As the omicron wave hits a nation weary of the pandemic, the first antiviral pills for Covid-19 promise desperately needed protection for those at risk of serious illness. However, many people who have prescribed the new drugs from Pfizer or Merck will require careful monitoring by doctors and pharmacists, and antivirals may not be safe for everyone, experts warn.
The Food and Drug Administration has cleared Pfizer’s Paxlovid for mild to moderate Covid in people as young as 12 years old who have underlying conditions that increase the risk of hospitalization and death from coronavirus, such as heart disease or diabetes. However, one of the two drugs in the antiviral cocktail could cause serious or life-threatening interactions with widely used drugs, including statins, blood thinners, and some antidepressants. And the FDA does not recommend Paxlovid for people with severe kidney or liver disease.
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Due to expert concerns about the potential side effects of Merck’s molnupiravir, the FDA has limited its use to adults and only in scenarios in which other authorized treatments, including monoclonal antibodies, are not available or are not ” clinically appropriate ”.
The Paxlovid cocktail consists of two tablets of the antiviral drug nirmatrelvir and one tablet of ritonavir, a medicine that has long been used as a booster in anti-HIV regimens. Ritonavir suppresses a key liver enzyme called CYP3A, which metabolizes many drugs, including nirmatrelvir. In the case of treatment with Paxlovid, ritonavir slows down the breakdown of the active antiviral by the body and helps it to remain at a therapeutic level for a longer time.
The stimulating effect was likely to have been crucial in driving the high efficacy of Paxlovid in clinical trials.
When Paxlovid is combined with other drugs which are also metabolized by the CYP3A enzyme, the main concern is that the ritonavir component may increase the co-administered drugs to toxic levels.
To complicate matters, drugs that pose interaction risks are widely prescribed to those most at risk for Covid due to other health conditions.
Medications include, but are not limited to: blood thinners; anti-epileptic drugs; medicines for irregular heart rhythms, high blood pressure and high cholesterol; antidepressants and anxiolytics; immunosuppressants; steroids (including inhalers); HIV treatments; and erectile dysfunction drugs.
“Some of these potential interactions are not insignificant and some pairings should be avoided altogether,” said Peter Anderson, professor of pharmaceutical sciences at the University of Colorado medical campus at Anschutz. “Some are probably easy to manage. But for some, we will have to be very careful. “
In his Paxlovid fact sheet, the FDA has published a detailed list of drugs that may interact harmful with ritonavir, including those that should not be taken with Covid antivirals.
However, pharmacists stress that many of the drug interactions are manageable and should not stop most people from taking Paxlovid.
“Pharmacists are highly trained experts in drug safety and monitoring and are an excellent source of information and advice on drug interactions, as well as supplements and herbal products,” said said Emily Zadvorny, clinical pharmacist and executive director of the Colorado Pharmacists Society. “They will help determine if there is a meaningful interaction and design solutions to mitigate the interaction if possible.”
“A revolutionary drug”
The good news is that healthcare providers are experienced in using ritonavir in people with HIV, a group who often take drugs for other health problems in addition to therapy. antiretroviral.
Dr William Werbel, an assistant professor of medicine at Johns Hopkins University who specializes in transplant infectious diseases, has advised people at high risk for complications from Covid-19 to speak to their health care providers, as well as to a knowledgeable pharmacist about changes they might make to their medication regimens if they need Paxlovid – even before they get infected with the virus.
Anyone seeking Paxlovid, which should be prescribed within five days of the first symptoms, should make sure to inform their prescribers and pharmacists of the full listings of other over-the-counter medications and supplements they are taking, Anderson said.
Certain medications, such as particular statins, can most likely be safely stopped while being treated with Covid pills, Anderson said. For example, it might be better to stay on certain blood thinners but reduce the doses. Some heart rhythm medicines cannot be taken with Paxlovid.
Conversely, some anti-seizure drugs can stimulate the metabolic action of liver enzymes and thus lower the levels of Paxlovid in the body, just like the herbal supplement St. John’s Wort. The FDA has warned that they should not be combined with Paxlovid.
Because Paxlovid treatment is short – 30 tablets, taken as three tablets twice a day for five days – experts hope that the risk of unwanted interactions with other drugs is low.
“Five days of interactions isn’t a big deal for most drugs,” said Jason Gallagher, clinical pharmacy specialist in infectious diseases at Temple University Hospital in Philadelphia.
If a drug’s potential interaction with Paxlovid poses too great a risk, Anderson said, a safe and effective alternative therapy for Covid-19 would be GlaxoSmithKline’s sotrovimab – the only licensed monoclonal antibody treatment that research shows , reliably neutralizes the omicron variant of the virus. Otherwise, the antiviral molnupiravir is an option, although with much lower effectiveness than either Paxlovid or sotrovimab.
Even with concerns about taking Paxlovid with other prescription drugs, experts are excited about the drug’s potential.
“Paxlovid is a revolutionary drug,” Anderson said. “It could make a real difference in the pandemic by making effective Covid treatment available to many people. “