Warfarin with fluoroquinolones, sulfonamides, or azole antifungals: interactions and the risk of hospitalization for gastrointestinal bleeding.
The aim of this study was to determine whether a potential pharmacokinetic interaction between warfarin and orally administered anti-infectives increases the risk of hospitalization for gastrointestinal (GI) bleeding in warfarin users. We conducted a nested case-control and case-crossover study using US Medicaid data. Logistic regression was used to determine the association between GI bleeding and prior use of ciprofloxacin, levofloxacin, gatifloxacin, co-trimoxazole, or fluconazole vs. no exposure and also vs. use of cephalexin, which would not be expected to interact with warfarin. All of the anti-infectives examined were associated with elevated odds ratios (ORs) when compared to no exposure to these drugs. With cephalexin data as the reference, the ORs for co-trimoxazole (OR: 1.68 (95% confidence interval (CI): 1.21-2.33) in the prior 6-10 days) and fluconazole (OR: 2.09 (95% CI: 1.34-3.26) in the prior 11-15 days) were significantly elevated. Warfarin users who had received an anti-infective agent showed a substantially increased risk of GI bleeding. However, a drug-drug interaction with warfarin was evident only for co-trimoxazole and fluconazole.
Schelleman
H
H
Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. hschelle@mail.med.upenn.edu
Bilker
W B
WB
Brensinger
C M
CM
Han
X
X
Kimmel
S E
SE
Hennessy
S
S
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001393:Azoles / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000009:adverse effects*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006760:Hospitalization; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012306:Risk; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D000935:Antifungal Agents; D001393:Azoles; D024841:Fluoroquinolones; D013449:Sulfonamides; D014859:Warfarin