University of Minnesota limits off-label use of drug championed by an anesthesiologist paid by its manufacturer

The University of Minnesota Medical Center is scaling back its controversial use of a post-surgery painkiller — a drug championed by an anesthesiologist who has received hundreds of thousands of dollars from its manufacturer.

Nurses received a memo this summer that the medical center was restricting its use of Exparel, citing a lack of published research to justify broad use of the injectable anesthetic. The memo stated "there was inadequate literature to support [Exparel's] use in the majority of the surgical population."

The announcement is a departure for the medical center under Dr. Jacob Hutchins, a medical director of the university's acute pain service. He not only encouraged the use of Exparel in "off-label" ways that the U.S. Food and Drug Administration hadn't approved, but at one point in a way the federal agency rejected.

Hutchins has received $800,298 from Exparel's manufacturer, Pacira Pharmaceuticals, since 2013, according to federal records, mostly to travel and speak on the company's behalf at advisory meetings and conferences. He has fully disclosed the relationship to U officials and patients, and defended the arrangement as a way of improving the practice of pain control.

Hutchins' advocacy was based on an enticing premise — that Exparel could reduce reliance on addictive opioid painkillers that have led to a wave of overdose deaths across the nation.

In an e-mail Friday, Hutchins said the change by Fairview Health, which operates the university hospital, doesn't mean that Exparel has failed, just that research hasn't proved its broader uses yet.

"Absence of data does not mean absence of effect," he wrote. "The use of this medication has resulted in a significant decrease in opioid use for our patients in all procedures where it was being used."

The FDA has taken a cautious approach, first approving Exparel in 2011 for direct injection, or infiltration, into surgical sites for post-procedure pain relief. The agency in 2015 rejected Exparel for nerve blocks, injections higher up the nervous system from surgical sites that produce broader and longer pain relief. In 2018, the FDA reversed course and approved nerve blocks, but only for shoulder surgeries.

Hutchins used Exparel for nerve blocks before this approval, and encouraged colleagues to do so, doctors told the Star Tribune in 2016. His advocacy caused some anesthesiologists to leave the university, they said.

While many drugs are prescribed off-label without patient consent, the U gave patients written information about Exparel and off-label uses of drugs in general.

Exparel contains the same active ingredient, bupivacaine, that is given to patients via spinal epidural injection, but is formulated in a way to release the medicine slowly. As a result, Exparel's pain relief after surgeries can last 72 hours, whereas intravenous alternatives last only 24 hours. But this benefit is also a concern, because doctors can't stop the medication's slow release — even if it produces side effects — once the drug has been injected.

The FDA has received increasing reports of problems with Exparel, although that can be an unreliable measure because claims are submitted to the agency's Adverse Event Reporting System without proof that the drug caused harm. There have been 69 claims regarding Exparel this year, an increase from 35 in 2018, including reports of bowel problems due to paralyzed intestinal muscles.

One Twin Cities patient told the Star Tribune she suspects Exparel caused complications following her cesarean section childbirth at the U medical center in 2016. She has suffered numbness in her abdomen ever since, and wonders if the drug blocked her production of breastmilk to feed her newborn.

The 41-year-old Minneapolis woman, who spoke on condition of anonymity due to her ties to the university, said her doctors can't prove the drug caused her complications. Even so, she said she is upset that she was informed of the planned use of Exparel after delivery, when she was medicated and dazed in the recovery room, and received paperwork about the experimental use of the drug when she was being discharged. And she still received opioids during recovery.

"This was a planned C-section," she said. "It wasn't an emergency C-section where any chance to talk about this could have been missed. ... In no way can it be considered consent when I was just sort of 'eyes-only-half-open.' "

Hutchins co-authored this summer's nursing memo along with Dr. James Flaherty, who also serves as a medical director of acute pain and regional anesthesia services. It indicated that Exparel would still be used for open surgeries and orthopedic shoulder surgeries, but not for closed, laparoscopic procedures, or other orthopedic procedures.

Restricting Exparel could save the hospital $500,000 a year and was part of a re-examination of the use of all high-cost drugs, said Dr. Mark Welton, Fairview's chief medical officer. "Other pain medications are as effective as Exparel in these specific instances, but less costly," he said.

Welton commended Hutchins for his "significant role in defining" how best to use the drug.

The research case for Exparel remains mixed. A top orthopedic surgeon in Florida recently suspended an Exparel study after the drug failed to adequately control pain after outpatient rotator cuff surgeries.

However, Pacira in January released results of a study that it funded showing that the drug reduced opioid use and controlled pain in women after C-section births at 13 medical centers, including the University of Minnesota.

Exparel will continue to be an option for C-section births at the medical center and a topic for research. The university has funded two studies by a maternal-fetal medicine fellow to study how the drug controls pain after childbirth and whether it enters breast milk.

Jeremy Olson • 612-673-7744