fitusiran
Thrombotic Events and Acute and Recurrent Gallbladder Disease
Thrombotic Events
Serious thrombotic events have been reported in fitusiran -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 fitusiran 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 fitusiran.
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 fitusiran prophylaxis in patients with a thrombotic event and manage as clinically indicated.
Inform patients treated with fitusiran to monitor for and report signs and symptoms of thrombotic events. Consider the benefits and risks of resuming fitusiran prophylaxis following resolution of the thrombotic event.
Acute and Recurrent Gallbladder Disease
Treatment with fitusiran is associated with an increased occurrence of acute and recurrent gallbladder disease including cholelithiasis and cholecystitis. Fitusiran at a fixed dose (including 80 mg once monthly) is not approved or recommended for use. In the 270 patients in the fitusiran 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 fitusiran if gallbladder disease occurs.
Patient care
- Monitor patients for signs and symptoms of thrombotic events. Interrupt fitusiran prophylaxis in patients with a thrombotic event and manage as clinically indicated
Patient counseling
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
Use of BPAs or CFCs
Advise the patient and/or caregiver to discontinue prophylactic use of BPA or CFC no later than 7 days after starting QFITLIA to reduce the risk of thrombotic events. Discuss the appropriate dosing and frequency of BPA or CFC for breakthrough bleed management with the patient and/or caregiver prior to starting QFITLIA prophylaxis [see Dosage and Administration (2.3)].
Thrombotic Events
Advise the patient and/or caregiver of the risk of thrombotic events while receiving QFITLIA. Inform the patient and/or caregiver of the need for periodic measurements of AT activity that may result in changes to the QFITLIA dose and/or frequency of administration to reduce the risk for thrombosis. Educate patients on the signs and symptoms of thrombotic events and to seek immediate medical attention if new symptoms of thrombotic events occur [see Warnings and Precautions (5.1)].
Acute and Recurrent Gallbladder Disease
Inform the patient and/or caregiver of the risk of acute and recurrent gallbladder disease while receiving QFITLIA. Educate patients on the signs and symptoms of gallbladder disease and to seek medical attention if new symptoms of gallbladder disease occur [see Warnings and Precautions (5.2)].
Communications
To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation 1-800-745-4447 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.