SILVER SPRING, Md. -- An FDA advisory committee urged the agency to modify labels of certain formulations of corticosteroids in an attempt to make epidural injections safer, following a 2-day meeting that ended Tuesday.
After discussing the risks and benefits of epidural steroid injections on Monday, the Anesthesia and Analgesic Drug Products Advisory Committee voted 15-7 Tuesday in favor of calling so-called "particulate" steroids contraindicated for epidural injection because they appear to carry greater risk of adverse neurological effects than "nonparticulate" agents.
Most of the dissenting members said the contraindication would be too restrictive, instead preferring label warnings on the risks of such injections. One member abstained from the vote.
At issue during the meeting was the large number of adverse event reports following corticosteroid injections for back, neck, and radicular pain, which had already led the FDA to issue new warnings earlier this year.
The voting results demonstrate panel members' concern about the use of particulate steroids -- often referred to as suspensions -- in certain situations and the drugs' relationship to serious neurological events.
, associate professor of epidemiology, neurology and anesthesia at the University of Pennsylvania and senior scholar at the Center for Clinical Epidemiology and Biostatistics, voted yes, he said, "with a clear intention of a contraindication to the use of the particulate form of a variety of steroids."
Farrar said animal studies have already demonstrated the risk of ischemia when particulate steroids are injected arterially. "If you put particles into the bloodstream headed toward any structure you're going to cause ischemia. That's what leads ultimately to the infarction of the cord of the brain."
, professor and chair of the department of anesthesiology and perioperative medicine at the Oregon Health and Science University of Portland, Oregon, agreed with Farrar, "I think it's too risky to administer particulate medications in the cervical region because of the risk of interarterial injection, which I believe causes the contraindication."
On the dissenting side, , director of Pain Trials at Brigham and Women's Hospital in Boston, opposed label language that contraindicates particulate steroids for epidural use, but said he would support a warning on transforaminal cervical injections with particulate steroids.
, said the current warning is broad enough to encompass "the known risks." Added Golish, a spinal surgeon and medical director of research at Jupiter Medical Center in Palm Beach, Fla., "I think the most worrisome practices we've discussed are being eliminated in the clinical practice of medicine by increased awareness and leadership."
But Golish, like Michna, said he would also favor a warning, even a "black-box" warning, for transforaminal cervical injections with particulate steroids in the cervical spine.
More patients are receiving injectable corticosteroid injections to relieve back, neck, and radicular pain but a number of reports of catastrophic injuries associated with epidural use of these drugs has prompted the FDA to consider clearer labeling.
In July, the FDA approved a new label for epidural steroid injection sponsors which reads: "Serious neurologic events, some resulting in death, have been reported with epidural injection of corticosteroids (see WARNINGS: Neurologic). Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke." The warning noted that the events occurred with and without fluoroscopy and that the safety and effectiveness of cortical steroids had not been approved for epidural injections.
Tuesday's vote is in line with the recommendations of the FDA's Safe Use Initiative working group. chief of pain medicine in Massachusetts General Hospital's anesthesia department, who warned the FDA of the dangers of epidural steroid injection in 2009 and who led the working group, also presented at the hearing. Rathmell called transforaminal injections the "greatest culprit" in terms of epidural steroid injection risk.
Panelists heard that, while there is some evidence that transforaminal injections -- those delivered at the opening of the spine where a nerve root exists -- may be more effective for pain reduction than intralaminar (mid-line) or caudal approach, their proximity to an artery may also increase the risk of an embolic event.
The 17 "clinical considerations" developed by Rathmell's working group advised that particulate steroids, specifically, should not be used in therapeutic cervical transforaminal injections.
Also, the American Society of Anesthesiology's Closed Claims Reports II found 78 complications, 30 infarctions, and 13 instances of death following cervical transforaminal epidural steroid injections.
Several committee members said more research of both particulate and nonparticulate steroids is needed, but Farrar argued that there was no need to duplicate the animal studies in humans. "You don't need to prove that a gun's going to kill you [for you] not to use it."