Ocaliva (obeticholic acid): Drug Safety Communication - Increased Risk of Serious Liver Injury
AUDIENCE: Pharmacy, Hepatology, Gastroenterology
ISSUE: FDA is warning that the liver disease medicine Ocaliva (obeticholic acid) is being incorrectly dosed in some patients with moderate to severe decreases in liver function, resulting in an increased risk of serious liver injury and death. These patients are receiving excessive dosing, particularly a higher frequency of dosing than is recommended in the drug label for them. Ocaliva may also be associated with liver injury in some patients with mild disease who are receiving the correct dose. The recommended dosing and monitoring for patients on Ocaliva are described in the current drug label. FDA is working with the drug manufacturer, Intercept Pharmaceuticals, to address these safety concerns.
BACKGROUND: Ocaliva is used to treat a rare, chronic liver disease known as primary biliary cholangitis (PBC). PBC causes the bile ducts in the liver to become inflamed, damaged and destroyed. This causes bile, a fluid that helps in digestion, to build up in the liver. This build-up damages the liver over time, eventually causing it to lose its ability to function. Ocaliva has been shown to improve a certain blood test that measures liver problems.
RECOMMENDATIONS:
Health care professionals
‧ Determine the patient's baseline liver function prior to starting Ocaliva.
‧ Patients with moderate to severe liver impairment (Child-Pugh B and C) should be started on the approved dosing schedule of 5 mg once weekly, rather than the 5 mg daily dosing used for other PBC patients, and if needed, can be increased up to a maximum approved dose of 10 mg twice weekly.
‧ Health care professionals should monitor patients frequently for disease progression, and reduce the dosing frequency to once- or twice-weekly for patients who progress to moderate or severe liver impairment.
‧ In all patients treated with Ocaliva, monitor frequently for liver injury (e.g., worsened liver blood tests and adverse liver-related reactions that may be inconsistent with the patient's extent of disease). If liver injury is suspected, discontinue Ocaliva. After the patient has stabilized, weigh the benefits against the risks when deciding whether to re-initiate treatment.
‧ Educate patients on the symptoms of potential liver injury.
Patients
‧ Contact your health care professional if you have questions or concerns about taking Ocaliva.
‧ Report new or worsening severe skin itching to your health care professional.
‧ Contact your health care professional immediately if you develop any of the following symptoms that may be signs of liver injury:
－New or worsening fatigue
－Diarrhea
－Weight loss
－Abdominal pain
－Decreased appetite
－Nausea and vomiting
－Change in behavior or confusion
－Vague symptoms such as anxiety or unease
－Abdominal swelling
－Yellow eyes or skin
－Bloody stools
Read the MedWatch Safety Alert, including a link to the FDA Drug Safety Communication, at:
https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm576861.htm
Ocaliva（obeticholic acid）之適應症為用於治療罕見之慢性肝病：原發性膽汁性肝硬化（primary biliary cholangitis, PBC）。PBC會導致膽管發炎、損傷和破壞，進而使的原本幫助消化之膽汁累積在肝臟中造成肝臟的破壞，最終造成肝功能受損。Ocaliva顯示可改善一些測量肝功能之血液生化檢驗數值。
美國FDA發布藥物安全警訊，Ocaliva在中度及重度肝功能不全病人使用高於仿單建議之劑量，會導致增加嚴重肝損傷及死亡的風險。Ocaliva在使用正確劑量下於某些輕度肝功能不全者，也可能會出現肝損傷之相關副作用。Ocaliva之仿單中皆有記載相關建議劑量和監測，而美國FDA目前也正在與廠商合作解決這些安全性議題。
醫療專業人員注意事項：
1. 病人於使用Ocaliva前，需監測肝功能。
2. 中度及重度肝功能不全者（Child-Pugh B and C）起始劑量需從每週5 mg開始，而非使用一般建議劑量每天5 mg。最大可增加至每週兩次，共10 mg。
3. 醫療專業人員需頻繁監測病人疾病之病程，依照病人肝功能適時調整成每週一次或兩次的劑量。
4. 使用Ocaliva之病人，需頻繁監測有無肝損傷之副作用(例如：肝臟相關之血液生化檢驗數值不正常，或出現與病人疾病病程不一致之肝臟相關不良反應)。如懷疑有肝損傷，請立即停用Ocaliva。等到病人狀況穩定後，是否需再度使用Ocaliva需謹慎評估。
5. 教育病人可能與肝損傷相關之症狀。
病人注意事項：
1. 若對於使用Ocaliva有任何疑慮，請與醫療專業人員連絡。
2. 如服藥後出現新的或惡化嚴重皮膚搔癢之症狀，請與醫療專業人員連絡。
3. 如出現以下症狀（疲憊、腹瀉、體重減輕、腹痛、降低食慾、噁心嘔吐、行為改變或混亂、焦慮不安、腹部腫脹、皮膚或眼睛變黃或血便），可能與肝損傷相關，請立即與醫療專業人員連絡並就醫。
相關訊息與連結請參考FDA網址：
https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm576861.htm
[Posted 09/21/2017]
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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