Drug repurposing of dextromethorphan as a cellular target for the management of influenza

• Published in: Pharmacotherapy 2021-10, Vol.41 (10), p.796-803
• Main Authors: Cummings, Tammy H., Magagnoli, Joseph, Hardin, James W., Sutton, S. Scott
• Format: Article
• Language: English
• Subjects: Cough; Dextromethorphan; Dextromethorphan - therapeutic use; Diagnosis; Drug Repositioning; drug repurposing; Electronic medical records; Fever; Generalized linear models; Genetic screening; Hospitalization; Humans; Influenza; Influenza, Human - drug therapy; Influenza, Human - epidemiology; Informatics; Laboratories; Pandemics; Patients; Retrospective Studies; siRNA; United States - epidemiology
• ISSN: 0277-0008; 1875-9114
• DOI: 10.1002/phar.2618

Background Influenza viruses are responsible for seasonal epidemics and sporadic pandemics of varying severity in humans, and additional treatment options are needed. High‐throughput siRNA screens and a pre‐clinical research model demonstrated that dextromethorphan (DM) has anti‐viral activity as a cellular target for treatment of influenza. This study examined DM usage and hospitalization rates among patients with laboratory‐confirmed influenza in a national cohort of United States veterans. We aimed to evaluate the potential drug repurposing of DM as a cellular target for the management of influenza utilizing a large, national claims and electronic health record database. Methods This retrospective drug‐disease association cohort study was conducted using data from the Veterans Affairs Informatics and Computing Infrastructure (VINCI). We used a cohort with laboratory‐confirmed diagnosis of influenza and international classification of disease (ICD)‐9/10 diagnosis codes of fever, cough, influenza, or acute upper respiratory infection in an outpatient setting. The study outcome is inpatient hospitalization (all‐cause and respiratory) within 30 days of influenza diagnosis. We estimated the relative risk for all‐cause and respiratory hospitalizations using Poisson generalized linear model (GLM) and a greedy nearest neighbor propensity score 1:1 matched sub‐analysis for both hospitalization models. Findings A total of 18,677 patients met the inclusion and exclusion criteria and were evaluated in our study. The cohorts consisted of 2801 patients dispensed DM and 15,876 untreated patients (no DM). The Poisson GLM adjusted for covariates demonstrated a relative risk reduction of 34% for all‐cause hospitalizations (Relative Risk (RR) 0.66, 95% Confidence Interval (CI) 0.525–0.832) and 40% for respiratory hospitalizations (RR 0.597, 95% CI 0.423–0.843) in patients with influenza treated with DM. Conclusion Influenza viruses continue to emerge and cause infection (including pandemics) in humans, so there remains a critical need to advance the understanding of influenza treatment. Our results demonstrated reduced hospitalization rates for influenza patients treated with DM. Further research on cellular targets and/or DM is warranted for the treatment of influenza.