bylvay

Important safety information

Hepatoxicity : Obtain baseline liver tests and monitor patients frequently for the first 6 to 8 months after starting therapy, and as clinically indicated thereafter during treatment. If liver test abnormalities or signs of clinical hepatitis occur, consider dose reduction or treatment interruption. For persistent or recurrent liver test abnormalities relative to baseline, discontinue BYLVAY. Monitor patients with compensated cirrhosis or portal hypertension more frequently. Permanently discontinue BYLVAY if hepatic decompensation occurs. ( 2.3 , 5.1 ) Diarrhea : Treat dehydration. Treatment interruption or discontinuation may be required for persistent diarrhea. ( 5.2 ) Fat-Soluble Vitamin (FSV) Deficiency : Obtain baseline levels and monitor during treatment. Supplement with FSV if deficiency is observed. If FSV deficiency persists or worsens despite FSV supplementation, consider discontinuing BYLVAY treatment. Fracture: Consider interrupting BYLVAY treatment. Supplement with FSV if indicated. Bleeding: Interrupt treatment with BYLVAY. Optimize treatment of FSV deficiency and consider restarting BYLVAY once the patient is clinically stable. ( 5.3 ) 5.1 Hepatoxicity BYLVAY treatment is associated with a potential for drug-induced liver injury (DILI). In the PFIC and ALGS trials, treatment-emergent elevations of liver tests or worsening of liver tests occurred. Of the six patients who experienced DILI, two underwent liver transplant. Obtain baseline liver tests because some ALGS and PFIC patients have abnormal liver tests at baseline. Monitor patients frequently for the first 6 to 8 months after starting therapy and as clinically indicated thereafter during treatment with BYLVAY. Monitor for elevation in liver tests, for the development of liver-related adverse reactions, and for physical signs of hepatic decompensation. If liver test abnormalities or signs of clinical hepatitis occur in the absence of other causes, consider dose reduction or treatment interruption. Permanently discontinue BYLVAY if a patient experiences the following: persistent or recurrent liver test abnormalities, or upon rechallenge, signs and symptoms consistent with clinical hepatitis, or a hepatic decompensation event. The safety and effectiveness of BYLVAY have not been established in patients with decompensated cirrhosis. Monitor patients with compensated cirrhosis or portal hypertension more frequently and discontinue BYLVAY if hepatic decompensation occurs. IBAT inhibitors, including BYLVAY, are contraindicated in patients with prior or active hepatic decompensation events [see Contraindications (4) ] . 5.2 Diarrhea In Trial 1, diarrhea in PFIC patients 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 [see Adverse Reactions (6.1) ] . One patient treated with BYLVAY 120 mcg/kg/day withdrew from Trial 1 due to persistent diarrhea. In Trial 3, diarrhea in ALGS patients was reported in 1 placebo-treated patient (6%) and in 10 (29%) BYLVAY-treated patients [see Adverse Reactions (6.1) ] . 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. 5.3 Fat-Soluble Vitamin Deficiency BYLVAY may adversely affect absorption of fat-soluble vitamins (FSV). FSV include vitamin A, D, E, and K (measured using INR levels). PFIC and ALGS patients can have FSV deficiency at baseline and are frequently supplemented with FSV. In Trial 1 in PFIC patients, 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 patients treated with BYLVAY dosage 40 mcg/kg/day had new onset or worsening of existing FSV deficiency. In Trial 3 in ALGS patients, new or worsening of existing FSV deficiency was reported in 3 (17.6%) placebo- treated patients and 3 (8.6%) BYLVAY-treated patients [see Adverse Reactions (6.1) ]. Obtain serum FSV levels at baseline and monitor during treatment, along with any clinical manifestations of FSV deficiency. If FSV deficiency is diagnosed, supplement with FSV. If FSV deficiency persists or worsens despite adequate FSV supplementation, consider permanent discontinuation of BYLVAY depending on the benefit and risk balance. If complications of FSV deficiency occur, consider interrupting BYLVAY treatment and reassess to ensure adequate supplementation with FSV. Consider restarting BYLVAY once the patient is clinically stable. Bone Fracture Fracture events have been observed with BYLVAY-treated patients in two open-label postmarketing studies (5% in PFIC patients and 4% in ALGS patients) [see Adverse Reactions (6) ] . If fracture occurs, consider interrupting BYLVAY treatment and supplement with FSV if indicated. Bleeding Interrupt treatment with BYLVAY if bleeding occurs. Optimize treatment of FSV deficiency and consider restarting BYLVAY once the patient is clinically stable.