High Prevalence of Potential Drug-Drug Interactions Among Patients Treated with Off-label Therapies for COVID-19

Allan Ramos-Esquivel; Cristina Fernández; Luis  Garro-Zamora; Ana Victoria Chaves; Álvaro  Viquez-Jaikel

doi:10.18502/jpc.v10i2.9972

Allan Ramos-Esquivel Department of Pharmacology, School of Medicine, University of Costa Rica, Costa Rica.
Cristina Fernández Pharmacy Department, Hospital San Juan de Dios, Caja Costarricense de Seguro Social, Costa Rica.
Luis Garro-Zamora Pharmacy Department, Hospital México, Caja Costarricense de Seguro Social, Costa Rica.
Ana Victoria Chaves Pharmacy Department, Hospital Rafael Ángel Calderón Guardia, Caja Costarricense de Seguro Social, Costa Rica.
Álvaro Viquez-Jaikel Pharmacy Department, Hospital San Juan de Dios, Caja Costarricense de Seguro Social, Costa Rica.

DOI: https://doi.org/10.18502/jpc.v10i2.9972

Keywords: COVID-19; Drug Interactions; Hydroxychloroquine; Lopinavir-ritonavir

Abstract

Background: During the first wave of the COVID-19 pandemic, severe patients were treated with the off-label drugs hydroxychloroquine and lopinavir/ritonavir. The aim of the study was to determine the prevalence of potential drug-drug interactions (DDIs) between hydroxychloroquine, lopinavir/ritonavir and concomitant medications used by hospitalized patients treated for COVID-19 in Costa Rica.

Methods: We included all patients that received lopinavir/ritonavir or hydroxychloroquine as treatment for COVID-19. Clinical pharmacists reviewed the prescription profile of each patient and determined the probability and severity of any DDI through two databases (The Lexi-Interact program) and the Micromedex online interaction checker. A logistic regression model was used to identify variables associated with the occurrence of potential DDIs.

Results: We identified a total of 108 potential DDIs in 34 inpatients (n=34). At least one of these DDIs occurred in 27 patients (79.4%; 95% CI: 65.8-92.9%). A total of 70 DDIs (64.8%) were classified as clinically relevant (grade D or X) by the clinical pharmacists. Only the number of concomitant drugs was associated with the occurrence of a probable DDI. The most common drugs associated with any DDI were fentanyl (n=12, 11.1%), midazolam (n=11, 10.2%), and insulin (n=10, 10.2%).

Conclusion: A large proportion of patients treated with hydroxychloroquine and lopinavir/ritonavir for severe COVID-19 were at risk for clinical meaningful DDIs.