Antiviral drugs for influenza, the best known of which is Tamiflu, are—let’s be honest—not exactly miracle cures. They marginally shorten the course of illness, especially if taken within the first 48 hours. But amid possibly the worst flu season in 25 years, driven by a variant imperfectly matched to the vaccine, these underused drugs can make a bout of flu a little less miserable. So consider an antiviral. And specifically, consider Xofluza, a lesser-known drug that is in fact better than Tamiflu.
The culprit behind this awful flu season is subclade K, a variant of H3N2 discovered too late to be incorporated into this year’s flu vaccine. Early data suggest the shot likely does confer at least some protection against this variant, but the jury is still out on whether that protection is much eroded from usual. What is undeniable, though, is a recent explosion of influenza cases. In New York, which was hit early and hard, the number of people hospitalized for flu broke records. Across the rest of the country, cases have been going up a “straight line,” nearly everywhere all at once, which is highly unusual, Arnold Monto, an epidemiologist at the University of Michigan who has been studying influenza for some 60 years, told me last week. Cases seem to be finally leveling off now, but much misery still lies ahead.
For flu, antivirals are a second but oft-overlooked line of defense after vaccines. “We are dramatically and drastically underutilizing influenza antivirals,” Janet Englund, a pediatric-infectious-disease specialist at the University of Washington, told me. Even the older, more commonly prescribed drug Tamiflu reaches only a tiny percentage of flu patients every year. Actual numbers are hard to come by, but compare the estimated 1.2 million prescriptions for Tamiflu and its generic form in 2023 with the some 40 million people who likely got the flu in the winter of 2023–24. Xofluza is even less popular, and exact prescription numbers even harder to find. But they are possibly somewhere from just 1 to 10 percent that of Tamiflu.
The two antivirals are equally effective at allaying symptoms, both shortening the duration of flu by about a day. But Xofluza, which was approved in 2018, offers some tangible benefits over Tamiflu.
First, Xofluza is simply more convenient, a single dose compared with Tamiflu’s 10, which are taken over five days, twice a day. It also causes fewer of the gastrointestinal side effects, such as vomiting and nausea, that patients on Tamiflu will sometimes experience. All in all, a course of Xofluza might be easier for you—or your kid already queasy from the flu itself—to get down and keep down. (That is, if they are old enough to take it: Xofluza is approved for kids ages 5 and up in the United States, but ages 1 and up in Europe; only Tamiflu is recommended for kids down to newborn age as well as for women who are pregnant or breastfeeding.)
Second, Xofluza makes you less contagious to the rest of your family. It drives down the amount of virus spewed by sick patients more quickly than Tamiflu, possibly because of differences in how the two drugs work. Whereas Xofluza stops the virus from replicating, Tamiflu can only prevent already replicated viruses from exiting infected cells to infect others. In a study that Monto led last year, Xofluza cut household transmission by almost one-third compared with a placebo. Tamiflu might reduce transmission too, according to other studies, but probably to a lesser degree than Xofluza.
Third, Xofluza is better at heading off serious post-flu complications such as pneumonia or myocarditis. Patients on Xofluza needed fewer ER visits and hospitalizations than did those on Tamiflu, according to studies of large real-world data sets from insurance claims and medical records. This means that Xofluza should be the antiviral of choice for high-risk patients, including those over 65, who are most prone to these complications, Frederick Hayden, a flu expert at the University of Virginia who led one of the original Xofluza trials, told me. (Hayden has consulted on an unpaid basis, aside from travel expenses, for the companies behind Xofluza.)
The fourth advantage is less relevant to this season because the dominant subclade belongs to the influenza A family. But Xofluza is noticeably more effective against influenza B than Tamiflu, which tends to falter against this family of viruses.
Despite these benefits, awareness of Xofluza remains low. “It hasn’t been used as much as it should be,” Monto said, for reasons of cost and accessibility. Tamiflu, first approved in 1999, is available as a generic for less than $30 even without insurance. Xofluza is still patented and runs $150 to $200 a person. Because it’s less popular, pharmacies are less likely to stock it, making doctors less eager to prescribe it, and so on. In October, though, the company that markets Xofluza in the U.S. launched a direct-to-customer program that sells the drug for the comparably bargain price of $50 without insurance, along with same-day delivery in some areas. Even the flu-drug experts I spoke with, though, were not all aware of this new, more accessible route. The CDC still lists Tamiflu first and foremost in its recommendations, too.
For flu antivirals to be more widely used would also require better testing. Both Xofluza and Tamiflu are most effective within the first 48 hours of symptoms, and the earlier the better. Traditionally, a sick person would have to get to a doctor, get a flu test, get a prescription, and finally get to a pharmacy—which can easily put them past the first 48 hours. But COVID popularized at-home rapid testing, and combination COVID-flu tests have landed on pharmacies shelves recently. With telehealth and home delivery, you can get an antiviral without ever leaving the house.
Still, the at-home tests are expensive, Englund pointed out, about $20 a pop here, compared with just a couple of bucks in Europe. The expense can add up for a whole family. In Japan, where antivirals are widely used, nearly everyone with a flu-like illness gets a routine rapid test and, if necessary, antivirals, both largely covered by the public health-care system. (Xofluza was developed by the Japanese company Shionogi, which also makes Xocova, a promising COVID antiviral my colleague Rachel Gutman-Wei has written about that is not available in the U.S.)
If the U.S. were better at using antivirals, especially in the high-risk patients, the number of Americans dying of flu—roughly 38,000 last year—would likely drop, Cameron Wolfe, an infectious-diseases expert at Duke, told me. Doctors recommend that people at high risk for flu take antivirals prophylactically, upon exposure to anyone with flu, before symptoms appear. Both Xocova and Tamiflu as prophylaxis can cut the chances of getting sick by upwards of 80 percent.
For healthy people who fall ill, antivirals can ease the burden of flu, which is nasty even when it is not deadly. “I don’t want you to be out of work longer than you need to be. I don’t want you to not be a caregiver for your kids,” Wolfe said. “Maybe you have business travel coming up, and I don’t want you to be sick still on that plane.” With challenges around access to antivirals, he said that “the best drug is the one you can get.” Both Tamiflu and Xofluza can make this historically bad flu season a little more bearable.
