Warfarin with fluoroquinolones, sulfonamides, or azole antifungals: interactions and the risk of hospitalization for gastrointestinal bleeding

Abstract

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.

Figure 1. Association between drugs of interest and hospitalization for gastrointestinal bleeding in patients receiving warfarin in case-control study after adjustment for confounders with cephalexin as the reference group

Each diamond represents the OR of interest versus cephalexin and the vertical line the 95% CI. All analyses are adjusted for age, gender, race, state, use of proton pump inhibitors, metronidazole, acetaminophen, and prednisone, prior GI bleed, chronic renal disease, liver disease, cellulitis, gastroenteritis, pneumonia, and urinary tract infection.

Figure 1. Association between drugs of interest and hospitalization for gastrointestinal bleeding in patients receiving warfarin in case-control study after adjustment for confounders with cephalexin as the reference group

Each diamond represents the OR of interest versus cephalexin and the vertical line the 95% CI. All analyses are adjusted for age, gender, race, state, use of proton pump inhibitors, metronidazole, acetaminophen, and prednisone, prior GI bleed, chronic renal disease, liver disease, cellulitis, gastroenteritis, pneumonia, and urinary tract infection.