One of the longest-brewing legal debates of this decade was settled on March 4, 2009, when the U.S. Supreme Court decided, by a 6-3 majority, that state drug product liability laws are not preempted by the Food, Drug, and Cosmetic Act (FDCA) or regulations promulgated by the FDA pertaining to federally imposed drug labeling requirements. This is nearly 100% opposite of the predicted outcome.1 The FDA, with the blessing of the prior presidential administration, argued that it is the only agency with enough expertise to regulate drug company labeling and that liability decisions about the adequacy of warning labels should not be “second guessed” by a jury in a product liability lawsuit.2
This is of significance to pharmacists and pharmacy owners because it means that when you are sued for dispensing a drug without adequate directions for a use that could have prevented a foreseeable danger, you will not have to defend the allegations alone. More often than not, the drug manufacturer will be a named defendant and, because the drug company will almost always have the “deeper pockets,” it will be the primary target of the plaintiff. Under this ruling, pharmacists and pharmacies may not even be named as defendants when the theory of liability advanced by an injured patient is that the drug company knew of a specific danger and took no action to change the labeling to include warnings that a particular risk exists and how best to avoid it.
The case, Wyeth v. Levine, has been subject to significant media attention in the health care literature, legal circles, and the lay press.3 Speculation about the outcome was wide-ranging and contentious, with good and objective arguments for both sides of the dispute.4,5
Facts of the Case
Diana Levine was a Vermont musician who suffered from migraine headaches. In 1989, she started a children’s record label with her husband to record songs she wrote and played on the guitar and piano. She often performed with her husband and sister in local music groups.
On April 7, 2000, Ms. Levine went to an emergency room at the Northeast Washington Community Health Center for treatment of a migraine headache, as she had on previous occasions. Two medications were administered. The first drug was an IM injection of the narcotic Demerol (meperidine) for pain relief, and the second was the antihistamine Phenergan (prometh azine), made by Wyeth Pharmaceuticals, which was given to ease the nausea that often accompanies a migraine and use of narcotics.6
Phenergan received FDA approval in 1955.7 According to the drug’s labeling, the injectable form may be administered IM or IV through either the “IV-push” method, whereby the drug is injected directly into a patient’s vein, or the “IV-drip” method, where it is introduced into a saline solution in a hanging IV bag and slowly descends through a catheter inserted in a patient’s vein.
As on prior occasions, the Phenergan was administered to Ms. Levine via an IV drip accompanied by a normal saline diluent. Later that same day, she was still experiencing pain and nausea, so she returned to the health center. As before, she received an IM injection of Demerol. On this trip, however, the Phenergan was administered by a physician assistant via IV push. This practice is usually discouraged because the drug is highly corrosive and can cause irreversible gangrene if any of it gets into an artery8that is exactly what happened to Ms. Levine. The Phenergan either was directly injected into an artery or escaped into an artery from the vein. This process is well known and is described in the medical literature as perivascular extravasation, meaning that the drug has come into contact with arterial blood. The warning on the 2000 label read in relevant part:
Inadvertent Intra-arterial Injection: 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 inadvertent intra-arterial injection. Reports compatible with inadvertent intra-arterial injection of Phenergan, 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. Intravenous injection was intended in all the cases reported but perivascular extravasation or arterial placement of the needle is now suspected. There is no proven successful management of this condition after it occurs. When used intravenously, Phenergan should be given in a concentration no greater than 25 mg per mL and at a rate not to exceed 25 mg per minute. When administering any irritant drug intravenously it is usually preferable to inject it through the tubing of an intravenous infusion set that is known to be functioning satisfactorily.9
Following this incident, Ms. Levine’s arm was excruciatingly painful for the next 2 or 3 weeks. She returned to her family physician several times over this period and was given blood thinners, morphine, and other medications designed to save her hand and arm from the gangrene that had already set in. Toward the end of this ordeal, the only treatment available was to amputate her right hand and lower arm. As imaginable, this put an end to her musical career and business and disrupted nearly every facet of her life. Nevertheless, she considers herself “lucky” because she could have died without the expert medical treatment she received after the botched administration of a drug she was used to taking.10
Initially, Ms. Levine sued the health center and the clinician who prescribed the Phenergan. These claims were settled relatively early in favor of the patient. She then filed a lawsuit against Wyeth, claiming that the company was negligent and that it failed to adequately warn of dangers known to be associated with an IV-push method of administration. The allegations were claimed to be in violation of Vermont’s consumer protection product liability law. Wyeth asked the trial court to dismiss the lawsuit on the grounds that the FDA mandated the language used in its labeling and that it would be a violation of FDA regulations for it to unilaterally change the labeling without first obtaining FDA approval. Wyeth also argued that the FDA’s labeling restrictions preempted Vermont’s product liability law. The trial court judge refused to dismiss the case and, at trial, told the jury that it could consider the FDA-approved labeling, but the label’s compliance with FDA requirements did not establish the adequacy of the warning or prevent the defendant from adding to or strengthening the warning.
Evidence produced during the trial demonstrated that the physician assistant administered a greater dose than the label prescribed, that she may have inadvertently injected the drug into an artery rather than a vein, and that she continued to inject the drug after Ms. Levine complained of pain. The plaintiff’s experts testified that the label should not have allowed IV push as a means of administration, as it was safer to use other available options, such as IM injection or IV drip.11 The defendant’s expert testified that allowing IV push with instructions cautioning against inadvertent arterial injection was sufficient. At the end of the 5-day trial, a jury found Wyeth liable in the amount of $2.4 million for economic damages (e.g., loss of income, health care payments) and $5 million for noneconomic damages (e.g., pain and suffering, loss of consortium). The trial court judge adjusted the amount to $6.8 million to take into account a pretrial settlement award from the health center and clinician.
Wyeth appealed to the Vermont Supreme Court, which affirmed the lower court’s judgment for the plaintiff. It concluded that “the jury’s verdict did not conflict with FDA’s labeling requirements for Phenergan because Wyeth could have warned against IV-push administration without prior FDA approval.”12 The court expressed its opinion that federal labeling requirements “create a floor, not a ceiling, for state regulation.”13
U.S. Supreme Court
Wyeth next appealed to the U.S. Supreme Court, again claiming that federal laws usurp conflicting state laws. The Court granted certiorari, (i.e., agreed to hear the appeal).14 In recent years, the Court has taken on several preemption cases and decided them with mixed results. In a 2008 decision, the majority of justices ruled that the FDA’s regulation of medical devices does in fact preempt product liability claims asserted in state courts.15 But there is a major distinction between the FDA’s authority to regulate medical devices compared with drugs. The Medical Device Amendments of 1976 created a scheme of federal safety oversight for all medical devices, while sweeping back state oversight. The difference is that Congress explicitly stated that it intended the medical device law to preempt state laws. The statute does not contain the same language for the regulation of drugs.16
Justice Stevens issued the opinion for the majority.17 In these proceedings, Wyeth argued that a conflict existed between what the FDA mandates in its labeling regulations and the jury’s finding in favor of the patient under Vermont’s consumer protection laws. In essence, the company prayed that it could not serve two masters with conflicting goals and missions. In examining the historical relationship between Wyeth and the FDA regarding labeling of injectable Phenergan, Justice Stevens noted that there had been sparse correspondence between the two about the drug’s labeling. He concluded that there was no evidence to support the contention that Wyeth had “earnestly attempted” to strengthen the intra-arterial injection warning or that the FDA had “specifically disallowed” stronger language. Referencing the Vermont decision, he concluded there was no evidence to support the claim that the FDA had set a “ceiling” in its drug labeling requirements. The policies employed by the Court in matters claiming federal preemption of state laws are premised on the notion that if Congress intends to occupy the entire forum for this type of litigation, it will expressly state the intent. Without such an expression, the Court presumes against preemption.18
The most telling of the reasons why the Court held in favor of the injured patient rests upon some amendments to the FDCA. In 2007, Congress amended the statutes and, for the first time, it granted the FDA statutory authority to require a manufacturer to change its drug label based on safety information that becomes available after a drug’s initial approval.19,20 However, Congress did not enact a provision in the Senate bill that would have required the FDA to pre-approve all changes to drug labels.21 Instead, it adopted a rule of construction to make it clear that manufacturers remain responsible for updating their labels.22
Wyeth argued that it could not unilaterally amend FDA mandated labeling without prior approval. That argument failed, according to Justice Stevens, because there is an FDA regulation that permits a manufacturer to make certain changes to its label before receiving the agency’s approval. The changes being effected 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.23
One of the key elements establishing that Wyeth could or should have changed the labeling was evidence that since the last time the Phenergan label was changed, Wyeth received notice of at least 20 incident reports that people who received the drug by the IV-push method developed gangrene resulting in amputation of the affected parts. The evidence also showed that Wyeth received information about the first instance of gangrene and amputation in 1967. As additional reports came to Wyeth of the same injuries, the Court stated, Wyeth should have done more to warn about the obviously foreseeable harm even if the FDA did not make the warnings necessary. The Court also took notice that “through many amendments to the FDCA and to FDA regulations, it has remained a central premise of federal drug regulation that the manufacturer bears responsibility for the content of its label at all times. It is charged both with crafting an adequate label and ensuring that its warnings remain adequate as long as the drug is on the market.”24
While the dialogue of the Supreme Court may be strained or even arcane, the importance of this decision cannot be overstated. People who are injured by the use of a prescription-only drug have retained the constitutional guarantee that their harm may be redressed in a court of law. Consumer protection laws adopted by states to ensure that citizens have a right to demand freedom from harmful products remain intact through this decision. This is another David v. Goliath case where the plain folk can stand up to major corporations, unlimited by cash reserves, to have their day in court. Take note that Ms. Levine had to wait almost 9 years for any recompense from the drug’s manufacturer. It takes an tremendous amount of courage and patience to stand up through a jury trial, the Vermont Court of Appeals decision, and then all the way to the Supreme Court of last chance.
2. 21 CFR Parts 201, 314, and 601. www.fda.gov/OHRMS/DOCKETS/
3. Slip Op No 06-1249, 2009 U.S. Lexis 1774, 555 U.S. (2009).
4. The upcoming Supreme Court case of Wyeth v. Levine and the preemption temptation. September 23, 2008. http://writ.news.findlaw.com/
5. Wyeth v. Levine: inside the preemption case. PharmExecBlog. November 10, 2008. http://blog.pharmexec.com/
6. Levine v. Wyeth, Slip Op No 2004-384 (October 27, 2006; 2006 Vermont Supreme Court 107). www.jenner.com/files/tbl_
7. FDA approval of drug warning labels does not protect drug manufacturers from state based lawsuits alleging inadequate warnings. www.salawus.com/news.aspx?pid=
8. See note 2, supra.
9. Phenergan. www.drugs.com/phenergan.html. Accessed April 8, 2009.
10. See Silverman, note 3, supra.
11. See note 6, supra.
12. Levine v. Wyeth, 944 A 2d 179 (Vt. 2006). Petition for Certiorari granted January 18, 2008.
13. 183 Vt. 76, 84, 944 A.2d 179, 184 (2006), as quoted in Levine, note 1, supra.
14. Definition of certiorari. http://encarta.msn.com/
15. Reigel v. Medtronic, 552 U.S., 128 S. Ct. 999, 1018, 169 L. Ed. 2d 892, 914 (2008).
16. 21 U. S. C. §360k (a).
17. Justice John Paul Stevens is characterized as “second in conference after [Chief Justice] Roberts; and Stevens can assign opinions in the event that he is in the majority and Roberts is in minority. Still, Stevens’ influence remains uncertain. Many observers point to his quirky and unconventional jurisprudence as a constraint on his ability to lead the Court...However, as the Court has turned further to the right...Stevens has emerged as the voice of moderation on an increasing conservative bench.” www.oyez.org/justices/john_
18. Medtronic, Inc. v. Lohr, 518 U.S. 470, 485, 116 S. Ct. 2240, 135 L. Ed. 2d 700 (1996).
19. FDCA. 121 Stat. 823.
20. § 901(a), id, at 924-926.
21. S. 1082, 110th Cong., 1st Sess., § 208, pp. 107-114 (2007) (as passed) (proposing new § 506D).
22. 121 Stat. 925-926.
23. §§ 314.70(c)(6)(iii)(A),&(C).
24. 21 CFR § 201.80(e), requiring a manufacturer to revise its label “to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug,” and §314.80(b), placing responsibility for postmarketing surveillance on the manufacturer; see also 73 Fed Reg 49605, “Manufacturers continue to have a responsibility under Federal law to maintain their labeling and update the labeling with new safety information.”
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