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2012年6月28日，美国食品与药物管理局（FDA）批准了米拉贝隆(mirabegron)治疗成人膀胱过度活动症，包括尿频、尿急和尿失禁。该药是一种每日服一次的缓释片，可改善充盈膀胱的存储量。
3项纳入4116例患者的多中心、双盲、安慰剂对照试验证明了米拉贝隆的安全性和有效性。这些膀胱过度活动症患者分别接受每日一次的米拉贝隆25 mg或50 mg或100 mg或安慰剂治疗12周。结果显示，米拉贝隆25 mg和50 mg有效减少患者24小时的排尿次数。患者服用米拉贝隆50 mg可排除较大量的尿液，表明该药是通过改善膀胱容量起效的。
试验中观察到的最常见不良反应包括血压升高，鼻咽炎，泌尿系统感染，便秘，乏力，心动过速和腹痛。FDA不推荐米拉贝隆用于那些难以控制的严重高血压或终末期肾病或严重肝损伤的患者。
INDICATIONS AND USAGE
Myrbetriq™ (mirabegron) is a beta-3 adrenergic agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.
IMPORTANT SAFETY INFORMATION
Myrbetriq can increase blood pressure. Periodic blood pressure determinations are recommended, especially in hypertensive patients. Myrbetriq is not recommended for use in severe uncontrolled hypertensive patients (defined as systolic blood pressure ≥ 180mm Hg and/or diastolic blood pressure ≥ 110 mm Hg).
Urinary retention in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medications for the treatment of OAB has been reported in postmarketing experience in patients taking mirabegron. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in Myrbetriq patients; however, Myrbetriq should be administered with caution to patients with clinically significant BOO. Myrbetriq should also be administered with caution to patients taking antimuscarinic medications for the treatment of OAB.
Since Myrbetriq is a moderate CYP2D6 inhibitor, the systemic exposure to CYP2D6 substrates such as metoprolol and desipramine is increased when co-administered with Myrbetriq. Therefore, appropriate monitoring and dose adjustment may be necessary, especially with narrow therapeutic index drugs metabolized by CYP2D6, such as thioridazine, flecainide, and propafenone.
Most commonly reported adverse reactions (>2% and >placebo) for Myrbetriq 25 mg and 50 mg vs placebo, respectively, were hypertension (11.3%, 7.5% vs 7.6%), nasopharyngitis (3.5%, 3.9% vs 2.5%), urinary tract infection (4.2%, 2.9% vs 1.8%), and headache (2.1%, 3.2% vs 3.0%).
MYRBETRIQ
Manufacturer:
Astellas Pharma
Pharmacological Class:
Beta-3 adrenergic agonist.
Active Ingredient(s):
Mirabegron 25mg, 50mg; extended-release tablets.
Indication(s):
Treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.
Pharmacology:
Mirabegron is an agonist of the human beta-3 adrenergic receptor. It relaxes the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle by activation of beta-3 AR which increases bladder capacity.
Clinical Trials:
Myrbetriq was evaluated in three, 12-week, double-blind, randomized, placebo-controlled, parallel group, multicenter studies in patients with OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency (Studies 1, 2, and 3). Entry criteria required that patients had symptoms of OAB for at least 3 months duration, at least 8 micturitions per day, and at least 3 episodes of urgency with or without incontinence over a 3 day period. The population included both naïve patients who had not received prior antimuscarinic pharmacotherapy (48%) and those who had received prior antimuscarinic pharmacotherapy (52%).
In Study 1, patients were randomized to placebo, Myrbetriq 50mg, Myrbetriq 100mg, or an active control once daily. In Study 2, patients were randomized to placebo, Myrbetriq 50mg or Myrbetriq 100mg once daily. In Study 3, patients were randomized to placebo, Myrbetriq 25mg or Myrbetriq 50mg once daily.
The co-primary efficacy endpoints in all 3 trials were (1) change from baseline to end of treatment (Week 12) in mean number of incontinence episodes per 24 hours and (2) change from baseline to end of treatment in mean number of micturitions per 24 hours, based on a 3-day micturition diary. An important secondary endpoint was the change from baseline to end of treatment in mean volume voided per micturition.
At Week 12, treatment with Myrbetriq 25mg and 50mg resulted in statistically significant improvement in efficacy parameters of incontinence episodes and number of urinations per 24 hours. In treatment with Myrbetriq 25mg, incontinence episodes were reduced by 1.36 episodes from a baseline of 2.65, a statistically significant reduction of 0.40 vs. placebo. The number of urinations was reduced by 1.65 urinations from a baseline of 11.68, a statistically significant reduction of 0.47 vs. placebo. In treatment with Myrbetriq 50mg, incontinence episodes were reduced by 1.49 episodes from a baseline of 2.71, a statistically significant reduction of 0.40 vs. placebo. Number of urinations was reduced by 1.75 urinations from a baseline of 11.70, a statistically significant reduction of 0.55 vs. placebo.
Legal Classification:
Rx
Adults:
Swallow whole. Initially 25mg once daily. May increase to 50mg once daily as needed or tolerated. Severe renal impairment or moderate hepatic impairment: max 25mg once daily. End-stage renal disease (ESRD) or severe hepatic impairment: not recommended.
Children:
Not established.
Warnings/Precautions:
Severe uncontrolled hypertension: not recommended. Monitor blood pressure periodically. Significant bladder outlet obstruction, patients taking antimuscarinic drugs for OAB: risk of urinary retention. Pregnancy (Category C). Nursing mothers: not recommended.
Interaction(s):
May potentiate CYP2D6 substrates (eg, metoprolol, desipramine). Adjust dose and monitor esp. with narrow therapeutic index drugs metabolized by CYP2D6 (eg, thioridazine, flecainide, propafenone). Concomitant digoxin: use lowest digoxin dose initially (monitor and titrate).
Adverse Reaction(s):
Hypertension, nasopharyngitis, urinary tract infection, headache.
How Supplied:
Tabs—30, 90
Last Updated:
10/15/2012
米拉贝隆批准上市 -可用于治疗膀胱过度活动症
膀胱过度活动症是一种以尿急、尿频、急迫性尿失禁等为特征的症候群。食品和药物管理局的数据显示，美国约有３３００万人受这种疾病困扰。美国食品和药物管理局２８日批准一种学名为米拉贝隆的药物上市，这种药物主要用于治疗膀胱过度活动症。
新上市的药物商品名为MYRBETRIQ，此前已在日本获批上市，由日本第二大制药公司安斯泰来生产。这种缓释药片每日服用一次可帮助服用者放松膀胱肌肉，并舒缓膀胱过度活动症引起的尿频等症状。
据介绍，４０００多名膀胱过度活动症患者参加的安慰剂对照临床试验显示，在１２周的试验期间，每日服用２５毫克或５０毫克新药物的患者，小便次数都有所减少。试验中，膀胱过度活动症患者的不良反应主要有血压升高、感冒症状、尿道感染、头晕等。美国药管局表示，严重高血压患者、末期肾病和严重肺损伤者不宜服用米拉贝隆药物。
米拉贝隆药品的上市为广大的膀胱过度活动症患者带来希望，而且用法与用量都很简单，不必再为膀胱过度活动症而痛苦，这是为患者带来的福音。 | 
