PDPH Update – Ritonavir-boosted nirmatrelvir (Paxlovid) for Non-hospitalized Adults

The Philadelphia Department of Public Health released the following health update on October 26, 2022:

Health Update: Ritonavir-boosted nirmatrelvir (Paxlovid) for Non-hospitalized Adults
October 26, 2022


  • Paxlovid is under prescribed among older adults and those with certain underlying conditions who
    could most benefit.
  • Paxlovid has been shown to reduce the risk of hospitalization in these groups, regardless of
    vaccination status.
  • Many drug-drug interactions can be managed by pausing or dose adjusting a medication during the
    course of treatment with Paxlovid. Many tools are available to assist providers in managing
    patients with multiple medications.

The NIH recommends ritonavir-boosted nirmatrelvir (Paxlovid) for non-hospitalized adults who are at
high risk of progressing to severe COVID-19. This includes those with certain medical conditions,
including, but not limited to, obesity, inactivity, diabetes, asthma, and smoking. See the CDC’s
Underlying medical conditions for an exhaustive list. In a clinical trial, Paxlovid provided an 88%
reduction in hospitalization or death when compared to the placebo. Other studies have shown that
Paxlovid is highly effective at preventing hospitalization and death in vulnerable groups,
regardless of vaccination status.

Additional risk factors include older age, a prolonged amount of time since the most recent vaccine
dose (i.e., >4–6 months), and a decreased likelihood of an adequate immune response to vaccination
due to a moderate to severe immunocompromising condition or the receipt of immunosuppressive
medications. The number and severity of the risk factors affects the level of risk.

Patients in the at-risk population who report a positive home test result from a rapid antigen
diagnostic test to their provider and those with a positive PCR test are eligible for Paxlovid
under the emergency use authorization (EUA). Confirmation of a positive home rapid antigen
diagnostic test with additional direct SARS-CoV-2 viral testing, such as a PCR, is not required.

Drug-Drug Interactions
Because Paxlovid is the only highly effective oral antiviral for the treatment of COVID-19, drug
interactions that can be safely managed should not preclude the use of this medication. Clinicians
should be aware that many commonly used medications can be safely co-administered with Paxlovid
despite its drug-drug interaction potential. Multiple tools exist to aid in medication management,
including the FDA’s patient eligibility checklist, Ontario’s Advisory Table from the University of
Waterloo, and an interactive tool from the University of Liverpool, also available as a smartphone
app (COVID-19 iChart).

Renal Dosing
In patients 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

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

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. For patients with a high
likelihood of renal impairment, providers may consider ordering a serum creatinine or calculating
the estimated glomerular filtration rate (eGFR) after assessment on a case-by-case basis.

Viral Rebound
There is evidence from Paxlovid’s clinical trials as well as other studies that suggest that the
amount of virus can fluctuate during the course of COVID-19 infection, independent of Paxlovid use.
Recent clinical trial data shows there was no significant difference in viral load rebound between
the Paxlovid group and the placebo.

Viral rebound may occur but should not preclude the use of Paxlovid in vulnerable groups that
benefit from reduced risk of hospitalization and death.

Information Sheet: Paxlovid Eligibility and Effectiveness (hhs.gov) (PDF)
COVID-19 Therapeutics Decision Aid (hhs.gov) (PDF)

Visit the PDPH Health Information Portal

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