Ocaliva (obeticholic acid): Drug Safety Communication - Boxed Warning Added To Highlight Correct Dosing
AUDIENCE: Pharmacy, Hepatology, Gastroenterology
ISSUE: FDA is warning that the liver disease medicine Ocaliva (obeticholic acid) has been incorrectly dosed daily instead of weekly in patients with moderate to severe primary biliary cholangitis (PBC), a rare chronic liver disease, increasing the risk of serious liver injury. To ensure correct dosing and reduce the risk of liver problems, FDA is clarifying the current recommendations for screening, dosing, monitoring, and managing PBC patients with moderate to severe liver disease taking Ocaliva. FDA is adding a new Boxed Warning, FDA's most prominent warning, to highlight this information in the prescribing information of the drug label. FDA is also requiring a Medication Guide for patients to inform them about this issue.
As a condition of approval, FDA required the manufacturer of Ocaliva, Intercept Pharmaceuticals, to continue studying the medicine in patients with advanced PBC. These clinical trials are currently ongoing and FDA expects to receive results in 2023. FDA is adding the additional warnings to the drug label after receiving reports that Ocaliva is being given to PBC patients with moderate to severe liver impairment more often than is recommended in the prescribing information, resulting in liver decompensation, liver failure, and sometimes death. FDA will continue to monitor this medicine and will update the public if new information becomes available.
BACKGROUND: This is an update to the MedWatch safety alert for Ocaliva (obeticholic acid) - Increased Risk of Serious Liver Injury, issued 09-21-2017.
RECOMMENDATION: Health care professionals should follow the Ocaliva dosing regimen in the drug label, which is based on calculating a Child-Pugh score in PBC patients with suspected liver cirrhosis before treatment to determine their specific classification and starting dosage (see Table for the Clarified Ocaliva Dosage Regimen and more detailed instructions). Dosing higher than recommended in the drug label can increase the risk for liver decompensation, liver failure, and sometimes death. Routinely monitor all patients for biochemical response, tolerability, and PBC progression, and re-evaluate Child-Pugh classification to determine if dosage adjustment is needed. Close monitoring is recommended for patients at an increased risk of liver decompensation, including those with laboratory evidence of worsening liver function (e.g., total bilirubin, INR, albumin) or progression to cirrhosis.
Educate patients and caregivers on the symptoms of worsening liver function. Temporarily stop Ocaliva in those with laboratory or clinical evidence of worsening liver function that may indicate decompensation and monitor the patient's liver function. If a patient's condition returns to baseline, weigh the potential risks and benefits of restarting Ocaliva. Re-initiate, using the recommended starting dosage based on Child Pugh classification. Consider discontinuing Ocaliva in patients who have experienced clinically significant liver-related adverse reactions.
Patients should be aware that your prescriber should do regular tests to check how well your liver is working while you are taking Ocaliva. If your liver problems get worse, your dose may need to be changed or stopped. Report new or worsening severe skin itching to your health care professional. See the Drug Safety Communication for additional information.
Read the MedWatch Safety Alert, including a link to the FDA Drug Safety Communication, at:
https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm594901.htm
美國FDA更新2017年9月發布之Ocaliva (obeticholic acid)-嚴重肝損傷風險之藥品安全警訊：使用治療肝臟疾病藥品Ocaliva (obeticholic acid)於中度至重度原發性膽管炎(primary biliary cholangitis, PBC)之病人，若未依照肝功能調整劑量，由每日服用改為每週服用，將增加嚴重肝損傷的風險。為了確保能正確使用劑量和降低肝臟問題的風險，美國FDA正在擬訂中重度PBC病人使用Ocaliva的建議(包含如何篩選適合使用之病人、建議劑量、監測等)。美國FDA亦新增新的加框警語(boxed warning)，突顯此藥品安全警訊的重要性，並要求給予病人用藥指南已告知相關警訊。
醫療專業人員應遵循藥品仿單中的Ocaliva劑量給藥，起始劑量應於治療前計算PBC疑似肝硬化病人Child-Pugh評分，以確定建議劑量(參見Ocaliva劑量調整表）。高於建議劑量可能增加肝功能失償、肝衰竭和死亡的風險。用藥後應定期監測病人的生化實驗數據、耐受性和PBC進程，並重新評估Child-Pugh分數以確認是否需調整劑量。對於肝功能失償風險較高的病人，包括實驗室數值（如總膽紅素、INR、白蛋白）顯示肝功能惡化或肝硬化的病人，更應密切監測。
醫療專業人員也應教育病人和照護者肝功能惡化的症狀。實驗室數值或臨床證據顯示肝功能惡化，可能表示肝功能失償，需暫時停止Ocaliva並監測病人的肝功能。如果病人的病情恢復到基本狀態，則需權衡重新使用Ocaliva的潛在風險和益處。若考慮重新開始使用此藥，應基於Child Pugh分數決定起始劑量，如有臨床顯著肝相關不良反應，則應考慮停用Ocaliva。
病人應了解若服用此藥，醫師應定期為病人檢查肝臟功能。若肝臟問題惡化，其使用劑量可能需改變或停止。若有新的或惡化的嚴重皮膚搔癢，請與醫療專業人員聯繫。
相關訊息與連結請參考FDA網址：
https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm594901.htm
[Posted 2/1/2018]
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
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