NIRMATRELVIR/RITONAVIR-INDUCED HYPONATREMIA PRESENTING WITH SIADH AND GASTROINTESTINAL LOSS

Abstract

INTRODUCTION/BACKGROUND
Nirmatrelvir/ritonavir (Paxlovid™) is an antiviral used to treat mild to moderate COVID-19 infection. Hyponatremia in COVID-19 has been documented in several case reports but none related to treatment with nirmatrelvir/ritonavir to date.

CASE
A 75-year-old female with diabetes mellitus, hypertension and bronchial asthma was treated as COVID-19 Category 2b with symptoms of fever, diarrhoea and poor oral intake. Serum sodium on admission was 138 mmol/L. She was given nirmatrelvir/ritonavir and intravenous drip due to ongoing gastrointestinal losses. Her symptoms resolved in the next two days. On day 7 of illness, she started having new-onset diarrhoea. Repeat Na was 112 mmol/L. Further hydration led to declining Na levels until she became symptomatic at 105 mmol/L. Her paired sample results suggested SIADH, with serum osmolarity 228 mOsm/kg, urine osmolarity 233 mOsm/kg and urine Na 84 mmol/L despite ongoing gastrointestinal losses and clinical signs of hypovolemia. Nirmatrelvir/ritonavir was already discontinued. She was treated with hypertonic 3% saline until her symptoms improved. Her diarrhoea resolved, and her Na levels normalized with fluid restriction and oral salt treatment.

CONCLUSION
Nirmatrelvir/ritonavir has been reported to cause elevated transaminases, hypertension and diarrhoea, apart from its known drug-drug interactions. This case highlights the importance of SIADH as one of the possible adverse effects of this new drug which is now widely used for the management of COVID-19. It is important for clinicians to be vigilant about drug-induced SIADH when investigating the cause of hyponatremia in patients with COVID-19.