Paxlovid (nirmatrelvir/ritonavir) was touted as a “breakthrough” and “wonder drug” to treat COVID-19 when Pfizer released preliminary data in late 2021. Now that it is widely used, cases of viral rebound or rebound of COVID -19 has been reported. This is what we know about the efficacy and rebound of Paxlovid.
What is Paxlovid®?
Paxlovid consists of two separate agents: nirmatrelvir and ritonavir. Nirmatrelvir prevents the SARS-CoV-2 virus from replicating by blocking its protease enzyme. Ritonavir is a boosting agent that helps nirmatrelvir last long enough in the body to be effective.
Paxlovid is taken orally twice daily for five days and should be started as soon as possible after diagnosis of COVID-19 in selected patients described below, and within five days of symptom onset. Dysgeusia (altered sense of taste) and diarrhea are the most common side effects.
Who is eligible for Paxlovid?
Paxlovid is the first-line option for outpatients at least 12 years old (and weighing more than 40 kg) with mild to moderate COVID-19 and at high risk of severe disease. High risk includes people over 64 years of age, people with obesity, people who are pregnant, and patients with other underlying conditions described by the Public Health Agency of Canada and the US Centers for Disease Control and Prevention.
Drug interactions are a problem with Paxlovid and a careful review of a patient’s current medications for possible interactions is necessary before starting treatment. The concomitant use of rivaroxaban or salmeterol is contraindicated. A variety of other drug interactions must also be considered, and adjustments and monitoring may be necessary. Importantly, Paxlovid is also contraindicated in patients with severe renal or hepatic dysfunction.
How effective is Paxlovid?
In the EPIC-HR trial, Paxlovid resulted in a nearly 90% reduction in hospitalization or death among unvaccinated patients with mild to moderate COVID-19 and at high risk of severe disease. Paxlovid also led to faster viral clearance.
What is the viral rebound or COVID-19 rebound?
Viral rebound is the phenomenon in which a patient has a new positive result after having tested negative, although they remain asymptomatic. COVID-19 rebound is an outbreak of symptoms after resolution of an acute illness. The timing of viral or COVID-19 rebound appears to be two to eight days after recovery, and both disease recurrence and positive test results have resolved in the few case reports documenting rebound.
How many patients experience a rebound after Paxlovid?
There is no concrete answer to this question and estimates vary widely. It is believed to be a rare occurrence.
Interestingly, the EPIC-HR trial investigators measured viral load up to 14 days, but chose to report the mean change in viral load by group, which may hide viral rebound among a subset of patients. On a Pfizer earnings call, William Pao, executive vice president and chief development officer, said that about 2% of EPIC-HR participants taking Paxlovid had a rebound in viral load, but that it was about the same percentage in the placebo group. Therefore, Pfizer’s interpretation was that the viral load rebound was a natural progression of the viral infection and not caused by Paxlovid therapy.
One difference between the EPIC-HR study and the current situation could be the SARS-CoV-2 virus. The EPIC-HR trial took place during the Delta wave, while we are currently in the midst of several Omicron sub-variant waves. Another difference could be vaccination status. The EPIC-HR trial included only unvaccinated participants, while the actual use of Paxlovid includes many vaccinated people. However, it could be assumed that vaccination reduces the probability of rebound and does not increase the risk.
What should I do if my patient has rebound COVID-19 and what are the concerns?
An obvious problem with viral rebound is the possibility that, despite treatment, patients who recover will progress to severe COVID-19 requiring hospitalization. Although there are limited reports at this time, rebound does not appear to be associated with disease progression. Rebound patients should be monitored and reassessed if symptoms persist. Repeat treatment with Paxlovid is not recommended. Healthcare providers should consider reporting the event to Health Canada’s Canada Surveillance online adverse reaction database.
Another problem with viral rebound is the potential for patients to become infectious again and unknowingly contribute to transmission. Thus, if a patient has been diagnosed with viral rebound or COVID-19, they should isolate themselves for at least five days and continue to wear a mask for 10 days (isolation can end after five days if symptoms have improved and there is no fever for 24 hours). without fever-reducing drugs).
Finally, just like the growth of bacteria in the presence of antibiotics, viruses can develop resistance to antiviral agents. The limited research to date does not indicate that the SARS-CoV-2 virus in rebound infections contains additional mutations that would confer resistance. In the long term, viral resistance remains a possibility and will continue to be monitored.
Ultimately, we need to understand how often viral rebound occurs and its clinical ramifications before changing Paxlovid advice. Until that time, Paxlovid remains a first-line option for high-risk patients.
Related Posts
Outpatient therapy for COVID-19: What are the options and who is eligible?
An antiviral pill for COVID-19 — Is molnupiravir too good to be true?
PrEP and PEP: Can medications work to prevent COVID-19? (cma.ca)
Original article published in EBM Focus. Written by:
Heather D. Marshall, PhD, Public Health Content Manager at DynaMed; and Vito Iacoviello, MD, deputy editor for infectious diseases, allergies, and immunology at DynaMed.
CMA members have access to DynaMed, a point-of-care referral tool valued at $399 per year, as part of their membership.
Do you have a question about COVID-19 or another clinical topic? Contact the Ask a Librarian team to request a bibliographic search.
Source: boldly.cma.ca