藥物警訊

Arzerra (ofatumumab) and Rituxan (rituximab): Drug Safety Communication - New Boxed Warning, Recommendations to Decrease Risk of Hepatitis B Reactivation

AUDIENCE: Oncology, Pharmacy, Rheumatology, Patient

ISSUE: FDA approved changes to the prescribing information of the immune-suppressing and anti-cancer drugs Arzerra (ofatumumab) and Rituxan (rituximab) to add new Boxed Warning information about the risk of reactivation of hepatitis B virus (HBV) infection. The revised labels also will include additional recommendations for screening, monitoring, and managing patients on these drugs to decrease this risk.

In patients with prior HBV infection, HBV reactivation may occur when the body's immune system is impaired. HBV reactivation has occurred in patients with prior HBV exposure who are later treated with drugs classified as CD20-directed cytolytic antibodies, including Arzerra (ofatumumab) and Rituxan (rituximab). Some cases have resulted in fulminant hepatitis, hepatic failure, and death.

See the FDA Drug Safety Communication for additional information, including a Data Summary.

BACKGROUND: Arzerra is used to treat chronic lymphocytic leukemia (CLL) in patients who have further disease after treatment with the anti-cancer drugs fludarabine and alemtuzumab. Rituxan is used to treat non-Hodgkin's lymphoma and CLL. It is also used to treat other medical conditions, including rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

RECOMMENDATIONS: To decrease the risk of HBV reactivation, FDA recommends that health care professionals:

‧ Screen all patients for HBV infection before starting treatment with Arzerra or Rituxan by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc).

‧ Consult with hepatitis experts regarding monitoring and use of HBV antiviral therapy when screening identifies patients at risk of HBV reactivation due to evidence of prior HBV infection.

‧ Monitor patients with evidence of prior HBV infection for clinical and laboratory signs of hepatitis B or HBV reactivation during Arzerra or Rituxan therapy and for several months thereafter, since reactivations have occurred several months following completion of therapy with these drugs.

‧ In patients who develop reactivation of HBV while on Arzerra or Rituxan, immediately discontinue the drug and start appropriate treatment for HBV. Also discontinue any chemotherapy the patient is receiving until the HBV infection is controlled or resolved. Because of insufficient data, no recommendation can be made regarding the resumption of Arzerra or Rituxan in patients who develop HBV reactivation hepatitis.

For Patients:

‧ Before receiving Arzerra or Rituxan, tell your health care professional if you have or have had any severe infections, including HBV.

‧ If you have had HBV infection, your health care professional should monitor you for HBV infection during treatment and for several months after you stop treatment with Arzerra or Rituxan.

Read the MedWatch safety alert, including a link to the FDA Drug Safety Communication, at:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHuma...
 

FDA新增免疫抑制及抗癌藥物Arzerra (ofatumumab) 及Rituxan (rituximab)可能引起B肝病毒再活化風險的加框警語。此次修訂也建議應篩選、監測與管控服用此藥的病人，以降低風險。曾有B型肝炎感染之病人，當免疫系統低下時，可能會發生再活化。目前已接獲使用CD20-directed cytolytic antibodies如Arzerra (ofatumumab)或Rituxan (rituximab)治療之病人發生再活化的案例，部份導致猛爆性肝炎、肝衰竭甚至死亡。

背景：Arzerra (ofatumumab)為用來治療已使用過抗癌藥物fludarabine和alemtuzumab的慢性淋巴性白血病(CLL)病人；而Rituxan (rituximab)常用於治療非何傑金氏淋巴瘤(non-Hodgkin’s lymphoma)及慢性淋巴性白血病(CLL)，也可用於風濕性關節炎、肉芽腫多血管炎和顯微性多血管炎。
 

為了降低B肝再活化的風險，FDA建議醫療人員遵循以下建議：

‧ 在使用此兩種藥物治療前，先檢測B 型肝炎表面抗原(HBsAg)和B 型肝炎核心抗體(anti-HBc)。

‧ 若發現有B肝再活化風險之病人，請與專科醫師諮詢是否需監測和使用抗B肝病毒治療。

‧ 在治療期間及完成治療後的數個月內，仍有再活化之風險，應持續監測病人之臨床症狀與檢驗數值。

‧ 病人若於用藥期間發生B肝再活化，應立即停藥且開始B型肝炎治療。在B型肝炎獲得控制或改善之前，也應停止任何化學治療。由於資料不足，目前尚無建議恢復使用ofatumumab或rituximab之時機。
 

FDA給病人的建議如下：

‧ 在開始服藥之前，請告知醫療人員您是否有或曾有過任何嚴重感染，如B型肝炎。

‧ 若您有B型肝炎，醫療人員應於服藥期間及停止治療後數月內持續監測您的感染情況。
 

相關訊息與連結請參考FDA網址：

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

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