BYLVAY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BYLVAY (BYLVAY).
Ileal bile acid transporter (IBAT) inhibitor; reduces bile acid reabsorption in the terminal ileum, increasing hepatic clearance of bile acids and decreasing serum bile acid levels.
| Metabolism | Primarily metabolized via glucuronidation by UGT1A1 and UGT1A3; also minor oxidation by CYP3A4. |
| Excretion | Primarily fecal (biliary) excretion of unchanged drug and metabolites; minimal renal excretion (<1% of dose). |
| Half-life | Terminal half-life approximately 4.6 hours in healthy subjects; may be prolonged in hepatic impairment. |
| Protein binding | >99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 15 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Absolute bioavailability not established; absorption is enhanced with fat-containing food. |
| Onset of Action | Clinical effect observed within 1-2 hours after oral administration. |
| Duration of Action | Duration of action approximately 12 hours; recommended dosing is three times daily with fat-containing meal. |
400 mg orally once daily with food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease; use with caution. |
| Liver impairment | Child-Pugh Class A: No dose adjustment. Child-Pugh Class B: Reduce dose to 200 mg orally once daily. Child-Pugh Class C: Not recommended. |
| Pediatric use | Not established; safety and efficacy in pediatric patients have not been determined. |
| Geriatric use | No specific dose adjustment; monitor renal function due to age-related decline. Limited data in patients aged ≥65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BYLVAY (BYLVAY).
| Breastfeeding | There are no data on the presence of infigratinib in human milk, its effects on the breastfed infant, or its effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from BYLVAY, advise women not to breastfeed during treatment and for 1 month after the last dose. M/P ratio: Unknown. |
| Teratogenic Risk | Based on animal studies and its mechanism of action (FGFR inhibitor), BYLVAY (infigratinib) is expected to cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, administration of infigratinib to pregnant rats during organogenesis resulted in embryofetal mortality and structural abnormalities at maternal exposures below the recommended human dose. Advise pregnant women of the potential risk to a fetus. First trimester: High risk of teratogenicity. Second and third trimesters: Potential for fetal growth restriction and oligohydramnios due to antiangiogenic effects. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Patients with biliary obstruction.","Patients with complete bile duct obstruction."]
| Precautions | ["Hepatic toxicity: monitor liver function; dose adjustment or discontinuation if transaminases or bilirubin rise significantly.","Gastrointestinal adverse reactions: diarrhea, abdominal pain; may require dose adjustment.","Fat-soluble vitamin deficiency: monitor and supplement vitamins A, D, E, K."] |
| Food/Dietary | Take with food to reduce GI upset. Avoid high-fat meals that may worsen steatorrhea. No specific food or drink interactions aside from grapefruit juice (potential CYP3A4 inhibition). Monitor vitamin E and other fat-soluble vitamin levels as absorption may be impaired; supplementation may be needed. |
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| Fetal Monitoring | Monitor pregnant women for potential fetal harm. Perform pregnancy testing prior to initiation of BYLVAY in females of reproductive potential. Confirm pregnancy status before starting treatment. Monitor for signs of fetal distress, such as decreased fetal movement, and perform ultrasound monitoring for oligohydramnios and fetal growth if drug is used during pregnancy. Monitor for maternal adverse reactions including ocular toxicity (serous retinal detachment), hyperphosphatemia, and nail disorders. |
| Fertility Effects | Based on findings from animal studies, BYLVAY may impair fertility in females and males of reproductive potential. In female rats, infigratinib caused disruption of estrous cycles and reduced fertility at exposures below the human exposure. In male rats, infigratinib caused decreased sperm motility and increased abnormal sperm morphology at exposures below the human exposure. The effects on human fertility are unknown. |
| Clinical Pearls | BYLVAY (odevixibat) is an ileal bile acid transporter (IBAT) inhibitor approved for pruritus in Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC). Requires baseline and periodic liver function tests, fat-soluble vitamin levels, and growth monitoring. May cause diarrhea/steatorrhea; adjust fat intake and use pancreatic enzymes if needed. Monitor for vitamin A, D, E, K deficiencies. Not studied in severe hepatic impairment (Child-Pugh C). Contraindicated with concomitant TGR5 agonists or strong CYP3A4 inducers. |
| Patient Advice | Take exactly as prescribed, usually once daily in the morning with food. · You may experience diarrhea, frequent stools, or oily stools; report persistent symptoms. · Fat-soluble vitamin supplements (A, D, E, K) may be necessary; do not stop without consulting your doctor. · Keep a record of growth (height/weight) and report any significant changes. · Do not take other medications or supplements without first discussing with your healthcare provider. · Avoid grapefruit juice; it may affect how the drug works. · Inform your doctor if you become pregnant or plan to breastfeed. · Store at room temperature away from moisture and heat. |