Potentiation of fluindione or warfarin by dexamethasone in multiple myeloma and AL amyloidosis.
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.
Sellam
Jérémie
J
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.
Costedoat-Chalumeau
Nathalie
N
Amoura
Zahir
Z
Aymard
Guy
G
Choquet
Sylvain
S
Trad
Salim
S
Vignes
Bénédicte Lebrun
BL
Hulot
Jean-Sébastien
JS
Berenbaum
Francis
F
Lechat
Philippe
P
Cacoub
Patrice
P
Ankri
Annick
A
Mariette
Xavier
X
Leblond
Véronique
V
Piette
Jean-Charles
JC
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*
D000925:Anticoagulants; D005938:Glucocorticoids; D010630:Phenindione; D014859:Warfarin; D003907:Dexamethasone; D003404:Creatinine; C017673:fluindione