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Samsca (tolvaptan): Drug Warning - Potential Risk of Liver Injury
AUDIENCE: Gastroenterology, Nephrology, Pharmacy
ISSUE: Otsuka and FDA notified healthcare professionals of significant liver injury associated with the use of Samsca. In a double-blind, 3-year, placebo-controlled trial in about 1400 patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and its open-label extension trial, 3 patients treated with the drug developed significant increases in serum alanine aminotransferase (ALT) with concomitant, clinically significant increases in serum total bilirubin. In the trials the maximum daily dose of Samsca administered (90 mg in the morning and 30 mg in the afternoon) was higher than the maximum 60 mg daily dose approved for the treatment of hyponatremia.
Most of the liver enzyme abnormalities were observed during the first 18 months of therapy. Following discontinuation of treatment, all 3 patients improved. An external panel of liver experts assessed these 3 cases as being either probably or highly likely to be caused by tolvaptan. These findings indicate that Samsca (tolvaptan) has the potential to cause irreversible and potentially fatal liver injury. These data are not adequate to exclude the possibility that patients receiving Samsca for its indicated use of clinically significant hypervolemic and euvolemic hyponatremia are at a potential increased risk for irreversible and potentially fatal liver injury.
BACKGROUND: Samsca is a selective vasopressin V2-receptor antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia. Samsca is not approved for the treatment of ADPKD.
RECOMMENDATION: Healthcare providers should perform liver tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice. If hepatic injury is suspected, Samsca should be promptly discontinued, appropriate treatment should be instituted, and investigations should be performed to determine probable cause. Samsca should not be re-initiated in patients unless the cause for the observed liver injury is definitively established to be unrelated to treatment with Samsca.
Read the MedWatch safety alert, including links to the Dear Health Provider letter and prescribing information, at:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHuma...
FDA和大塚製藥股份有限公司 (otsuka) 通知醫療專業人員一則藥物安全警訊，服用Samsca可能會造成肝臟受損。1400名自體顯性遺傳之多囊腎疾病（ADPKD）病人進行一為期三年、有安慰 組對照的雙盲試驗和其開放性延續試驗時，其中三名使用此藥之病人產生顯著的ALT升高，伴隨著血清總膽紅素（serum total bilirubin）增加。在此試驗中，此藥給予之每日最大劑量 （早上90 毫克和下午30毫克）高於核准於治療低血鈉症的每日最大建議劑量（60毫克）。
三名病人於停止服藥後即獲得改善。肝臟專家小組評估此三案例可能為tolvaptan所造成。這些研究結果顯示Smasca (tolvaptan)具有造成不可逆且致命性肝損害的可能性。而目前這些資料尚無法排除臨床上使用Samsca於高容積與正常容積之低血鈉症之病人發生 此風險之可能性。
Samsca為選擇性血管加壓素V2受器之拮抗劑，用來治療臨床上顯著之高容積與正常容積的低血鈉症。Samsca尚未核准於治療ADPKD。
醫療人員應立即協助可能已產生肝受損症狀例如疲倦、厭食、右上腹不適、深色尿或黃疸之病人進行肝臟功能檢查。若懷疑有肝臟受損，Samsca應立即停藥， 並給予適當的治療與檢查，以確定可能造成之原因。除非確定肝臟受損與Samsca無關，不然請勿再次服用Samsca。
相關訊息與連結請參考FDA網址：http://www.fda.gov/Safety/MedWatch/SafetyInformation /SafetyAlertsforHumanMedicalProducts/ucm336669.htm
[Posted 01/25/2013]
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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資料來源：藥師週刊（第1813期）