Drug Interactions between aspirin / pravastatin and donanemab

MONITOR CLOSELY: Coadministration with drugs that can affect hemostasis such as anticoagulants, antiplatelet agents, and thrombolytics may potentiate the risk of bleeding complications observed with amyloid beta-directed antibody therapy. Use of monoclonal antibodies directed against aggregated forms of beta amyloid such as aducanumab, donanemab, and lecanemab has been associated with amyloid related imaging abnormalities (ARIA) with hemosiderin deposition (ARIA-H), including microhemorrhage, superficial siderosis, and intracerebral hemorrhage greater than 1 cm in diameter, the latter of which can be fatal. Based on limited clinical trial data, concomitant use of these monoclonal antibodies with an antithrombotic medication (aspirin, other antiplatelet agents, or anticoagulants) does not appear to significantly increase the risk of ARIA-H or intracerebral hemorrhage compared to use without an antithrombotic medication or placebo with an antithrombotic medication. However, the majority of antithrombotic exposures in trial patients were to aspirin only; therefore, no definitive conclusions regarding safety concerns can be drawn. In addition, patients with known risk factors for intracerebral hemorrhage were excluded from clinical trials.

MANAGEMENT: Due to the risk of potentially fatal intracerebral hemorrhage, caution and close monitoring are recommended with the use of antithrombotic or thrombolytic agents in patients receiving amyloid beta-directed antibody therapy, particularly those with risk factors for ARIA and intracerebral hemorrhage such as apolipoprotein E epsilon 4 carriers (approximately 15% of patients with Alzheimer's disease are apoE epsilon 4 homozygotes) or patients with baseline radiographic findings suggestive of cerebral amyloid angiopathy (e.g., evidence of prior intracerebral hemorrhage greater than 1 cm in diameter, at least two cerebral microhemorrhages, cortical superficial siderosis, vasogenic edema, diffuse white matter disease) or other lesions (e.g., aneurysm, vascular malformation). Because ARIA with edema (ARIA-E) can cause focal neurologic deficits that may mimic an ischemic stroke, clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy in patients being treated with an amyloid beta-directed antibody.