Black Box Warning
The FDA's most serious safety warning, displayed in a bordered box at the top of prescribing information. Black box warnings indicate significant risks that must be weighed before prescribing. GLP-1 receptor agonists carry a black box warning for thyroid C-cell tumour risk based on rodent studies.
Technical Context
Notable boxed warnings for peptide drugs: GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide, exenatide, lixisenatide, tirzepatide) — risk of thyroid C-cell tumours in rodents, contraindicated in MTC/MEN2 history; Corticotropin (ACTH) — risk of serious infections due to immunosuppressive effects; Cyclosporine — risk of neoplasms, serious infections, and nephrotoxicity (at systemic doses). The FDA can require a boxed warning at the time of approval (based on clinical trial data) or post-marketing (based on emerging safety signals). Black box warnings require enhanced informed consent discussions with patients and are typically accompanied by REMS programmes for the highest-risk drugs. Removal of a boxed warning is possible if subsequent data demonstrate the risk is lower than initially assessed, but this is rare.