WASHINGTON -- In the 13 months after obeticholic acid (Ocaliva) was approved in May 2016, 19 patient deaths were reported to the FDA, the agency said Thursday, at least some of which appeared to stem from on the drug's label.
Of these 19 fatalities, the agency determined that seven were in patients with moderate to severe liver impairment who were taking the drug at 5 mg daily; the drug's label states that patients with this degree of impairment should not receive more than 10 mg twice weekly, the FDA said. For most of the other fatal cases, not enough information was provided to identify causes or contributing factors.
The agency also received reports of additional non-fatal cases of serious liver injury involving patients with liver impairment in whom dosing was excessive.
Obeticholic acid is in combination with ursodeoxycholic acid.
"Healthcare professionals should determine the patient's baseline liver function prior to starting Ocaliva. Patients with moderate to severe liver impairment (Child-Pugh B and C) should be started on the approved dosing schedule of 5 mg once weekly, rather than the 5 mg daily dosing used for other PBC patients, and if needed, can be increased up to a maximum approved dose of 10 mg twice weekly," the FDA said in its Drug Safety Communication about the issue.
Patients' liver function should be monitored while on therapy, the agency added, with doses reduced if patients progress to moderate or severe impairment.
The drug "may also be associated with liver injury in some patients with mild disease who are receiving the correct dose," the FDA noted. It said it was working with drugmaker Intercept Pharmaceuticals to address the apparent dosing confusion.