New IDSA guidance covers drug interactions with Paxlovid


IDSA. Management of drug interactions with nirmatrelvir/ritonavir (Paxlovid): Resource for Clinicians. Accessed on May 9, 2022.

Gallagher reports no relevant financial disclosures.

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The Infectious Diseases Society of America issued guidance to help clinicians manage drug interactions between Paxlovid and the 100 most prescribed medications.

Additionally, the FDA said there is no evidence to suggest that a longer course of Paxlovid will benefit patients who experience a rebound in COVID-19 symptoms after completing a 5-day course of the medication.

Source: Adobe Stock.

The IDSA issued clinician guidance for Paxlovid to minimize patient drug interactions. Source: Adobe Stock.

Pfizer received an emergency use authorization for Paxlovid — which consists of the protease inhibitor nirmatrelvir and a low dose of ritonavir — in late December, making it the first available oral antiviral for COVID-19. It has been shown to reduce the risk for hospitalization and death from COVID-19 by close to 90%.

The Biden administration announced last month that it was purchasing 20 million courses of Paxlovid, which is a focus of its test-to-treat initiative. The medication is now available at many U.S. pharmacies after an initial supply shortage, said Jason Gallagher, PharmD, a clinical professor at Temple University School of Pharmacy in Philadelphia.

Jason Gallagher

“Availability has improved considerably in the past few months, and it is much easier to access than many people think,” Gallagher told Healio. “Perceptions are not in line with the reality of the current supply.”

Reported cases of relapse following a 5-day course of Paxlovid for COVID-19 are mostly anecdotal, Gallagher said, “but that doesn’t mean they are not real.”

“The relapse rate in the study that led to its approval was similar between the Paxlovid and placebo groups — about 2% — but that was in an unvaccinated population with different variants,” he explained.

In a recent update for providers, the FDA said it was aware of reports of patients developing COVID-19 symptoms after completing a course of Paxlovid, including some who tested negative for SARS-CoV-2 and then positive again, but that there is “no evidence of benefit at this time for a longer course of treatment” — for example, 10 days instead of 5.

The FDA reanalyzed clinical trial data and said the reports “do not change the conclusions from the Paxlovid clinical trial, which demonstrated a marked reduction in hospitalization and death.”

“The only duration of therapy for Paxlovid that we have evidence to support is the 5-day course that received the EUA,” Gallagher said. “EUAs are specific, and prescribers do not have a choice but to follow it. There is no specific guidance, but FDA has said that if someone does relapse on Paxlovid there is nothing preventing a second course from being prescribed.”

In the event a second course is prescribed, the IDSA says the duration of therapy should be used to guide adjustments to concomitant medications.

Paxlovid is authorized to treat mild-to-moderate COVID-19 in patients aged 12 years or older who are at high risk for progression to severe disease and weigh at least 40 kg. IDSA guidelines state that Paxlovid should be initiated within 5 days of symptom onset. Additionally, the guidance says patients with mild-to-moderate COVID-19 who are at high risk for progression to severe disease and who are admitted to the hospital for something other than COVID-19 can also receive Paxlovid.

“That covers a lot of people,” he said. “People with diabetes, people who are obese, elderly people, immunocompromised people.”

He said the potential for drug interactions with Paxlovid may have “scared away” many prescribers. However, among the top 100 most prescribed drugs, the IDSA said only two have interactions so severe that Paxlovid should be avoided altogether: rivaroxaban and salmeterol.

“A few combinations rule out Paxlovid use, but most can be managed during the 5 days of therapy. There are other drugs that cannot be combined with Paxlovid, so each patient needs individual assessment done,” Gallagher said.

According to the IDSA guidance, clinicians should obtain a complete list of a patient’s current medications including over-the-counter agents and herbal supplements — confirming that the patient is taking each medication as prescribed. They should review the FDA Paxlovid health care provider fact sheet to identify any medications contraindicated with Paxlovid, review potential drug interactions between Paxlovid and the patient’s current medications, and advise patients of any dose adjustments.


IDSA. Management of drug interactions with nirmatrelvir/ritonavir (Paxlovid): Resource for Clinicians. Accessed on May 9, 2022.

FDA updates on Paxlovid for health care providers. Published May 4. 2022. Accessed May 10, 2022.