvay if a patient progresses to portal hypertension or experiences a hepatic decompensation event.
Diarrhea
In a 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.
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.
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.
Adverse Reactions
The most common adverse reactions for Bylvay are diarrhea, liver
test abnormalities, vomiting, abdominal pain, and fat-soluble
vitamin deficiency.
Drug Interactions
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 1-855-252-4736.
INDICATIONS AND USAGE
Bylvay is indicated for the treatment of pruritus in patients 3 months of age and older with progressive familial intrahepatic cholestasis (PFIC).
Limitation of Use
Bylvay 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).
Please see full Prescribing Information.
IMPORTANT SAFETY INFORMATION AND INDICATION
IMPORTANT SAFETY INFORMATION
Warnings and Precautions:
Liver Test Abnormalities
Patients enrolled in a clinical trial had abnormal liver tests at
baseline. In a clinical trial, treatment-emergent elevations of
liver tests or worsening of liver tests relative to baseline values
were observed during the clinical trial. Most abnormalities included
elevation in AST, ALT, or total and direct bilirubin. Treatment
interruption days ranged from 3 days to 124 days; none of the
patients in the pivotal clinical trial permanently discontinued
treatment due to liver test abnormalities.
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 patients with cirrhosis. Closely monitor for liver test abnormalities; permanently discontinue Bylvay if a patient progresses to portal hypertension or experiences a hepatic decompensation event.
Diarrhea
In a 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.
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.
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.
Adverse Reactions
The most common adverse reactions for Bylvay are diarrhea, liver
test abnormalities, vomiting, abdominal pain, and fat-soluble
vitamin deficiency.
Drug Interactions
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 1-855-252-4736.
INDICATIONS AND USAGE
Bylvay is indicated for the treatment of pruritus in patients 3 months of age and older with progressive familial intrahepatic cholestasis (PFIC).
Limitation of Use
Bylvay 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).
Please see full Prescribing Information.