Public Health Advisory - Anticoagulants

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Food and Drug Administration
Rockville, MD 20857

15 December 1997

FDA PUBLIC HEALTH ADVISORY

Subject: Reports of epidural or spinal hematomas with the concurrent use of low molecular weight heparin and spinal/epidural anesthesia or spinal puncture

Dear Health Care Professional:

The Food and Drug Administration (FDA) would like to call to your attention recent post marketing reports of patients who have developed epidural or spinal hematomas with the concurrent use of low molecular weight heparin and spinal/epidural anesthesia or spinal puncture. Many of the hematomas caused neurologic injury, including long-term or permanent paralysis. Because these events were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. However, given the potential seriousness of this complication, we believe that patients and health care professionals should be notified of this information.

The postmarketing reports received to date involved patients who were treated with Lovenox, (enoxaparin sodium) Injection. However, the adverse event would be expected to occur drugs with similar pharmacological activity were used in the same manner. Therefore, the FDA has asked all manufacturers of low molecular weight heparins and heparinoids to revise their package inserts to provide further information for the safe and effective use of these drugs. Specifically, the manufacturers have been asked to include additional safety information and recommendations in a boxed warning in their package inserts.

SUMMARY OF REPORTS

As of November, 1997, there have been more than 30 spontaneous safety reports describing patients who have developed epidural or spinal hematomas with concurrent use of enoxaparin sodium and spinal/epidural anesthesia or spinal puncture. Many of the epidural or spinal hematomas caused neurologic injury, including long-term or permanent paralysis.
Approximately 75% of the patients were elderly women undergoing orthopedic surgery.

At this time, the FDA believes practitioners should be aware of the following points if using these products:

When neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture is employed patients anticoagulated or scheduled to be anticoagulated with low molecular weight heparins or heparinoids for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis.
The risk of these events is increased by the use of indwelling epidural catheters for administration of analgesia or by the concomitant use of drugs affecting hemostasis such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants. The risk also appears to be increased by traumatic or repeated epidural or spinal puncture.
Patients should be frequently monitored for signs and symptoms of neurological impairment. If neurologic compromise is noted, urgent treatment is necessary.
Practitioners should consider fully the potential benefit versus risk before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.

The FDA will continue to monitor closely post marketing reports for additional events. We encourage all health care professionals to report any serious adverse events, including cases of epidural or spinal hematomas, occurring with the use of low molecular weight heparins, heparinoids, or other anticoagulant to the FDA's MEDWATCH program at 1-800-FDA-1088/fax 1-800-FDA-0178; or to the respective pharmaceutical manufacturers:

Fragmin (dalteparin sodium injection); Pharmacia & Upjohn; 1-800-253-8600, ext. 38244.
Lovenox (enoxaparin sodium) Injection; Rhone-Poulenc Rorer Pharmaceuticals Inc.; 1-800-340-7502.
Normiflo (ardeparin sodium) Injection; Wyeth Laboratories Inc.; 1-800-934-5556.
Orgaran (danaparoid sodium) Injection; Organon Inc.; 1-800-631-1253.

Sincerely yours,

Murray M. Lumpkin, M.D.
Deputy Center Director (Review Management)
Center for Drug Evaluation and Research

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