Intense effort is underway to evaluate potential therapeutic agents for the treatment of COVID-19. In order to respond quickly to the crisis, the repurposing of existing drugs is the primary pharmacological strategy. Despite the urgent clinical need for these therapies, it is imperative to consider potential safety issues. This is important due to the harm-benefit ratios that may be encountered when treating COVID-19, which can depend on the stage of the disease, when therapy is administered and underlying clinical factors in individual patients. Treatments are currently being trialled for a range of scenarios from prophylaxis (where benefit must greatly exceed risk) to severe life-threatening disease (where a degree of potential risk may be tolerated if it is exceeded by the potential benefit). In this perspective, we have reviewed some of the most widely-researched repurposed agents in order to identify potential safety considerations using existing information in the context of COVID-19.

In a recent issue of Br J Clin Pharmacol Smith et al1 published an outstanding commentary titled ‘Dosing will be a key success factor in repurposing antivirals for Covid-19’. They highlighted that the success in our repurposing efforts will be dependent on ‘getting the dose right’ for drugs which have been developed for different indications and stressed some of the unique challenges of treating this particular disease. They pointed the reader to lopinavir/ritonavir (LPV/r) as an example of a repurposed antiviral and the limited experience of this drug regimen (and other treatments) in the elderly population with comorbidities – ie those most at risk from Covid-19. It is on the issue of comorbidities, polypharmacy and drug-drug interactions (DDIs) that we wish to comment.