Prasugrel — gone, but not forgotten

Abstract

Human immunodeficiency virus (HIV) infection and certain retroviral therapies are associated with an increased risk of atherosclerosis with plaque rupture resulting in acute coronary syndromes. Therefore, there is often a need to co-prescribe antiretroviral and cardiovascular therapies, including antiplatelet agents. Antiplatelet agents, such as the P2Y12 receptor antagonists clopidogrel and prasugrel, require activation by cytochrome P450 3A4 (CYP3A4). The P2Y12 receptor antagonist ticagrelor is also metabolised by CYP3A4. Pharmacokinetic enhancers, such as ritonavir and cobicistat, are utilised to increase the systemic exposure of certain agents within multidrug HIV regimens and are potent CYP3A4 inhibitors. Using these drugs together can result in unintended and undesirable drug–drug interactions. A 55-year-old male with a history of HIV presented to the emergency department with central chest pain. He was found to have had a non-ST-elevation myocardial infarction and was commenced on dual antiplatelet therapy including ticagrelor, anticoagulation and statin therapy, in addition to his usual HIV therapy, Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide). A drug–drug interaction between Genvoya and ticagrelor was identified by the pharmacist, and the patient was switched to prasugrel on the pharmacist's recommendation. Although prasugrel was delisted from the Pharmaceutical Benefits Scheme (PBS) in July 2020, it remains accessible as a non-PBS medicine. Prasugrel should be considered the P2Y12 antagonist of choice for patients who are on HIV regimens containing a pharmacokinetic enhancer such as ritonavir or cobicistat.