What fallout shelters were to worries about the Bomb, and duct tape and plastic sheeting were to fears of terrorism after Sept. 11, Tamiflu is starting to be for the specter of pandemic influenza.
Across the country, people appear to be building home stockpiles of the prescription antiviral medicine, according to reports by drugstores, pharmaceutical benefit managers and physicians.
The run on Tamiflu was apparently spurred by government warnings, here and abroad, that chances for a worldwide flu epidemic are rising, and by news that Southeast Asia's H5N1 bird flu -- the leading candidate for a pandemic -- is moving westward.
For more than a year, demand for the drug, known generically as oseltamivir, has been rising as more than three dozen countries began to lay in millions of doses for national stockpiles. Retail demand, however, took a sharp upturn last month. A five-day course of two pills a day costs $80 to $90.
The trend worries many physicians and public health experts because widespread home stockpiling could undermine international efforts to fight a flu pandemic. Some doctors are refusing their patients' requests except in special circumstances.
"I do know that I personally can't give everybody who wants Tamiflu a prescription for it. It just doesn't seem right to me," said Harry Oken, 51, an internist in Columbia. "If there really was an avian flu epidemic, people who don't need it have it, and people who really need it can't get it."
Oken said he and his four partners at Charter Internal Medicine are each getting one or two calls a week from patients seeking the medicine. They have agreed not to prescribe it for home stockpiles.
"Last week a patient of mine called about having Tamiflu on hand, and I must have been on the phone with him for 20 minutes. He wanted four prescriptions. We went back and forth on all the issues, and he finally asked, 'Well, what would you do?' "
"I told him, 'Well, I'm not writing it for my family,'" Oken said. He knows that some doctors are keeping a supply for their own use but believes "that's not right, either."
The Centers for Disease Control and Prevention and the Infectious Diseases Society of America are each drawing up advice to practitioners on the issue of home stockpiles, spokesmen said this week. With no vaccine available yet, an abundant supply of Tamiflu is one of the few weapons public health agencies could wield to try to stop an emerging pandemic. Mathematical models published this summer by two research teams concluded that spread of a contagious new strain of influenza virus could be slowed or even stopped by widespread use of Tamiflu at the outbreak site. Other experts, however, think that even with unlimited quantities of the drug, this is unrealistic.
Human infections with the H5N1 strains are extremely rare -- but frequently fatal. Since late 2003, 118 people have contracted the disease and 61 have died. The most recent was a 48-year-old Thai man who died Wednesday. During the same period, 140 million domestic birds, mostly chickens, have been killed or culled in efforts to halt the spread of the virus.
H5N1 is transmitted easily among birds but is not easily passed between people -- and may never develop that capacity.
Tamiflu is taken once a day to prevent influenza or twice a day to lessen symptoms once infection has occurred.
Ironically, the drug's surging popularity comes as new research suggests that some of the H5N1 strains that have infected human beings are so virulent that conventional doses may not be effective. How the drug should be used in a pandemic -- or whether it would even work -- is uncertain.
Although some doctors in the Washington area are writing stockpile prescriptions for Tamiflu, they are reluctant to talk about it. Queries to 15 practitioners found none who said they prescribed the drug without a specific need.
Audrey P. Corson, a physician in Bethesda who has practiced for 20 years, agreed that "this is a tough issue." She said she firmly believes, however, "that you don't give out drugs without a sick patient." Her only exceptions have been for two or three patients traveling to Southeast Asia, where all 118 human cases of H5N1 influenza infection have occurred. She thinks practitioners should consider both public health and patients' desires when confronted with the requests.
"If there is an outbreak, we're going to have to rely on the CDC and state governments to put those drugs where we need them. And I don't want them in people's bathrooms," she said.
Nevertheless, retail pharmacies and pharmacy benefit managers have noticed the rising demand.
Express Scripts, which handles prescriptions for more than 50 million people, has seen "a spike" in orders for Tamiflu, said Raulo Frear, vice president for clinical evaluation and policy. The St. Louis-based company, whose clients include 16,000 private employers, labor unions, HMOs and government agencies, typically sees prescriptions for the drug rise in early fall. Many doctors prescribe a course of treatment for high-risk patients to have on hand once flu season begins.
Last year, Frear said, Tamiflu prescriptions rose for about a month starting in late September, then plateaued for more than two months before rising again when flu season began after the new year. This year, the rise began in early September and has not yet peaked.
From January through August, about 1.7 million prescriptions for Tamiflu were filled in the United States -- more than three times the 2004 total of 497,000 prescriptions according to IMS Health, a pharmaceutical information and consulting company.
The pharmacies in the 165 Giant Food stores in the Baltimore-Washington area have filled about 1,000 prescriptions for Tamiflu in the past three weeks, 10 times as many as in the same period last year.
"We're not in the flu season by any stretch of the imagination, so it appears to be some stockpiling. I don't know what other reason there would be for it," said Russell B. Fair, Giant's vice president for pharmacy operations.
Terence J. Hurley, a spokesman for Roche, the giant Swiss pharmaceutical house that makes Tamiflu, confirmed that "prescriptions are up considerably compared to last year at this time." Specific numbers were not available.
Roche is the only maker of Tamiflu, which takes more than six months to synthesize in a complicated and dangerous manufacturing process. The company said this week it is in discussions with four makers of generic drugs over possibly letting them produce Tamiflu, too.
Roche will soon start making the drug in the United States in an operation that involves six factories, the last approved for use on Monday by the Food and Drug Administration. Previously, Tamiflu was made only in Europe.
Hurley said about 40 countries have ordered Tamiflu, and the company expects to sell up to $270 million worth for national stockpiles in the second half of this year.
How many people those stockpiles could treat is a big question mark, however.
Experiments published in August by Hui-ling Yen, Elena A. Govorkova and others at St. Jude Children's Research Hospital in Memphis found that Tamiflu was much less useful against recent strains of H5N1 than it was against strains that circulated in Hong Kong in 1997.
Mice infected with a fatal strain of the virus circulating in Vietnam were given a five-day course of oseltamivir at amounts roughly equivalent to a human dose. Half died. In previous experiments, treated animals infected with the Hong Kong strain all survived. But when mice with the Vietnam virus were treated for a longer period -- eight days -- 80 percent survived.