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Paxlovid (nirmatrelvir + ritonavir) — key information

Paxlovid is the brand name given to a combination of two drugs:

  • nirmatrelvir (formerly PF-07321332)
  • ritonavir

Paxlovid is meant for the treatment of mild-to-moderate COVID-19 in adults who test positive for SARS-CoV-2 and who are at high risk for developing severe symptoms of COVID-19.

Nirmatrelvir is an antiviral drug designed to attack SARS-CoV-2. Nirmatrelvir impairs the activity of a viral enzyme called main protease. By weakening the activity of this enzyme, nirmatrelvir reduces the production of new copies of SARS-CoV-2.

A low dose of the drug ritonavir is taken with each dose of nirmatrelvir. The purpose of this low dose of ritonavir is to slow the breakdown of nirmatrelvir in the body. Ritonavir has no antiviral activity against SARS-CoV-2.

Pfizer, the developer of Paxlovid, recommends the following dose and schedule:

  • nirmatrelvir 300 mg (two 150-mg tablets)
  • ritonavir 100 mg (one 100-mg tablet)

A total of three tablets (as above) are taken twice daily for five consecutive days.

Paxlovid is not approved for the following:

  • treating people with COVID-19 who require hospitalization
  • pre-exposure prophylaxis (PrEP; that is, taking Paxlovid prior to exposure to SARS-CoV-2) 
  • to be taken for more than five consecutive days

Pfizer advises that there are many factors that can increase the risk for developing severe symptoms of COVID-19 in people who have been infected with SARS-CoV-2, such as the following:

  • age 60 and older
  • being overweight or obese
  • smoking
  • chronic kidney disease
  • diabetes
  • having a condition that weakens the immune system
  • taking medicines that weaken the immune system
  • cardiovascular disease
  • chronic lung disease
  • the presence of cancer
  • sickle cell disease
  • cerebral palsy and Down’s syndrome

Kidney injury or dysfunction

The estimated glomerular filtration rate (eGFR) is used to assess the health of the kidneys. Pfizer advises that in people with a moderate degree of kidney injury or dysfunction—an eGFR of 31 or from 31 to less than 60 mL/min—the dose of Paxlovid be reduced as follows:

  • nirmatrelvir 150 mg (one tablet)
  • ritonavir 100 mg (one tablet)

These two tablets are taken every 12 hours for five consecutive days.

Pfizer further advises that Paxlovid should not be used in people who have an eGFR less than 30 mL/min.

Liver health

Pfizer advises that no dose adjustments are needed in people with the following degrees of liver impairment:

  • mild liver impairment (graded as Child-Pugh class A)
  • moderate liver impairment (graded as Child-Pugh class B)

There is no safety data about Paxlovid in people with severe liver impairment (graded as Child-Pugh class C).

Drug interactions

The drugs nirmatrelvir and ritonavir interfere with enzymes in the liver that break them down. These enzymes include the following: CYP3A, CYP3A4 and CYP2D6. Many other medicines are affected by the liver enzymes CYP3A and CYP3A4. As a result, there is the potential for ritonavir, and to a lesser extent, nirmatrelvir, to raise or in some cases lower levels of other medicines in the body or vice versa. These interactions can potentially have the following effects:

  • enhance pre-existing side effects (from other medicines)
  • cause new side effects
  • decrease the benefit of other medicines
  • decrease the benefit of Paxlovid

Therefore, before taking Paxlovid, always discuss with a pharmacist any other medicines that you may be taking, both prescription and over the counter, as well as any supplements and herbs that you may be taking. Your pharmacist can provide advice about potential drug interactions and how to avoid or minimize them.

Common side effects

In clinical trials, common side effects with Paxlovid included the following:

  • altered sense of taste
  • diarrhea

This article is just a summary of some information on Paxlovid. Your pharmacist will have more information.

—Sean R. Hosein

REFERENCES:

  1. Lamb YN. Nirmatrelvir plus ritonavir: First approval. Drugs. 2022 Apr;82(5):585-591. 
  2. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, non-hospitalized adults with COVID-19. New England Journal of Medicine. 2022 Apr 14;386(15):1397-1408.