2008年10月30日,辉瑞(Pfizer)公司宣布美国FDA批准Toviaz(fesoterodinefumarate)缓释片治疗膀胱过度活动症(OAB)。Fesoterodine是选择性毒蕈碱M3受体拮抗剂,每日一次Toviaz(4mg/8mg)可以显著的减少患者急迫性尿失禁次数和排尿次数,明显改善患者生活质量。
Manufacturer:

Pfizer LabsPharmacological Class:Muscarinic receptor antagonistActive Ingredient(s):Fesoterodine fumarate 4mg, 8mg;

ext-rel tabs.

Indication(s):Overactive bladder (OAB) with urge urinary incontinence, urgency, and frequency.

Pharmacology:

Fesoterodine is a pro-drug that is metabolized to an active metabolite, 5-hydroxymethyl tolterodine, following oral administration. It relaxes the smooth muscle of the bladder by competitive inhibition at muscarinic receptor sites.

Clinical Trials:

Two 12-week studies were conducted to evaluate fesoterodine in the treatment of OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency. Patients had symptoms for ≥6 months, with ≥8 micturitions/day and ≥6 urinary urgency episodes or 3 urge incontinence episodes/3-day diary period. They were randomized to fesoterodine 4mg/day, fesoterodine 8mg/day, or placebo. One of the studies included an active control arm. The primary efficacy endpoints were the
mean change in the number of urge urinary incontinence episodes/24hrs and the mean change in the number of micturitions/24hrs. A secondary endpoint was the mean change in voided volume per micturition.
In study 1, the change in baseline in the number of urge incontinence episodes for patients given fesoterodine 4mg/day was -2.06, compared to -1.20 for placebo and -2.27 for patients given fesoterodine 8mg/day.
For the number of micturitions/24 hours, the change from baseline for fesoterodine 4mg/day was -1.74 and -1.94 for patients given 8mg/day of fesoterodine, compared to -1.02 for placebo. For the volume voided per micturition, patients given fesoterodine 4mg/day reported 27mL and 33mL for those taking fesoterodine 8mg/day, compared to 10mL for those given placebo.
In study 2, the change in baseline for the number of urge incontinence episodes for patients taking fesoterodine 4mg/day was -1.77 and -2.42 for those taking fesoterodine 8mg/day, compared to -1.00 for placebo.
For the number of micturitions/24 hours, the change from baseline for fesoterodine 4mg/day was -1.86, and -1.94 for those taking 8mg/day of fesoterodine, compared to -1.02 for placebo. For the volume voided per micturition, patients given fesoterodine 4mg/day reported 17mL and 33mL for those taking fesoterodine 8mg/day, compared to 8mL for those given placebo.

These statistically and clinically significant findings indicate that fesoterodine is an effective agent in the treatment of OAB.

Legal Classification:

Rx

Adults:Swallow whole. 4mg once daily; max 8mg once daily. Severe renal insufficiency (CrCl<30mL/min) or concomitant potent CYP3A4 inhibitors: ax 4mg/day.

Children:Not recommended.

Contraindication(s):Urinary or gastric retention. Uncontrolled narrow angle glaucoma.
Precaution(s):Severe hepatic impairment: not recommended. Bladder outlet obstruction. Controlled narrow angle glaucoma. Hepatic or renal dysfunction. Myasthenia gravis. Decreased gastric motility. Exposure to high environmental temperatures. Pregnancy (Cat.C). Nursing mothers.
Interaction(s):Increased levels with CYP3A4 inhibitors (eg, erythromycin).
CNS depression with alcohol, other CNS depressants.
Adverse Reaction(s):Dry mouth, constipation, urinary retention/UTI, blurred vision, dry eyes, back pain, insomnia, dyspepsia.
How Supplied:Tabs—30, 90
Last Updated:

FDA通过治疗患者膀胱过度活动症新药(OAB)。Toviaz(fesoterodine fumarate)通过放松膀胱平滑肌发挥效用，从而减少尿频，尿急和突发尿失禁（漏尿）等OAB典型症状。
“罹患膀胱过度活动症会影响患者自理能力，从而使其生活质量下降”FDA药品评价与研究中心生殖泌尿产品部副主管，医学博士George Benson说“新药将为他们治疗活动过度的膀胱问题提供额外治疗选择”
Toviaz将只以处方药，4mg或8mg缓释片形式销售。每天服药一次。推荐开始剂量为4mg，在个人反应和耐受能力基础上如需要可增至8mg。Toviaz只用于成年人。
Toviaz的安全性和有效性在两个12周随机控制的4mg和8mg剂量试验中得到证实。在混合研究中，554名患者获得安慰剂，554名患者获得每天4mg
Toviaz，566名患者每天获得8mg。患者大多数为女性，平均年龄58岁。Toviaz不能用于儿科。
在两个研究中，与安慰剂相比，产品在减少患者每天排尿次数和漏尿发生率方面效果显著，临床意义得到明显改善。
与Toviaz相关的普遍副作用包括，口干和便秘。眼干和膀胱排空问题方面的副作用报道较少。
对于那些有严重肾功能不足，或服用诸如酮康唑等其他药物的病人Toviaz推荐剂量不大于4mg，这些情况可抑制Toviaz作用发挥。Toviaz不宜用于患有尿潴瘤或胃潴瘤以及难控制的狭角性青光眼患者。也不能用于严重肝损伤的患者。患有胃肠蠕动减少如严重便秘的患者应该慎用。
卫生保健医生和患者可以通过网络或常规邮件、传真和电话向FDA药物不良反应组报告产品严重不良反应和使用中的质量问题。