Approximately 13% of health care expenditures in the United States are for prescription drug spending, nearly $420 billion in 2015.1 High-priced pharmaceuticals, therapies that cost more than $600 per month, are projected to eclipse 50% of total drug spending by 2018.2 Price increases for these therapies have been persistent, with unit costs increasing 164% between 2008 and 2015.2 Pharmacy benefit managers are third-party administrators that process and pay prescription drug claims and negotiate drug prices with manufacturers. Pharmacy benefit managers have sought to manage prescription drug use and mitigate cost increases through such measures as prior authorization and step therapy requirements for physicians, increased copayment requirements for patients, and exclusion of some expensive medications from health plan formularies. Using the illustrative example of Duexis, a single-tablet, fixed-dose combination of the nonsteroidal anti-inflammatory (NSAID) ibuprofen and the histamine H2-receptor antagonist famotidine marketed by Horizon Pharma (Dublin, Ireland), we describe how some pharmaceutical companies have sought to circumvent such restrictions and maintain high prices for drugs, even for those with generic alternatives.