One way to get the attention of doctors is to question the safety of a drug used by 10 million Americans and hold a press conference to highlight a case of brain damage in a 7-year-old girl whose family won a multi-million dollar settlement.
Especially if the attention-callers happen to be lawyers. The Association of Trial Lawyers of America last week issued an "alert" about the potential hazards of theophylline, the most commonly prescribed medication for people with chronic asthma, and called for a ban on the drug in nonprescription medicines.
"Our message about theophylline is that this medication can be a life-saver or a life-taker," said Michael Maher, president of ATLA.
But many allergists took issue with both the message and its medium, saying ATLA overemphasized the rare cases of harmful side effects of a drug that, properly used, helps millions of Americans manage a chronic and life-threatening disease.
"What we've got here is a wonderful P.R. job with a kernel of truth, greatly exaggerated," said Henry Fishman, a Washington allergist who was asked to participate in the press conference but dropped out after meeting with ATLA officials. Fishman concluded that the lawyers' alert was based on "no new information" and could do more harm than good by alarming patients needlessly.
"Asthma therapy was nowhere, before theophylline," Fishman said. "There's no perfect asthma drug."
The issue is complicated not only because it involves a complex drug with both clear benefits and clear hazards but also because it underscores the wariness with which two powerful professions, medicine and law, view each other.
"The tenor of the thing was what bothered me," said Peyton A. Eggleston, head of the pediatric allergy program at Johns Hopkins Medical Center in Baltimore.
Both Eggleston and Fishman said they agree with ATLA that theophylline should be available by prescription only. Nor do they take issue with the suggestion that physicians and patients become better educated about the drug.
"It's just that you don't start it with a press conference yelling 'Fire!' in a theater," Eggleston said.
The press conference highlighted the case of 7-year-old Jennifer Pollock of Everett, Wash., who sustained severe brain damage in 1986, when the prescribed theophylline dose she was taking for a respiratory illness was increased when she had the flu.
A lawsuit by the Pollocks against the drug company, Fisons Corp., was settled out of court this year for $6.9 million. An earlier suit against their pediatrician was settled for $500,000. In turn, the doctor sued Fisons and was awarded damages of nearly $3.2 million.
The Food and Drug Administration banned over-the-counter sale of single-ingredient theophylline in 1986 and is considering a ban on nonprescription products that contain the drug. ATLA called on the FDA to impose the ban and require stronger and clearer warnings about the drug to both doctors and patients.
About 10 million Americans, including 3 million children, have asthma, a chronic condition that narrows the airways in the lungs and causes difficult or "wheezy" breathing. There is no cure, but a growing array of treatments help patients keep the illness under control by preventing attacks or reducing their severity. A key one is theophylline, which is taken by about 10 million Americans with chronic obstructive lung disease or asthma.
Theophylline, a chemical cousin of caffeine, can help prevent asthma attacks or relieve their symptoms by opening the airways. The difficulty is its narrow "therapeutic range" -- the small difference between a safe dose and a potentially toxic dose.
Doctors monitor theophylline by measuring its level in the blood, as often as twice a week in a patient whose dose is still being fine-tuned. "The physician must prescribe enough, and not too much," said Theodore W. Rall, professor of pharmacology at the University of Virginia Medical School, who spoke at the ATLA press conference.
The proper dose varies with individuals and can change suddenly even in a given patient, because infections, flu or high fever can alter the rate at which the body absorbs the drug. Antibiotics also can affect that rate.
When blood levels of theophylline get too high, they can lead to side effects such as headache, nausea, vomiting and irritability. In rare cases, a heavy overload of theophylline can cause seizures, brain damage and even death. ATLA said it has uncovered 26 cases of severe injury or death since 1976, and Rall called that "the tip of the iceberg."
Finding the right dose requires careful monitoring and close cooperation between doctor and patient, both ATLA and asthma specialists said. "There are absolutely no rules for how often you should get blood levels for theophylline," allergist Fishman said. "It's like asking how often you should check somebody's blood pressure."
"There isn't a single patient that falls into a formula," agreed Donald W. Aaronson, a Chicago allergist and former president of the American College of Allergy and Immunology. "Every asthma patient has to be treated individually."
Asthma is treated with four basic types of medications: broncho-dilators, in inhaled form, that help open the airways; cromolyn, a preventive; cortisone drugs, which have serious known side effects, and theophylline.
"That's our whole therapeutic armamentarium," Aaronson said. "Theophylline is no longer necessarily the first drug a doctor prescribes for asthma, but we'd be stuck without having all of these drugs available."
Jennifer Pollock's brain damage is "a terrible tragedy under any circumstances," Aaronson said. "Whether it was preventable or not I don't know."
ATLA took pains to emphasize theophylline's usefulness in treatment of asthma. ATLA president Maher said the purpose of the consumer alert was to prevent dangerous use of the drug by advocating steps that would increase doctor and patient awareness of its potential hazard.
But Schering-Plough Corp., the leading maker of prescription theophylline, accused ATLA of conducting "self-serving publicity campaigns" aimed at drumming up lawsuits under the guise of a consumer protection program.
"Patients should not be deceived by these lawyers' tactics, but should continue taking their medication as recommended by their physician," the company said in a statement.
Out of 60 million prescriptions filled since 1985, Schering-Plough said, there were only about 780 reports of serious adverse drug reactions, which the company called a "very good and reassuring safety record."
One measure of the sensitivity of the issue is that press officers at the National Institute of Allergy and Infectious Diseases allowed experts to discuss theophylline only if they were not identified as employees of the institute. They referred calls to the FDA and the American Academy of Allergy and Immunology, a professional group for allergists.
"We think it's an FDA issue . . . not our issue," said a spokesperson for NIAID.
Mainly, doctors said they were puzzled by the timing of the ATLA alert. "This isn't something new," said R. Michael Sly, chairman of allergy and immunology at Children's National Medical Center.
"We certainly don't understand why there was a press conference," said Aaronson, adding that he feared it could cause "hysteria" among some patients who would misinterpret the cautionary message as a reason to stop taking properly prescribed medicine.
"Theophylline may not be right for everybody, but one thing is for sure: It is a safe and effective drug when properly used," said Allan Weinstein, a Washington allergist.
"I'm looking at four phone messages right now from patients asking: 'Can I take my theophylline?' The answer is yes."