Abstract
Real-world drug repurposing—the immediate “off-label” prescribing of drugs to address urgent clinical needs—is an indispensable strategy gaining rapid traction in the current COVID-19 crisis. Although off-label prescribing (ie, for a nonapproved indication) is legal in most countries, it tends to shift the burden of liability and cost to physicians and patients, respectively. Nevertheless, in urgent public health crises, it is often the only realistic source of a meaningful potential solution. To be considered for real-world repurposing, drug candidates should ideally have a track record of safety, affordability, and wide accessibility. Although thousands of such drugs are already available, the absence of a central repository of off-label uses presents a barrier to the immediate identification and selection of the safest, potentially useful interventions. Using the current COVID-19 pandemic as an example, we provide a glimpse at the extensive literature that supports the rationale behind six generic drugs, in four classes, all of which are affordable, supported by decades of safety data, and pleiotropically target the underlying pathophysiology that makes COVID-19 so dangerous. Having previously fast-tracked this paper to publication in summary form, we now expand on why cimetidine/famotidine (histamine type-2 receptor antagonists), dipyridamole (antiplatelet agent), fenofibrate/bezafibrate (cholesterol/triglyceride-lowering agents), and sildenafil (phosphodiesterase-5 inhibitor) are worth considering for patients with COVID-19 based on their antiviral, anti-inflammatory, renoprotective, cardioprotective, and anticoagulation properties. These examples also reveal the unlimited opportunity to future-proof public health by proactively mining, synthesizing, and cataloging the off-label treatment opportunities of thousands of safe, well-established, and affordable generic drugs.
Highlights
Since the first report of a viral pneumonia of unknown cause in Wuhan, China, in December 2019, followed by the identification of the virus SARS-CoV-2 and the designation of the disease it causes as COVID-19, we have witnessed the rapid development of a pandemic that has become a global public health crisis
Having recently published a short summary of our thesis [2], the current paper expands on why cimetidine or famotidine, dipyridamole, fenofibrate or bezafibrate, and sildenafil are worth considering for patients with COVID-19
Under the extraordinary COVID-19 pandemic conditions that have brought the world to the brink of an irreversible crisis, time is of the essence for the success of life-saving efforts
Summary
Since the first report of a viral pneumonia of unknown cause in Wuhan, China, in December 2019, followed by the identification of the virus SARS-CoV-2 and the designation of the disease it causes as COVID-19, we have witnessed the rapid development of a pandemic that has become a global public health crisis. A number of clinical studies have confirmed the antiviral effects of dipyridamole which, at a dose of 8-100 mg weekly, significantly reduced the risk of acute respiratory diseases, including influenza, when administered prophylactically to at-risk individuals [57,58,59].
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