藥物警訊（藥師週刊 第1660期）

Rapamune (sirolimus): Drug Monitoring Recommendations
Audience: Transplantation and nephrology healthcare professionals, hospital laboratory directors
Wyeth notified healthcare professionals of changes to the Rapamune Prescribing Information regarding changes in the performance of an immunoassay used for therapeutic drug monitoring (TDM) of sirolimus. The TDM results reported from the assay are both assay and laboratory-dependent. In addition, the results may change over time. Therefore, adjustment to the targeted therapeutic range must be made with a detailed knowledge of the site-specific assay used.
Sirolimus whole blood concentrations can be measured by either chromatographic or immunoassay methodologies. These two methodologies are not directly interchangeable and the measured sirolimus whole blood concentrations depend on the type of assay used. As such, if different assays are used in monitoring a single patient, the dose of Rapamune might be adjusted improperly with potential consequences, such as allograft rejection if drug exposure is too low or toxic side effects if exposure is too high.
Wyeth has advised healthcare providers involved in the management of patients taking Rapamune to determine: 1) which assay is being used in their laboratory(ies); 2) if there is any change to the assay used; 3) if there is a change to the laboratory's reference range and/or a subsequent change to the institution's or referring center's recommended range for sirolimus. With this information, target levels can be appropriately adjusted in order to achieve optimal clinical results.
It is critical that the clinician caring for a patient on sirolimus maintain communication with their laboratory to determine whether the assay used for measuring sirolimus concentrations has been changed.
Read the complete MedWatch 2010 Safety summary, including a link to the Wyeth Dear Healthcare Professional letter, at:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm197059.htm

Wyeth公司和FDA發佈藥物安全警訊，通知醫護人員Rapamune仿單的修訂，更動內容是有關以免疫分析法來監測sirolimus藥物治療血中濃度(TDM)的效果。這些治療藥物血中濃度的監測結果會依分析檢驗方法不同或實驗室的不同而異。此外，分析結果也可能會隨著時間而改變。因此，必須充分了解所採用的分析方法才能調整治療的目標範圍。

Sirolimus的全血濃度可用色層分析法(HPLC、UV或LC/MS/MS)或是免疫分析法來測量。此兩種方法不能直接替換，而且sirolimus的血中濃度會因使用的檢驗方式不同而有所差異。因此，如果採用不同的分析方式監測同一位病人，可能會因Rapamune的劑量調整不當而造成不良後果，例如：劑量不足導致排斥反應，或是劑量過高而產生毒性副作用。

Wyeth公司建議參與照護使用Rapamune病人的醫療人員需確認：1) 實驗室所採用的分析方式為何；2) 所使用的分析方式是否有任何改變；3) 實驗室的參考範圍或相關中心與機構的sirolimus建議範圍是否有變動。確認以上的資訊，藥物劑量才能恰當地調整至治療目標而達到最佳的臨床療效。

最重要的是，治療使用sirolimus病人的臨床醫師應與實驗室保持聯繫以確定測量sirolimus血中濃度的分析方式是否有改變。
相關訊息請參考FDA網址：http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm197059.htm [Posted 1/11/2010]