Nirmatrelvir combined with ritonavir for preventing and treating COVID-19

Abstract

Background Oral nirmatrelvir/ritonavir (Paxlovid®) aims to avoid severe COVID‐19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. Due to its novelty, there are currently few published study results. It remains to be evaluated for which indications and patient populations the drug is suitable. Objectives To assess the efficacy and safety of nirmatrelvir/ritonavir (Paxlovid®) plus standard of care compared to standard of care with or without placebo, or any other intervention for treating COVID‐19 and for preventing SARS‐CoV‐2 infection. To explore equity aspects in subgroup analyses. To keep up to date with the evolving evidence base using a living systematic review (LSR) approach and make new relevant studies available to readers in‐between publication of review updates. Search methods We searched the Cochrane COVID‐19 Study Register, Scopus, and WHO COVID‐19 Global literature on coronavirus disease database, identifying completed and ongoing studies without language restrictions and incorporating studies up to 11 July 2022. This is a LSR. We conduct monthly update searches that are being made publicly available on the open science framework (OSF) platform. Selection criteria Studies were eligible if they were randomized controlled trials (RCTs) comparing nirmatrelvir/ritonavir plus standard of care with standard of care with or without placebo, or any other intervention for treatment of people with confirmed COVID‐19 diagnosis, irrespective of disease severity or treatment setting, and for prevention of SARS‐CoV‐2 infection. We screened all studies for research integrity. Studies were ineligible if they had been retracted, or if they were not prospectively registered including appropriate ethics approval. Data collection and analysis We followed standard Cochrane methodology and used the Cochrane risk of bias 2 tool. We rated the certainty of evidence using the GRADE approach for the following outcomes: 1. to treat outpatients with mild COVID‐19; 2. to treat inpatients with moderate‐to‐severe COVID‐19: mortality, clinical worsening or improvement, quality of life, (serious) adverse events, and viral clearance; 3. to prevent SARS‐CoV‐2 infection in post‐exposure prophylaxis (PEP); and 4. pre‐exposure prophylaxis (PrEP) scenarios: SARS‐CoV‐2 infection, development of COVID‐19 symptoms, mortality, admission to hospital, quality of life, and (serious) adverse events. We explored inequity by subgroup analysis for elderly people, socially‐disadvantaged people with comorbidities, populations from LICs and LMICs, and people from different ethnic and racial backgrounds. Main results As of 11 July 2022, we included one RCT with 2246 participants in outpatient settings with mild symptomatic COVID‐19 comparing nirmatrelvir/ritonavir p...

Simultaneous green TLC determination of nirmatrelvir and ritonavir in the pharmaceutical dosage form and spiked human plasma

“…The ability to quantitatively analyze drugs at extremely low levels, in the Nano gram range, allows for their detection in biological fluids. One such drug combination is nirmatrelvir and ritonavir, which is a recently approved co-packaged medication by the FDA for the treatment of COVID-19 [13][14][15][16][17] . As these drugs have recently been introduced to the market, it is advisable to establish a validated analytical method for detecting nirmatrelvir and ritonavir in their pure form, as well as in their pharmaceutical form and in spiked plasma samples.…”

“…1, is a protease inhibitor of human immunodeficiency virus type 1 and also a CYP3A inhibitor. Nirmatrelvir plus ritonavir was recently approved in US, United Kingdom and Europe as a new co-packaged dosage form for the treatment of COVID-19 in adults who are at high risk of infection [13][14][15][16][17] .…”

Pragmatic and open science-based solution to a current problem in the reporting of living systematic reviews

“…15 Therefore, the Cochrane Review evaluating Pfizer's new antiviral was designed as an LSR with continuous monitoring of new and ongoing studies. 16 Kahale and colleagues recently proposed to document the search and selection process for each LSR update through tailored Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams. 17 However, they do not address the lack of transparency between updates.…”

“…18 Monthly searches for the LSR began on 11 April 2022, the day the protocol was published in the Cochrane Library. 16 The information specialist (MIM) provides the author team with the search results the same day, having first removed duplicates as well as all previously screened records using EndNote. Two members of the author team then independently screen the search results in Covidence and document the outcomes of the selection process in the Excel spreadsheet.…”

Involvement of the STING signaling in COVID-19

“…Remdesivir, a broad-spectrum antiviral drug, is the first drug approved by FDA for COVID-19 treatment ( 5 ). Another small molecule antiviral agent, Paxlovid (nirmatrelvir/ritonavir), was approved for the treatment of adult patients with mild-to-moderate COVID-19 ( 6 ). Meanwhile, oral or intravenous administration of dexamethasone was reported to reduce the 28-day mortality in patients hospitalized with COVID-19 ( 7 ).…”