vicky3 2009-11-23 16:29
FDA核准Exenatide作為第一線使用 但警告可能有腎衰竭風險
作者：Yael Waknine
出處：WebMD醫學新聞
【24drs.com】November 3, 2009 — 美國食品藥物管理局（FDA）發布了有關於仿分泌素（incretin）藥物exenatide（Byetta，Amylin製藥有限公司）的警訊，在同一天當局核准了此藥物的更多適應症，核准其與飲食控制及運動用於改善第二型糖尿病患者的血糖控制。
這項警訊包括了78件有關腎功能不全的上市後報告，這些報告在2005年4月到2008年10月之間接獲，期間總共有660萬位使用者。根據MedWatch日前發布的一項警訊，某些案例發生在過去即有腎臟疾病病史者，或是有發生腎臟問題一個以上危險因子的病患身上；MedWatch是FDA的安全性資訊與不良反應通報系統。
FDA強調，exenatide不應該用於嚴重腎臟功能不全患者（肌酐酸廓清率低於30 ml/min），或是末期腎臟疾病患者，而使用於腎功能不全患者（肌酐酸廓清率介於30~50 ml/min）時，在起始治療與劑量調整上應該特別小心。
使用exenatide患者應仔細地監測是否有腎功能改變的病徵與症狀，包括血清肌酐酸濃度上升、排尿出現變化、肢體無法解釋的水腫、血壓上升、疲倦、食慾或消化習慣改變、或是中下背部出現鈍痛感。
當局表示，腎臟功能改變也可能肇因於糖尿病併發症本身或是其他慢性疾病（例如胰臟炎與高血壓）、或是併用特定藥物（例如非類固醇抗發炎藥物、利尿劑與降血壓藥物）。如果腎功能不全由這些或其他原因，例如噁心、嘔吐或脫水來解釋，應該考慮停用exenatide。
Exenatide單一療法的核准，是根據臨床研究顯示以5或10 μg的劑量治療3個月，可以降低平均血紅素A1C達0.7%與0.9%，且體重平均下降6.0磅與6.4磅。
最常報告的不良反應為噁心，每天接受exenatide 5 μg的病患，約有3%發生這個反應，每天10μg者有13%。低血糖發生率分別為5%與4%；並沒有發生嚴重低血糖的報告。
Exenatide過去核准用於metformin、一種sulfonylurea藥物、一種thiazolidiendione藥物、或合併metformin與sulfonylurea、或是合併metformin與thiazolidiendione治療，但仍未達足夠血糖控制的第二型糖尿病患者，改善血糖控制的輔助治療。
更多的資訊請造訪FDA的MedWatch網站。
有關於使用exenatide相關的不良反應該通報到FDA的MedWatch通報系統，打電話到1-800-FDA-1088、或傳真到-800-FDA-0178、線上於[url]http://www.fda.gov/medwatch[/url]通報，或郵寄到5600 Fishers Lane, Rockville, Maryland 20852-9787。
FDA Approves Exenatide for First-Line Use; Warns of Renal Failure Risk
By Yael Waknine
Medscape Medical News
November 3, 2009 — The US Food and Drug Administration (FDA) has issued a warning about the incretin-mimetic exenatide (Byetta, Amylin Pharmaceuticals, Inc) the same day the agency approved an expanded indication for the drug, allowing its first-line use along with diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.
The warning includes 78 postmarketing reports of kidney dysfunction (including acute renal failure and insufficiency), received between April 2005 and October 2008, in 6.6 million users. "Some cases occurred in patients with pre-existing kidney disease or in patients with one or more risk factors for developing kidney problems," according to an alert sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program.
The FDA emphasizes that exenatide should not be used in patients with severe renal impairment (creatinine clearance < 30 mL/minute) or end-stage renal disease, and it advises caution during initiation of therapy and dose increases in patients with moderate renal dysfunction (creatinine clearance, 30 – 50 mL/minute).
Patients receiving exenatide should be carefully monitored for signs and symptoms of altered renal function, including increased serum creatinine, changes in urination, unexplained swelling in the extremities, blood pressure increases, lethargy, changes in appetite or digestion, or the emergence of a dull ache in the mid- to lower back.
The agency notes that alterations in kidney function may also occur as a consequence of diabetes itself, other chronic conditions (eg, pancreatitis and hypertension), or concomitant use of certain medications (nonsteroidal anti-inflammatory drugs, diuretics, and antihypertensives). Discontinuation of exenatide should be considered if kidney dysfunction cannot be explained by these or other causes such as nausea, vomiting, and dehydration.
The approval of exenatide monotherapy was based on clinical data showing that 3 months of treatment at doses of 5 or 10 μg significantly reduced mean hemoglobin A1C levels by 0.7% and 0.9%, respectively, and yielded mean weight losses of 6.0 and 6.4 pounds, respectively.
The most commonly reported adverse event was nausea, which occurred in 3% of patients receiving the 5-μg dose and 13% of those taking 10 μg of exenatide daily. Hypoglycemia was reported at rates of 5% and 4%, respectively; no severe hypoglycemic events were noted.
Exenatide was previously approved as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus who have not achieved adequate glycemic control on metformin, a sulfonylurea, a thiazolidinedione, a combination of metformin and a sulfonylurea, or a combination of metformin and a thiazolidinedione.
More information is available on the FDA's MedWatch Web site.
Adverse events related to the use of exenatide should be communicated to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at [url]http://www.fda.gov/medwatch[/url], or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.