Medical Device Daily Washington Editor

The recall of heparin sodium for injection by Baxter Healthcare (Deerfield, Illinois) has created a public health dilemma worthy of Solomon, but while the best minds at FDA and the Center for Disease Control and Prevention hammer away at the data to find the source of the problem, physicians and dialysis patients face an ugly choice: take the chance of suffering severe – and potentially deadly – side effects or delay a critical dialysis session.

The only silver lining yet observed to this cloud is that as of yesterday afternoon, no fatalities had been reported.

FDA reported that Baxter had temporarily suspended manufacture of multiple-dose heparin pending the outcome of the investigation into the reactions, which include very low blood pressure, difficulty breathing, and nausea and vomiting. While no fatalities have been reported, the hypotension problem is potentially lethal in the wrong patient.

At the beginning of the month, the company recalled nine lots of heparin sodium injection 1000 units/ml 10ml and 30ml multi-dose vials (Medical Device Daily, Feb. 1, 2008).

The drug is typically introduced intravenously, but can be injected subcutaneously. The larger doses connected with the adverse events are usually introduced intravenously, and leading public health professionals are warning doctors to go slowly with the anticoagulant.

Heparin sodium is derived from pig intestines, but to date there is no indication that the source matter is the source of the problem.

In a statement posted at the FDA web site Monday, Janet Woodcock, MD, FDA’s chief medical officer, said the agency “concurs with Baxter’s decision to halt manufacture of heparin sodium in multiple-dose vials,” but also suggested that “patients and healthcare professionals who cannot obtain alternative sources of heparin should use caution in administering any Baxter multiple-dose vials.”

FDA has received about 350 reports of adverse events associated with the Baxter product in 2008, a sharp upturn from the total of less than 100 reported in 2007. The majority of the reports are for patients on high doses who are under treatment at hemodialysis centers. Most of the vials implicated are those containing multiple doses, but some single-dose vials are also suspect. Baxter makes about half the heparin used in the U.S.

Alex Kallen, MD, an officer in the epidemic intelligence service at CDC, told Medical Device Daily “this is a high-priority investigation for FDA and CDC, and we’re bringing all the resources to bear that we can.”

He confirmed that “For dialysis patients, Coumadin is probably not” a good substitute for heparin, but doctors may want to look at it for other applications.

As to whether the incidence of adverse reactions shows any uneven geographic distribution, Kallen said “this product is widely distributed across the U.S., and we’ve seen reactions from more than 12 states” with no indication yet of any disproportionate areas of adverse reactions. However, he added that FDA has more of the updated reports and he could not vouch for what the additional data might suggest.

“It seems like bacterial contamination and endotoxins have been problems in the past, but almost all those have been eliminated” in this case, Kallen said, adding that “this is almost certainly not a biological pathogen.” He said that chances are that it is either a stray protein or some sort of chemical contaminant from the manufacturing process.

Unfortunately, medical science has not even pinned down the specific immune system agents involved, information that might be telling. “The reports we have are inconclusive about the mechanism of reaction,” Kallen said.

When asked if this is the medical mystery of the year, Kallen said that while the year is young, “it’s definitely a medical mystery,” partly because “there clearly are differences in the level of reactions” compared to past events of this type.

Baxter spokesperson Erin Gardner told MDD that Baxter has “launched a thorough investigation, which is ongoing” and is examining processing, shipping, storage and any other possible sites of contamination. However, she said, “we have not identified the root cause yet.”

Gardner said the root cause cannot be connected to a change of manufacturing equipment or to the site of manufacturing because “we have not changed manufacturing recently.”

Whatever the outcome for patients, Gardner said, “this is not financially material to the company,” which sells only about $130 million a year in heparin sodium, a small sum against what she described as $11.3 billion in annual sales.

Icy Hot patches pulled

OTC drug maker Chattem (Chattanooga, Tennessee) has its own recall to deal with, but the company may be hoping that basketball behemoth and company spokesman Shaquille O’Neal wont’ find out.

Chattem has recalled its topical therapeutic patch Icy Hot due to persistent reports of burns of all three degrees and “skin irritation resulting from the use or possible misuse of the product,” according to a company press release. The hypothesized misuse would be keeping the patch on for more than eight hours in any 24-hour period.

According to the company’s numbers, the reported adverse events come to about one tenth of 1% of total sales of the product, which number about 1.8 million units. The problem first arose late last year and Chattem responded with a warning label that was designed to ward off inappropriate use, but FDA informed the company that further action is required, hence the current recall. The company did not indicate whether it intends to reintroduce the product at a future date.

The company said it does not anticipate a significant impact on its sales due to the small portion of total sales generated by Icy Hot, which accounts for about 2.3% of total revenues, which came in at $423 million in 2007. The firm stated that it expects to take a charge of as much as $9 million in fiscal 2008, which was said to amount to $.30 per share. Chattem’s product line includes Gold Bond medicated powder and the weight loss supplement Dexatrim.