Transitioning to Oral ADT and Drug-Drug Interactions

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Transitioning patients from injectable to oral androgen deprivation therapy (ADT) requires careful consideration of overlap periods and dosing strategies. Patients currently receiving injectable GnRH agonists may benefit from switching to oral therapy, particularly those with cardiovascular risk factors who could benefit from the improved safety profile demonstrated in the HERO study. The transition involves overlapping the medications, with oral therapy initiated while the injectable agent gradually wears off over time.

Loading dose requirements remain important during transitions, with the standard 3-pill loading dose recommended even when switching from injectable therapy. Similarly, if patients interrupt oral therapy for more than a week or two due to hospitalization, travel, or other circumstances, reloading is recommended before resuming daily dosing. These practical considerations ensure maintained testosterone suppression during treatment transitions and interruptions.

Drug-drug interactions between oral ADT and androgen receptor pathway inhibitors represent a theoretical concern that rarely manifests clinically. Despite pharmacy alerts suggesting dose modifications when combining relugolix with agents like apalutamide or enzalutamide, clinical experience and ongoing trials demonstrate safety and efficacy at standard doses. The lack of clinical evidence supporting these interactions, combined with the historical safety record of similar GnRH antagonists like degarelix, provides confidence for using standard dosing in combination regimens while monitoring testosterone levels to ensure adequate suppression.