HEPARIN: Problems in Blood Drug Lead to Halt by Factory

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Problems in Blood Drug Lead to Halt by Factory

By GARDINER HARRIS
NY TIMES
Published: February 12, 2008

A major maker of heparin, a blood thinner used widely in surgery and dialysis, has stopped making it after hundreds of patients reported severe allergic reactions to the drug, which is made from pig intestines.

At least four people died.

Shortages of the drug are all but certain, federal regulators said. Although alternatives exist, doctors warned of serious consequences if heparin became truly scarce.

“Inadequate heparin would cause a health care crisis in this country,” said Dr. Daniel Coyne, a professor of medicine at Washington University in St. Louis.

Public health officials first noticed a problem late last year in four children undergoing dialysis at a hospital in Missouri. Within minutes of being injected with heparin, the children experienced serious allergic reactions.

As officials investigated, they found a total of 350 reports of patients’ experiencing problems after being injected with large doses of heparin made by Baxter Healthcare. Baxter supplies about half the nation’s heparin. Most of the cases were reported in late December or January; 40 percent were deemed serious.

The reactions included difficulty breathing, nausea, vomiting, excessive sweating and rapidly falling blood pressure that in some cases led to life-threatening shock.

A spokeswoman for Baxter, Erin M. Gardiner, said the company had not changed its heparin manufacturing for several years. The company initially recalled nine lots of the drug, but problems continued.

Baxter suspended manufacturing multidose vials that have been associated with most of the problems. Baxter continues to make single-dose vials.

Dr. John Jenkins, director of the Food and Drug Administration’s office of new drugs, said the agency decided to allow the company to continue distributing the multidose vials that it had made because a full recall “would result in an immediate and severe shortage of this medically necessary drug.”

APP Pharmaceuticals in Schaumburg, Ill., manufactures much of the rest of the heparin supply. Its president, Tom Silberg, said APP was rapidly increasing production.

“Can we ramp up to meet all of the demands?” Mr. Silberg said. “That’s yet to be said.”

Dr. Jenkins said doctors who had to continue to use Baxter heparin should use the lowest possible dose, infuse it slowly, monitor patients closely and consider administering steroids or antihistamines before heparin.

“There is going to be a shortage problem in the immediate and long-term future with the suspension of Baxter’s manufacturing,” Dr. Jenkins said. “Facilities and physicians will have to decide immediately what they do with the heparin on hand, and they’ll have to start looking for heparin for the long term.”

Doctors said they would face difficult choices if heparin supplies ran low.

“It’s an essential part of dialysis treatment,” said Dr. Jay Wish, professor of medicine at Case Western Reserve.

Heparin is used in dialysis to prevent clotting while blood circulates in a dialysis machine. Without heparin, many more patients would be likely to experience significant blood loss during dialysis, Dr. Wish said, worsening their chronic anemia.

Heparin is also used to prevent clotting in catheters, which 25 percent of dialysis patients have to use for treatment. The drug is commonly used in heart-bypass surgery and for the bedridden.

Other drugs thin blood, but their effects are rarely as rapid or as easily reversed. Heparin has been manufactured since 1930.

“Trying to operate without heparin would be a scary proposition for the dialysis industry,” Dr. Wish said.

Dr. Christina Beckwith, a drug information specialist at University of Utah Hospital, said newer versions of heparin, all far more expensive, could be used.

“It’s not going to be an easy thing, but there’s still going to be options to treat these patients,” Dr. Beckwith said.

Heparin is made from pig intestines that must pass through multiple purification steps to extract microbes and problem proteins, Dr. Jenkins said. The drug agency is inspecting whether something amiss occurred in the purification process. Even a factor as mundane as the rubber stoppers on the vials has to be considered a possible source of the problem, Dr. Jenkins said.

http://www.nytimes.com/2008/02/12/health/12drug.html?_r=1&oref=slogin