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A case illustrating multiple considerations in choosing safe and effective dual antiplatelet therapy for a patient with a history of clopidogrel allergy—including concerns relating to a national drug shortage—is described.A 75-year-old woman required dual antiplatelet therapy (aspirin plus a thienopyridine) after a cardiac catheterization procedure; during a prior emergency department visit for acute coronary syndrome, she had experienced an allergic reaction within 24 hours of receiving dual therapy including clopidogrel. A team of pharmacy and allergy staff determined that challenging the patient with prasugrel was the best treatment option. Key considerations in the decision-making process included (1) concerns that an alternative thienopyridine, ticlopidine, might be unavailable for long-term outpatient use due to an ongoing national drug shortage, (2) the patient's concomitant use of metoprolol (cessation of β-blocker use is recommended for four days before attempted clopidogrel desensitization), and (3) recent reports of the safe use of prasugrel in three patients with a history of clopidogrel allergy. In the case described here, prasugrel administration was effective and did not result in adverse effects; however, the risk of cross-reactivity of clopidogrel and ticlopidine or prasugrel remains largely unknown. The case highlights the importance of careful consideration of a number of patient- and drug-specific factors in the selection of the most appropriate antiplatelet dual therapy for patients with a history of allergic reactions to clopidogrel.A shortage of ticlopidine prompted the use of prasugrel in a clopidogrel-allergic patient requiring dual antiplatelet therapy. Prasugrel therapy was well tolerated, with no evidence of allergic reaction.