藥物警訊

Hepatitis C Treatments Viekira Pak and Technivie: Drug Safety Communication - Risk of Serious Liver Injury

AUDIENCE: Patient, Infectious Disease, Pharmacy

ISSUE: FDA is warning that hepatitis C treatments Viekira Pak and Technivie can cause serious liver injury mostly in patients with underlying advanced liver disease. As a result, FDA is requiring the manufacturer to include information about serious liver injury adverse events to the Contraindications, Warnings and Precautions, Postmarketing Experience, and Hepatic Impairment sections of the Viekira Pak and Technivie drug labels.

FDA review of adverse events reported to the FDA Adverse Event Reporting System (FAERS) database and to the manufacturer of these medicines, AbbVie, identified cases of hepatic decompensation and liver failure in patients with underlying liver cirrhosis who were taking these medicines. Some of these events resulted in liver transplantation or death. These serious outcomes were reported mostly in patients taking Viekira Pak who had evidence of advanced cirrhosis even before starting treatment with it.

Since the approvals of Viekira Pak in December 2014 and Technivie in July 2015, at least 26 worldwide cases submitted to FAERS were considered to be possibly or probably related to Viekira Pak or Technivie. In most of the cases, liver injury occurred within 1 to 4 weeks of starting treatment. Some of the cases occurred in patients for whom these medicines were contraindicated or not recommended (see the Drug Safety Communication Data Summary section). FAERS includes only reports submitted to FDA, so there are likely additional cases about which FDA is unaware.

BACKGROUND: Viekira Pak and Technivie are used to treat chronic hepatitis C. Viekira Pak is a fixed-dose combination of dasabuvir, ombitasvir, paritaprevir, and ritonavir used with or without ribavirin, another hepatitis C medicine. Technivie is a fixed-dose combination of ombitasvir, paritaprevir, and ritonavir, used in combination with ribavirin.

RECOMMENDATION: Health care professionals should closely monitor for signs and symptoms of worsening liver disease, such as ascites, hepatic encephalopathy, variceal hemorrhage, and/or increases in direct bilirubin in the blood.

Patients taking these medicines should contact their health care professional immediately if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, as these may be signs of liver injury. Patients should not stop taking these medicines without first talking to their health care professionals. Stopping treatment early could result in drug resistance to other hepatitis C medicines.

Read the MedWatch safety alert, including a link to the drug safety communication, at:

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

美國FDA發布藥物安全警訊，C型肝炎藥品Virkira PakR及TechnivieR可能使本身患有晚期肝臟疾病之病人產生嚴重的肝臟損害副作用。因此，美國FDA要求廠商將此副作用之相關訊息列入藥品仿單中，以提醒大眾注意。

Viekira PakR及TechnivieR為用於治療慢性C型肝炎之藥品，兩者皆為固定劑量之複方藥品。Viekira PakR含有dasabuvir、ombitasvir、paritaprevir及ritonavir，可選擇是否搭配另一種C肝藥品ribavirin使用；而TechnivieR則內含ombitasvir、paritaprevir及ritonavir，需與ribavirin合併使用。Viekira PakR及TechnivieR於2014年12月及2015年7月核准上市後，美國FDA不良反應系統陸續接獲至少26例可能與Viekira PakR或TechnivieR有關之全球性通報案例，多數肝臟損傷副作用案例在開始接受治療1到4週內發生，部分案例為該藥禁忌或不建議使用的病人。

美國FDA回顧不良反應通報系統資料庫及藥商接獲之案例報告，部分有肝硬化病史之個案在服用此藥後發生代償不全肝病及肝臟衰竭，部分導致病人需進行肝臟移植或死亡。而多數發生嚴重不良反應之病人在接受Viekira PakR治療前已有晚期肝硬化診斷。

美國FDA建議醫療人員應密切監測服用此藥之病人是否出現疑似肝功能惡化之症狀，例如腹水、肝性腦病變、靜脈曲張出血及/或血中直接膽紅素增加等；而正在服用此藥之病人若有異常疲倦、虛弱、食慾降低、噁心嘔吐、眼睛或皮膚變黃或淺色軟便等疑似肝臟受損情形，應立即就醫。在醫療人員尚未評估前，請勿自行停用此藥，中斷用藥可能導致對其他C肝藥品之抗藥性機率增加。

相關訊息與連結請參考FDA網址：

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

[Posted 10/22/2015]

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