key: cord-0803950-dkjycaao
authors: Back, David; Marzolini, Catia; Hodge, Catherine; Marra, Fiona; Boyle, Alison; Gibbons, Sara; Burger, David; Khoo, Saye
title: COVID‐19 treatment in patients with comorbidities: Awareness of drug‐drug interactions
date: 2020-05-13
journal: Br J Clin Pharmacol
DOI: 10.1111/bcp.14358
sha: c2a00753bedfbff6ea741048c2e671489070139b
doc_id: 803950
cord_uid: dkjycaao

nan

In a recent issue of Br J Clin Pharmacol, Smith et al. 1 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-that is, 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.

Age-related comorbidities result in complex polypharmacy and an increased risk of DDIs. 2 Furthermore, physiological changes related to ageing may affect both pharmacokinetics (PK) and pharmacodynamics (PD) thereby putting elderly patients at risk of inappropriate prescribing and adverse drug reactions. In the case of LPV/r, particular attention needs to be focussed on PK interactions involving inhibition of CYP3A4 and some transporters. 2 To aid health care professionals managing LPV/r (and other antiretroviral) DDIs in HIV patients, we developed the online resource www.hiv-druginteractions.org, 3 which is extensively cited in national and international treatment guidelines.

However, in addition to PK interactions, LPV/r is known to cause QT prolongation and is on the CredibleMeds listing 4 for drugs with a possible risk of torsades de pointes (TdP). Indeed, the drug label for LPV/r includes the warning to "avoid use with QT-prolonging drugs" because of DDIs and effects on PR and QTc. 5 Possibly of greater topicality at present is the risk of QT prolongation and TdP in Covid-19 patients given the repurposed drugs chloroquine and hydroxychloroquine. This has been highlighted in recent cohort studies 6, 7 and in warnings from the EMEA 8 and FDA. 9 Patients given experimental COVID-19 therapies will often be clinically unstable with organ dysfunction, and the development of 

Dosing will be a key success factor in repurposing antivirals for COVID-19

The challenge of HIV treatment in an era of polypharmacy

Kaletra ® prescribing information

Effect of high vs low dose chloroquine diphosphate as adjunctive therapy for patients hospitalised with severe respiratory syndrome coronavirus 2 (Sars-Cov-2) infection: a randomised clinical trial

The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin

FDA drug safety communication