STEPS

New Drug Reviews

Idarucizumab (Praxbind) for Dabigatran (Pradaxa) Anticoagulant Reversal

 

Am Fam Physician. 2017 Jun 15;95(12):798-800.

Idarucizumab (Praxbind) is an intravenous humanized monoclonal antibody fragment that binds to dabigatran (Pradaxa) and its active acyl-glucuronide metabolites to neutralize the direct thrombin inhibitor anticoagulant effects.1,2 Idarucizumab is labeled for immediate reversal of dabigatran's anticoagulant effect for an urgent surgical procedure or for life-threatening bleeding.2

 Enlarge     Print

DrugDosageDose formCost*

Idarucizumab (Praxbind)

5 g once, given as two consecutive intravenous 2.5-g doses

2.5-g/50-mL vial

$3,662


*—Estimated cost to hospital for 5-g dose (2 vials, 100 mL total).

DrugDosageDose formCost*

Idarucizumab (Praxbind)

5 g once, given as two consecutive intravenous 2.5-g doses

2.5-g/50-mL vial

$3,662


*—Estimated cost to hospital for 5-g dose (2 vials, 100 mL total).

SAFETY

Patients requiring idarucizumab will likely be critically ill adults with comorbid conditions and have a high risk of mortality at baseline. The RE-VERSE AD study, a case series of 90 patients, demonstrated a low risk of adverse thrombotic effects within 72 hours of administration. However, there continued to be significant mortality (20% overall) for patients taking dabigatran, even with the administration of idarucizumab for life-threatening bleeding or emergency surgery.1 It is unknown if idarucizumab reduced or increased mortality compared with supportive care. Because this product contains sorbitol, it can theoretically cause significant reactions, including death, in patients with hereditary fructose intolerance. Safety has not been established in pregnant or lactating women.

TOLERABILITY

Rare adverse effects including dizziness, headache, and nasopharyngitis have been reported with the use of idarucizumab.3,4 However, most patients studied were critically ill and may not have been able to report adverse effects.1 Given the limited duration of use, tolerability issues beyond the appearance of adverse effects already mentioned should not be an issue.

EFFECTIVENESS

Based on laboratory measures (i.e., dilute thrombin time test and ecarin clotting time test), idarucizumab is effective in neutralizing the anticoagulant effects of dabigatran for patients who present with life-threatening bleeding or need emergency surgery.1 However, the clinical effectiveness of idarucizumab is unclear. Idarucizumab has not been compared with placebo, and published literature has included fewer than 150 patients receiving dabigatran. Multiple case reports have documented the failure of this medication in critically ill patients since the drug has been marketed.58 Because of the short duration of action of dabigatran, idarucizumab should not be used to reverse dabigatran for routine procedures. This medication has not been tested for effectiveness in combination with other anticoagulant reversal agents, such as prothrombin complex concentrate, and it should not be used with other medications.

PRICE

Idarucizumab costs $3,662 for a single treatment (i.e., two infusions). In one study, approximately 20% of patients required a second dose, doubling the cost.1

SIMPLICITY

Idarucizumab is available as two 2.5-g/50-mL vials for a total dose of 5 g/100 mL and is available on most hospital formularies. The 5-g dose can be administered as two consecutive infusions, at the fastest rate possible, or by consecutive bolus injection of the contents of each vial via syringe.2 Once the vial is punctured, the medication should be administered within 60 minutes.2

Bottom Line

Idarucizumab is the only anticoagulant reversal agent for dabigatran. Because of its high cost and limited data regarding clinical benefit, therapy should be reserved for patients taking dabigatran who have life-threatening bleeding or are in need of emergency surgery.

Address correspondence to Jennie B. Jarrett, PharmD, BCPS, MMedEd, at Jarrett8@uic.edu. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

REFERENCES

show all references

1. Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373(6):511–520....

2. Daily Med. Drug label information. Praxbind – idarucizumab injection. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7400f8a-dcf4-a6df-6d07-983081b1bf34. Accessed April 10, 2017.

3. Glund S, Moschetti V, Norris S, et al. A randomized study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran. Thromb Haemost. 2015;113(5):943–951.

4. Glund S, Stangier J, Schmohl M, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet. 2015;386(9994):680–690.

5. Thorborg C, Horn EP, Mofid H, Langer F. Reversal by the specific antidote, idarucizumab, of elevated dabigatran exposure in a patient with rectal perforation and paralytic ileus. Br J Anaesth. 2016;117(3):407–409.

6. Henderson RS Jr, Deshpande S, Williams B, Taylor BS, Tanaka KA. Idarucizumab for dabigatran reversal in emergency type-A aortic dissection [published ahead of print May 13, 2016]. J Cardiothorac Vasc Anesth. http://www.sciencedirect.com/science/article/pii/S105307701630088X. Accessed April 10, 2017.

7. Alhashem HM, Avendano C, Hayes BD, Winters ME. Persistent life-threatening hemorrhage after administration of idarucizumab. Am J Emerg Med. 2017;35(1):193.e3–193.e5.

8. Marino KK, Santiago RA, Dew RB III, et al. Management of dabigatran-associated bleeding with two doses of idarucizumab plus hemodialysis. Pharmacotherapy. 2016;36(10):e160–e165.

STEPS new drug reviews cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each independent review is provided by authors who have no financial association with the drug manufacturer.

This series is coordinated by Allen F. Shaughnessy, PharmD, MMedEd, Contributing Editor.

A collection of STEPS published in AFP is available at https://www.aafp.org/afp/steps.

 

 

Copyright © 2017 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions


More in Pubmed

MOST RECENT ISSUE


Oct 15, 2018

Access the latest issue of American Family Physician

Read the Issue


Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article