(1436) The Association Between Paxlovid and Severe Hyponatremia

Introduction: On December 22nd, 2021 the United States Food and Drug Administration granted emergency use authorization for the use of nirmatrelvir-ritonavir (Paxlovid) for outpatients with mild-to-moderate COVID-19 infection who were at high risk for progression to severe disease. Commonly reported side effects of Paxlovid include dysgeusia and diarrhea, but it is generally well-tolerated with only 0.8% discontinuing therapy in the EPIC-HR trial. Severe hyponatremia (Na+ < 125 mmol/L) is not reported as a side effect, however recent case reports have described this condition. Following observations of patients being admitted to our intensive care units with severe hyponatremia while using Paxlovid, we sought to identify these patients to determine a possible association, potential mechanisms, and patient risk factors.

Methods: This was a multi-centered retrospective observational study of inpatients between January 1st, 2022 and January 31st, 2024. We queried our healthcare system’s electronic medical record system for severely hyponatremic patients via ICD-10 coding. We then analyzed each patient’s demographic information, past medical history, medications, diagnostic work up, and hospital course.

Results: 13 patients with severe hyponatremia were identified after recent use of Paxlovid. The mean Na+ on presentation was 112 mmol/L. The mean duration from the last dose of Paxlovid to admission was 2.04 days. 8 patients were female, and the mean age was 80.67 years. 7 patients had a predominantly hypovolemic etiology, 3 patients had a diagnostic workup consistent with the syndrome of inappropriate antidiuretic hormone release, and 3 patients had a multifactorial etiology. All patients survived to discharge with a mean hospital length of stay of 7.59 days.

Conclusions: We propose there may be a clinically relevant association between the use of Paxlovid and the development of severe hyponatremia. Elderly patients and those with gastrointestinal side effects from Paxlovid appear to be at greater risk. The etiology of hyponatremia appears to be multifactorial with hypovolemia and SIADH being the predominant mechanisms. Further investigation using larger databases is required for validation.