Experts try to demystify the prescription of Paxlovid

Nirmatrelvir/ritonavir (Paxlovid) can interact with a number of drugs, but that doesn’t mean doctors should shy away from prescribing it, experts from the Infectious Diseases Society of America (IDSA) said Friday during a call for the press.

“People don’t prescribe it out of fear of interactions, but sometimes there are manageable interactions,” said Jason Gallagher, PharmD, of Temple University in Philadelphia.

The IDSA has published guidance on drug interactions with commonly used medications in the United States, which details when prescribers should keep medications on during the 5-day course of nirmatrelvir/ritonavir, when to adjust doses, and whether the medications are completely contraindicated.

Melanie Thompson, MD, a primary care physician in Atlanta, spoke about her experiences as an HIV physician and a “longtime survivor of prescription ritonavir,” explaining that the drug increases levels of other drugs that can cause toxicities or reduces their effectiveness.

“We don’t want clinicians to say, ‘I’m not going to worry about it because it’s way too complicated.’ It’s searchable knowledge,” she said. “Breathe deeply, it’s manageable, but it doesn’t have to be easy.”

Some mental health medications, cancer medications, and medications for organ transplant patients can be managed in consultation with specialists. However, most antiarrhythmics are contraindicated, as is sildenafil (Viagra, Revatio) when used to treat pulmonary hypertension, although the dose can be managed when treating erectile dysfunction.

For statins, however, Thompson said clinicians will need help because while two are contraindicated, others are not.

She further noted that clinicians prescribing carbamazepine (Tegretol), used to treat seizures, and St. John’s wort, which can be used to treat depression, should take extra precautions, due to their long half-lives, adding that these two drugs may not be able to be used within 2 weeks of the nirmatrelvir/ritonavir combination.

Thompson recommended two drug interaction websites from the University of Liverpool in England and the University of Waterloo in Ontario as resources for clinicians, but stressed that “we need a 24 hour helpline 24/7 for Paxlovid to make it truly accessible to clinicians.”

Another issue that clinicians may face when prescribing nirmatrelvir/ritonavir is polypharmacy, as elderly patients who may benefit from the antiviral may be taking multiple drugs. She recommended a “medication reconciliation” to review all medications patients are taking, including over-the-counter medications and herbal medications.

Training in the use of ritonavir is also needed for clinicians, since very few have experience with it, Thompson said. She recommended distributing the resources not only to specialists who need training, but also to pharmacists and nurses.

Gallagher lamented that pharmacists cannot prescribe nirmatrelvir/ritonavir because they are not listed as a prescribing group in the drug’s emergency use authorization, noting that the addition of pharmacists ” would greatly improve the program”.

“People who clearly should have received the drug are not receiving it because the prescribers do not know” the population who can benefit from it, he added.

During the call, reporters expressed curiosity about the nirmatrelvir/ritonavir rebound, to which Thompson replied, “That’s a great question and I don’t have a great answer.”

All we have is anecdotal data, she pointed out. “We don’t have a denominator, we don’t know what the relapse rate of Paxlovid is.” Studies will be needed to determine whether those most at risk should receive a second treatment if they rebound, she said.

“Experts have felt that it is probably safe and helpful to treat the most vulnerable people if they rebound, but we don’t have any supporting data,” Thompson noted.

The goal of this therapy is to prevent hospitalizations and deaths, Gallagher said, and even if symptoms return, it’s possible “using the drug has already saved a life.”

“The plural of anecdotes is not a given, but there is a signal that something is happening,” he added.

  • Molly Walker is associate editor and covers infectious diseases for MedPage Today. She is the winner of the J2 Achievement Award 2020 for her COVID-19 coverage. To follow

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