Dual-histamine receptor blockade with cetirizine - famotidine reduces pulmonary symptoms in COVID-19 patients

Key Messages

Antihistamines are safe and effective treatments for reducing inflammation and cytokine release. Combinations of Histamine-1 and Histamine-2 receptor antagonists (H1 and H2 blockers) are effective for treating skin hives and might reduce the histamine-mediated pulmonary cytokine storm in COVID-19.

This trial examined whether a combination of H1 and H2 blockers improved COVID-19 inpatient outcomes.

The study was conducted in a single medical center, and examined 110 COVID-19 patients who had severe to critical respiratory symptoms. They were given 10 mg of cetirizine (an H1 blocker) twice a day and 20 mg of famotidine (an H2 blocker) twice a day in addition to receiving normal care.

The drug combination resulted in reduced patient death rates and improved symptoms when compared to published reports for COVID-19 inpatients. 16.4% of patients required ventilation and the average hospital stay was 11.0 days.

The use of concomitant drugs were assessed and showed a worse outcome for patients also taking hydroxychloroquine.

This study of cetirizine and famotidine suggest that their dual treatment provides a safe and effective method to reduce symptom severity in COVID-19 patients, presumably by reducing the histamine-mediated cytokine storm.

Pulmonary Pharmacology & Therapeutics

Publication Date: May 5, 2020
Peer Reviewed: Yes
Publication Type: Original | Clinical Prospective
DOI: https://www.doi.org/10.1016/j.pupt.2020.101942

Dual-histamine receptor blockade with cetirizine – famotidine reduces pulmonary symptoms in COVID-19 patients

Reed B. Hogan II, Reed B. Hogan III, Tim Cannon, Maria Rappai, John Studdard, Doug Paul, Thomas P. Dooley

Abstract

Background:
The COVID-19 pandemic due to SARS-CoV-2 infection can produce Acute Respiratory Distress Syndrome as a result of a pulmonary cytokine storm. Antihistamines are safe and effective treatments for reducing inflammation and cytokine release. Combinations of Histamine-1 and Histamine-2 receptor antagonists have been effective in urticaria, and might reduce the histamine-mediated pulmonary cytokine storm in COVID-19. Can a combination of Histamine-1 and Histamine-2 receptor blockers improve COVID-19 inpatient outcomes?

Methods:
A physician-sponsored cohort study of cetirizine and famotidine was performed in hospitalized patients with severe to critical pulmonary symptoms. Pulmonologists led the inpatient care in a single medical center of 110 high-acuity patients that were treated with cetirizine 10 mg b.i.d. and famotidine 20 mg b.i.d. plus standard-of-care.

Results:
Of all patients, including those with Do Not Resuscitate directives, receiving the dual-histamine receptor blockade for at least 48 h, the combination drug treatment resulted in a 16.4% rate of intubation, a 7.3% rate of intubation after a minimum of 48 h of treatment, a 15.5% rate of inpatient mortality, and 11.0 days duration of hospitalization. The drug combination exhibited beneficial reductions in inpatient mortality and symptom progression when compared to published reports of COVID-19 inpatients. Concomitant medications were assessed and hydroxychloroquine was correlated with worse outcomes.

Conclusions:
This physician-sponsored cohort study of cetirizine and famotidine provides proof-of-concept of a safe and effective method to reduce the progression in symptom severity, presumably by minimizing the histamine-mediated cytokine storm. Further clinical studies in COVID-19 are warranted of the repurposed off-label combination of two historically-safe histamine receptor blockers.