Potentiation of fluindione or warfarin by dexamethasone in multiple myeloma and AL amyloidosis

ObjectivesPatients with primary systemic (AL) amyloidosis or multiple myeloma are frequently treated with cyclic dexamethasone (DXM) courses and often require oral anticoagulants. We previously reported a strong potentiation of oral anticoagulants with intravenous methylprednisolone and observed a similar potentiation with DXM in 3 patients, which led us to prospectively investigate the interaction between DXM and oral anticoagulants.MethodsNine patients with multiple myeloma (n = 6) or AL amyloidosis (n = 3), including 6 prospective patients, taking fluindione (n = 8) or warfarin (n = 1), were studied for a total of 10 cycles. DXM (40 mg/day for 4 days every 28 days) was administered alone (n = 4) or with melphalan (n = 5). One patient was studied for 2 consecutive cycles after a moderate increase in the international normalized ratio (INR) during the first course of DXM. International normalized ratio (INR) was measured serially during DXM administration. Plasma oral anticoagulant concentrations were measured for 5 cycles.ResultsThe mean INR increased from 2.75 (range: 1.80–3.6) at baseline to 5.22 (3.09–7.07) after DXM. Oral anticoagulants were transiently stopped during 8 cycles and 1 mg oral vitamin K was given during 2. No serious bleeding was observed. Plasma oral anticoagulant concentrations increased after DXM administration. In controls receiving DXM without oral anticoagulants, DXM alone did not increase prothrombin time.ConclusionHigh dose DXM can potentiate oral anticoagulants and elevate INR substantially. INR should therefore be monitored repeatedly during concomitant administration of these 2 drugs to allow individual adaptation of oral anticoagulant doses.