Whether you buy into a Food and Drug Administration conspiracy theory or not, there are many problems with the approval of Zohydro ER. Although there is certainly disagreement over the benefits and risks of the medication, almost everyone can agree that Zohydro is one the most controversial recent drug approvals by the FDA.

The opposition to the FDA’s approval of Zohydro includes consumer groups, doctors, state and federal leaders, and multiple governmental organizations. FDA Commissioner Margaret Hamburg has received letters protesting the decision to approve Zohydro ER from at least 28 state attorneys general and multiple US senators. Massachusetts Gov. Deval Patrick and Vermont Gov. Peter Shumlin, issued directives to either ban or make it more difficult to prescribe and dispense the medication. Health insurers claim that opioid abuse costs more than $70 billion a year in direct health care costs.

The potential conflicts involving Zohydro ER illustrate the involved process and complicated business operations and influence that the pharmaceutical industry might have on the approval process.

The Zohydro ER story centrally involves a company called Alkermes. This company owns a product called Vivitrol, an extended-release version of naltrexone that is given in a monthly injection to treat opioid dependence. The medication was supported by several very controversial studies and, in October 2010, was approved by the FDA to treat and prevent relapse in patients with opioid dependence who have undergone detoxification treatment. The product has had a very slow start and has failed to meet sales expectations.

In 2011, Alkermes purchased a part of another pharmaceutical company, Elan, that originally made Zohydro ER, and, with it, an exclusive marketing deal with a pharmaceutical company called Zogenix, which has the right to market the drug. Interestingly, Alkermes chose not to list Zohydro ER as one of its products and instead left the product under the Zogenix product line. Not surprisingly, many think it is a conflict of interest for Alkermes to have a product that treats opiate abuse as well as a product that has the potential to greatly increase opiate abuse.

The potential conflicts involving Zohydro ER illustrate the involved process and complicated business operations and influence that the pharmaceutical industry might have on the approval process.

In May 2012, a bipartisan Senate committee launched an investigation into the conflicts of interest and issued a series of subpoenas to various “consumer” groups, including the American Pain Foundation, University of Wisconsin Pain & Policy Studies Group, the American Pain Society, the Federation of State Medical Boards, and The Joint Commission. Within days, the American Pain Foundation shut down, and it was disclosed that the Federation of State Medical Boards commissioned the production of its Responsible Opioid Prescribing—A Physician’s Guide and other publications by the American Pain Foundation, which received 90 percent of its $5 million in funding from pain medication manufacturers. Interestingly, the American Pain Foundation was very active in lobbying for greater pain medication use. In 2011, under investigation, Scott M. Fishman, MD, the main author of the pain guide and the past president of the American Pain Foundation, acknowledged that he had to add additional disclosures including honoraria from the pharmaceutical industry not previously disclosed.

In October 2013, the Milwaukee Journal Sentinel disclosed that the University of Rochester created two organizations: IMMPACT (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials) and ACTTION (Analgesic Clinical Trial Translations, Innovations, Opportunities, and Networks). Some alleged potential pay-to-play arrangements involving meetings between pharmaceutical industry representatives and FDA officials occurred with these organizations. Pharmaceutical industries allegedly paid between $20,000 and $35,000 to send one representative to a two-day meeting. Zohydro ER’s original manufacturer may have participated in those meetings. Allegedly as a result of the meetings, the FDA approved a method, known as enriched enrollment, which allowed pharmaceutical companies doing pain studies to remove certain patients who did not respond well to a medication or could not tolerate it before the study began. This made it much easier for pharmaceutical companies to prove their medications were safe and effective.

On March 10, 2014, several senators called for a special investigation into these pay-to-play allegations against several pharmaceutical companies, physicians, and FDA officials. Sen. Joe Machin (D- WV) and Rep. Stephen Lynch (D-MA) introduced legislation to prohibit the FDA from approving similar drugs unless they are formulated to prevent abuse. Several Republican senators also demanded the FDA release safeguards to prevent abuse.

In March, Purdue Pharma announced it had developed a tamper-resistant version of its hydrocodone product for extended release. Interestingly, the company that markets Zohydro ER announced it will likely have a tamper-proof version of Zohydro ER ready by 2016.

On April 15, 2014, a US District Court issued a preliminary injunction citing that the ban ordered by Massachusetts Gov. Patrick was unconstitutional.

The investigations are just beginning, and the controversy will undoubtedly continue. It is an unintended, and unfortunate, coincidence that Zohydro ER happens to have the word “ER” in it.

Dr. Kivela is managing partner at Napa Valley Emergency Medical Group, medical director of Medic Ambulance, and part owner of Elan Medical Corporation. He is also the secretary-treasurer of the ACEP Board of Directors.