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11/3/2000

Zanamivir May Prevent Influenza Spread in Families

Kate Traynor

Researchers reported in yesterday’s New England Journal of Medicine that quick use of zanamivir can stop the spread of influenza in families, a finding that may be particularly important when influenza vaccine is in short supply. However, practical considerations could limit the typical household’s ability to effectively use the drug.

The researchers, before the start of the 1998 influenza season, assigned 169 families in the United States, Canada, the United Kingdom, and Finland to use zanamivir and its oral inhaler if a family member had symptoms of an influenza-like illness. Another 168 families were assigned to use a placebo and inhaler.

Yesterday, the Centers for Disease Control and Prevention (CDC), which pledged last month to make 9 million more doses of the vaccine available, released information on how health care practitioners can obtain this supply. CDC has contracted with Aventis-Pasteur Inc. to produce the additional doses, which are earmarked for health care providers who will vaccinate high-risk patients. Requesters must complete and fax an application (PDF) to receive the vaccine. Wholesalers may submit requests in mid-December.

Zanamivir, a viral neuraminidase inhibitor known by the brand name Relenza, is currently marketed in the United States for the treatment, but not prevention, of influenza types A and B.

People in the study started taking their assigned treatment once a laboratory confirmed influenza activity in the community and a family member had symptoms of an influenza-like illness. Within 36 hours of the first family member feeling ill—the index case—the rest of the family started treatment. In the families using zanamivir, the index cases inhaled 10 mg of the drug twice daily for five days—the dosage stated in the product’s labeling—and the rest of the family received 10 mg of the drug once daily for 10 days.

Among the households that used zanamivir, laboratory-confirmed influenza was identified in 4 percent of the family members. Nineteen percent of household contacts in the placebo group had laboratory-confirmed influenza. Zanamivir users were 79 percent less likely than placebo users to contract the flu from another household contact who had the illness.

Half of the index cases who took zanamivir had 2.5 fewer days with symptomatic illness than the placebo users had.

The authors of the study stressed that health care practitioners and patients should not use zanamivir as a replacement for the influenza vaccine. However, unvaccinated people, recently vaccinated people whose immune response is not yet complete, and people who do not respond to the vaccine could benefit from using zanamivir, the authors noted.

Household members participating in this study took their first dose of zanamivir within 36 hours of influenza symptoms appearing in the family. According to the product’s labeling, zanamivir should be taken within two days of symptom onset.

This short time frame can be problematic for the typical family, said Cynthia L. LaCivita, Pharm.D., clinical affairs associate with ASHP. "If a patient gets sick on Friday night and [the] physician doesn’t have office hours on weekends…you’ve missed your window of opportunity," said LaCivita. This delay in starting treatment "reduces the odds of suppressing the virus."

Timely use of zanamivir by all family members may also be difficult because of the current health care system. Not everyone in a family visits the same physician, noted LaCivita, so obtaining prescriptions for the entire family can take time. And drug cost is also an issue. "Are insurance companies going to pay for this drug therapy?," she asked. "Are patients willing to pay for it out of pocket?"

In the study, family members of any age could be considered index cases, but only those at least 5 years old could take the study drugs. Families with at least one adult and one child who could use zanamivir were eligible for the study. Pregnant or breast-feeding women and family members who were immunocompromized or hypersensitive to zanamivir were not treated.

Clinicians visited with family members classified as index cases on the first day that influenza-like symptoms occurred, five days after symptom onset, and on day 14 if flu symptoms persisted. Influenza symptoms were defined as a fever of at least 37.8 degrees Celsius, feverishness, cough, headache, sore throat, and myalgia.

Household contacts of the index cases were contacted by telephone on days 5 and 14 and seen by clinic staff on days 11 and 28. Study participants were asked to keep written records for 14 days, documenting their symptoms, any adverse events, and the number of doses taken. People with influenza-like symptoms were told to use acetaminophen and other symptom-relieving medications only when their illness was "disabling."

After laboratory analysis was completed, 8.4 percent of the so-called index cases taking placebo and 1.1 percent of index cases in the zanamivir group were found not to have had influenza after all. However, treatment of the study participants was based on symptomatic diagnosis of influenza, not laboratory confirmation, of the disease in the family.

Laboratory analysis showed that none of the viruses isolated during this study showed signs of resistance to zanamivir within five days of treatment. The authors noted that, according to one study, influenza type A viruses quickly develop resistance to amantadine and rimantadine, two other antiviral drugs used to treat influenza.

Compliance with the study’s treatment regimen was high—98 percent of all participants, including children 5 to 11 years old, took at least eight of their 10 prescribed doses. ASHP’s LaCivita speculated that this level of compliance might not be attainable in an uncontrolled setting, where patients’ treatment is not so closely monitored.

The frequency of adverse events was similar in the zanamivir and placebo groups. One serious adverse event—pneumonia—was reported during the study. The person with pneumonia was part of the zanamivir group, and the disease was diagnosed four days after the patient started taking zanamivir.

According to the product labeling for Relenza, the drug can be used by adults and children at least 7 years old. People with chronic lung disease who use the drug must be closely monitored for breathing difficulties.

FDA maintains a Web page with information about influenza antiviral drugs.

Glaxo Wellcome announced last month that the Food and Drug Administration (FDA) has set a priority to review the company’s request to include "influenza prevention" in Relenza’s labeling. The company funded the study published yesterday. Six of the eight authors were employees or paid consultants of the company.