Food and drug administration authorized Paxlovid (nirmatrelvir and ritonavir) in December 2021 for the treatment method of gentle-to-average COVID-19 in grownups and pediatric clients (12 a long time of age and older weighing at minimum 40 kg) with good success of direct SARS-CoV-2 viral screening who are also at higher possibility for progression to serious COVID-19, which includes hospitalization or dying.
Paxlovid is now commonly obtainable in community pharmacies. Though the number of COVID-19 hospitalizations has lessened considerably since early 2022, some large-possibility clients are nevertheless obtaining unwell enough to require hospital admission, and early cure with Paxlovid and other out there authorized or authorized therapeutics could make a variation.
In this CDER Discussion, Dr. John Farley, director of the Business office of Infectious Illnesses, provides handy information and facts that can aid health treatment companies in final decision creating with regards to Paxlovid, the desired treatment for the administration of non-hospitalized older people with COVID-19, in accordance to the Nationwide Institutes of Health COVID Procedure Recommendations.
What does “direct SARS-CoV-2 viral testing” suggest? Do individuals require a positive polymerase chain response (PCR) take a look at to be handled with Paxlovid?
Direct SARS-CoV-2 viral tests are used to diagnose infection by SARS-CoV-2, the virus that causes COVID-19. Immediate SARS-CoV-2 viral tests incorporate two sorts of diagnostic checks for COVID-19:
- Molecular assessments, this kind of as PCR checks, that detect the virus’s genetic content.
- Fast antigen diagnostic assessments that detect precise proteins from the virus.
There are a lot of quick antigen tests approved for dwelling use. Patients in the authorized inhabitants who report a favourable household exam consequence from a swift antigen diagnostic exam to their service provider are eligible for Paxlovid less than the emergency use authorization (EUA). A favourable result on a PCR test also fulfills the need under the EUA to have a good take a look at end result. Confirmation of a beneficial household quick antigen diagnostic check with further immediate SARS-CoV-2 viral testing, this kind of as a PCR, is not expected. Serologic checks are not considered to be direct SARS-CoV-2 viral assessments.
How should really overall health treatment companies assess a individual for “high threat for progression to significant COVID-19”?
Sufferers in the approved population with a threat component for development to severe COVID-19 are suitable for Paxlovid beneath the EUA even if they are absolutely vaccinated. Sufferers do not have to have a lot more than 1 danger variable to be considered “high risk”.
We realize that possibility components have transformed more than time, and that it is suitable to contemplate vaccination position in examining a patient’s threat for development to extreme COVID-19.
For a lot more information on clinical ailments and elements affiliated with greater chance for progression to severe COVID-19, remember to stop by the Facilities for Illness Handle and Avoidance (CDC) website.
Are there instruments to help overall health treatment providers take care of prospective drug-drug interactions?
Yes. Food and drug administration lately up to date the Reality Sheet for Wellness Treatment Suppliers for Paxlovid to provide far more unique suggestions for some prescription drugs. We also designed a Prescriber Affected individual Eligibility Screening Checklist. The checklist is meant to help medical decision building, and I believe it will be a useful addition to any prescriber’s “toolbox.”
Paxlovid has nirmatrelvir and ritonavir. Ritonavir is a potent inhibitor of cytochrome P450 3A. Likely drug-drug interactions are an vital consideration. However, a number of typically employed prescription drugs with likely interactions these as statins, oral contraceptives, and HIV medications can be effortlessly managed below provider supervision. Tips are furnished in the Wellbeing Care Supplier Fact Sheet and the Eligibility Screening Checklist Device alongside with an alphabetized record of other medications with most likely major drug interactions.
Other means with regards to management of medicine with probably important drug interactions with Paxlovid incorporate:
Is dose adjustment of Paxlovid wanted for patients with average renal impairment?
Yes. Paxlovid is now provided in two diverse dose packs, one for conventional dosing and a person for reasonable renal impairment dosing.
- In sufferers with moderate renal impairment (eGFR ≥30 to <60 mL/min), the dosage of Paxlovid is 150 mg nirmatrelvir (one 150 mg tablet) and 100 mg ritonavir (one 100 mg tablet) twice daily for five days.
- Patients with mild renal impairment (eGFR ≥60 to <90 mL/min) should receive the standard dose of 300 mg nirmatrelvir (two 150 mg tablets) and 100 mg ritonavir (one 100 mg tablet) with all three tablets taken together orally twice daily for five days.
- Paxlovid is not recommended at this time in patients with severe renal impairment (eGFR <30 mL/min).
Health care providers may rely on patient history and access to the patient’s health records to make an assessment regarding the likelihood of renal impairment. Providers may consider ordering a serum creatinine or calculating the estimated glomerular filtration rate (eGFR) for certain patients after assessment on a case-by-case basis.
How can I locate a community pharmacy that has Paxlovid in stock?
Paxlovid is now widely available at community pharmacies. The U.S. government maintains a locator tool for COVID-19 therapeutics that lists community pharmacies that have Paxlovid in stock. Use the search glass icon to enter the patient’s zip code. Pharmacies will be listed by proximity.
What do we know about the case reports of patients developing symptoms again after completing a course of Paxlovid?
FDA is aware of the reports of some patients developing recurrent COVID-19 symptoms after completing a treatment course of Paxlovid. In some of these cases, patients tested negative on a direct SARS-CoV-2 viral test and then tested positive again.
The benefit of a 5-day treatment course of Paxlovid was demonstrated in the clinical trial that supported the EUA. This study showed that among non-hospitalized patients at high risk of progression to severe disease, treatment with Paxlovid reduced the risk of hospitalization or death by 88%. Reductions in hospitalization and death were also demonstrated in clinical trials of other available approved (Veklury [remdesivir]) or authorized (Lagevrio [molnupiravir]) antiviral agents.
In light of these reports, additional analyses of the Paxlovid clinical trial data have been performed. In the Paxlovid clinical trial, some patients (range 1-2%) had one or more positive SARS-CoV-2 PCR tests after testing negative, or an increase in the amount of SARS-CoV-2 detected by PCR, after completing their treatment course. This finding was observed in patients treated with the drug as well as patients who received placebo, so it is unclear at this point that this is related to drug treatment. Additional analyses show that most of the patients did not have symptoms at the time of a positive PCR test after testing negative, and, most importantly, there was no increased occurrence of hospitalization or death or development of drug resistance.
These reports, then, do not change the conclusions from the Paxlovid clinical trial which demonstrated a marked reduction in hospitalization and death.
We are continuing to review data from clinical trials and will provide additional information as it becomes available. However, there is no evidence of benefit at this time for a longer course of treatment (e.g., 10 days rather than the 5 days recommended in the Provider Fact Sheet for Paxlovid) or repeating a treatment course of Paxlovid in patients with recurrent COVID-19 symptoms following completion of a treatment course.
In summary, Paxlovid reduces the risk of hospitalization and death for patients with mild-to-moderate COVID-19 at high risk of disease progression. Health care providers should consider treatment with Paxlovid or other approved or authorized therapeutics in accordance with the approved labeling or authorized Health Care Provider Fact Sheets. Patients who test positive for SARS-CoV-2 who have symptoms should discuss treatment options with their health care provider as soon as possible after testing positive. Health care providers and patients should refer to CDC recommendations regarding patient isolation, and should wear a mask and isolate if they have any symptoms regardless of whether or not they have been treated with an antiviral agent.
Thank you, Dr. Farley. Do you have any final remarks you’d like to share with health care providers about Paxlovid?
I would like to reiterate that Paxlovid is now widely available at community pharmacies. There is strong scientific evidence that it reduces the risk of hospitalization and death in patients with mild-to-moderate COVID-19 at high risk for progression to severe disease. It is also expected to be effective against the Omicron variant. For more information about the EUA for Paxlovid, including possible risks of use, the Fact Sheet for Health Care Providers, and Prescriber Patient Eligibility Checklist, please visit FDA’s Emergency Use Authorizations webpage.