Background: Omaveloxolone is an Nrf2 activator approved in the US and the EU for the treatment of Friedreich ataxia (FA) in patients aged ≥16 years. In the MOXIe Part 2 trial, elevations in alanine or aspartate aminotransferase (ALT or AST), a potential class effect of Nrf2 activators, were among the most common treatment-emergent adverse events (TEAEs). These TEAEs occurred early (median time to onset, 16 days), were transient in nature (median duration, 33 days), and were not accompanied by total bilirubin increases; no participants had laboratory abnormalities that met Hy’s law criteria. Per label recommendations, ALT, AST, and total bilirubin should be monitored prior to omaveloxolone initiation, monthly for the first 3 months, and periodically thereafter (frequency not specified). If aminotransferases increase to >5×ULN or >3×ULN with evidence of liver dysfunction (eg, elevated bilirubin), omaveloxolone should be discontinued. When aminotransferase levels stabilize or resolve, omaveloxolone may be reinitiated with more frequent liver function testing (LFT); the approach to reinitiation is not specified and may create ambiguity for clinicians. Objectives: We present expert opinions on use considerations for this topic based on real-world clinical practice that may help inform patient management decisions. Methods: Semi-structured interviews were conducted with 4 FA experts from the US and the EU and a US hepatologist. Results: The panel provided their interpretations of the label and use considerations. Experts suggested that after 3 months on treatment, the frequency of LFT may be reduced from monthly to every 6 months and then yearly for patients with normal ALT and AST levels. In real-world practice, clinicians may consider a more conservative approach of treatment interruption if ALT or AST levels increase to >3×ULN in the absence of liver dysfunction, due to practical considerations as patients are followed up less frequently than in the trial setting. Per experts’ experiences, patients who have a dose interruption due to ALT or AST elevations are indicated for LFT after 2 weeks; those with stabilizing or resolving ALT and AST may be reinitiated with stepwise dose titrations and close monitoring every 2 weeks. Conclusions: There are important clinical practice considerations for patient/laboratory monitoring regarding aminotransferase elevations in the real-world setting that may help inform patient monitoring and management decisions.