Volume 194 - Issue 11
High-dose intravenous flucloxacillin may affect warfarin therapy
Authors: Philip Y-I Choi, Katherine L Phillips and Ian Rae
Med J Aust 2011; 194 (11): 613. || doi: 10.5694/j.1326-5377.2011.tb03122.x
Published online: 6 June 2011
Published online: 6 June 2011
To the Editor: Warfarin is an orally administered vitamin K antagonist and has many well described interactions with commonly prescribed medications.1 However, only a handful of case reports worldwide have shown that flucloxacillin, a widely used antibiotic, may affect warfarin therapy by reducing its anticoagulant effect — in one instance contributing to the development of ischaemic stroke.2,3 There are several reports describing potential mech-anisms of interaction for flucloxacillin with warfarin.4,5
We describe the case of a 64-year-old man who was diagnosed with infective endocarditis on the basis of mitral valve vegetations and blood cultures that were positive for methicillin-sensitive Staphylococcus aureus. The patient underwent mitral valve replacement with a prosthetic valve and received prolonged antibiotic therapy with intravenous flucloxacillin for 8 weeks.
Initially, for nearly 4 weeks, therapeutic anticoagulation with warfarin was difficult to achieve with warfarin doses ranging between 5 and 10 mg per day (target international normalised ratio [INR], 2.5–3.5). During this time, the patient was receiving intravenous flucloxacillin at a total daily dose of 8 g (2 g every 6 h). Flucloxacillin was increased to 12 g per day (2 g every 4 h) and there was a subsequent fall in the patient’s INR, which was sustained despite increasing the dose of warfarin to 25 mg per day (Box). Completion of flucloxacillin therapy was associated with a rise in the patient’s INR and a reduction in his warfarin dose requirement.
No other relevant medications were commenced during this period of observation.
This case highlights the potential for a dose-related effect of intravenous high-dose flucloxacillin (up to 12 g per day) on warfarin metabolism and the need for vigilance when prescribing antibiotics in conjunction with oral vitamin K antagonists. Other penicillins such as amoxicillin can, conversely, enhance the anticoagulant effects of warfarin, so the warfarin–flucloxacillin interaction may not be intuitive for many clinicians.
Doses* for oral warfarin and intravenous flucloxacillin administered to a 64-year-old man with infective endocarditis, and corresponding INR
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INR = international normalised ratio. |
References
- Juurlink DN. Drug interactions with warfarin: what clinicians need to know. CMAJ 2007; 177: 369-371.
- Merwick A, Hannon N, Kelly PJ, O’Rourke K. Warfarin-flucloxacillin interaction presenting as cardioembolic ischemic stroke. Eur J Clin Pharmacol 2010; 66: 643-644. 0_CBBIAFDG
- Garg A, Mohammed M. Decreased INR response secondary to warfarin-flucloxacillin interaction. Ann Pharmacother 2009; 43: 1374-1375. 0_CBBEIFDI
- Huwyler J, Wright MB, Gutmann H, Drewe J. Induction of cytochrome P450 3A4 and P-glycoprotein by the isoxazolyl-penicillin antibiotic flucloxacillin. Curr Drug Metab 2006; 7: 119-126. 0_i1095857
- Tang W, Stearns RA. Heterotropic cooperativity of cytochrome P450 3A4 and potential drug-drug interactions. Curr Drug Metab 2001; 2: 185-198. ref5