ST LOUIS (MD Consult) - On August 28, 2009, Eurand announced that the US Food and Drug Administration (FDA) has approved Zenpep (pancrelipase) delayed-release capsules for the treatment of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis (CF) or other conditions. According to the manufacturer, Zenpep (a pancreatic enzyme product [PEP]) is a highly stable formulation of a porcine pancreatic extract that is biologically similar to the endogenous human pancreatic secretions necessary for proper human digestion. Zenpep replaces missing pancreatic enzymes and improves the digestion and absorption of food.

 

Zenpep was developed specifically to meet FDA guidelines. Historically, PEPs have not been regulated and approved by the FDA, though manufacturers of EPI drug products are now being required to file New Drug Applications and receive marketing approval by April 2010.

 

Exocrine pancreatic insufficiency can be described as the inability to properly digest food as the result of a lack of pancreatic digestive enzymes. This loss of digestive enzymes leads to maldigestion and malabsorption of nutrients. This disorder is common in patients with CF and other conditions that compromise the exocrine function of the pancreas (eg, pancreatic cancer and chronic pancreatitis) as well as in patients who have undergone gastrointestinal surgery. The malnutrition that occurs as a result of EPI can impair a patient's growth and immune response and can lead to shortened life expectancy.

 

The investigation of Zenpep for the treatment of EPI was conducted in two phase 3 multicenter clinical trials: one in older children, adolescents, and adults; and one in younger children aged 1 to 6 years. Evidence of the safety and efficacy of Zenpep in patients with CF and EPI was found in both studies. In the placebo-controlled, randomized, double-blind pivotal study in older children and adult patients (aged 7 to 23 years), the primary efficacy end point was the mean coefficient of fat absorption (CFA), which many consider to be the gold standard for assessing EPI severity. In that study, the CFA value was statistically higher with Zenpep treatment than with placebo (88.3% vs 62.8%, P < .001). In an open-label, single-arm study of younger participants whose PEP regimen was switched from their usual treatment to Zenpep at similar doses, symptom control was maintained. The safety and efficacy in pediatric patients evaluated in this study were similar to that observed in adults.

 

In clinical trials, Zenpep was not associated with any serious drug-related adverse events. The most common adverse events reported were gastrointestinal complaints, which were similar in type and frequency across all age ranges in the two studies. The most commonly reported adverse events occurring in at least 2 patients (≥6% of patients) included abdominal pain, flatulence, headache, cough, weight loss, early satiety, and contusion. The type and incidence of adverse events were similar in children and adults.

 

The total daily dose of Zenpep should not exceed 10,000 lipase units/kg of body weight per day, and caution should be used with doses exceeding 2,500 lipase units/kg of body weight per meal. Care should be taken to ensure that Zenpep is not chewed or retained in the mouth to avoid irritation of oral mucosa, and the capsules or beads should be swallowed immediately with adequate amounts of liquid. Zenpep capsules were formulated to allow the contents to be sprinkled on food when necessary.

圣路易斯(MD Consult)——Eurand公司在2009年8月28日宣布：美国食品药品管理局(FDA)已经批准胰脂酶Zenpep(胰腺酶制剂，PEP)缓释胶囊用于治疗囊性纤维化(CF)或其他疾病引起的胰腺外分泌机能不全(EPI)。据该公司称，Zenpep是一种高稳定性制剂，提取自猪的胰腺，其生物学特性类似于在消化中不可或缺的人类内源性胰腺分泌物。Zenpep可替代缺失的胰腺酶，以促进食物的消化和吸收。

 

Zenpep符合FDA的药品规范。过去，FDA并未对PEP类药物加以规范，也从未批准相关的药物，因此，目前FDA要求EPI药品制造商在2010年4月前提交新药申请，并获得销售许可。

 

胰腺外分泌机能不全是一种因胰腺消化酶缺乏而导致无法正常消化食物的疾病。缺少胰酶会引起消化不良以及营养吸收不良。该疾病常见于CF和其他原因造成的胰腺外分泌功能受损(例如胰腺癌和慢性胰腺炎)以及曾接受胃肠手术者。EPI所引起的营养不良会影响患者的生长发育和免疫反应，并可导致寿命缩短。

 

两项III期多中心临床试验对Zenpep治疗EPI的疗效进行了研究：其中一项的受试者为大龄儿童、青少年以及成年人，另一项的受试者为年龄在1~6岁的低龄儿童。2项研究均发现Zenpep在治疗CF和EPI上既安全又有效。在大龄儿童与成年人(7~23岁)的随机、双盲、安慰剂对照的关键性研究中，主要疗效终点为平均脂肪吸收系数(CFA)，CFA被视为EPI严重程度的金标准。在该研究中，Zenpep治疗组的CFA 值显著高于安慰剂组(88.3%比 62.8%，P <0.001)。在低龄儿童的开放性单组试验中，将常用的PEP方案换成相似剂量的Zenpep 方案，并维持症状控制治疗。该试验中，Zenpep在儿童患者的安全性和有效性与成年人组相似。

 

Zenpep在临床试验中并未发生任何严重的药物相关副作用。报告最多的副作用为胃肠道并发症，上述2项试验的各个年龄段在副作用类型及发生频率上均比较相似。最常见的副作用(至少发生2例，大于等于患者总数的6%)包括腹痛、腹胀、头痛、咳嗽、体重减轻、早饱和挫伤。发生于儿童患者的副作用类型和发生率与成年患者类似。

 

Zenpep每天的总剂量不应超过10,000 LU/(kg·d)，如果单餐剂量超过2,500 LU/(kg·d)，应谨慎服用。应努力确保Zenpep不被咀嚼或含化，以免刺激口腔黏膜。胶囊或胶珠应配以足量液体送服，迅速吞咽。当必要时，Zenpep胶囊可与食物混合后服用。