Hawaii Reaches Settlement With Plavix Makers Over Deceptive Labeling

Background and Facts of the Case

Initially approved by the FDA in 1997, clopidogrel (Plavix; Bristol Myers Squibb/Sanofi Pharmaceuticals) is a platelet aggregation inhibitor used to prevent stroke or myocardial infarction in patients at high risk of these events. Clopidogrel is a prodrug that requires activation by enzymes in the patient’s liver. Hepatic cytochrome 2C19 is one of the key enzymes known to activate clopidogrel. However, there is substantial genetic variation in the levels of hepatic cytochrome enzymes; 2C19, in particular, is much lower in persons with East Asian or Pacific Islander ethnicity.^1,2

In 2010, the FDA required Plavix labeling to include a boxed warning that individuals with East Asian or Pacific Islander ethnicity are poor metabolizers of clopidogrel and are, therefore, at higher risk of adverse cardiac events from subtherapeutic responses.³

In 2014, the Hawaii attorney general filed a state lawsuit against the manufacturers of Plavix, Bristol Myers Squibb and Sanofi Pharmaceuticals, alleging unfair or deceptive acts or practices against consumers (ie, patients receiving the drug). The attorney general alleged the defendants were aware of the risk of poor response years before the FDA requirement for a boxed warning but continued to market Plavix as safe and effective. The lawsuit states that 834,012 prescriptions for Plavix were dispensed prior to the boxed warning.⁴

Legal Process and Settlement Agreement

Damages of $834,012,000 ($1000 per prescription) were requested. Among other affirmative defenses, the manufacturers asserted they were preempted by federal law from making changes to the product labeling.⁴

During the court proceedings, it was determined that the manufacturers could have applied for a labeling modification through an FDA process known as changes being effected. For the deceptiveness claim, the Hawaii First Circuit Court found the defendants equally responsible and assessed a civil penalty of $417,006,000 against each defendant (a total of $834,012,000). For the unfairness claim, the court found the defendants equally responsible and assessed a civil penalty of $41,000,000 against each defendant (a total of $82,000,000). The defendants and Hawaii entered a settlement on May 9, 2025, for $700,000,000 ($350,000,000 per defendant).⁴

REFERENCES

1. Beavers CJ, Patel P, Naqvi IA. Clopidogrel. In: StatPearls [Internet]. StatPearls Publishing; 2025. Accessed December 10, 2025. https://www.ncbi.nlm.nih.gov/books/NBK470539/

2. Hashemizadeh Z, Malek-Hosseini SA, Badiee P. Prevalence of CYP2C19 genetic polymorphism among normal people and patients with hepatic diseases. Int J Organ Transplant Med. 2018;9(1):27-33.

3. FDA drug safety communication: reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of drugs. Updated August 3, 2017. Accessed December 16, 2025. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-reduced-effectiveness-plavix-clopidogrel-patients-who-are-poor

4. Hawaiʻi Circuit Court. Findings of Fact, Conclusions of Law. State of Hawai‘i ex rel. Attorney General v. Bristol-Myers Squibb Co., Civil No. 1CC141000708 (Haw. 1st Cir. Ct. Feb. 15, 2021). Accessed December 16, 2025. https://ag.hawaii.gov/wp-content/uploads/2024/05/24-05-21-2039-Findings-of-Fact-Conclusions-of-Law.pdf?utm_source=chatgpt.com