Probable interaction between warfarin and rifaximin in a patient treated for small intestine bacterial overgrowth.

OBJECTIVE: To report a case in which the anticoagulant effects of warfarin were attenuated during concomitant administration of rifaximin, possibly through induction of CYP3A4 following increased absorption of rifaximin in a patient with small intestine bacterial overgrowth (SIBO). CASE SUMMARY: A 49-year-old African American female had received effective anticoagulant therapy for 5 months with a target international normalized ratio (INR) of 2.0-3.5 on a warfarin regimen of 7.5 mg daily. Five days following initiation of rifaximin 400 mg 3 times daily to treat SIBO, her INR had fallen to 1.2 and remained suppressed throughout the duration of her rifaximin regimen despite incremental warfarin dosage increases (highest dose, 15 mg/day for 2 days, followed by 11.25 mg/day). Twelve days after completion of the rifaximin treatment course, the INR was supratherapeutic at 4.2, requiring titration to her baseline warfarin dosage to achieve an INR within the target range. Similar results were obtained following rechallenge with rifaximin. DISCUSSION: Rifaximin has been shown in vitro to induce the CYP3A4 enzyme for which the R-isomer of warfarin is a known substrate. The lack of in vivo CYP3A4 induction with rifaximin in other patient populations has repeatedly been attributed to its minimal oral bioavailability, while a recent study found that patients with SIBO had a clinically significant increase in intestinal permeability. In this patient population it is plausible that rifaximin bioavailability increases enough to induce CYP3A4, leading to clinically significant reductions in the bioavailability of CYP3A4 substrates, including R-warfarin. An objective causality assessment of this case revealed that a warfarin-rifaximin interaction was probable. No other drug dosages were altered during the timeframe in question, and the patient had an impeccable medication adherence history; we therefore ruled out these potential etiologies. CONCLUSIONS: To our knowledge, an interaction between warfarin and rifaximin has not been previously reported. While further research needs to be conducted to confirm these results, practitioners should be aware of this possibility because of the increasing use of rifaximin as a first-line choice in the treatment of SIBO.

[Institutionalization without gaining reputation. The incomplete establishment of pharmaceutical science in the universities of the German Reich and the Federal Republic of Germany until the 1970s]. / Institutionalisierung ohne Reputationsgewinn. Die unvollständige Etablierung der Pharmazie an den Hochschulen des Deutschen Reiches und der Bun- desrepublik bis in die 1970er Jahre.

This article analyzes the highly problematic institutionalization of pharmacy as an independent discipline at universities. Focussing on contemporary documents, collected from 'gateways' of reputational allocation such as appointment procedures, the nominations of examination boards, and the granting of certificates, it can be shown that institutionalization was not identical with reputational allocation, distributed by the scientific community. This means that the cycle of credibility developed by Latour and Woolgar could not be completed. Furthermore the pharmaceutical sub disciplines are assessed differently by the scientific community. The main reason can be seen in specific mechanism of reputational allocation within those scientific fields from which pharmacy adopted its methods and instruments. For this end the article uses the comparative analysis of scientific fields from Richard Whitley.