Concomitant and sequential administration of nirmatrelvir-ritonavir and azvudine in patients with COVID-19 caused by the Omicron variant: Safety and efficacy

Abstract

Background

This study assessed the safety and efficacy of nirmatrelvir-ritonavir (Paxlovid®) and azvudine when administered sequentially or concomitantly in patients with coronavirus 2019 (COVID-19) caused by the Omicron variant.

Methods

Ninety-three patients confirmed to be infected with the Omicron variant by nucleic acid detection were retrospectively investigated. Information was collected on general health status, medication, and adverse drug reactions (ADRs) according to whether nirmatrelvir-ritonavir and azvudine were administered sequentially or concomitantly. Data on times of onset, clinical manifestations, and outcomes of ADRs and on conversion to a negative nucleic acid test were also recorded.

Results

Possible ADRs were recorded in 41 patients (44.1%). There were 22 gastrointestinal reactions in 18 patients and 18 hematological abnormalities in 16 after sequential or concomitant treatment with nirmatrelvir-ritonavir and azvudine. Liver enzyme levels increased in nine cases and creatinine clearance decreased in two. Cases of atrial fibrillation (n = 1), sleep disorder (n = 2), rash (n = 2), dizziness (n = 1), and weakness (n = 5) were also documented. Only vomiting, poor appetite, diarrhea, xerostomia, bitter taste, and rash were considered probable ADRs; others were thought to be possible ADRs. In all cases, the nucleic acid test did not turn negative after the first antiviral was applied. The nucleic acid test of 28 patients did not turn negative before discharge. The remaining 65 patients (69.9%) returned a negative nucleic acid test after receiving the second antiviral agent.

Conclusions

Treatment with nirmatrelvir-ritonavir and azvudine is safe and effective whether administered sequentially or concomitantly in patients with COVID-19 caused by the Omicron variant.