武田公司与该公司的独立子公司武田北美制药于2009年2月3日对外宣布称：美国FDA已经批准该公司的dexlansoprazole（Kapidex）口服缓释胶囊每日一次用于治疗胃食管返流病（GERD）引起的胃灼热症状外，还用于腐蚀性食管炎（EE）的治疗，以及愈后腐蚀性食管炎的维持治疗。本品分别有30mg和60mg两个规格，而且为第一个双层PPI缓释片，该剂型设计可以使药用成分阶段缓慢释放。

质子泵抑制剂通过与胃液中H+-K+-ATP酶结合从而抑制胃酸的分泌，本品内置两层肠溶包衣单位，从而使药物分两个两段时间释放出现两个血药浓度峰值，一个血药浓度峰值出现在给药后2小时，第二个血药浓度峰值出现随后的4到5个小时内。而且本品的给药时间不受用餐时间的影响。

GRED的患者通常都会在白天和夜间出现胃灼热的症状，弗吉尼亚大学卫生系统的药学教授Peura博士，对外评论时称：“在Kapidex的关键Ⅲ期临床中，它可以在24小时内使患者的胃灼症状得到有效缓解，且本品的不良反应与兰索拉唑（lansoprazole）相似。双层缓释释放制剂的出现，将为GERD患者带来激动人心的新选择.”

Kapidex的获批是基于在全球20个国家6000名腐蚀性和非腐蚀GERD患者中的临床研究结果。两项临床方案一致、为期8周在EE患者中进行的随机、双盲、对照实验表明，本品（60mg）与兰索拉唑（30mg）相比，前者的治愈率更高，耐受性更好。两组实验的治愈率分别为：本品：85%；兰索拉唑：79%。本品87%，；兰索拉唑：85%。

Kapidex是一种新的质子泵抑制剂，为兰索拉唑对映异构体的双层释放片，适用于各种程度腐蚀性食管炎其治疗周期可长达8周，而且治愈后的维持期治疗可长达6个月，可以对于GERD患者的胃灼热症状具有明显的效果，其治疗时间可以长达4周。

KAPIDEX

Manufacturer:
Takeda Pharmaceuticals North America, Inc.

Pharmacological Class:
Acid pump inhibitor.

Active Ingredient(s):
Dexlansoprazole 30mg, 60mg; delayed-release caps.

Indication(s):
Treatment of erosive esophagitis (EE) and heartburn related to non- erosive gastroesophageal reflux disease (GERD). Maintenance of healing of EE.

Pharmacology:
Dexlansoprazole is an acid pump inhibitor that suppresses gastric acid secretion by specific inhibition of the (H+,K+)-ATPase in the gastric parietal cell. By acting specifically on the proton pump, dexlansoprazole blocks the final step of acid production. Dexlansoprazole is the R-enantiomer of lansoprazole and is supplied as a dual delayed-release formulation for oral administration.

Clinical Trials:
Two double-blind, active-controlled, 8-week studies were conducted in 4092 patients with endoscopically confirmed EE. Based on the LA Classification, 71% had mild EE and 29% had moderate to severe EE before treatment. Patients were given one of the following treatments: dexlansoprazole 60mg daily, dexlansoprazole 90mg daily, or lansoprazole 30mg daily. The primary efficacy endpoint was % healed at week 8 of treatment. In study 1, 87% of patients given dexlansoprazole 60mg were healed compared with 85% of patients given lansoprazole 30mg. In study 2, 85% of patients given dexlansoprazole 60mg were healed compared with 79% of patients given lansoprazole 30mg. Both studies demonstrated non-inferiority to lansoprazole.

A double-blind, placebo-controlled study was conducted in patients who successfully completed an EE study and showed endoscopically confirmed healed EE. Maintenance of healing and symptom resolution over a 6-month period was evaluated with dexlansoprazole 30mg or 60mg once daily compared to placebo. A total of 445 patients were enrolled; 66% of patients treated with dexlansoprazole 30mg remained healed over the 6-month period as confirmed by endoscopy. Dexlansoprazole 30mg demonstrated a higher median percent of 24-hour heartburn free days compared to placebo over the 6-month period.

A double-blind, placebo-controlled 4-week study was conducted in patients with a diagnosis of symptomatic, non-erosive GERD. Patients were randomized to one of the following groups: dexlansoprazole 30mg daily, dexlansoprazole 60mg daily, or placebo. A total of 947 patients were enrolled. Dexlansoprazole 30mg provided statistically significantly greater median percent of days with heartburn-free 24-hour periods (54.9%) over placebo (18.5%) as assessed by daily diary over 4 weeks.

Legal Classification:
Rx

Adults:
≥18yrs: Swallow whole, or sprinkle granules on 1 tbsp of applesauce and swallow immediately. EE treatment: 60mg once daily for up to 8 weeks. Maintenance of healed EE: 30mg once daily for up to 6 months. Symptomatic GERD: 30mg once daily for 4 weeks. Moderate hepatic impairment (Child-Pugh Class B): max 30mg/day.

Children:
<18yrs: not recommended.

Warnings/Precautions:
Severe hepatic impairment. Pregnancy (Cat.B). Nursing mothers: not recommended.

Interaction(s):
Concomitant atazanavir: not recommended (may decrease atazanavir levels). May alter absorption of pH-dependent drugs (eg, ketoconazole, digoxin, iron, ampicillin). Monitor warfarin.

Adverse Reaction(s):
GI upset, abdominal pain, upper respiratory tract infection, flatulence.

How Supplied:
Caps—30, 90, 1000

Last Updated:
3/23/2009