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Author: Brent N. Reed, PharmD, BCPS-AQ Cardiology, FAHA

About five years ago, I wrote a post on the approach we used at my prior institution to desensitize patients to aspirin. In the time since then, I’ve received several follow-up questions, most of which have been related to the stability of aspirin in oral solution. Below is a long overdue update of that post, including information on aspirin stability. 

Given the time and resources required for a drug desensitization, the most important initial steps are determining if aspirin is indicated and whether reasonable alternatives exist. Equally important is determining whether the patient has a history of a type I hypersensitivity reaction (e.g., anaphylaxis) to aspirin. In the case of the former, all of our aspirin desensitizations were performed for the purposes of providing dual antiplatelet therapy following acute coronary syndrome (ACS), often with coronary stent placement. For patients with stable coronary disease or those in whom monotherapy may mitigate bleeding risk, clopidogrel alone may serve as a suitable alternative to aspirin. Based on the results of the CAPRIE trial, clopidogrel is associated with comparable rates of ischemic and bleeding outcomes compared to aspirin (1). Unfortunately, the number of patients for whom this is a reasonable strategy is small, making aspirin desensitization necessary in most cases.

If aspirin is clinically indicated, a thorough interview of the patient should be performed to determine the type of reaction experienced. In many cases, the reported allergy is not a type I hypersensitivity reaction, or it is simply an adverse effect (e.g., gastritis) that has been mislabeled as an allergy. If the history is unclear, or if the patient provides any information that might be concerning (e.g., a rash occurred but unsure whether swelling or wheals were involved), I usually err on the side of caution.

At our institution, we transfer patients undergoing aspirin desensitization to the intensive care unit, where they can receive frequent monitoring of vital signs and observation for adverse reactions. We use the procedure described by Wong, et al. (2) to reach a target dose of 325 mg over a 3-hour period. For the doses preceding 81 mg, we compound the liquid formulation by crushing an 81 mg chewable tablet and mixing it with a sufficient quantity of sterile water to create a 1 mg/mL solution. The half-life for the hydrolysis of aspirin in water is 153.3 ± 3.7 hours, so minimal degradation should be expected during the time required to prepare the oral solution and complete the desensitization (3). Lastly, we compound two batches in case the patient vomits up a dose.

The desensitization is then performed as follows:

  1. Pre-medicate with oral diphenhydramine 25 mg and famotidine 20 mg (of note, the need for pre-medication remains controversial but it is associated with minimal risk so we do it).
  2. Check vital signs at baseline and every 20 minutes thereafter.
  3. At 20 minute intervals, administer the following doses of aspirin:
    [Time 00:00] 0.1 mg (0.1 mL)
    [Time 00:20] 0.3 mg (0.3 mL)
    [Time 00:40] 1 mg (1 mL)
    [Time 01:00] 3 mg (3 mL)
    [Time 01:20] 10 mg (10 mL)
    [Time 01:40] 20 mg (20 mL)
    [Time 02:00] 40 mg (40 mL)
    [Time 02:20] 81 mg (one 81 mg tablet)
    [Time 02:40] 162 mg (two 81 mg tablets)
    [Time 03:00] 325 mg (one 325 mg tablet)
  4. After the last dose of the desensitization, a normal administration time (i.e., every 24 hours) may be resumed.
  5. If an allergic reaction is observed at any time, rescue medications (intravenous diphenhydramine, epinephrine) should be administered.

We target an initial dose of 325 mg because it is the standard loading dose at our institution for patients presenting with ACS (some institutions use 162 mg for this purpose); however, after achieving this dose during the desensitization process, we then administer a maintenance dose of 81 mg daily.

 

Acknowledgement: Special thanks to Abigail Miller Cook, PharmD, BCPS, with whom I originally collaborated on the above process; Abbie is currently a clinical pharmacy specialist at Loyola University Medical Center in Chicago, IL.

 

 
Brent N. Reed, PharmD, BCPS-AQ Cardiology, FAHA

Dr. Reed is an associate professor in the Department of Pharmacy Practice and Science at the University of Maryland School of Pharmacy, and practices as a clinical pharmacy specialist in advanced heart failure at the University of Maryland Medical Center in Baltimore, MD. Follow him on his website or on Twitter @brentnreed.

Note: the above entry initially appeared on Reed’s personal blog The Unit in 2013.

References

  1. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996 Nov 16;348(9038):1329-39.
  2. Wong JT, Maclean JA, Bloch KJ, et al. Rapid oral challenge-desensitization for patients with aspirin-related urticaria-angioedema. J Allergy Clin Immunol. 2000 May;105(5):997-1001.
  3. Bakar SK, Niazi S. Stability of aspirin in different media. J Pharm Sci. 1983 Sep;72(9):1024-6.
Desensitizing Patients with an Aspirin Allergy

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