Prescription of Off-Label Medications in Patients on Dialysis: Time to Challenge Contraindications?

Abstract Prescribing off-label medications for patients undergoing dialysis presents significant clinical challenges that require careful judgment to optimize the risk-benefit ratio. The altered pharmacokinetic profile in this population, characterized by impaired renal elimination, modified non-renal clearance pathways, and complex polypharmacy has traditionally led to numerous contraindications, not solely due to concerns about drug accumulation but also to prevent serious adverse events. While established dosing protocols exist for certain drug classes, robust pharmacological data remain insufficient for many contemporary medications, leaving clinicians without evidence-based guidance for commonly prescribed authorized therapies in subjects without significant chronic renal disease. The categorical off-label medication contraindications in hemodialysis warrants new reconsideration in the light of emerging evidence that has successfully challenged these constraints through well-designed clinical studies and real-world experiences. In this review, we aim to examine the evidence on selected examples of off-label medications previously deemed contraindicated that have been successfully evaluated in patients treated by dialysis; and explore emerging therapeutic agents. Finally, we discuss the clinical, research, methodological, and regulatory barriers that must be addressed to improve evidence-based prescribing in patients on dialysis.