qfitlia

Important safety information

Hepatotoxicity: Obtain liver tests at baseline and then monthly for at least 6 months after initiating QFITLIA and after dose increases, and periodically thereafter. Liver test elevations may require QFITLIA interruption or discontinuation ( 5.3 ). 5.1 Thrombotic Events Serious thrombotic events have been reported in QFITLIA-treated patients. Thrombotic events were reported in 2.6% of patients receiving the 80 mg once monthly dose (2.3 events per 100 person-years), including a fatal event of cerebral venous sinus thrombosis. The 80 mg once monthly dose is not approved or recommended for use. Thrombotic events were reported in 1.4% of patients receiving QFITLIA prophylaxis using the antithrombin-based dose regimen (AT-DR) that targeted AT activity 15-35% (0.8 events per 100 person-years). Participants with established thrombophilia or a history of thrombosis were generally excluded from studies with QFITLIA. The risk of thrombosis is greater in patients with persistent AT activity <15%, with comorbidities that predispose to thrombosis, when bleed management guidelines are not followed in the post-operative setting, when there is an indwelling venous catheter, and with use of the 80 mg once monthly (non-AT-based) dose. Treatment of breakthrough bleeding episodes with CFC or BPA at a dose greater or more frequent than recommended may also increase thrombotic risk [see Dosage and Administration (2.3) ] . The decision to utilize higher dosing regimens of CFC or BPA in the setting of inadequate hemostasis requires an assessment of the benefits and risks and close clinical monitoring. Monitor AT activity using an FDA-cleared test and target AT activity 15–35% to reduce the risk of thrombosis [see Dosage and Administration (2.1 , 2.2) and Warnings and Precautions (5.1) ] . Monitor patients for signs and symptoms of thrombotic events. Interrupt QFITLIA prophylaxis in patients with a thrombotic event and manage as clinically indicated. Inform patients treated with QFITLIA to monitor for and report signs and symptoms of thrombotic events. Consider the benefits and risks of resuming QFITLIA prophylaxis following resolution of the thrombotic event. 5.2 Acute and Recurrent Gallbladder Disease Treatment with QFITLIA is associated with an increased occurrence of acute and recurrent gallbladder disease including cholelithiasis and cholecystitis. QFITLIA at a fixed dose (including 80 mg once monthly) is not approved or recommended for use. In the 270 patients in the QFITLIA clinical studies who received the fixed dose (non-AT-based dose) once monthly regimen, 17% experienced gallbladder events and 4% (11 patients) underwent cholecystectomy. In 286 patients who received the AT-DR, 3.8% experienced gallbladder events and 0.3% (1 patient) underwent cholecystectomy. All but one of the patients who underwent cholecystectomy resumed QFITLIA after surgery. One patient who started on fixed dosing experienced cholangitis and pancreatitis caused by gallstone disease more than a year after cholecystectomy while receiving AT-DR. Patients diagnosed with acute or recurrent gallbladder disease most commonly presented with epigastric pain, generalized abdominal pain, indigestion, nausea and/or vomiting. If gallbladder disease is suspected, appropriate imaging and clinical follow-up are indicated. Consider alternative treatment for hemophilia in patients with a history of symptomatic gallbladder disease. Consider interruption or discontinuation of QFITLIA if gallbladder disease occurs. 5.3 Hepatotoxicity In the two randomized studies testing QFITLIA 80 mg once monthly, serum alanine transaminase (ALT) and aspartate transaminase (AST) elevations above 3 times the upper limit of normal (ULN) occurred in 32% of patients with hemophilia with inhibitors and 18% of patients with hemophilia without inhibitors compared to no events of AST or ALT elevation greater than 3× ULN in the control groups. There was one case of moderate hepatic injury (ALT elevation >300 U/L and total serum bilirubin >3 mg/dL) attributable to QFITLIA use. This patient had elevation of liver tests after a single 80 mg dose that continued to rise with repeated dosing of QFITLIA 80 mg once monthly. This patient's liver tests recovered with drug discontinuation. QFITLIA 80 mg once monthly is not approved or recommended for use. On the AT-DR, 3.4% of patients treated with QFITLIA had at least one ALT value greater than 3× ULN with a median onset of 89 days after initial dosing (range 15 to 768 days). Avoid use of QFITLIA in patients with hepatic impairment (Child-Pugh Class A, B and C). Obtain baseline liver tests including AST, ALT, and total bilirubin prior to initiating QFITLIA, monthly for at least the first 6 months of QFITLIA use, and monthly for at least 6 months after a dose increase, and periodically thereafter as clinically indicated. If new or worsening liver test abnormalities occur, perform appropriate diagnostic evaluations, initiate medical management as appropriate and monitor laboratory parameters until they return to baseline. If ALT or AST elevations greater than 5× ULN occur, interrupt QFITLIA treatment. Consider the benefits and risks of resuming QFITLIA prophylaxis following resolution of transaminase elevations. If you decide to restart QFITLIA, wait until liver tests have returned to baseline. If QFITLIA is restarted and ALT or AST elevations greater than 5× ULN reoccur or the patient experiences jaundice (total bilirubin ≥2.5 mg/dL) thought to be from hepatotoxicity with other causes of liver test elevation ruled out, permanently discontinue QFITLIA.