In this episode I’ll:

1. Discuss an article about the toxicology of rivaroxaban and apixaban.

2. Answer the drug information question “Is vancomycin compatible with piperacillin-tazobactam at Y-site?”

3. Share a resource I use when taking care of a pregnant patient in the ICU.

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Article

An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers

Lead author: Henry A. Spiller

Published in the Annals of Emergency Medicine in February 2016

Background

Rivaroxaban and apixaban have been approved for use by the FDA since 2011 and 2012. Little is known about the toxicology of these oral factor Xa inhibitors.

Purpose

The purpose of this study was to characterize the clinical effect in patients exposed to supratherapeutic doses of rivaroxaban and apixaban.

Methods

The study was a retrospective collection of data from 8 regional poison centers covering 9 states spanning 3 years. Inclusion criteria included single-substance exposure to rivaroxaban or apixaban. Exclusion criteria were animal exposure, polysubstance exposure, or informational calls.

Results

223 patients met the inclusion criteria. The mean age of the study population was 60 years old. 56% of patients were female, 89% had ingested rivaroxaban, and 9% were children under 12 years of age.

For rivaroxaban the mean dose ingested was 64.5 mg (range 15 to 1,200 mg), and for apixaban the mean dose ingested was 9.6 mg (range 2.5 to 20 mg).

Prothrombin time, partial thromboplastin time, or international normalized ratio (INR) appeared to be unreliable predictors of the risk of bleeding.

Bleeding occurred in 7% of patients; 11 who ingested rivaroxaban and 4 who ingested apixaban. All of the patients who bled were chronically taking rivaroxaban or apixaban.

12 of the ingestions were suicide attempts, and all of these involved rivaroxaban. One of these patients had an INR >12 and was given fresh frozen plasma. None of the suicide attempt patients bled.

Hepatic injury as evidenced by an AST >1000 U/L occurred in a 25 year old man with hepatitis C and an 82 year old man.

Conclusion

The authors concluded that bleeding after Xa inhibitor ingestion as a single agent is uncommon and that single

exploratory ingestion by children was not associated with toxicity.

Discussion

Thankfully, much like warfarin, single dose ingestions by children were not associated with significant consequences. It is likely that data from this study will be used by poison control centers to advise that children who took single doses of rivaroxaban or apixaban can be safely managed at home.

One interesting point the authors made is that the saturation of Xa binding sites may create a ‘ceiling effect’ which may limit the risk of bleeding after an acute overdose of rivaroxaban or apixaban.

Drug information question

Shout out to Pharmacy Nation member Caleb for bringing up this question!

Q: Is vancomycin compatible with piperacillin-tazobactam at Y-site?

A: It is now!

A recent study concluded:

Visual, microscopic, and absorbance analyses showed no evidence of incompatibility when piperacillin-tazobactam 33.75-90 mg/mL was combined with vancomycin ≤7 mg/mL. Reversible and irreversible precipitates formed when piperacillin-tazobactam was combined with vancomycin ≥8 mg/mL.

Resource

The Society of Critical Care Medicine published a brief review titled: Care of the Critically Ill Parturient – Easy as ABCDE. The topics of airway, breathing, circulation, delivery, and early transfer are discussed.

Because it is rare for me to encounter a critically ill pregnant patient, I review this article each time it happens.

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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