Supreme Court rules against Wyeth in Wyeth v Levine

In a decision handed down March 4, 2009, the U.S. Supreme Court ruled in favor of Levine in the court case Wyeth v Levine, upholding the ruling of the Vermont Supreme Court. This decision may set a precedent for rejecting the argument of pre-emption, a tenet holding that FDA regulations connected with drug approvals and medication safety supersede state laws.

In 2000, Diana Levine was treated with Wyeth’s promethazine (Phenergan) for nausea resulting from a migraine headache. Levine received 2 administrations of the drug at a Vermont clinic. The first was given by intramuscular injection; the second by direct intravenous (IV) injection into the arm (“IV push”). This second administration was inadvertently injected into an artery, which led to arterial damage and then to gangrene. Levine’s hand and forearm had to be amputated.

Levine sued Wyeth in Vermont, citing negligence and failure-to-warn product liability, and a jury found in favor of Levine. The Vermont Supreme Court upheld this finding when Wyeth appealed the original ruling. In response to Wyeth’s assertion that federal law should supersede state law, the court stated, “We hold that there is no conflict between state and federal law that requires pre-emption of plaintiff’s [Levine’s] claim,” adding, “We hold that the jury’s verdict against defendant [Wyeth] did not conflict with the FDA’s labeling requirements for Phenergan because defendant could have warned against IV-push administration without prior FDA approval, and because federal labeling requirements create a floor, not a ceiling, for state regulation.” Wyeth appealed this decision, and the case was sent to the U.S. Supreme Court.

The oral arguments presented to the Court November 3, 2008, centered around several key issues: whether FDA had considered the risks of IV push versus IV administration by infusion, whether Wyeth had new information or new analyses of old information regarding these potential risks, and whether the product labeling approved by FDA sufficiently outlined the risks associated with IV push administration.

Wyeth’s attorney, Seth Waxman, argued that FDA was aware of the risks associated with IV push administration and that the agency did not think it necessary to revise the product labeling. He stated that FDA “provided ample, lavish warnings about the risk of intra-arterial injection and exposure of an irritant drug like Phenergan to arterial blood. It provided in the labeling to the physicians a cascading hierarchy of methods of administration.” He added, “All that information was available to physicians and the FDA has to understand and does understand that in labeling to allow medical professionals to make their judgments, taking options away from physicians is not always better.”

Levine’s attorney David Frederick asserted that “FDA never considered any comparative risks of IV push versus IV drip,” pointing to a lack of correspondence between the agency and Wyeth on the subject as evidence. He added that “because the catastrophic risks of IV push are so dramatic, no reasonable person could have made a safety determination to allow this drug with its risks when there are corresponding benefits that create exactly the same kind of treatment of care for the patient.” He stated that his case is “dependent on a finding that the manufacturer had a duty of due care and it didn’t live up to that.”

In the written majority opinion of the Court handed down March 4, Justice Stevens stated, “It is a central premise of the Food, Drug, and Cosmetic Act (FDCA) and the FDA’s regulations that the manufacturer bears responsibility for the content of its label at all times.” Stevens pointed out that there is “an FDA regulation that permits a manufacturer to make certain changes to its label before receiving the agency’s approval. Among other things, this ‘changes being effected’ (CBE) regulation provides that if a manufacturer is changing a label to ‘add or strengthen a contraindication, warning, precaution, or adverse reaction’ or to ‘add or strengthen an instruction about dosage and administration that is intended to increase the safe use of the drug product,’ it may make the labeling change upon filing its supplemental application with the FDA; it need not wait for FDA approval.” Because Wyeth “failed to demonstrate that it was impossible for it to comply with both federal and state requirements,” the Court affirmed the judgment of the Vermont Supreme Court.

In an opinion written by Justice Thomas, who stated that he concurred with the judgment but not with “the majority’s implicit endorsement of far-reaching implied pre-emption doctrines,” Thomas said, “Initial approval of a label amounts to a finding by the FDA that the label is safe for purposes of gaining federal approval to market the drug. It does not represent a finding that the drug, as labeled, can never be deemed unsafe by later federal action, or as in this case, the application of state law.”

In the written dissenting opinion, Justice Alito said, “The FDA has long known about the risks associated with IV push in general and its use to administer Phenergan in particular. Whether wisely or not, the FDA has concluded-over the course of extensive, 54-year-long regulatory proceedings-that the drug is ‘safe’ and ‘effective’ when used in accordance with its FDA-mandated labeling. The unfortunate fact that respondent’s [Levine’s] healthcare providers ignored Phenergan’s labeling may make this an ideal medical-malpractice case. But turning a common-law tort suit into a ‘frontal assault’ on the FDA’s regulatory regime for drug labeling upsets the well-settled meaning of the Supremacy Clause and our conflict pre-emption jurisprudence.” Alito concluded, “The FDA told Wyeth that Phenergan’s label renders its use ‘safe.’ But the State of Vermont, through its tort law, said: ‘Not so.’ The state-law rule at issue here is squarely pre-empted.”

In a press release about the ruling, Wyeth stated, “The U.S. Supreme Court’s ruling in Wyeth v Levine is disappointing, not only for Wyeth, but for patients and public health in general. Patients are best served by a national standard for the labeling of prescription medications-set by the medical and scientific experts at the U.S. FDA. When lay juries are permitted to second-guess the experts at FDA on the benefits and risks of particular medicines, the result is uncertainty for patients and doctors alike about how and when to use prescription drugs.”

The full Supreme Court ruling, majority and concurring opinions, and dissenting opinion can be accessed here.