ABSTRACT
INTRODUCTION: Paxlovid (nirmatrelvir-ritonavir) received Emergency Use Authorization (EUA) for mild to moderate COVID-19 among those at high risk for severe disease. Hyponatremia is not yet listed as an adverse reaction to either Paxlovid or ritonavir alone in UpToDate. The package insert lists hyponatremia if Paxlovid is administered with finerenone, due to the increased concentration of finerenone caused by a drug-drug interaction. The EUA lists one case of mild hyponatremia in a patient with 10 other adverse events, none of which thought to be related to Paxlovid. The Liverpool COVID-19 website allows review of concomitant medications for drug interaction prior to prescribing, although it is unclear how widespread its use is among prescribers. The objective of this case series is to review 4 cases of severe hyponatremia in patients receiving Paxlovid that required intensive care unit (ICU) admission. DESCRIPTION: During a 6-week period from June to July 2022, our community hospital treated 7 adult patients in the ICU for severe hyponatremia, defined as sodium (Na) less than 120 mEq/L. Of those 7, three patients did not have COVID-19. The remaining four patients had been prescribed and were taking Paxlovid for COVID-19, with Na levels upon admission ranging from 112 to 115 mEq/L. Weakness, nausea and dehydration were all common side effects upon presentation. Use of the Liverpool COVID-19 interaction checker revealed a potential weak interaction in only 1 of 4 patients that venlafaxine concentrations could potentially be increased and venlafaxine has been associated with hyponatremia. With cessation of the drug and conventional treatment measures for severe hyponatremia including hypertonic saline, the hyponatremia corrected appropriately in all four cases. DISCUSSION: COVID-19 itself has been associated with hyponatremia of unclear mechanism, however two large studies of 1099 & 5700 patients hospitalized for COVID-19 showed average Na levels of 138 & 136 mEq/L, respectively. We admitted 4 patients to the ICU in a 6-week period for severe hyponatremia while taking Paxlovid. Although the mechanism is unknown, this could be a signal that warrants further investigation. Vigilant review of concomitant medications when prescribing Paxlovid using the Liverpool interaction checker is needed.