+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Comparison of the effects of azole antifungal agents on the anticoagulant activity of warfarin



Comparison of the effects of azole antifungal agents on the anticoagulant activity of warfarin



Biological and Pharmaceutical Bulletin 37(12): 1990-1993



The package insert of the antithrombotic agent warfarin warns users of its interaction with azole antifungals. However, information on the frequency or degree of these interactions is limited. In particular, the time to onset of azole-mediated prothrombin time prolongation, expressed as the international normalized ratio (INR), is poorly characterized. Therefore, we retrospectively examined the INR in 29 patients administered warfarin with fluconazole (FLCZ), voriconazole (VRCZ), or itraconazole (ITCZ). INRs in 18 patients taking FLCZ and in 5 patients taking VRCZ significantly increased from 1.40 to 2.94 and from 1.95 to 2.89, respectively. The warfarin sensitivity index (WSI), calculated as INR/daily warfarin dose, also significantly increased from 1.06 to 1.89 with FLCZ and showed an upward trend from 1.13 to 2.23 with VRCZ. ITCZ had no influence on the INR or WSI in 6 patients. The INRs observed when warfarin was coadministered with azoles (Y) correlated significantly with those observed in the absence of azoles (X): FLCZ, Y=4.94X-3.96, r(2)=0.80; VRCZ, Y=2.13X-1.27, r(2)=0.93. Moreover, in all 8 patients with closely monitored INRs, the WSI increased within 1 week of FLCZ or VRCZ coadministration. In conclusion, FLCZ and VRCZ augmented the anticoagulant activity of warfarin. The INR should be closely monitored within 1 week of initiating FLCZ or VRCZ coadministration with warfarin, especially in patients with high INRs.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 057472230

Download citation: RISBibTeXText

PMID: 25451849


Related references

Comparison of the Effects of Azole Antifungal Agents on the Anticoagulant Activity of Warfarin. Biological & Pharmaceutical Bulletin 37(12): 1990-1993, 2014

Synergic effects of tactolimus and azole antifungal agents against azole-resistant Candida albican strains. Journal of Antimicrobial ChemoTherapy 42(6): 747-753, 1998

The combination effects of MDR inhibitors and azole antifungal agents against azole resistant Candida albicans strains. Clinical Infectious Diseases 25(2): 487, 1997

Fungicidal activity of azole antifungal agents. 2008

Hepatic and endocrine effects of azole antifungal agents. Chemotherapy of fungal diseases: 205-229, 1990

Adverse Effects Associated with Long-Term Administration of Azole Antifungal Agents. Drugs 79(8): 833-853, 2019

Amino acid substitutions in the cytochrome P-450 lanosterol 14alpha-demethylase (CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents. Antimicrobial Agents and ChemoTherapy 42(2): 241-253, 1998

A single amino acid substitution in the cytochrome P-450 lanosterol 14alpha-demethyalase from azole-resistant Cryptococcus neoformans clinical isolate contributed to resistance to azole antifungal agents. Abstracts of the General Meeting of the American Society for Microbiology 101: 370, 2001

Different effects of azole-antifungal agents on the regulation of intracellular calcium concentration of Trichophyton rubrum. Journal of Dermatological Science 12(2): 156-162, 1996

Effects of terconazole and other azole antifungal agents on the sterol and carbohydrate composition of Candida albicans. Diagnostic Microbiology and Infectious Disease 13(1): 31-35, 1990

Different effects of azole-antifungal agents on ionomycin-response of intracellular calcium in Trichophyton rubrum. Journal of Investigative Dermatology 108(4): 664, 1997

Cooperative anti-Candida effects of lactoferrin or its peptides in combination with azole antifungal agents. Microbiology and Immunology 40(11): 821-825, 1996

The role of azole antifungal agents for systemic antifungal therapy. Cleveland Clinic Journal of Medicine 64(2): 99, 1997

Enhanced anti-Candida activity of neutrophils and azole antifungal agents in the presence of lactoferrin-related compounds. Advances in Experimental Medicine and Biology 443: 229-237, 1998

In Vitro activity of the new azole isavuconazole (BAL4815) compared with six other antifungal agents against 162 Cryptococcus neoformans isolates from Cuba. Antimicrobial Agents and ChemoTherapy 52(4): 1580-1582, 2008