Pre‐Emptive Amlodipine for FOLFIRINOX ‐Induced Hypertensive Crises Without Primary Hypertension: A Novel Chronotherapeutic Strategy

ABSTRACT FOLFIRINOX remains a cornerstone therapy for advanced pancreatic ductal adenocarcinoma (PDAC), but its toxicity profile extends beyond myelosuppression and neuropathy to include even rarer complications such as treatment‐associated hypertension. Infusion‐related hypertensive episodes represent a clinically challenging and underrecognized complication, as conventional daily antihypertensive strategies may control acute elevations yet precipitate inter‐cycle hypotension. We describe a 46‐year‐old woman with metastatic PDAC who developed recurrent hypertensive crises (peak 190/102 mmHg) temporally associated with FOLFIRINOX infusions. A trial of daily losartan (50 mg) mitigated infusion‐related hypertension but resulted in symptomatic inter‐cycle hypotension, limiting dose escalation. To better align antihypertensive therapy with the predictable timing of blood pressure surges, a chronotherapeutic strategy was implemented using low‐dose daily losartan (25 mg) combined with a single pre‐emptive dose of amlodipine (5 mg) administered 8–12 h prior to chemotherapy infusion after informed decision‐making. This approach resulted in consistent control of infusion‐related blood pressure elevations (systolic ~125–145 mmHg during treatment), elimination of hypertensive crises, and maintenance of stable inter‐cycle hemodynamics without symptomatic hypotension. Importantly, this strategy enabled uninterrupted delivery of full‐dose chemotherapy. This case highlights a novel, hypothesis‐generating chronotherapeutic approach to chemotherapy‐induced hypertension. Timed antihypertensive administration may represent a targeted strategy to control infusion‐related blood pressure surges while preserving baseline hemodynamic stability; however, further validation in larger studies is required before clinical generalization.