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DRUG CLASS
EFFECT ON
RECOMMENDATION/COMMENTS
WARFARIN/MECHANISM
Azole antifungals
Increased response due to inhibition of
Increased INR also reported with intravaginal and topical miconazole. Fluconazole (Diflucan)
INR can be increased significantly with single doses of fluconazole. Itraconazole (Sporanox)
Dose-related interaction, but can be seen with lower doses. Ketoconazole (Nizoral)
Monitor INR when therapy started, stopped, or dose changed.a,b,c Some Miconazole (Monistat)
clinicians consider empirically lowering the warfarin dose by about 25% Posaconazole (Noxafil
[U.S.], Posanol [Canada])
Voriconazole (Vfend)
Cephalosporins
Oral cephalosporins such as cefaclor, cefixime, cefpodoxime, cefuroxime cephalosporins might increase the effect
have generally not been shown to interact with warfarin. of warfarin by inhibiting the production Avoid use of cefotetan. It can increase INR directly.
Consider monitoring INR when therapy started or stopped. Fluoroquinolones
Increased response possibly due to
Increase in INR is typically seen within first week of quinolone therapy. Ciprofloxacin (Cipro)
Monitor INR when any fluoroquinolone started or stopped. Gemifloxacin (Factive)
Levofloxacin (Levaquin)
binding sites, or disruption of intestinal Moxifloxacin (Avelox)
Norfloxacin (Noroxin)
Ofloxacin (Floxin)
Griseofulvin
Decreased response possibly due to
Effect on warfarin is gradual. Maximum effect might not be seen for (Fulvicin, etc)
several weeks or more. Monitor INR when therapy started, stopped, or dose changed. Continue to monitor until INR stable. Isoniazid
Increased response possibly due to
Slow INH acetylators are at greatest risk. Monitor INR when therapy started, stopped, or dose changed. Macrolides
Macrolides can increase the effect of
Increased INR reported with all macrolides. Strongest evidence with Azithromycin
erythromycin. Increased INR reported with ophthalmic erythromycin. (Zithromax)
Monitor INR when any macrolide is started or stopped. Clarithromycin (Biaxin)
Erythromycin
Metronidazole
Increased response caused by inhibition
Avoid use if possible. Metronidazole can dramatically increase INR.
(Flagyl)
Topical preparations are less of a problem due to minimal systemic absorption. If used, monitor INR closely when therapy started or stopped. Some clinicians consider empirically lowering the warfarin dose by 25% to 40%. Penicillins
High doses of IV penicillins increase the
Oral penicillin G or V and ampicillin do not appear to interact with Monitor INR several days after start of dicloxacillin or nafcillin, and again after treatment ends. Effects might persist for weeks after dicloxacillin or nafcillin is discontinued. For high-dose IV penicillins and amoxicillin or amoxicillin/clavulanic Exception: Decreased response seen
acid, monitor INR when therapy started or stopped. with dicloxacillin and nafcillin possibly due to enhanced metabolism of warfarin. Rifampin
Decreased response due to increased
Avoid use if possible.
(Rifadin)
Effect usually seen within one to three weeks after starting rifampin. Rifabutin
If used, monitor INR closely for at least two weeks when therapy is (Mycobutin)
started, stopped, or dose is changed.12 Some clinicians consider empirically increasing the dose of warfarin by 25% to 50%. Sulfonamides
Increased effect resulting from reduced
Increased INR reported with TMP/SMX, sulfamethoxazole, sulfisoxazole. Sulfamethoxazole,
(Including with 3-day courses of TMP/SMX for acute cystitis.) Sulfisoxazole, etc.
Avoid use if possible. A case study showed a more than three-fold
increase in INR after six days of concomitant therapy with TMP/SMX. Increased risk of bleeding may be especially significant in the elderly. If used, monitor INR when therapy is started or stopped. Some clinicians consider empirically lowering the warfarin dose by 25% to 40%. Telithromycin
Increased effect likely due to reduced
Monitor INR closely when telithromycin is started or stopped. A case (Ketek)
report noted an increase in INR over the first five days of concomitant therapy. Tetracyclines
Increased response due to unknown
Increased INR seen with doxycycline and tetracycline. Doxycycline
Monitor INR when therapy with any tetracycline is started or stopped. Minocycline
Tetracycline

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