Desensitization in patients with an aspirin allergy

After tweeting about an aspirin desensitization we performed last week, I have received several requests for our approach in patients with aspirin allergies, as well as the protocol that we use to desensitize those in whom we feel therapy is clinically indicated.

Given the time and resources required for a desensitization (e.g., drug preparation, admission to an intensive care unit, frequency of monitoring, etc.), the most important initial steps are determining if aspirin is indicated (and no other reasonable alternatives exist), and whether the patient has a history of a true type I hypersensitivity reaction (e.g., anaphylaxis) to aspirin.  In the case of the former, all of our aspirin desensitizations have been performed for the purpose of providing dual antiplatelet therapy in the setting of an acute coronary syndrome (ACS), often with coronary stent placement. For patients with stable coronary disease (or for those in whom monotherapy may mitigate excess bleeding risk), clopidogrel monotherapy may serve as a suitable alternative to aspirin; based on the results of the CAPRIE trial, clopidogrel is associated with comparable rates of both ischemic and bleeding outcomes compared to aspirin [1]. Unfortunately, the number of patients for whom this would be a reasonable strategy is quite small, making aspirin desensitization necessary in the majority of cases.

If aspirin is clinically indicated, a thorough interview of the patient should be performed to determine the type of allergic 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, unsure about timing related to exposure, etc.), I usually err on the side of caution.

At our institution, we transfer patients undergoing aspirin desensitization to the cardiac 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 a 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.  Additionaly, 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.
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 this 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 collaborated on the above process at our institution; Abbie is currently a clinical pharmacy specialist at Loyola University Medical Center in Chicago, IL.

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.