Heparin may be in short supply

Blood-drug supply may thin
Baxter stops making heparin after ill effects

By Bruce Japsen, Tribune reporter
Tribune reporter James P. Miller contributed to this story
February 12, 2008

The federal government Monday braced U.S. health facilities for potential shortages of a popular blood thinner after Baxter International Inc. stopped making certain heparin vials over concerns of a mysterious allergic reactions in some patients receiving high dosages.

The U.S. Food and Drug Administration said potentially dangerous and "life-threatening" allergic reactions have been linked to the Deerfield-based medical product giant's multidose vials of heparin blood thinner.

The reactions so far are believed to be limited to "initial loading" dosages before undergoing in-center dialysis treatment or heart surgery. They have included nausea, difficulty breathing and rapidly falling blood pressure that can lead to death. Problems have not been reported with continuous use of the product.

Four people have died after receiving heparin, but the FDA said these cases did not "follow the pattern" of patients experiencing reactions from initial high dosages, known as "bolus" doses.

Still, the FDA said the concerns are serious enough that hospitals should consider switching to another maker. Baxter makes 35 million vials annually, or half the U.S. hospital supply of heparin, making federal officials concerned about a growing problem, especially if the agency uncovers more adverse events with patients.

"There is going to be a shortage problem in the immediate and longer-term future with the suspension of the Baxter manufacturing," said Dr. John Jenkins, director of the FDA's Office of New Drugs. "We are facing a complex situation. It's clear that there are going to problems that health-care providers are going to be facing."

The agency said it has begun investigating Baxter's manufacturing processes to determine the allergic reactions first reported by Missouri state health officials to the Centers for Disease Control and Prevention in mid-January.

The FDA said it did not encourage a recall of the product in part because Baxter has such a large market share. It also said the reactions currently appear to be limited to high dosages and not lower dose continuous infusions. Jenkins said the government wanted to give medical-care providers latitude to manage the risk and leave the product available given the "medical necessity" of heparin.

But some hospitals were not taking any chances and began switching when Baxter sent a notice of recall Jan. 17. The University of Chicago Medical Center, for example, said it switched last month to another manufacturer, Schaumburg-based APP, formerly known as Abraxis Bioscience Inc.

And the FDA said it would be discussing with APP and suppliers outside the U.S. ways to ramp up production if the situation worsens and a recall is broadened. On Jan. 17, Baxter announced a recall of nine lots of multidose heparin injection units in 10- and 30-milliliter doses, as a "precautionary measure," saying it had received reports of allergic reactions to patients who used heparin from those lots.

Baxter said Monday that it was conducting an investigation to determine the cause of the problem.

The nine recalled lots all came from a Baxter facility in Cherry Hill, N.J., the CDC reported.

On Monday, the FDA said about 350 adverse events linked to Baxter's heparin have been reported since the end of last year compared with less than 100 reports in 2007. Most of the allergic reactions have taken place in dialysis centers and "almost exclusively" involving patients receiving a "bolus" dose given before dialysis to prevent blood from clotting. Such dosages also can be given before heart surgery.

The number of adverse events is small considering Baxter makes 100,000 vials of heparin a day. The company urged physicians to continue prescribing heparin when needed, but to use the lowest amount needed and "balance the clinical need to use these products with the increased potential for experiencing adverse drug reactions."

Derived from pig intestines, heparin has been sold in the U.S. since the 1930s. The intravenous medication has helped millions of patients benefit by avoiding potentially life-threatening blood clots in arteries, veins and lungs, the FDA said.

Heparin represents only a fraction, or about $30 million, of Baxter's more than $11 billion in annual sales. Shares of Baxter rose 23 cents, to $60.88, on the New York Stock Exchange.

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What is heparin?

A blood-thinning drug, it's most commonly used before certain surgeries, many involving the heart, and is also given to dialysis patients before treatment.

The problem: Large doses given intravenously over a short period of time have caused severe allergic reactions and low blood pressure in about 350 patients this year. These events involved multiple-dose vials.

The scope: Only heparin made by Baxter International Inc. and packaged in multiple-dose vials is involved; however, this represents half of the U.S. supply, or 35 million vials annually.

What now? Baxter has stopped making the multiple-dose vials of the drug. The FDA advises doctors to use a different drug or heparin provider when possible and to administer heparin differently and monitor patients closely when these are not viable options.

Source: Food and Drug Administration