藥物警訊

Low Molecular Weight Heparins: Drug Safety Communication - Recommendations to Decrease Risk of Spinal Column Bleeding and Paralysis

AUDIENCE: Pharmacy, Cardiology, Anesthesiology

ISSUE: The U.S. Food and Drug Administration (FDA) is recommending that health care professionals carefully consider the timing of spinal catheter placement and removal in patients taking anticoagulant drugs, such as enoxaparin, and delay dosing of anticoagulant medications for some time interval after catheter removal to decrease the risk of spinal column bleeding and subsequent paralysis after spinal injections, including epidural procedures and lumbar punctures. These new timing recommendations, which can decrease the risk of epidural or spinal hematoma, will be added to the labels of anticoagulant drugs known as low molecular weight heparins, including Lovenox and generic enoxaparin products and similar products.

BACKGROUND: Epidural or spinal hematomas are a known risk of enoxaparin in the setting of spinal procedures and are already described in the Boxed Warning and the Warnings and Precautions sections of the labels for Lovenox and generic enoxaparin products. However, these serious adverse events continue to occur (see Data Summary). To address this safety concern, FDA worked with the manufacturer of Lovenox, Sanofi-Aventis, to further evaluate this risk and to update the Warnings and Precautions section of the Lovenox label with these additional timing recommendations. The labels for generic enoxaparin products will also be revised accordingly, as will those of other low molecular weight heparin-type products.

It is important to note that all anticoagulants carry the risk of causing spinal bleeding when used in conjunction with epidural/spinal anesthesia or spinal puncture. We are continuing to evaluate the safety of other anticoagulants to determine if additional label changes are needed.

RECOMMENDATION: Health care professionals and institutions involved in performing spinal/epidural anesthesia or spinal punctures should determine, as part of a preprocedure checklist, whether a patient is receiving anticoagulants and identify the appropriate timing of enoxaparin dosing in relation to catheter placement or removal. To reduce the potential risk of bleeding, consider both the dose and the elimination half-life of the anticoagulant:

‧ For enoxaparin, placement or removal of a spinal catheter should be delayed for at least 12 hours after administration of prophylactic doses such as those used for prevention of deep vein thrombosis. Longer delays (24 hours) are appropriate to consider for patients receiving higher therapeutic doses of enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily).

‧ A post procedure dose of enoxaparin should usually be given no sooner than 4 hours after catheter removal.

‧ In all cases, a benefit-risk assessment should consider both the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors.

For Complete MedWatch Safety Alert including link to Drug Safety Communication: 

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHuma...

FDA建議醫療人員應謹慎評估使用抗凝血藥物如enoxaparin的病人其脊髓導管置入與移除的時機，並建議導管移除後應隔一段時間後才可再給予抗凝血藥物，以降低因硬膜外或腰椎穿刺導致脊柱出血或癱瘓之風險。並建議將此警語加入low molecular weight heparins之仿單中。

背景

硬膜外或脊髓血腫為使用enoxaparin病人於進行脊髓手術時的已知風險之一，且已標註於仿單中，然而這些嚴重不良反應仍不斷發生。為了處理此問題，FDA與廠商進一步的評估此風險且於仿單中新增給藥時間的建議，重要的是應注意當進行硬膜外/脊髓麻醉或穿刺時，使用任何抗凝血劑都可能造成脊髓出血的風險。FDA將持續評估其他抗凝血劑的安全性以確認是否需要更新仿單。

建議

參與執行脊髓/硬膜外麻醉或穿刺的醫療人員和機構應將確認病人是否正在服用抗凝血劑與評估適當的給藥時機列為術前核對清單的一部分。為了減少潛在的出血風險，應同時考慮抗凝血劑的劑量及半衰期：

1. Enoxaparin用於預防深層靜脈血栓時，給藥後至少12小時才可放置或移除脊髓導管。當給予較高的治療劑量時 (如1 mg/kg、一天兩次或1.5 mg/kg、一天一次)，建議可再延長至24小時。

2. 應於導管移除後至少4小時，再給予術後的enoxaparin劑量。

對於所有使用抗凝血劑須進行髓/硬膜外麻醉或穿刺的病人，應考量手術及病人自身的危險因子，就發生血栓或出血的風險做適當的效益及風險評估。

相關訊息與連結請參考FDA網址：http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm373918.htm

資料來源：美國FDA之藥物安全警訊

資料提供：台大醫院藥劑部