PPA litigation on the rise after FDA warning.

Plaintiff attorneys across the country are filing suit on behalf of victims of strokes allegedly caused by phenylpropanolamine (PPA). The chemical is an ingredient in hundreds of popular over-the-counter (OTC) cold and flu medications and weight-loss products--including such household names as Dimetapp, Robitussin CF, Dexatrim, and Contac.

Plaintiff attorney Paul Rheingold of New York City said at press time that there were probably "at least 50 cases already filed, with hundreds coming."

The PPA litigation repeats what has become a familiar chronology of events in the drug industry--what Rheingold calls a "one-two-three punch." First, a medical study shows a safety risk; then the FDA issues a warning; and finally, drug manufacturers recall the product. Although the agency asked manufacturers to voluntarily discontinue marketing products containing PPA, no formal recall occurred. Products containing the chemical may still be on store shelves, and certainly are in home medicine cabinets.

The FDA has estimated that PPA may cause between 200 and 500 strokes per year. But attorney Roger Phillips of Concord, New Hampshire, a cochair of ATLA's new PPA Litigation Group, said this estimate "may be low." Phillips said that according to the FDA, U.S. consumers bought about 6 billion doses of drugs with PPA last year, and that based on data from the medical study preceding the FDA warning, the number of PPA-related strokes could be much higher.

Assessing the risk

The Hemorrhagic Stroke Project, an industry-sponsored review commonly referred to as the Yale study, began in 1992 in response to many published reports of PPA-related strokes. In May 2000, the FDA and Yale University researchers concluded that "the association of PPA with risk for hemorrhagic stroke is present ... for both customary indications for PPA (as a cough-cold remedy and an appetite suppressant)." (The Yale study is available online at http://www.fda.gov/ohrms/dockets/ac/00/ backgrd/3647b1_tab19.doc.)

On October 19, 2000, the FDA's Nonprescription Drugs Advisory Committee (NDAC) recommended that PPA not be considered generally safe for OTC use, for either purpose.

The Consumer Healthcare Products Association (CHPA), a trade association representing U.S. manufacturers and distributors of OTC drugs and dietary supplements, disagreed. In a news release issued the same day, CHPA called the Yale study "inconclusive" and affirmed its own view that PPA is safe when a drug is used according to label directions.

Nevertheless, in a November 3, 2000, letter, the FDA asked certain PPA manufacturers, packagers, and distributors to voluntarily cease marketing products containing the chemical, and three days later it issued a public health advisory.

Who knew what, when?

Sidney Wolfe, director of the Public Citizen Health Research Group in Washington, D.C., said in a statement that "PPA is just another example in a long history of many serious public health hazards caused by drugs that were allowed to continue endangering people much longer than they should--after sufficient evidence for action was available."

The FDA began reviewing the safety of several OTC drugs, including PPA, in the early 1970s. The NDAC recommended that PPA be considered safe and effective as a nasal decongestant in 1976 and for weight control in 1982. But the Yale study cites 30 published case reports, going back to 1979, of intercranial hemorrhage associated with the chemical. The Public Citizen Health Research Group first warned of PPA's dangers in 1981.

Unquestionably, PPA manufacturers knew of its dangers long before the Yale study, Rheingold said. "The manufacturers funded the study to buy time, because they knew how it would come out."

Phillips said beginning the study "took the pressure off a recall." Moreover, he said, "manufacturers were well prepared for the FDA warning" and had begun reformulating their products in anticipation of a ban.

Scope of the litigation

The Yale study focused on women because most of the reported strokes involved young female victims. Subjects were between 18 and 49; because so few men were involved, the study didn't determine whether their risk of stroke from using PPA differed from that of women.

Yet the range of potential plaintiffs is much broader than young women. Gerson Smoger of Oakland, California, another cochair of ATLA's PPA Litigation Group, said that "a younger population is easier to study, but mechanically and chemically the damage is the same regardless of a person's age. In fact, older people may be more at risk because they tend to use more medications."

Phillips said that though the Yale study was valuable, "it left out those who could not speak after their strokes, and those who died." One of his clients is a 48-year-old, previously healthy man who suffered a stroke after taking Dimetapp for the first time.

Other factors also point to the possibility of extensive litigation. For example, unlike prescription drugs, generally manufactured by a small number of companies under only a few names, OTC drugs with PPA were ubiquitous until the voluntary recall. And while there are probably about 12 major manufacturers of such drugs--including such familiar names as Bayer Corp., Bristol-Meyers Squibb Co., and ScheringPlough Corp.--there are hundreds of smaller ones, including supermarket and drugstore brands, Rheingold said.

Smoger noted that many prescription drugs also contain PPA, and even though it might not be the primary ingredient, "the damage would be the same." Plus, strokes are not the only danger associated with PPA, Phillips said. "For example, cardiac arrythmia problems are just beginning to surface."

What does the future hold?

As PPA litigation emerges, it may bear some similarities to other pharmaceutical cases. For example, although the FDA regulatory process for OTC medications differs from that for prescription drugs, the events leading to litigation often follow the same one-two-three punch chronology, Rheingold said.

PPA litigation has also been compared to litigation over fen-phen, a drug combination linked to potentially fatal heart valve damage that was, like PPA, used widely in diet aids.

But "there really is no close analogy to PPA," Rheingold said. "The course of the litigation remains to be seen." Although there may be fewer PPA cases than there were fen-phen suits, he said, damages will be larger because of the severity of injury caused by strokes.

Phillips predicted that PPA litigation will be more widespread than any involving a prescription drug because of the sheer number of products involved. Smoger said that PPA litigation may more closely resemble the asbestos model, featuring many defendants and many products.

Because most uses of PPA are in OTC drugs, the cases will not involve prescribing doctors. Manufacturers will not, therefore, be able to use the "learned intermediary" defense to shift the blame to doctors. But the, absence of defendant doctors means that PPA cases filed in state courts may be removed by defendants to federal courts because there is no local defendant. Attorneys who want to litigate PPA cases in state court, Smoger said, will have to ask whether there was "secondary malpractice" by a local party--for example, a local distributor or pharmacy.

Phillips said the biggest difficulty in PPA litigation will be proving causation. In most cases, there will be no prescription records to identify which product a consumer used, and there could be more than one. Potential plaintiffs also could have other risk factors associated with stroke, such as overweight or heart disease.

Discovery challenges lie ahead. Because there are so many defendants, more individual discovery will be required, and "we'll be less likely to see global solutions," Smoger said.

Several class actions have been filed across the country, including six in the Seattle federal district court by Cohen, Milstein, Hausfeld & Toll, based in Washington, D.C. None of the classes had been certified at press time, but Barry Steelman of Baltimore, cocounsel in the class actions with the Cohen firm, said the chances for certification are good.

Steelman said that the class actions raise consumer protection rather than personal injury claims, alleging that manufacturers' failure to warn of PPA's dangers was a deceptive trade practice. Remedies sought in the class actions include a "Dear Doctor" letter advising physicians to question patients about PPA use and a requirement for manufacturers to get PPA products off store shelves and send warning notices to consumers.

Other attorneys doubt that class actions will succeed. Smoger noted that in the asbestos litigation, efforts to certify a class were unsuccessful because of the number of products and defendants. He predicted that most PPA litigation is likely to be conducted individually. A petition for multi-district litigation also has been filed.

Phillips said that what bothers him most about PPA is that it is still out there. His daughter recently visited a sundries shop at an airport and found a PPA product on the shelves.

"PPA should have been taken off the market years ago," he said. "There are plenty of products to help people with the sniffles, and a diet and a support group will help with weight loss. The consequences of a stroke are irreversible."