Researchers conducted a retrospective drug-disease cohort study utilizing information from the Veterans Affairs Informatics and Computing Infrastructure database to evaluate the potential drug repurposing of dextromethorphan as a cellular target for the management of influenza. Dextromethorphan was identified as a potential drug for repurposing through the cross-matching of host proteins for viral replication with known cellular targets. This process was facilitated by the use of high-throughput small interfering RNA or short interfering RNA whole genome screens.
Data of veterans with a laboratory-confirmed diagnosis of influenza and International Classification of Diseases 9/10 codes for fever, cough, influenza, and acute upper respiratory tract infection in the outpatient setting were utilized in this study. Patients were included in the study if they had had a prescription or a claim during the baseline period, which was the period of time prior to the laboratory-confirmed influenza results; were diagnosed in a primary care or emergency department setting; were not transferred to the emergency department; had no hospitalizations in the 30 days prior to the influenza diagnosis; were not admitted to the hospital as the same day as the influenza diagnosis; and had vital sign data on the day of diagnosis. Patients had to be vaccinated against influenza and had to have received an oseltamivir prescription dispensed on the date of influenza diagnosis.
The primary outcome of this study was an inpatient hospitalization within 30 days of the influenza diagnosis. Hospitalizations were further broken down into all-cause hospitalizations or respiratory hospitalizations. Additionally, patients were analyzed as to whether they had or had not received dextromethorphan. Oseltamivir was controlled for as a covariate.
There were 18,677 patients enrolled in this trial. Of these, 2,801 received dextromethorphan and 15,876 patients did not receive the cough suppressant. The median age of the study population was 57 years, and the majority were Caucasian and male (69% white, 87% male). Statistically significant, more patients who had received dextromethorphan also received oseltamivir (77.7% vs. 59.6%, respectively, P <.0001).
While hospitalizations rates were low for both groups, the dextromethorphan group had significantly less all-cause (2.9% vs. 5.6%, respectively, P <.0001) and respiratory (1.3% vs. 3.0%, respectively, P <.0001) hospitalizations compared with those who did not receive dextromethorphan.
Dextromethorphan was associated with a relative risk reduction of 34% and 40% for all-cause hospitalizations and respiratory hospitalizations, respectively. Age, Charlson Comorbidity Index scores, and BMI <18.5 kg/m2 were associated with higher rates of hospitalizations. Propensity score matching also consistently supported the beneficial effects on hospitalizations associated with dextromethorphan use.
While these results are preliminary, pharmacists should be aware of the potential role that dextromethorphan may have in reducing the risk of hospitalizations associated with influenza.
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