Experts Attempt to Demystify Paxlovid Prescribing

Nirmatrelvir/ritonavir (Paxlovid) may interact with a number of medications, but that does not mean doctors should shy away from prescribing it, Infectious Diseases Society of America (IDSA) experts said during a press call on Friday.

“People are not prescribing it for fear of interactions, but sometimes interactions exist that are manageable,” said Jason Gallagher, PharmD, of Temple University in Philadelphia.

The IDSA released a drug interaction guide with commonly used medications in the U.S., which details when prescribers need to hold medications during the 5-day course of nirmatrelvir/ritonavir, when to adjust dosages, and whether medications are completely contraindicated.

Melanie Thompson, MD, a primary care physician in Atlanta, spoke about her experiences as an HIV doctor and “a long-time survivor of prescribing ritonavir,” explaining that the medication either boosts the levels of other drugs that can cause toxicities or reduces their efficacy.

“We don’t want clinicians to say, ‘I’m not going to bother with it because it’s way too complicated.’ This is look up-able knowledge,” she said. “Take a deep breath, this is manageable, but it’s not necessarily easy.”

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

For statins, however, Thompson said that clinicians are going to 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, need to take extra precautions, due to their long half-life, adding that these two drugs may not be able to be used within 2 weeks of nirmatrelvir/ritonavir.

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 24/7 clinician hotline for Paxlovid to really make it accessible to clinicians.”

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

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

Gallagher lamented the fact that pharmacists cannot prescribe nirmatrelvir/ritonavir, as they are not listed as a prescriber group in the drug’s emergency use authorization, noting that adding pharmacists would “improve the program considerably.”

“People who clearly should’ve received the medication are not receiving it due to prescribers not being familiar” with the population who can benefit from it, he added.

During the call, reporters expressed their curiosity about the issue of nirmatrelvir/ritonavir rebound, to which Thompson replied, “That is an excellent question and I don’t have an excellent answer.”

All we have are anecdotal data, she pointed out. “We don’t have a denominator, we don’t know what the rate of Paxlovid relapse is.” Studies will be necessary to ascertain if people who are more at risk should be given a second course of the therapy if they rebound, she said.

“Experts weighed in with the opinion that it is probably safe and worthwhile to treat the most vulnerable people if they rebound, but we have zero data to support that,” Thompson noted.

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

“The plural of anecdotes is not data, but there’s a signal something is going on,” he added.