The drugmaker has temporarily halted production of multiple-dose vials of the injectable blood-thinning drug due to reports of serious allergic reactions and low blood pressure in patients who receive high “bolus” doses, the FDA says. Serious reactions included difficulty breathing, nausea, vomiting, excessive sweating, and rapidly falling blood pressure that can lead to life-threatening shock. Four people have died after receiving heparin, although the relationship to the drug is unclear, according to the agency.
About 350 adverse events associated with the Baxter product have been reported since the end of last year compared to less than 100 reports in 2007, the FDA says. Most of the events have taken place at hemodialysis centers, almost exclusively involving patients receiving a bolus dose – which is a high dose administered over a short time. While most of the reports involve multiple-dose vials, several cases include patients who received a bolus dose after their health care professional combined heparin from single-dose vials.
The Missouri Department of Health and Senior Services first notified the Centers for Disease Control and Prevention in January of several severe allergic-type reactions to heparin that occurred at a single pediatric hospital beginning in November. The CDC in turn alerted FDA and Baxter, prompting the company’s voluntary recall of nine lots of heparin on Jan. 17. Since then, FDA has learned of adverse events that extend beyond the recalled lots and involve patients receiving heparin for other purposes besides hemodialysis. Recent cases have included patients undergoing cardiac surgery and a specialized blood cell treatment known as photopheresis.
You may recall that actor Dennis Quaid and his wife sued Baxter maker two months ago after their newborn twins were inadvertently given massive doses of the blood thinner at a hospital. The product liability lawsuit seeks more than $50,000 in damages and claims Baxter was negligent in packaging different doses of the product in similar vials with blue backgrounds. The lawsuit also says Baxter should have recalled the large-dosage vials after overdoses killed three children at an Indianapolis hospital in 2007.
The “FDA is vigorously investigating to determine the root cause of these serious reactions associated with the use of heparin made by Baxter. In the meantime, patients and health care professionals who cannot obtain alternative sources of heparin should use caution in administering any Baxter multiple-dose vials that remain," says Janet Woodcock, the agency's deputy commissioner for scientific and medical programs, chief medical officer, and acting director of its Center for Drug Evaluation and Research, in a statement.
Heparin sodium is derived from pig intestines and has been marketed in the US since the 1930s. Millions of patients benefit from the intravenous administration of this drug every year to avoid potentially life-threatening blood clots in the veins, arteries, and lungs. Over one million multiple-dose vials of heparin are sold per month in the US; half of the vials are made by Baxter. The FDA says it's currently investigating whether similar events have been seen with other heparin manufacturers.
Heparin is commonly used before certain types of surgery, including coronary artery bypass graft surgery, and in kidney patients before they undergo dialysis. In some situations, heparin treatment is initiated using a high bolus dose given intravenously over a short period of time, usually less than one hour. The reported adverse events occurred in patients who were given heparin in this form of administration. There are many other uses of heparin involving lower doses or administration over a longer period of time; adverse events have not been seen with those uses.