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Clinical Pharmacist, Medicines Information, Middlemore Hospital, Private Bag 93311, Otahuhu, Manukau 1640, Auckland, New Zealand, fax 0064 9 276 0057, garga{at}middlemore.co.nz
Senior House Officer, Counties Manukau District Health Board, Auckland
Published Online, July 7, 2009. www.theannals.com, DOI 10.1345/aph.1L676
We present the first case, to our knowledge, of flucloxacillin exerting a similar effect on the INR when administered with warfarin. Flucloxacillin, closely related to dicloxacillin, is the standard β-lactamase-resistant penicillin widely used in New Zealand.
Case Report. A 58-year-old man was admitted to a tertiary-care hospital for interim care after having undergone elective joint fusion for osteoarthritis of his thumb. His history was significant for atrial fibrillation, for which he had been taking warfarin for 7 years, and an ischemic stroke. He had been on a stable dosage of warfarin 3 mg and 4 mg on alternate days for at least 6 months preoperatively. Warfarin was stopped 1 week before surgery. He resumed his usual regimen on postoperative day 1; his INR was 2.4 on postoperative day 8. The INR remained within the therapeutic range of 2.0-3.0 on subsequent tests. On postoperative day 12, he was started on oral flucloxacillin. His INR was 2.9 on postoperative day 14; the patient received his usual dosage of warfarin on that day. On postoperative day 16 the INR was 1.1, so the patient's warfarin dose was doubled to 8 mg. There had been no other changes in the patient's regular medications, including his analgesics, and he denied taking any herbal preparations or any recent changes to his diet. The INR was 0.9 on postoperative day 17, although it may have been too early to see an effect from the dosage increase to warfarin 8 mg the day before. Given the implications of this patient having a subtherapeutic INR after a previous thromboembolic stroke, a decision was made on postoperative day 17 to change the flucloxacillin to oral amoxicillin/clavulanic acid 625 mg 3 times daily. The patient received warfarin 5 mg on that day, and the INR increased to 2.7 by the next morning. The INR remained within the therapeutic range while the patient continued to be treated with a warfarin dose of 5 mg daily and with oral and intravenous amoxicillin/clavulanic acid for 4 days and 3 weeks, respectively (Figure 1).
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Discussion. The temporal association between treatment with flucloxacillin and the decreased INR suggests that the drug was responsible for the subtherapeutic INR in our patient, given that there were no other changes to his medications. Evaluation of this case using the Horn Drug Interaction Probability Scale indicated a possible likelihood of a true interaction taking place between warfarin and flucloxacillin.8 We considered rechallenging the patient with flucloxacillin to see whether a similar decrease in the INR would recur but decided against this because there were good alternative antibiotics and because of the possibility of a thromboembolic event, however small the risk may have been.
To our knowledge this is the first reported case of reduction of the anticoagulant effect of warfarin by flucloxacillin. Of particular interest is the speed of the decrease and increase in INR following the initiation and stopping of flucloxacillin, respectively. This highlights the importance of close monitoring of the INR level of patients taking concomitant flucloxacillin and warfarin.
References
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