藥物警訊

Direct-Acting Antivirals for Hepatitis C: Drug Safety Communication - Risk of Hepatitis B Reactivating

AUDIENCE: Infectious Disease, Gastroenterology, Patient

ISSUE: The FDA is warning about the risk of hepatitis B virus (HBV) becoming an active infection again in any patient who has a current or previous infection with HBV and is treated with certain direct-acting antiviral (DAA) medicines for hepatitis C virus. In a few cases, HBV reactivation in patients treated with DAA medicines resulted in serious liver problems or death. HBV reactivation usually occurred within 4-8 weeks.

As a result, FDA is requiring a Boxed Warning, our most prominent warning, about the risk of HBV reactivation to be added to the drug labels of these DAAs directing health care professionals to screen and monitor for HBV in all patients receiving DAA treatment. This warning will also be included in the patient information leaflet or Medication Guides for these medicines.

BACKGROUND: Direct-acting antiviral medicines are used to treat chronic hepatitis C virus (HCV) infection, an infection that can last a lifetime. These medicines reduce the amount of HCV in the body by preventing HCV from multiplying, and in most cases, they cure HCV. Without treatment, HCV can lead to serious liver problems including cirrhosis, liver cancer, and death (see List of Direct-Acting Antivirals in the FDA Drug Safety Communication).

FDA identified 24 cases of HBV reactivation reported to FDA and from the published literature in HCV/HBV co-infected patients treated with DAAs during the 31 months from November 22, 2013 to July 18, 2016. This number includes only cases submitted to FDA, so there are likely additional cases about which FDA is unaware. Of the cases reported, two patients died and one required a liver transplant. HBV reactivation was not reported as an adverse event in the clinical trials submitted for the DAA approvals because patients with HBV co-infection were excluded from the trials. See the data summary section in the Drug Safety Communication for more detailed information.

RECOMMENDATION: Health care professionals should screen all patients for evidence of current or prior HBV infection before starting treatment with DAAs, and monitor patients using blood tests for HBV flare-ups or reactivation during treatment and post-treatment follow-up.

Patients should tell your health care professional if you have a history of hepatitis B infection or other liver problems before being treated for hepatitis C. Do not stop taking your DAA medicine without first talking to your health care professional. Stopping treatment early could result in your virus becoming less responsive to certain hepatitis C medicines. Read the patient information leaflet or Medication Guide that comes with each new prescription because the information may have changed. Contact your health care professional immediately if you develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, as these may be signs of serious liver problems.

Read the MedWatch safety alert, including a link to the Drug Safety Communication, at:http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm523690.htm

m美國FDA發布藥品安全警訊，曾有或目前有B型肝炎病毒感染之病人接受直接作用型抗C型肝炎病毒藥品(direct-acting antivirals, DAAs)治療後，可能有B型肝炎病毒再活化之風險，此風險通常於開始治療後之四至八週內發生。少數案例因而導致嚴重肝臟疾病或死亡。

直接作用型抗C型肝炎病毒藥品(direct-acting antivirals, DAAs)為用於慢性C型肝炎病毒感染之治療。藉由干擾C型肝炎病毒之複製，達到減少病人體內C型肝炎病毒量之目的。多數案例可得到完全的治癒。C型肝炎若未接受治療，可能導致嚴重的肝臟疾病，如肝硬化，肝臟相關癌症，甚至死亡。

統計2013年11月至2016年6月通報至美國FDA之案例報告，其中24例同時有B型肝炎及C型肝炎感染之病人，在使用DAAs治療C型肝炎後發生B型肝炎病毒再活化，部分案例死亡或需接受肝臟移植治療。此類藥品於臨床試驗時因未納入同時患有B型肝炎之病人，故未有B型肝炎病毒再活化之相關不良反應報告。

美國FDA擬於此類藥品仿單中加註加框警語，並提醒醫療人員應注意此安全議題，建議所有將接受DAAs治療之病人應先進行HBV病毒篩檢與定期監測。

美國FDA也提醒病人在開始接受DAAs治療前，應主動告知醫療人員是否曾有B型肝炎病毒感染病史。在未於醫療人員討論前，請勿自行停藥，擅自中斷治療可能增加抗藥性之機率。若出現疲倦、虛弱、食欲不振、噁心嘔吐、皮膚或眼部黃疸、淺色糞便等肝功能異常症狀，請立即就醫。

相關訊息與連結請參考FDA網址：http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm523690.htm

[Posted 10/05/2016]

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