Baxter International Inc on Monday said it has temporarily stopped making the blood-thinner heparin in multi-dose vials after four patients who took the drug died and hundreds of others became ill.
The U.S. Food and Drug Administration said it had received about 350 reports of health problems associated with Baxter's injectable heparin product since the end of 2007. Four patients died, but the relationship to the drug is unclear, an FDA statement said.
FDA on Monday advised doctors to use an alternative source of heparin or another blood-thinning agent when possible and said it was investigating whether similar problems had been seen with heparin made by other manufacturers.
Baxter makes about half of all multiple-dose vials of heparin sold in the United States, FDA said.
Patients reported side effects that included difficulty breathing, nausea, vomiting, excessive sweating and rapid drop in blood pressure. Almost all the adverse reactions were seen in patients who received a "bolus" dose, or high dose given over a short period of time, FDA said.
Heparin, which has been in widespread clinical use since the 1930s, is administered in operating rooms and other critical care areas to prevent blood clots and is crucial in hemodialysis and heart surgery. Millions of patients each year receive the product intravenously.
Adverse events were not seen in patients who received lower doses of the drug -- which is derived from pig intestines -- or who received higher doses spread over a longer period of time, FDA said.
In January, Deerfield, Illinois-based Baxter voluntarily recalled nine lots of its injectable heparin sodium injection in 1,000-unit vials, citing an increase in adverse patient reactions.
Since then, the company said, it has received reports of adverse reactions in additional lots of multi-dose vials of 1,000 units, 5,000 units and 10,000 units, and in single-dose vials of 5,000 units when single doses were combined to create a larger bolus dose.
As a result, the company said it has temporarily suspended the manufacture of multi-dose heparin vials as it investigates the cause of the increase in adverse reactions.
However, Baxter said it is not recalling any additional lots because to do so might cause a shortage of supply and create more risk to patients requiring heparin therapy than the increased potential for an adverse reaction.
"We're doing an exhaustive investigation," Baxter spokeswoman Erin Gardiner said, "but at this point we really don't have a cause identified."
Baxter said it will continue to distribute the products to assure adequate supply in the market. Heparin generates about $29 million in annual revenue for Baxter, less than 1 percent of the company's total revenue, Gardiner said.
FDA is conducting inspections of all facilities and processes involved in the manufacture of Baxter's heparin, said Dr. John Jenkins, director of the FDA's Office of New Drugs. FDA scientists also are testing samples of the product.
The other FDA-approved manufacturer of multiple-dose vials of heparin is APP Pharmaceuticals Inc.
FDA said health care providers should use Baxter heparin if it is the only product available and should use the lowest dose necessary at the slowest infusion rate, avoiding administering a bolus dose when possible.
The medicine is also at the center of a lawsuit filed by actor Dennis Quaid over an overdose given to his newborn twins. However, the Quaid case involved single dose vials that are not involved in the recall or current side-effect mystery.
The Quaid suit accuses Baxter of failing to put clear distinguishing labels on certain vials of heparin, and failing to recall the product after three infants died because of a mix-up.
Baxter's shares were up 16 cents to $60.81 in late afternoon trading on the New York Stock Exchange. Shares of APP Pharmaceuticals were off 3 cents to $10.30 on Nasdaq.
(Additional reporting by Toni Clarke in Boston and Lisa Richwine in Washington, editing by Gerald E. McCormick)