Doxifluridine

As a 5-FU prodrug, doxifluridine carries the fluoropyrimidine-class potential for endothelial injury and rare thrombotic microangiopathy. Pharmacokinetic data show that, while nonrenal pathways dominate elimination, doxifluridine itself has a meaningful renal clearance component (renal clearance roughly half of total clearance after IV dosing), so reduced kidney function could increase parent-drug and 5-FU exposure and the risk of systemic toxicity. Most renal events are likely prerenal/electrolyte-related from chemotherapy GI toxicity rather than direct tubular injury.

Generally renally well tolerated. If TMA/HUS occurs (class effect): microangiopathic hemolytic anemia, thrombocytopenia, rising creatinine, hypertension. Volume depletion from diarrhea/vomiting can cause prerenal azotemia.

Variable; class-level TMA typically after prolonged cumulative exposure.

5'-Deoxy-5-fluorouridine is a prodrug converted to 5-fluorouracil, predominantly by pyrimidine nucleoside phosphorylase (thymidine phosphorylase), which is often elevated in tumor tissue. The liberated 5-FU is metabolized to FdUMP and FUTP, inhibiting thymidylate synthase and disrupting RNA/DNA synthesis.

For suspected fluoropyrimidine-associated TMA, stop the drug and provide supportive care (blood pressure control, transfusion, renal support/dialysis as needed) with nephrology/hematology input. Manage prerenal AKI with volume resuscitation and electrolyte correction.