Bristol-Myers Warning Ignored on Steroid Shots Tied to Deaths

FDA Keeps Patients in Dark on Steroid Shots
A Bristol-Myers Squibb Co. logo is displayed during an investor meeting in New York. Photographer: Daniel Acker/Bloomberg

Doctors are still injecting a steroid made by Bristol-Myers Squibb Co. in a way the company warns they shouldn’t, following reports that patients have died or become paralyzed after receiving steroidal shots.

Bristol-Myers changed the label on its steroid Kenalog seven months ago to say that it’s “not recommended” for injection into the epidural space near the spine because of “reports of serious medical events, including death,” associated with administering steroids in that fashion. The label doesn’t specify if Kenalog patients died and a spokesman for the company declined to comment.

Used for neck and back pain, Kenalog and the Pfizer Inc. drug Depo-Medrol are the most frequently administered steroids in epidural injections. Over eight million such shots were given in the U.S. in 2010.

Physicians are either ignoring the Bristol-Myers warning or aren’t aware of it, according to doctors who use Kenalog or who work with others who do. “It is still being given in abundance,” said Christopher Gharibo, head of pain medicine in the anesthesiology department at NYU-Hospital for Joint Diseases in New York.

Neither Bristol-Myers nor the U.S. Food and Drug Administration publicized the revision, even though the FDA is reviewing the safety of epidural steroid shots. While not required to alert doctors or patients, the FDA has broadcast changes to other drugs’ prescribing information. In June, around the time the Kenalog label was rewritten, it issued a press release about a muscle injury risks warning that Merck & Co. applied to its Zocor cholesterol pill.

‘A Better Way’

The FDA should notify physicians in every case of a new caution and require companies to make changes to labels stand out, said Curt Furberg, an epidemiologist at the Wake Forest School of Medicine in Winston-Salem, North Carolina.

“I think they are irresponsible,” he said of the FDA.

Charles Bennett, a medication safety expert at the South Carolina College of Pharmacy in Charleston, said it’s the FDA’s duty to be more aggressive because most physicians “don’t even look at the label” on a drug they’ve used for years.

“There has to be a better way of making sure doctors know about very serious side effects of drugs,” he said.

Morgan Liscinsky, a spokesman for the agency, said decisions about taking steps such as issuing press releases are made on a “case by case basis.” She said a notice about the label change was e-mailed to 200,000 people who have signed up to receive agency safety alerts.

Reviewing Data

“The FDA acknowledges that communicating risk is challenging, and the agency remains committed to improving the capacity to provide the public with timely, accurate, evidenced-based safety information,” she said.

Bristol-Myers added the Kenalog warning after reviewing “post-marketing safety data,” said Ken Dominski, a spokesman for the New York-based company, in an e-mail. He said the company wouldn’t provide additional information.

The FDA -- which approves the prescribing information that companies write for their drugs -- declined to provide the data. Liscinsky said it would only be released through a Freedom of Information Act request, which can take months to process. Bloomberg filed one Jan. 13.

Manufacturers sometimes alert doctors to safety updates, which Bristol-Myers Squibb has done in the past with other drugs. Dominski didn’t explain why that wasn’t done with Kenalog.

Primary Suspects

The use of epidural steroid injections is booming, thanks to an aging population and generous reimbursement by insurers. The shots can calm inflamed nerves and are popular for easing pain in hips, knees and others parts of the body.

The FDA is conducting what Liscinsky called a “multi-faceted” review of epidural steroid shots and reports of serious complications. One focus is injections made with a transforaminal approach, which brings the needle within millimeters of critical arteries. Outside experts working with the agency on the review say they are also concerned about the use of so-called particulate steroids like Kenalog and Depo-Medrol, which may create blockages that could trigger strokes if accidentally shot into arteries.

Since 2004, epidural steroids have been cited as the primary suspect in serious complications suffered by 198 patients, according to an evaluation of FDA data performed for Bloomberg by AdverseEvents Inc., a company in Healdsburg, California, that analyzes drug safety reports and sells the results to drug makers, insurers and financial institutions.

‘Life-Threatening Events’

Depo-Medrol and generic versions were cited most often, in 90 of the cases, including in those of three people who died. Kenalog and generic equivalents were named as the main suspects in 88 cases. Three other steroids comprised the remaining 20 cases of serious complications.

In all, 52 of the patients were hospitalized, 30 suffered disabilities from their complications and 10 were listed as having “life-threatening events.” Bristol-Myers and Pfizer declined to comment on those numbers.

Other research into the injections has uncovered incidents of death or serious complications following pain shots. A survey of physicians reported in the journal Spine in 2007 found 78 cases where patients who got epidural steroids shots in the neck -- known as the cervical area of the upper spine -- suffered serious injuries; there were 13 deaths, all following injections of methylprednisolone, a steroid that includes Depo-Medrol and generic versions of the drug.

Little Reporting

In a separate review of case studies in medical journals, Mark Wallace, the author of the physicians’ survey, also found two cases in which patients died after epidural injections with the steroid triamcinolone, which is found in Kenalog. Wallace is chairman of the pain-medicine division for the University of California at San Diego’s health system.

The FDA posted a notice on its website in May 2010 that it has identified a “potential safety issue” with the class of steroids that includes Kenalog and Depo-Medrol, based on its own analysis of reports it’s received about complications. The FDA’s noting that there might be a risk doesn’t mean the agency has discovered a direct causal relationship, according to the site.

While manufacturers are supposed to tell the FDA about any adverse events they learn of, doctors and other health professionals are under no such obligation. Only 1 to 10 percent of drug-related complications are reported to the FDA, according to government estimates.

Kenalog Sales

U.S. sales of steroids used in epidural shots were $350 million in the first 11 months of 2011, according to IMS Health, a Danbury, Connecticut data firm, which said sales of Kenalog for all uses were 52 percent higher than those of Depo-Medrol. Kenalog sales were $112.3 million in those 11 months, compared to $113.2 million for full year 2010, IMS Health numbers show. Bristol-Myers wouldn’t disclose its sales of Kenalog for epidural use alone.

Depo-Medrol’s label doesn’t include a warning about epidural use. Pfizer spokeswoman Joan Campion said in an e-mail that epidural use of the steroid isn’t approved by the FDA and that “physicians should not administer the product” that way. As for why its competitor added a warning and Pfizer hasn’t, she said that while the two drugs are in the same class of products they are not the same product.

Generic drug makers must update their labels to reflect changes made to the brand-name version, according to the FDA.

‘No Absolute Safety’

No steroids are specifically approved for epidural injections and the drug makers haven’t on their labels recommended they be used that way. Doctors may administer them that way if they believe it’s medically beneficial, in what is called off-label use, even if a manufacturer’s prescribing information cautions against it.

At NYU-Hospital for Joint Diseases, Gharibo said he uses Kenalog because it’s effective and severe complications from epidural shots are rare, estimating the risk at one in 100,000.

“In injections, there is no absolute safety,” he said, adding that other steroids have comparable risks to Kenalog.

Richard Rosenquist, chairman of the pain management department at the Cleveland Clinic in Ohio, said doctors there use Kenalog epidural shots to treat neck and back pain because it works well. He added that he would have no reason to look at the label of a drug he’s been using “in a safe and efficacious fashion” for years.

“I am unlikely to go back and spend time reading the package insert unless I have been made aware of a change,” Rosenquist said.

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