FDA heralds Baxter's voluntary recall of heparin

ROCKVILLE, Md. Baxter International announced Thursday that the company is proceeding with the voluntary recall of all remaining lots and doses of its heparin sodium injection multi-dose, single-dose vials and HEP-LOCK heparin flush products. The move was heralded by the Food and Drug Administration as the responsible move in a press conference Thursday afternoon, though the agency promised it would continue its investigation into heparin-related adverse events. While the agency has not yet determined what caused the adverse events, “We are determined to get to the root cause of these adverse events,” asserted Rear Admiral Sandra Kweder, deputy director of FDA’s Office of New Drugs, Center for Drug Evaluation and Research.

Initially, the FDA was concerned that a full recall of Baxter’s blood-thinner heparin would create an acute shortage in the American market. “APP [Pharmaceuticals] is now able to adequately supply the U.S. market,” Kweder said.

To date there are 448 reports of adverse events associated with heparin products, 389 associated with Baxter products, though it is not yet known how much duplication of adverse events is evident in those 448 reports. The FDA stated that there are presently 215 AERs “of interest.”

FDA has sent a team to inspect the Changzhou, China plant where Baxter International contracted the manufacture of its heparin products, and has identified a number of “objectionable” conditions at the manufacturing plant—inefficiencies in removing impurities and waste material flow issues to name two. “The facility is currently not manufacturing at this time,” commented Michael Rogers, director, FDA’s Division of Field Investigations, Office of Regulatory Affairs, though he cautioned there has been no concrete evidence linking production of heparin at the Chinese facility and the spike in adverse events reported. 

Nearly all reported adverse reactions have occurred in three specific areas of product use—renal dialysis, invasive cardiovascular procedures and apheresis procedures. Reported adverse patient reactions have included: stomach pain or discomfort, nausea, vomiting, diarrhea, decreased or low blood pressure, chest pain, fast heart rate, dizziness, fainting, unresponsiveness, shortness of breath, the feeling of a strong or rapid heartbeat, drug ineffectiveness, burning sensation, redness or paleness of skin, abnormal sensation of the skin, mouth or lips, flushing, increased sweating, decreased skin sensitivity, headache, feeling unwell, restlessness, watery eyes, throat swelling, thirst, bleeding tendencies and difficulty opening the mouth. Some of these reactions, particularly profound and refractory hypotension, may be severe or life-threatening.

The FDA identified four deaths that are apparently linked to the use of heparin, out of more than 20 that have been reported.

Baxter initially recalled nine lots of heparin sodium injection multi-dose vials on Jan. 17, 2008 as a precautionary measure due to a higher-than-usual number of reports of adverse patient reactions involving the product and suspended production earlier this month. “We have had reports of, all total, among that 448, we have had, there are reports, remember we asked for everything, we have reports of 21 deaths. But it’s really important to know that these are deaths from all causes. Most of these events occurred before December. Twelve of them, the report tells us that it was a Baxter heparin product the patient received. Nine of them, it was not stated, we don’t know. But if you look at cases, deaths, that we think have the same kind of clinical picture as the allergic-type reactions that brought this up in the first place, it appears that there are four,” Kweder said.

Given the widespread use of this blood thinner and the impact a product shortage would have on operating rooms, dialysis centers and other critical care areas, the FDA and Baxter concluded that removing additional lots and doses of Baxter’s heparin from the market earlier would have created more risk to patients requiring heparin therapy than the increased potential for experiencing an adverse reaction. Accordingly, the FDA and Baxter decided not to recall all Baxter heparin vial products at that time. The FDA has now concluded that there is sufficient capacity on the part of other suppliers that Baxter’s recall will not jeopardize access to this drug, and has told Baxter that the company can now proceed with recalling its remaining heparin sodium injection and heparin flush products.

Although the vast majority of the reports of adverse reactions have been associated with the multi-dose products, Baxter is taking the precautionary step of recalling all remaining heparin sodium injection and heparin flush products that are currently on the market. In addition to the previously recalled lots of heparin sodium injection 1000 units/mL 10mL and 30mL multi-dose vials, Baxter’s recall will now include the remaining lots of those products and heparin sodium injection 5000 units/mL 10mL multi-dose vials, heparin sodium injection 10,000 units/mL 4mL multi-dose vials, heparin sodium injection 1000 USP units/mL, 5000 USP units/mL, and 10,000 USP units/mL single-dose vials, and all HEP-LOCK and HEP-LOCK U/P, 10 USP units/mL and 100 USP units/mL vials, both preserved and preservative-free.

This recall does not involve Baxter’s heparin pre-mix IV solutions in bags: heparin sodium in 5 percent dextrose injection and heparin sodium in 0.9 percent sodium chloride injection.

Customers have been instructed to discontinue use and segregate the recalled product from the rest of their inventory. Customers should then contact Baxter to arrange for return and replacement product. Customers with recalled product purchased indirectly should contact their wholesaler or distributor for return and replacement product. Customers with questions may contact the Center for One Baxter at 1-800-4-BAXTER (1-800-422-9837). Representatives will be available twenty-four hours a day, seven days a week.