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

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.