AstraZeneca

December 10, 1999

Dear Hospital Pharmacy and Physicians:

The purpose of this letter is to inform you of the occurrence of serious adverse events associated with an off-label use of Streptase^® (streptokinase). Under postmarketing surveillance, AstraZeneca has received an increasing number of reports of adverse events associated with the use of STREPTASE to restore patency of intravenous catheters (including central venous catheters). The serious adverse events that have been reported that are specifically related to the use of STREPTASE in catheter clearance include hypotension, hypersensitivity reactions, apnea, and bleeding, some of which were life threatening. While the events themselves are not inconsistent with those currently listed in the approved labeling, they represent an increase in frequency and appear to follow the reduced availability of Abbokinaseâ (urokinase).

STREPTASE is not indicated for restoration of patency of intravenous catheters. Most of the serious adverse events relating to the use of streptokinase in the restoration of patency of occluded intravenous catheters reported to AstraZeneca have involved the use of high doses of streptokinase in small volumes (250,000 IU in 2 mL). Uses of lower doses of streptokinase in infusions over several hours, generally into partially occluded catheters, or local instillation into the catheter lumen and subsequent aspiration, have been described in the medical literature.

Health care professionals should report serious adverse events possibly associated with the use of Streptase to the Information Center at AstraZeneca at 1-800-236-9933. Alternatively, this information may be reported to FDA’s MedWatch reporting system by phone (1-800-FDA-1088), facsimile (1-800-FDA-0178), the MedWatch website at www.fda.gov/medwatch, or mailed to MedWatch, HF-2, 5600 Fishers Lane, Rockville, MD 20852-9787. Both health care professionals and consumers should use the Form 3500 for reporting adverse events.

Sincerely,

Garry Neil, MD

Vice President, Clinical Research

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