Drug Interactions for Patients with Respiratory Diseases Receiving COVID-19 Emerged Treatments

Abstract

Pandemic of coronavirus disease (COVID-19) is still pressing the healthcare systems worldwide. Thus far, the lack of available COVID-19-targeted treatments has led scientists to look through drug repositioning practices and exploitation of available scientific evidence for potential efficient drugs that may block biological pathways of SARS-CoV-2. Till today, several molecules have emerged as promising pharmacological agents, and more than a few medication protocols are applied during hospitalization. On the other hand, given the criticality of the disease, it is important for healthcare providers, especially those in COVID-19 clinics (i.e., nursing personnel and treating physicians), to recognize potential drug interactions that may lead to adverse drug reactions that may negatively impact the therapeutic outcome. In this review, focusing on patients with respiratory diseases (i.e., asthma or chronic obstructive pulmonary disease) that are treated also for COVID-19, we discuss possible drug interactions, their underlying pharmacological mechanisms, and possible clinical signs that healthcare providers in COVID-19 clinics may need to acknowledge as adverse drug reactions due to drug-drug interactions.

Drug-Drug Interactions among Patients Hospitalized with COVID-19 in Greece

“…Clinically significant DDIs may result in ADRs and side effects that further impair patients’ health, obscuring the treatment outcome and prolonging hospitalization [ 16 , 17 ]. In the case of COVID-19, the scientific community gave an early warning of the risk for DDIs from the several applied protocols [ 14 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Even with the introduction of nirmatrelvir/ritonavir (Paxlovid TM ), there were regulatory check lists to assist clinicians in evaluating potential DDIs and other patient factors prior to any administration [ 25 ].…”

Evaluating Risk: Benefit Ratio of Fat-Soluble Vitamin Supplementation to SARS-CoV-2-Infected Autoimmune and Cancer Patients: Do Vitamin–Drug Interactions Exist?

“…Another medication suggested in COVID-19 therapy due its anti-inflammatory effects is colchicine [ 204 ]. Additionally, colchicine is a substrate for CYP3A, and hence, inducers of CYP3A such as vitamin D might lead to a sub-therapeutic dose of colchicine [ 205 ]. In contrast, other medications are categorized as CYP3A inhibitors, such as the combination of lopinavir and ritonavir, which is expected to raise the plasma concentrations of any medication that is processed by CYP3A such as vitamin D [ 205 ].…”

“…Additionally, colchicine is a substrate for CYP3A, and hence, inducers of CYP3A such as vitamin D might lead to a sub-therapeutic dose of colchicine [ 205 ]. In contrast, other medications are categorized as CYP3A inhibitors, such as the combination of lopinavir and ritonavir, which is expected to raise the plasma concentrations of any medication that is processed by CYP3A such as vitamin D [ 205 ]. This supports another study’s findings, where treatment with lopinavir/ritonavir for 48 weeks dramatically increased serum levels of vitamin D [ 206 ].…”

“…On the other hand, elevated cytokine levels in COVID-19 are known to downregulate the expression of hepatic enzyme CYP450 [ 207 ]. Vitamin D and immunomodulatory agents such as monoclonal antibodies and some antiviral drugs might hold a possible synergistic effect in restoring the CYP450 enzymes [ 205 ]. This goes in line with a study that concluded that combinations of vitamin D and remdesivir, enhanced treatment results in the fight against COVID-19 infection [ 208 ].…”

“…This goes in line with a study that concluded that combinations of vitamin D and remdesivir, enhanced treatment results in the fight against COVID-19 infection [ 208 ]. Furthermore, a study demonstrated that the use of monoclonal antibodies as anakinra, infliximab, canakinumab, sarilumab, and tocilizumab restored CYP450 enzyme levels back to normal [ 205 ]. Particularly in COVID-19 patients who are continuing to receive therapeutic administration of drugs with a narrow therapeutic index that are substrates for CYP450 enzymes such as warfarin, a potential synergistic effect of these drugs on the restoration of enzymes should be thoroughly investigated.…”