title: Potentiation of fluindione or warfarin by dexamethasone in multiple myeloma and AL amyloidosis.
abstract: OBJECTIVE
  Patients 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.
  
  
  METHODS
  Nine 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  High 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.
authors: Service de Médecine Interne, Centre Hospitalier Universitaire Pitié-Salpêtrière, Université Paris VI Pierre et Marie Curie, Centre de Reference National Pour les Lupus et le Syndrome des Antiphospholipides, Paris, France.
authors: Jérémie
authors: J
authors: Sellam
authors: Nathalie
authors: N
authors: Costedoat-Chalumeau
authors: Zahir
authors: Z
authors: Amoura
authors: Guy
authors: G
authors: Aymard
authors: Sylvain
authors: S
authors: Choquet
authors: Salim
authors: S
authors: Trad
authors: Bénédicte Lebrun
authors: BL
authors: Vignes
authors: Jean-Sébastien
authors: JS
authors: Hulot
authors: Francis
authors: F
authors: Berenbaum
authors: Philippe
authors: P
authors: Lechat
authors: Patrice
authors: P
authors: Cacoub
authors: Annick
authors: A
authors: Ankri
authors: Xavier
authors: X
authors: Mariette
authors: Véronique
authors: V
authors: Leblond
authors: Jean-Charles
authors: JC
authors: Piette
mesh_terms: D000368:Aged; D000686:Amyloidosis / Q000188:drug therapy*; D000925:Anticoagulants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001777:Blood Coagulation; D003404:Creatinine / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D018579:Patient Selection; D010630:Phenindione / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011517:Prothrombin Time; D014859:Warfarin / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D005938:Glucocorticoids; D010630:Phenindione; D014859:Warfarin; D003907:Dexamethasone; D003404:Creatinine; C017673:fluindione