Nirmatrelvir 300 mg (two 150-mg tablets) with 100 mg ritonavir (one 100-mg tablet) orally twice daily for 5 days.
Dosage adjustment in renal insufficiency
No dosage adjustment with mild renal impairment (eGFR ≥60 to <90 mL/min).
Moderate renal impairment (eGFR ≥30 to <60 mL/min),
One 150 mg nirmatrelvir and one 100 mg ritonavir twice daily for 5 days.
Not recommended in patients with severe renal impairment (eGFR <30 mL/min)
No dosage adjustment is needed in patients with mild or moderate hepatic impairment.
Paxlovid™ is not recommended for use in patients with severe hepatic impairment.
There have been case reports of patients having recurrent illness or “rebound” following the completion of a 5-day course of Paxlovid™.
These patients had an initial laboratory confirmed infection and the resolution of signs and symptoms after Paxlovid™ treatment. Approximately 2 to 8 days later, a recurrence of illness with a positive viral antigen and/or reverse transcriptase polymerase chain reaction testing.
Similar effects were seen in the Paxlovid™ clinical trial, with a small number of participants and was observed in both persons administered Paxlovid™ and in persons given placebo. There was no increased occurrence of hospitalization or death, and there was no evidence that the rebound in detectable viral RNA was the result of SARS-CoV-2 resistance to Paxlovid™.
Currently, there are no reports of severe disease among persons with COVID-19 rebound. Paxlovid™ continues to be recommended for early-stage treatment of mild to moderate COVID-19 among persons at high risk for progression to severe disease.
People with recurrence of COVID-19 symptoms or a new positive viral test after having tested negative should restart isolation and isolate again for at least 5 days. Per CDC guidance, they can end their re-isolation period after 5 full days if fever has resolved for 24 hours (without the use of fever-reducing medication) and symptoms are improving. The individual should wear a mask for a total of 10 days after rebound symptoms started.
A recent Israeli study conducted in the winter months of 2022 during their most recent surge confirms the efficacy of Paxlovid™ in patients over 65 years old at high risk for poor outcomes (both with and without prior immunity).
However, the study failed to show a benefit in those in the 40-64 year old age group.
Ian L. - June 14, 2022 5:16 AM
What about 10 days treatment - less long Covid possibly Primary HSimplex requires 10 days if given 5 days rebounds.
Ian L. - June 14, 2022 5:25 AM
Remdesivir 3 days Iv 200mg day 1 100mg day 2 and 3 given early has clearer proof but real world studies not revealed .In Australia being used in pregnant patients .
Sean N. - June 14, 2022 9:27 AM
Thanks for the comments Ian!
No data at this time to support giving longer course than 5 days of Paxlovid, this may change over time with additional studies.
James H. - June 15, 2022 8:14 PM
Noticed you didn’t discuss Molnupiravur. Would you still consider this a second option for patient with drug-drug interactions to Paxlovid?
Sean N. - June 18, 2022 3:57 PM
Thanks for the comments!
Yes, we did not include molnupiravir in our update.
We consider molnupiravir a third-line agent.
This is based on a few reasons including the data does not support molnupiravir is as efficacious but for a few other reasons.
Molnupiravir has an EUA for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing who are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate. Molnupiravir is a nucleoside analogue that inhibits SARS-CoV-2 replication by viral mutagenesis. There is a theoretical concern of the potential that molnupiravir may induce resistance in the virus and possibly to other antivirals.
The other concern is the concern for mutagenesis and embryo-fetal toxicity and risk to breastfeeding children.
From the EUA prescribing information.
Individuals of childbearing potential of the potential risk to a fetus and to use an effective method of contraception correctly and consistently, as applicable, during treatment with Molnupiravir and for 4 days after the final dose.
Breastfeeding: Breastfeeding is not recommended during treatment and for 4 days after the last dose of Molnupiravir. A lactating individual may consider interrupting breastfeeding and may consider pumping and discarding breast milk during treatment and for 4 days after the last dose of Molnupiravir.
Males: Advise sexually active individuals with partners of childbearing potential to use a reliable method of contraception correctly and consistently during treatment and for at least 3 months after the last dose of Molnupiravir.
Update of Paxlovid
Since our piece was published there is additional data on Paxlovid from the FDA based on Pfizer phase 2/3 study in standard risk patients.
“Pfizer’s COVID-19 drug Paxlovid (nirmatrelvir, ritonavir) has shown limited efficacy in reducing the risks of symptoms for standard-risk patients in a phase 2/3 study.
The FDA authorized the drug for emergency use for high-risk groups based on its efficacy in reducing hospitalizations and deaths in that group.
Due to a very low rate of hospitalization or death observed in the standard-risk patient population, Pfizer has decided to end enrollment in the study.”