<p>Self-administered calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are essential therapies, but their safe use depends on adequate patient training. This study examined temporal shifts in the adverse event (AE) reporting profile for CGRP mAbs during and after the COVID-19 pandemic. We conducted a retrospective disproportionality analysis of the FDA Adverse Event Reporting System (FAERS). Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated for the CGRP mAb class across three cohorts: pre-pandemic (2019), pandemic (April 2020–April 2023), and post-pandemic (July 2023–June 2025). Significant changes were defined by non-overlapping 95% CIs. The analysis identified two divergent trends in signals of disproportionate reporting (SDR). There was a significant increase in device-related and use-error AEs, including “drug dose omission by device” (ROR increased from 10.65 to 37.67) and “accidental underdose” (ROR from 0.29 to 16.80). Notably, the SDR for “wrong technique in product usage process” showed continuous intensification across all three periods. Conversely, there was a sustained and significant decrease in reporting of well-established clinical AEs, most notably for “medication overuse headache” (ROR dropped from 56.92 to 2.91) and “constipation” (ROR from 9.86 to 1.61). Reporting patterns shifted dynamically during the pandemic. The surge in use errors suggests vulnerabilities in patient support for self-administered therapies when in-person care is limited, highlighting a critical need for pharmacist intervention and remote education. The concurrent decline in known clinical AEs may indicate shifting reporting priorities. These findings underscore the importance of contextualizing pharmacovigilance data within public health events and warrant further investigation.</p>