Use antiviral drugs carefully, health officials warn

Pharmacies are bracing for an increased demand for antiviral medications even as health officials warned that the drugs, designed for treating and preventing influenza, should be used judiciously.

Two of the four antiviral drugs in production, Tamiflu (oseltamivir) and Relenza (zanamivir), appear to be effective against the strain of swine flu circulating in the United States, and on Sunday, Homeland Security Secretary Janet Napolitano announced that the government would release 25% of its emergency stockpiles -- about 12 million doses -- of Tamiflu and Relenza to various states in case they were needed. However, many questions remain about how to best use the drugs.

Indiscriminate use may ultimately limit their effectiveness.

“The medications can treat people who are ill and people who are exposed, so they are a good weapon for dealing with whatever might happen,” said Dr. Anne Moscona, an infectious-diseases specialist at Weill Cornell Medical Center in New York. “But I have serious concerns about misuse. There is a danger in using these drugs in a way that encourages the development of drug-resistant viruses.”


Vaccination is the best approach to curbing a viral outbreak. But it would take about six months to create a swine flu vaccine, according to officials at the Centers for Disease Control and Prevention. (A swine flu vaccine has not yet been ordered into production, although a seed stock has been prepared.) Thus, antivirals are used to try to curb transmission in the early days of an outbreak.

The U.S. government began collecting the drugs, called the Strategic National Stockpile, in recent years as concerns grew over the emergence of dangerous viruses, such as the bird flu that has killed more than 200 in Asia.

“This is where the preparations we’ve made over the past few years because of avian flu will prove useful,” Moscona said. “There is a strategy in place for this kind of situation.”

Small supplies of the antivirals are usually stocked by pharmacies year-round. But even with the federal government’s stockpile, not enough of the drugs are expected to be available should a swine flu pandemic occur.


Influenza viruses can become resistant to the drugs, so doctors should think carefully about how the drugs are prescribed if the swine flu outbreak widens, said Dr. John Flaherty, associate chief of infectious diseases at Northwestern University’s Feinberg School of Medicine.

“You don’t want to get panicked about this and start taking Tamiflu willy-nilly,” Flaherty said. “We really should save it and use it in very targeted situations.”

The medications can be useful in a number of ways: to prevent infection before exposure, to prevent infection after exposure and to treat people who already are sick.

Tamiflu and Relenza belong to a class of drugs known as neuraminidase inhibitors that prevent the release of new virus from infected cells. If the drugs are taken right after exposure, this can stop the spread of the infection through the lungs. The drugs can prevent the disease from worsening in infections that have already become entrenched.

In general, the drugs work best if they are started before signs of infection occur or early in the course of the illness. But a rush to obtain the medications and begin taking them may also lead to inappropriate use of the drugs, Flaherty said.

“The earlier you start them, the better,” he said. “But saying that causes people to go to the doctor or hospital with any symptoms,” however mild, and request the medications.

If the drugs are taken inappropriately -- in the wrong dose or for too short a time -- that could encourage development of virus strains that are resistant to the drugs. For prevention, antiviral medications are often taken for two weeks to one month.

“People should not take it upon themselves to share the drug,” Moscona said. “There should be enough medication in the country to treat people who need it.”


But doctors have no assurances yet that Tamiflu and Relenza, even if used properly, will work against swine flu in the same way the drugs have worked against seasonal influenza. The H5N1 avian flu virus, for example, was sensitive to Tamiflu but only in higher doses than is typically prescribed for seasonal flu.

“As we learned with some of the avian influenza virus, the typical doses we use in the United States may not be enough,” said Dr. Jeff Goad, associate professor of clinical pharmacy at USC’s School of Pharmacy. “Until we get more experience in the field, we won’t know if the dosing is enough for this virus.”

Goad said the USC medical center pharmacy has already reported an increase in requests for the medications from patients and doctors. “But the drugs are in short supply,” he said.

Adding to the complexity is that doctors are not all in agreement on which people with influenza, including swine flu, should be treated with antiviral medication, Flaherty said.

But because most healthy adults will recover from a flu infection without complications, doctors have tended to provide antiviral therapy only to those at greatest risk, such as people with other illnesses or immune system weakness, as well as the elderly and young children.

Some evidence exists, however, that the swine flu virus circulating in Mexico may target the group traditionally thought safest: healthy young or middle-aged adults.

Despite the questions, the CDC has already issued what it calls “interim guidance” for the use of the medications. The guidelines, which the agency says may change as the outbreak evolves, state that antiviral medications are:

* Recommended for an ill person suspected to have swine influenza A (H1N1).


* Recommended as a preventive measure for people at high risk for complications from flu who have close contacts with a confirmed or suspected case; schoolchildren at high risk for complications who have had close contact with a confirmed or suspected case; travelers to Mexico at high risk for complications; border workers in Mexico who are at high risk for complications; and healthcare workers or public health workers who have had unprotected close contact with a person ill from swine flu.

* Considered for any healthcare worker at high risk for complications who is working in an area with confirmed swine flu cases and caring for patients with acute febrile respiratory disease; non-high-risk people who are traveling to Mexico; and first responders or border workers working in areas with confirmed cases.

Details on the length of treatment and other information are available on the CDC’s swine flu website.

The Food and Drug Administration on Monday issued an emergency declaration authorizing certain broader uses of antiviral medications. For example, the order allows for prescribing Relenza and Tamiflu in young children, even though the labeling for the drugs calls for use only in children 7 years and older for treatment and 5 years and older for prevention. Tamiflu is used only in children 1 year or older.

The outbreak is already too extensive for health officials to use the antiviral drugs in the way that would have been best, Flaherty said.

“The hope was that [health officials] could target an area to contain an emergency pandemic flu by providing prophylaxis for an area,” he said. “But this virus is already beyond containing. It’s been seen in so many states that that really isn’t going to be possible.”