The antiviral medication Paxlovid interacts adversely with many medications meant for heart conditions and post-transplant patients, narrowing the pool of people who could benefit from the drug.
Paxlovid comprises two medications, one used as an enhancer for the other. That medication, ritonavir, can either boost or lower concentrations of other drugs in a person’s system, generating the risk that other drug toxicities will become dangerously too high. Those patients will require close monitoring while taking the medication.
“It’s not a one-size-fits-all. This requires some consideration of the individual patient in front of you and what drug it is and what role that drug is playing,” said Dr. Amesh Adalja, an infectious disease expert at the Johns Hopkins Center for Health Security who also practices medicine in Pittsburgh.
Ritonavir has long been used to boost HIV medication regimens. It suppresses a crucial liver enzyme called CYP3A, which metabolizes many other medications, including the second medication in Paxlovid, nirmatrelvir. In this case, ritonavir keeps the medication in the person’s system for longer by slowing the body’s breakdown, thus prolonging the drug’s therapeutic benefit.
When pairing other medications that are also metabolized by the CYP3A enzyme, doctors and pharmacists have to ensure that the ritonavir component of the treatment does not increase concentrations of other drugs to dangerous levels. People who take medications that prevent seizures, remedy heart arrhythmias, suppress the immune system using anti-rejection drugs, or prevent blood clots may be ineligible to take the antiviral if they become infected with COVID-19.
Many doctors and pharmacists will advise patients against taking their other medications during the five-day period during which Paxlovid is administered.
“If it’s a high blood pressure medication, it’s probably not that big of a deal if they’re off it for five days. But if it’s an anti-rejection drug, you might want to be careful,” Adalja said. “It all depends on each person’s condition, what they’re being treated for.”
Still, healthcare providers are well equipped to determine whether a patient is a good fit for the medication, whose components are not new. People at high risk of severe illness who should not take Paxlovid may be eligible for the monoclonal antibody treatment sotrovimab or Merck’s antiviral Molnupiravir.
Adverse drug-drug interactions are not a new pharmaceutical phenomenon. But the coronavirus has shed a brighter light on them because the treatment has been considered a game changer for high-risk people still nervous about getting seriously ill.
“I think that it’s [getting more attention] because it’s COVID-related where the impacts of it is a major advance in terms of its efficacy. But you know, drug-drug interactions are nothing new, and that’s why people go to medical school and to pharmacy school,” Adalja said.
Possible negative drug interactions notwithstanding, healthcare professionals are excited about Paxlovid, with its promise as the U.S. looks forward to when the coronavirus is a part of everyday life and requires surveillance like any other infectious disease as seasonal flu.
The drug, which was authorized by the Food and Drug Administration in December, has been shown to cause an 89% reduction in risk of hospitalization for patients who received the medicine within three days of symptom onset compared with those who received a placebo. People who took the drug within five days of experiencing symptoms were also 88% less likely to be hospitalized or die due to COVID-19. The drug was tested in adults at high risk of severe disease, including seniors and people with underlying health conditions.
While Paxlovid supplies are still pretty slim, Pfizer has said it continues to ramp up production with projections that it will produce 6 million to 7 million courses by the end of the quarter. The White House, meanwhile, said the U.S. would have 1 million courses of the Pfizer treatments by the end of March and double that by the end of April. To date, the U.S. has purchased 20 million courses.
