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New Drugs Should Help Fight Influenza This Winter

When influenza outbreaks start this season, physicians will have a new class of medication—neuraminidase inhibitors—that provide effective treatment while causing fewer side effects than older antiviral medications. In patients who don't receive the influenza vaccine, the new medications can shorten the duration of illness or, in some, prevent it.

Neuraminidase inhibitors prevent the release of influenza viruses from infected cells and are thought to increase viral inactivation by respiratory mucus. Zanamivir, an inhaled neuraminidase inhibitor that acts directly on the respiratory tract, was approved by the US Food and Drug Administration (FDA) in July. A second neuraminidase inhibitor, oseltamivir phosphate, an oral medication, was submitted for FDA review in April and received priority review status. The drug's developers, Hoffmann-La Roche, Inc, and Gilead Sciences, Inc, anticipate FDA approval in time for the 1999-2000 flu season, according to a company press release.

The US Centers for Disease Control and Prevention (CDC) reports that influenza causes about 110,000 hospitalizations and 20,000 deaths per year (1). The most recent CDC recommendations (1), published before zanamivir was approved, noted that neuraminidase inhibitors do not affect the central nervous system (CNS), unlike the older antiviral medications amantadine hydrochloride and rimantadine hydrochloride, which may cause nervousness, concentration difficulty, and lightheadedness in some patients. This might make the neuraminidase inhibitors a better choice for athletes and other active people who wish to avoid the CNS side effects.

Therapeutic Indications

Zanamivir is approved for the treatment of acute illness from type A and B influenza viruses in adults and adolescents 12 and older who have been symptomatic for no more than 2 days. The drug is well tolerated because little of it is systemically absorbed after inhalation (2). The most common side effects in clinical trials, at rates comparable with placebo, were sinusitis, diarrhea, and nausea.

The drug has not been approved for prophylaxis, but a recent study (3) in university communities showed that the drug was 67% to 84% effective in preventing influenza when taken once a day (10 mg) for 4 weeks. Arnold Monto, MD, a professor in the Department of Epidemiology at the University of Michigan in Ann Arbor, has published studies on zanamivir and foresees that the drug will be useful in the sports setting. "For example, take a situation where a team is going to the Rose Bowl and there's a flu outbreak in Pasadena," he says. In this instance, the influenza vaccine would take 2 weeks to take effect, but the protective effects of zanamivir would be immediate, says Monto, who has received honoraria for ad hoc consultation with Glaxo Wellcome, Inc, the maker of zanamiviro. "I would prescribe a 10-day course, even though the drug is not approved for prophylaxis yet."

Zanamivir has been shown to reduce the duration of illness by an average of 1 day; however, the benefit may be greater in patients who have more pronounced symptoms and in those who receive treatment within 30 hours of symptom onset (4).

What's the Clinical Niche?

When the first studies on zanamivir were published in the major medical journals, an editorial in The New England Journal of Medicine (5) questioned whether the drug would meet a clinical need, given the availability of the influenza vaccine, amantadine, and rimantadine. Robert B. Couch, MD, the author of the editorial, acknowledged that zanamivir is effective against both A and B type influenza, whereas amantadine and rimantadine affect only type A, but he noted that type B causes only about 35% of cases. Couch, who chairs the Department of Microbiology and Immunology at Baylor College of Medicine in Houston, suggested that zanamivir would find a clearer clinical niche if it were shown to be more effective than amantadine or rimantadine for treating type A influenza. He also wrote that the aerosol delivery would be difficult for many patients.

Monto says that zanamivir fills a clinical need because it is more effective than antipyretics and cough medicine for the treatment of influenza. He says that besides causing fewer side effects and providing coverage against type B influenza, zanamivir has been shown to prevent complications such as bronchitis and pneumonia, whereas the older antivirals have not.

The cost for the zanamivir inhaler and 5-day medication supply is about $52. For comparison, the cost for 28 100-mg tablets of amantadine is about $16, and the cost for 28 100-mg tablets of rimantadine is about $70.

Dosage and Administration

According to prescribing information from Glaxo Wellcome, Inc, the recommended dosage for zanamivir is two inhalations (10 mg) twice a day for 5 days. Two doses, at least 2 hours apart, should be taken on the first day of treatment if possible.

The drug should be used cautiously among patients who have asthma or other chronic respiratory diseases because these patients may experience bronchospasm or a decline in lung function after taking it. The company suggests that these patients have a fast-acting inhaled bronchodilator available when being treated with zanamivir; they should stop zanamivir if respiratory symptoms worsen. Patients who regularly use an inhaled bronchodilator should use it before taking zanamivir.

Patients receiving zanamivir should be taught how to use the inhaler and should receive a demonstration whenever possible. Patients should be told that though they can expect a shorter illness duration with zanamivir, use of the drug has not been shown to reduce the transmission of influenza to others.

Managing Influenza in Sports

Randall Swain, MD, a family physician at a sports medicine clinic in Charleston, West Virginia, says athletes who participate in winter sports are vulnerable to influenza because they are in close physical contact and share locker rooms and, often, water bottles. He says he sees zanamivir as an attractive prevention and treatment option because of its low side-effect profile, although he prefers that athletes in winter sports receive the influenza vaccine. "The best treatment is still prevention," he says. For athletes in winter sports, optimal timing for the vaccine is October for coverage through March, he says. "The vaccine is pretty effective in young people, and, when it fails, the illness is more benign."

Swain says he anticipates greater patient demand for zanamivir than for the older antiviral medications, but he says he's not worried about overprescribing. "The sudden onset of severe muscle ache, dizziness, chills, and fever is pretty obvious," he says. "The use of rapid in-office tests will make the diagnosis a little easier if the practitioner wants to be more discriminating about the diagnosis."

Another strategy for preventing the spread of influenza on sports teams is to isolate athletes who are ill. "We don't let them practice if symptoms are below the neck or if they have a fever," Swain says. Preventive measures also include promoting frequent hand-washing and discouraging the sharing of water bottles.

Lisa Schnirring


  1. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices. MMWR 1999;48(RR-04):1-28
  2. Cass LM, Efthymiopoulos C, Bye A: Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers. Clin Pharmacokinet 1999;36(suppl 1):1-11
  3. Monto A, Robinson DP, Herlocher ML, et al: Zanamivir in the prevention of influenza among healthy adults: a randomized controlled trial. JAMA 1999;282(1):31-35
  4. Hayden FG, Albert DME, Osterhaus JJ, et al: Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. N Engl J Med 1997;337(13):874-880
  5. Couch RB: A new antiviral agent for influenza: is there a clinical niche? N Engl J Med 1997;337(13):927-928

Field Notes

A New Guide for Assessing Heart Disease Risk
Signaling a shift from secondary to primary prevention, the American Heart Association and the American College of Cardiology have developed a new clinical tool for identifying patients at risk for coronary heart disease (CHD).

The risk assessment scale, using an algorithm based on the Framingham Heart Study, was published in the September 28 issue of Circulation and the October issue of the Journal of the American College of Cardiology. (The document is available on-line at The physician first totals the patient's global risk score based on age, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, and smoking and diabetes status. Then the global risk score is plotted on a chart that indicates the patient's absolute risk of developing CHD within the next decade and his or her relative risk, ie, the risk relative to age-matched persons who have no risk factors besides age.

The report classifies physical inactivity not as a major independent risk factor but as a "predisposing risk factor"—one that worsens the independent risk factors. The authors point out that there's no evidence that excess risk accumulated over many years can be erased by aggressive short-term measures in later life.

Relief for Side Stitches
Researchers from New Zealand recently studied the effects of fluid ingestion on side stitches in running, along with several methods for relieving side stitches. The results were published in the August issue of Medicine & Science in Sports & Exercise.

Though the researchers did not resolve whether side stitches are caused by activity-related visceral ligament strain or by changes in blood flow, they did list several practical suggestions based on their findings:

  • Wait 2 to 3 hours before exercising after a meal or large drink.
  • When drinking during exercise, take small, frequent sips to keep fluid mass in the stomach low.
  • Sports drinks may be less likely to cause stitches than water or soda pop.

Using one or more of following methods may help reduce stitch pain:

  • Bend forward and tighten the abdominal muscles.
  • Leave more air in the lungs at the end of each breath (increase functional residual capacity).
  • Use pursed lips to resist the airflow when breathing out.
  • Wear a light, wide belt that can be tightened when a stitch occurs.

Simple Ways to Reduce Kids' Ski Injuries
A recent report on children's downhill ski injuries at a Quebec City ski area suggests that two steps could make the sport safer for youngsters.

Researchers published their findings in the September-October issue of The American Journal of Sports Medicine. They found that low-skilled skiers were about seven times as likely to be injured as highly skilled skiers and that poorly adjusted bindings doubled the risk of injury. In addition, skiers who used rented equipment had a seven-fold increase in risk over those who owned their own equipment.

The authors suggested that parents make sure that equipment fits and is well-adjusted and that they help children improve skiing skills. However, the researchers found that basic ski lessons did not influence injury rate. They suggested that more study is needed to evaluate the nature of ski instruction and to identify situations in which low-skilled skiers are injured.

Mild Head Trauma by the Numbers
In a study of mild traumatic brain injury in 10 sports at 235 US high schools, football accounted for 63.4% of all cases, according to an article published September 8 in The Journal of the American Medical Association.

The observational study took place during one or more of the 1995 through 1997 school years. Athletic trainers recorded injury and exposure data, reporting a total of 1,219 cases. After football, the sports and shares of the totals were wrestling, 10.5%; girls' soccer, 6.2%; boys' soccer, 5.7%; girls' basketball, 5.2%; boys' basketball, 4.2%; softball, 2.1%; baseball, 1.2%; field hockey, 1.1%; and volleyball, 0.5%.

Football also ranked first in brain injury risk, with 3.66 cases per 100 player-seasons, followed by wrestling with 1.58. In most other sports, the rate was less than 1.0.

Finding a Healthy Health Club
Selecting a quality health club that offers an enjoyable exercise experience will help active people stick to their routines, according to Ken Germano, PhD, executive director of the American Council on Exercise (ACE). In a recent press release, ACE offered advice for selecting a good health club:

  • Classes: Look for a mix you like and times that fit your schedule.
  • Staff: To ensure a safe and efficient workout, check the credentials of certified personal trainers and group fitness instructors. Two nationally recognized certification organizations are ACE and the American College of Sports Medicine. ACE offers referrals to certified fitness professionals on its Web site (
  • Hours: Make sure the club's hours of operation meet your workout needs, and visit the club at the times you intend to work out to check for crowding.
  • Payments: Find a payment schedule that fits your budget, and ask about sign-up specials. When joining a club that hasn't opened yet, ensure that payments are held in an escrow account.
  • Location: Find a club close to home or work.
  • Reputation: Talk to current members about the club, or ask the Better Business Bureau about any complaints. Also, ask if the club is a member of the International Health, Racquet, and Sportsclub Association (IHRSA), which sets health, safety, and business standards. A list of member health clubs can be found on the IHRSA Web site (
  • Environmental details: When touring the club, note the level of cleanliness and volume of the music. Check to see if most of the equipment is working.