PharmD, PhD, Professor of Pharmacology, University of Milan, Italy
Since 1999, I was interested in the problem of drug-drug interaction (DDI) as related to lipid lowering therapy. In particular, as a pharmacologist, I was focused in understanding the different spectrum of drug interactions, which are important determinants of safety in patients with hypercholesterolemia. Although statin treatment is generally well-tolerated, the most common adverse effect is myopathy. The rate of myopathy with statin monotherapy is low, but factors that raise the circulating concentrations of statins, such as DDIs, can increase the risk of these adverse event. This is particular relevant especially in those requiring long-term therapy with drugs that are well-known CYP3A substrates and/or inhibitors. The issue of DDI has to be addressed in patients at high cardiovascular risk that usually received multiple medications necessary to provide optimal care, ‘polytherapy’ increases the risk of DDIs and consequent adverse drug reactions.
Hypercholesterolemia has been reported to be one of the most common comorbidities in patients with COVID-19 and, recently, an observational study demonstrated that in-hospital use of statins was associated with substantial improvement in survival among patients hospitalized with COVID-19.
The COVID-19 pandemic has driven unprecedented efforts to identify possible therapeutic strategies for the treatment of COVID patients. Over 100 different off-label and experimental drugs are under investigations from antiviral agents (e.g. lopinavir/ritonavir, darunavir/ritonavir, atazanavir, remdesivir) to hydroxychloroquine and to biotechnological drugs such as tocilizumab. Many of the tested drugs including cytokine modulators are inducer or inhibitor of several cytochromes involved in drug metabolism as well as of drug transporters such as P-gp. For example, tocilizumab (anti-IL-6 receptor antibody) may reverse the “inhibitory” effect of IL-6 on CYP substrates, resulting in a “normalization” of CYP activities and increased clearance of atorvastatin and simvastatin.
The potential DDI occurring between statins, other lipid lowering agents and drugs actually under investigation in COVID patients is the one of the topics discussed in the present EAS webinar