Utilization of apixaban anti-Xa levels in transition from apixaban to warfarin in a patient with chronic renal dysfunction

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose The effect of apixaban on anti–factor Xa (anti-Xa) assays and international normalized ratio (INR) complicates transitions between anticoagulant agents. When switching from apixaban to warfarin, the recommendation is to begin both a parenteral anticoagulant and warfarin at the time of the next apixaban dose and to discontinue the parenteral agent when INR is in an acceptable range. This proves challenging in renal dysfunction, as continued presence of apixaban contributes to both a prolonged effect on the INR and continued therapeutic levels of anticoagulation. Summary This case describes the transition of apixaban to warfarin in a patient with acute on chronic kidney disease and recent deep vein thrombosis, utilizing chromogenic apixaban anti-Xa assays to assess the level of anticoagulation and avoid unnecessary parenteral anticoagulation. Conclusion Utilization of apixaban anti-Xa levels aided in the transition from apixaban to warfarin in a patient with chronic renal failure and avoided need for parenteral bridging therapy.

Fludalanine: Nice Try But No Hallelujah

It is time that we experienced a tale of failure. As I have stated repeatedly, most drug discovery efforts fail. Choice of the wrong target dooms the effort from the start. Screening may fail to turn up actives, and molecular design may do no better. Given active molecules, medicinal chemistry efforts to improve properties may fail. Senior management’s heavy hand may terminate a promising effort. If one gets as far as development, a safety or efficacy issue may derail the project. Then, too, competitors may outrun you or financial support may dry up. There are many ways to fail, not so many to succeed. All five stories told so far have been successes: finasteride, ACE inhibitors, statins, imipenem/cilastatin, and the avermectins. Chapter 12 provides another example of a success: the gliptins. In this chapter, however, I pull together the threads of a failure: fludalanine. It is the most interesting failed drug discovery story that I know. There is much to learn from it, particularly about problem solving. It has a couple of surprises. By way of background, Merck had set its mind on finding an effective orally active antibiotic, driven in substantial part by the insistence of Max Tishler, Merck’s determined head of research. Orally active antibiotics are attractive. A patient with a bacterial infection may be treated in the hospital with an oral or a parenteral agent, one given by injection or inhalation. An injectable antibiotic may be given intravenously, intramuscularly, or subcutaneously. However, when the patient has been released from the hospital and sent home, it is convenient to have an antibiotic that can be taken by mouth, a tablet or capsule, for continued action against the infection. Ideally, an antibiotic should be available in both a parenteral (intravenous, intramuscular, or subcutaneous) formulation and an orally active formulation. In this way, the patient can be maintained on the same antibiotic when returning home from the hospital. Merck was having trouble meeting its objective.