In this episode I’ll:
1. Discuss an article comparing KCentra with FEIBA.
2. Answer the drug information question “Does ibuprofen accumulate in renal insufficiency?”
3. Share a resource for individualizing antibiotic dosing.
Article
Lead author: Shaun Rowe
Published in Critical Care Medicine March 2018
Background
Both 4-factor prothrombin complex concentrates (KCentra) and activated prothrombin complex concentrates (FEIBA) are known to reverse the effects of warfarin. The authors of this study sought to compare the INR normalization efficacy of KCentra and FEIBA, and to evaluate the thrombotic complications in patients treated with these products for warfarin-associated hemorrhage.
Methods
The study was a retrospective, multicenter cohort design in a large community teaching hospital. Patients were included if they were greater than 18 years old and received either FEIBA or KCentra for the treatment of warfarin-associated hemorrhage. There were several exclusion criteria including patients who received either agent for an indication other than warfarin-associated hemorrhage, had a baseline INR of less than 2, received a massive transfusion, received fresh frozen plasma, or were treated for an acute warfarin ingestion.
Patients in the FEIBA group with an INR of less than 5 received 500 units and those with an INR greater than 5 received 1,000 units. Patients in the KCentra group received the FDA approved dosing algorithm.
Results
A total of 158 patients were included in the final analysis, 118 who received FEIBA and 40 who received KCentra. Those in the 4-factor prothrombin complex concentrate group had a higher pretreatment INR (2.7 vs 3.5 ). However, the posttreatment INR was similar between the groups. There was also no difference in the ability to achieve a posttreatment INR of less than 1.4 in either group. Those in the FEIBA group did have higher odds of achieving a posttreatment international normalized ratio of less than 1.2 (odds ratio, 3.23). There was only one posttreatment thrombotic complication reported which occurred in the KCentra group.
Conclusion
The authors concluded:
A low, fixed dose of activated prothrombin complex concentrate was as effective as standard dose 4-factor prothrombin complex concentrate for normalization of international normalized ratio. In addition, we did not see an increase in thrombotic events.
Discussion
The concern with activated factor-based products like FEIBA is that the risk of thrombosis is perceived to be higher compared with non-activated products like KCentra. It is reassuring that the only thrombotic event, a stroke, occurred in the KCentra and not the FEIBA group. Hopefully, more comparisons of these two products will be made in the future.
The fixed dosing approach with FEIBA has a time-to-therapy advantage over KCentra. All patients with a major hemorrhage and history of warfarin use could receive a 500 unit dose immediately, and the balance of the dose could be given if the initial INR comes back above 5. In addition, FEIBA should be much less expensive that KCentra at the doses used in this study, although that does depend on your hospital acquisition cost.
Drug information question
Q: Does ibuprofen accumulate in renal insufficiency?
A: No. Ibuprofen is metabolized to inactive compounds hepatically via oxidation. Several of these compounds are dialyzable, and the half-life of ibuprofen in end-stage renal disease (ESRD) is unchanged compared to adult patients without ESRD. If a patient on dialysis does have residual urine output, ibuprofen, like any other NSAID, has the potential to be nephrotoxic and eliminate the patient’s residual urine output. While this is not likely to be clinically significant, it could be psychologically significant to a patient that values preserving their residual urine output.
Resource
The resource for this episode is an application designed to facilitate Individually Designed Optimum Dosing Strategies for antimicrobials. ID-ODS is a simulation tool with an extensive model library built from population pharmacokinetic models published in high quality, peer-reviewed literature. Based on patient demographic information readily available at the bedside, ID-ODS incorporates Monte Carlo simulation and Bayesian feedback into the design of personalized dosing regimens. The application is currently available on mobile and desktop devices, and as a web application as well. The information this application gives serves as an extra data point. I use it as a form of decision support whenever I have a patient at the extremes of both body weight and renal function.
To help you easily remember antibiotic spectrum of activity I created a free visual critical care antibiotic guide. You can get the guide in my download area by going to pharmacyjoe.com/free. It is download #1.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
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