BioWorld Perspectives Contributing Writer

Who is responsible for drug safety? Should a pharmaceutical company have to empty its deep pockets when the FDA has approved the use of its drug in a certain manner clearly labeled on the packaging, but a clinician fails to heed the warnings? Are clinicians reading the instructions on the packaging, and how can that be ascertained? Should jury opinions have more weight than FDA opinions? And who really gains and loses when a drug company gets sued?

All of these questions came to light in March when a $6.7 million jury award against Wyeth Pharmaceuticals, of Collegeville, Pa., a division of Madison, N.J.-based Wyeth, was allowed to stand after the U.S. Supreme Court rejected an appeal by the drug company. The Supreme Court upheld a ruling that federal law cannot protect pharmaceutical companies from liability lawsuits that are filed in state court. (See BioWorld Today, April 6, 2009.)

Defining a Proper Warning Label and Responsibility
The case against Wyeth was brought by guitarist Diana Levine. She went to a clinic in Vermont for migraine treatment and was so nauseated that the clinicians administered Wyeth's Phenergan to help ease her discomfort, reported Nancy Bonk in MyMigraineConnection.com.  A second injection, given by the IV-push method, pierced Levine's artery, causing gangrene. (The preferred method is deep intramuscular IV drip injection, as indicated on the label instructions.) After the anti-nausea drug was erroneously injected, she developed gangrene and lost part of her arm, reported the Philadelphia Business Journal.

Levine claimed that Wyeth's label for FDA-approved Phenergan did not provide a proper warning about the risks associated with quickly injecting the drug into a vein. Wyeth appealed the award, arguing that the FDA approval should protect the company against liability lawsuits pertaining to product labeling.

"The six-to-three high court vote means drug companies are still responsible for damages created by products even when the FDA has approved the warning labels on them," said Bonk, who wondered whether the warning could have been even stronger, since 20 people had suffered from gangrene and subsequent amputation when the drug was improperly administered.

"Wyeth's labeling of Phenergan provided clear instructions and warnings about its use, including clear warnings about the very risk at issue in this case," said Bert Rein, an attorney representing Wyeth, in the Philadelphia Business Journal article. "The medical and scientific experts at FDA are in the best position to weigh the benefits and risks of a medicine and to assess how those benefits and risks should be described in the product's label."

Wyeth said it believes patients are "best served by a national standard for the labeling of prescription medications, set by the medical and scientific experts at the Food and Drug Administration." The drug company, which is in the process of being acquired by New York-based Pfizer Inc., further claimed that if juries are permitted to second-guess the experts at FDA on the benefits and risks of particular medicines, the result is uncertainty for both patients and doctors about how and when to use prescription drugs. (See BioWorld Today, Jan. 27, 2009.)

An Excessive Ruling Against Wyeth
The Supreme Court ruling appears excessive. While the results of Levine's encounter with Phenergan are tragic and irreversible, the warning labels clearly stated:

"Under no circumstances should Phenergan injection be given by intra-arterial injection due to the likelihood of severe arteriospasm and the possibility of resultant gangrene ..." and "Due to the close proximity of arteries and veins in the areas most commonly used for intravenous injection, extreme care should be exercised to avoid perivascular extravasation or unintentional intra-arterial injection. Reports compatible with unintentional intra-arterial injection of Phenergan injection, usually in conjunction with other drugs intended for intravenous use suggest that pain, severe chemical irritation, severe spasm of distal vessels, and resultant gangrene requiring amputation are likely under such circumstances."

Having been duly warned, the doctor who ordered the injection and the technician who administered it seem more culpable than the company providing the warning and the federal agency approving the use of the drug with the appropriate caveats. Undoubtedly, the damage done was accidental and difficult to detect at first. If, as a blogger on Bonk's website suggests, it was less costly and expeditious, and meant "less time that a patient occupies an ER bed, and less time to administer the meds," then the clinicians should be held responsible for jeopardizing the patient's well-being for the sake of expediency. In fact, it was reported that Levine settled out of court with the clinic for an undisclosed amount.

The Future Meaning(lessness) of FDA Approvals
Meanwhile, the "deep pockets" of big biopharma will become the consumers' pockets as everyone pays for the settlement in terms of less research, higher prices and fewer prescriptions for effective drugs. Some biopharma companies may be unwilling to invest the time and cost of obtaining FDA approval if the end result is a risky business over which they have no control when the drug is actually administered.

Finally, this case could set a legal precedent of allowing judges and juries to decide what is medically appropriate, without having the knowledge to do so. It could undermine the role of the FDA and compromise the standards for patient care. Our legal system allows "Joe Average" to sit on a jury, but patients everywhere deserve something better.

Perhaps the real issue is finding a way to restructure the health care system to make sure that overworked clinicians in understaffed facilities are not required to take the course of action that costs less, takes less time, or takes less effort when it could jeopardize the outcome for the patient. Otherwise, FDA-approved labeling will simply become an exercise in leading a horse to water.

Published: June 19, 2009