Intranasal Chlorpheniramine Maleate for the treatment of COVID-19: Translational and Clinical Evidence

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Marcos A. Sanchez-Gonzalez Jonna B. Westover Syed A A Rizvi Joselit Torres Gustavo A. Ferrer, MD


Recently, the nasal cavity has been highlighted as an ideal route of administration for interventions as it is the portal of entry of the severe acute respiratory syndrome coronavirus (SARS-CoV-2). The present study aimed to demonstrate the feasibility and efficacy of intranasally administered Chlorpheniramine Maleate (CPM) spray to treat coronavirus disease 2019 (COVID-19).

Methods: The present study used a two-phase, non-clinical to clinical approach. The non-clinical phase evaluated CPM’s antiviral activity against SARS-CoV-2 delta (B.1.617.2) strain via a highly differentiated three-dimensional in vitro model of normal, human-derived tracheal/bronchial epithelial cells. CPM was tested in duplicate inserts of the tissue models of the human airway. Virus yield reduction assays measured antiviral activity on day six after infection. For the clinical phase, COVID-19 symptomatic (polymerase chain reaction positive) patients were recruited and assigned to a 7-day CPM treatment (n=32) or placebo (PLB; n=13). Close safety monitoring of all patients was conducted before and after administering the drug. The primary outcomes monitored were time to symptom resolution (days), progression to hospitalization, emergency room visits, and symptoms of the severity of the disease using a visual analog scale (VAS) on a scale of 1-10 (no symptoms to worst symptoms).

Results: The virus yielded a reduction in the assay such that the CPM solution log reduction value was 2.69 and Remdesivir 0.12, demonstrating much high antiviral activity of CPM. Results of the clinical phase demonstrate that VAS scores between the groups were evident after using CPM for two days (day 3). The CPM group VAS were significantly lower (P<0.001) starting from day three compared with day one. In contrast, there were no statistically significant (P>0.05) changes in the PLB during the 7-day treatment window. No subjects in the intervention group were hospitalized, while two in the PLB required hospitalization (15.4%; X2=5.15, P=0.023). Besides some mild discomfort felt by subjects immediately after applying the spray, the participants reported neither adverse reactions nor side effects.

Conclusion: If taken together, the results of the present two-phase study point towards the conclusion that CPM is an antiviral agent that can be administered intranasally to treat COVID-19 effectively.

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SANCHEZ-GONZALEZ, Marcos A. et al. Intranasal Chlorpheniramine Maleate for the treatment of COVID-19: Translational and Clinical Evidence. Medical Research Archives, [S.l.], v. 10, n. 3, mar. 2022. ISSN 2375-1924. Available at: <>. Date accessed: 28 nov. 2022. doi:
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