部分中文Entocort EC处方资料（仅供参考）

阿斯特拉捷利康公司（AstraZeneca）2001年10月3日宣布，该公司成分为布地奈德的Entocort EC胶囊获得了FDA的批准。所批准的适应证为累及回肠和升结肠的轻到中度活动性Crohn病。

Crohn病是一种慢性炎症性疾病，病变主要累及肠，目前还不清楚此病的确切病因。主要的症状包括腹泻、腹部绞痛、发热和直肠出血等。治疗此病一般会耗费包括诊疗、检查和药物等大量的医疗资源，而且，目前临床上很难控制这种疾病。

布地奈德是一种合成的皮质激素，主要起糖皮质激素的作用，也有微弱的盐皮质激素作用。Entocort EC是一种新型的局部起效的布地奈德制剂，它可以明显缓解多数患者通常难以治疗的症状。由于Crohn病是一种急需新治疗药物的疾病，FDA对此药的批准可以被认为是Crohn病治疗方面的一个重要进展。Entocort EC不仅具有很好的疗效，而且也能很好地被患者耐受，所以此药是治疗Crohn病时一种不错的选择。

约1000名患者参与了评价Entocort EC的5项临床试验，他们均为轻到中度的回肠和升结肠活动性Crohn病患者。在这些试验中，48~69%的用Entocort EC 9mg每日一次治疗的患者在用药8周后病情缓解。试验规定“病情缓解”的标准为CDAI（Corhn病活动指标）评分低于或等于150。而这些患者治疗前的CDAI评分在272~290之间。
Entocort EC的另一个优势在于其有效成分在肠内释放，而此部位正是Crohn病主要累及的部位。此药在肠内迅速而充分的代谢，因此防止了大量药物被吸收入血。

Entocort EC最常见的不良反应是头痛、呼吸道感染、恶心和肾上腺功能亢进样症状。与Crohn病的系统治疗用糖皮质激素氢化泼尼松相比，在相当剂量下，此药较少引起糖皮质激素通常引起的不良反应。

Entocort EC不宜用于对布地耐德过于敏感的患者。另外，糖皮质激素能减弱下丘脑—垂体—肾上腺轴的应激能力，所以使用Entocort EC的患者在手术等应激情况发生前应系统性地补充糖皮质激素。接受系统性糖皮质激素治疗的患者改用Entocort EC治疗时，需监测肾上腺皮质功能。使用皮质激素的患者还应注意预防水痘、麻疹等感染性疾病

英文药名: Entocort(Budesonide Capsules)

中文药名: 布地奈德胶囊

药品简介
轻-中度远端结肠炎的治疗：病变累及结肠远端30～40cm称远端溃疡性结肠炎，也称直乙状结肠炎。多有血性大便，轻中度患者一般无全身症状或轻微。
对表现为直肠炎或远端结肠炎的患者来说，采用口服或局部作用的治疗方式一般均可奏效，其治疗方案在一定程度上取决于患者本身的选择(如是否愿意经口服药，是否能适应局部给药，或经济承受力如何等)。
布地奈德(Budesonide，商品名为Entocort，即盐酸丁地松灌肠剂)保留灌肠。具有极高的首过效应，因此几乎无全身作用。当应用2mg剂量时，可相当于20～30mg泼尼松(或100mg氢化可的松)的作用。反复多个疗程使用布地奈德灌肠剂治疗后并不具有抑制机体下丘脑-垂体-肾上腺轴的不良作用。因此，长期使用布地奈德具有较好的安全性。其标准剂量为9mg，加大至15mg并不增加疗效，且有抑制肾上腺皮质的作用，出现晨间血浆皮质醇浓度减低。18mg的剂量不良反应增多，但仍低于全身用药。

药理作用
布地奈德是一具有高效局部抗炎作用的糖皮质激素。它能增强内皮细胞、平滑肌细胞和溶酶体膜的稳定性，抑制免疫反应和降低抗体合成，从而使组胺等过敏活性介质的释放减少和活性降低，并能减轻抗原抗体结合时激发的酶促过程，抑制支气管收缩物质的合成和释放而减轻平滑肌的收缩反应。急性、亚急性和长期毒性研究发现，布地奈德的全身作用，如体重下降、淋巴组织及肾上腺皮质萎缩，比其他糖皮质激素弱或者与其他糖皮质激素相当。经过六个不同的试验测试系统评价，布地奈德无致突变作用，亦无致癌作用。

药动学
吸入给药后，约10%～15%在肺部吸收，吸入单剂布地奈德1mg，约10分钟后达最大血药浓度2nmol/L。经气雾剂吸入布地奈德的全身生物利用度约为26%，其中2/5来自经口吞咽的部分。分布容积(Vd)约3L/kg，平均血浆蛋白结合率为85%～90%。本品主要经肝首过代谢(约90%)，代谢物的糖皮质激素活性较低。主要代谢物6β-羟布地奈德和16α-羟泼尼松龙的活性不到布地奈德的1%。布地奈德的代谢物以其原形或结合的形式经肾排泄。尿中检测不到原型布地奈德。

生产厂家
AstraZeneca

ENTOCORT (budesonide)
3.0 mg Controlled Ileal Release Capsules

THERAPEUTIC CLASSIFICATION

Glucocorticosteroid for the treatment of Crohn's disease affecting the ileum and/or the ascending colon.

ACTIONS AND CLINICAL PHARMACOLOGY

The active ingredient of ENTOCORT capsules, budesonide, is a potent non-halogenated synthetic glucocorticosteroid with high topical potency and weak systemic effects.

The exact mechanism of action of glucocorticosteroids in the treatment of Crohn's disease is not fully understood. Anti-inflammatory actions, such as the inhibition of inflammatory mediator release and inhibition of immunological cellular responses, are probably important.

Data from clinical pharmacology studies and controlled clinical trials indicate that ENTOCORT capsules, at least partly, act topically. Budesonide undergoes an extensive degree (approximately 90%) of biotransformation in the liver to metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the major metabolites, 6b-hydroxybudesonide and 16a-hydroxyprednisolone, is less than 1% of that of budesonide.

The favourable separation between topical anti-inflammatory and systemic effect is due to strong glucocorticosteroid receptor affinity and an effective first pass metabolism by the liver with a short half-life. A glucocorticosteroid with such a profile is of particular importance for the local treatment of inflammatory bowel diseases such as Crohn's disease. With regard to treatment of this disease with glucocorticosteroids, it is essential to achieve a high local anti-inflammatory activity in the bowel wall with systemic side-effects, e.g. on the hypothalamic pituitary adrenal (HPA) axis function, as low as possible.

INDICATIONS AND CLINICAL USE

ENTOCORT (budesonide) capsules are indicated for the induction and maintenance of remission in patients with mild to moderate Crohn's disease affecting the ileum and/or ascending colon.

CONTRAINDICATIONS

ENTOCORT (budesonide) capsules are contraindicated for the following:

1. Systemic or local bacterial, fungal or viral infections.

2. Known hypersensitivity to any of the ingredients.

3. Active tuberculosis.

WARNINGS

Glucocorticosteroids can reduce the response of the HPA-axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a conventional glucocorticosteroid is recommended.

Special care is demanded in treatment of patients transferred from conventional systemic steroids to ENTOCORT (budesonide) capsules as disturbances in the HPA-axis could be expected in these patients.

PRECAUTIONS

Glucocorticosteroids may mask some signs of infections and new infections may appear. A decreased resistance to localized infection has been observed during glucocorticosteroid therapy. Viral infections such as chicken pox and measles can have a more serious or fatal course in patients on immunosuppressant glucocorticosteroids. In adults who have not had these diseases, particular care should be taken to avoid exposure. If exposed to chicken pox or measles, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If chicken pox develops, treatment with antiviral agents may be considered.

Although treatment with ENTOCORT (budesonide) capsules causes significantly less lowering of plasma cortisol compared to conventional glucocorticosteroids, the knowledge with regard to treatment during the following conditions is limited and therefore cautioned: active peptic ulcer, osteoporosis, acute glomerulonephritis, myasthenia gravis, exanthematous diseases, diverticulitis, thrombophlebitis, psychic disturbances, diabetes, hypertension, hyperthyroidism, acute coronary disease, limited cardiac reserve and pregnancy. In such cases the benefits of an oral glucocorticosteroid must be weighed against the risks.

With the recommended therapeutic doses of budesonide, the risk/benefit ratio seems to be low for the long-term systemic effects. However, as with any other glucocorticosteroid, patients should be carefully followed up for systemic adverse effects. During long-term therapy, adrenal function and haematological status should be periodically assessed.

Particular care is needed in patients who are transferred from systemic glucocorticosteroid treatment with higher systemic effect to ENTOCORT capsules. These patients may have adrenal cortical suppression. Therefore, monitoring of adrenocortical function may be considered in these patients. Some patients feel unwell in a non-specific way during the withdrawal phase, e.g., pain in muscles and joints. A general insufficient glucocorticosteroid effect should be suspected if, in rare cases, symptoms such as tiredness, headache, nausea and vomiting should occur. In these cases a temporary increase in the dose of systemic glucocorticosteroids is sometimes necessary.

Patients should be advised to inform subsequent physicians of the prior use of glucocorticosteroids.

Glucocorticosteroids should be used with caution in patients if there is a probability of bowel perforation as well as the probability of obstruction, abscess or other pyogenic infection and fresh intestinal anastomoses.

Aggravation of diabetes mellitus or stimulation of manifestations of latent diabetes mellitus may be caused by glucocorticosteroid therapy.

There may be an enhanced systemic effect of budesonide in patients with liver cirrhosis since the metabolism of budesonide may be impaired and, as with other glucocorticosteroids, there may be enhanced effects in those with hypothyroidism. Reduced liver function may affect the elimination of corticosteroids. The intravenous pharmacokinetics of budesonide are, however, similar in cirrhotic patients and in healthy subjects. The pharmacokinetics after oral ingestion of budesonide were affected by compromised liver function as evidenced by increased systemic availability.

Glucocorticosteroid therapy may cause hyperacidity of peptic ulcer.

Acetylsalicylic acid should be used cautiously in conjunction with glucocorticosteroids in hypoprothrombinemia.

Glucocorticosteroids should be used with caution in patients with cataracts, and may cause elevation of intraocular pressure in glaucoma patients.

Usage During Pregnancy

Administration of ENTOCORT capsules during pregnancy should be avoided unless there are compelling reasons. In experimental animal studies, budesonide was found to cross the placental barrier. Like other glucocorticosteroids, budesonide is teratogenic to rodent species. High doses of budesonide administered subcutaneously produced fetal malformations, primarily skeletal defects, in rabbits, rats, and in mice. The relevance of these findings to humans has not yet been established. In the absence of further studies in humans, budesonide should be used during pregnancy only if the potential benefits clearly outweigh the risk to the fetus. Infants born of mothers who have received substantial doses of glucocorticosteroids during pregnancy should be carefully observed for hypoadrenalism.

Lactation

Glucocorticosteroids are secreted in human milk. It is not known whether budesonide would be secreted in human milk, but it is suspected to be likely. The use of ENTOCORT capsules in nursing mothers requires that the possible benefits of the drug be weighed against the potential hazards to the mother, or infant.

Children

The safety and effectiveness of ENTOCORT capsules in children have not been established, therefore use in this age group is not recommended.

Drug Interactions

To date, budesonide has not been observed to interact with other drugs used for the treatment of intestinal bowel diseases.

Cimetidine    The kinetics of budesonide were investigated in healthy subjects without and with cimetidine, 1000 mg daily. After a 4 mg oral dose the values of Cmax (nmol/L) and systemic availability (%) of budesonide without and with cimetidine (3.3 vs 5.1 nmol/L and 10 vs 12%, respectively) indicated a slight inhibitory effect on hepatic metabolism of budesonide, caused by cimetidine. This should be of little clinical importance.

Ketoconazole  Ketoconazole, a potent inhibitor of cytochrome P 450 3A, the main metabolic enzyme for corticosteroids, increases plasma levels of orally ingested budesonide.

Omeprazole   At recommended doses, omeprazole has no effect on the pharmacokinetics of oral budesonide.

ADVERSE REACTIONS

In clinical trials, most adverse events experienced by patients or healthy volunteers receiving ENTOCORT (budesonide) capsules were of mild to moderate intensity and were classified as non-serious. A total of 530 patients with Crohn's disease were treated with ENTOCORT capsules for induction and maintenance of remission, in controlled clinical trials.

Adverse events reported in patients during induction of remission (n=399) with ENTOCORT capsules included dyspepsia (9%), muscle cramps (4%), palpitations (2%), blurred vision (3%), skin reactions including rash and urticaria (6%), and menstrual disorders (2%).

A similar adverse event profile was reported in patients during maintenance treatment (n=131) with ENTOCORT capsules. The incidence of adverse events was the same or less than observed during treatment for induction of remission.

Side effects typical of systemic glucocorticosteroid (such as Cushingoid features) may occur. The systemic effects of budesonide on the HPA-axis were found to be dose-dependent.

SYMPTOMS AND TREATMENT OF OVERDOSAGE

Acute overdosage with ENTOCORT (budesonide) capsules, even in excessive doses, is not expected to be a clinical problem.

Occasional overdosing will not give any obvious symptoms in most cases but it will decrease the plasma cortisol level and increase the number and percentage of circulating neutrophils. The number and percentage of eosinophils will decrease concurrently. Stopping the treatment or decreasing the dose will abolish the induced effects.

Habitual overdosing may cause hypercorticism and HPA-suppression. Decreasing the dose or stopping the therapy, with the accepted procedures for discontinuing prolonged oral therapy with systemic steroids, will abolish these effects, although the restitution of the HPA-axis may be a slow process and during periods with pronounced physical stress (severe infections, trauma, surgical operations, etc.) it may be advisable to supplement with conventional systemic steroids.

DOSAGE AND ADMINISTRATION

Active Disease

The recommended daily dose for induction of remission is 9 mg, administered once daily in the morning, for up to 8 weeks. The dose should be taken before meals.

Maintenance of Remission

The recommended daily starting dose for the maintenance of remission is 6 mg, administered once daily in the morning before breakfast. The maintenance dose should be kept as low as necessary for control of disease symptoms.

During prolonged treatment, dosing may have to be adjusted depending on the disease activity.

Treatment with ENTOCORT capsules should be tapered before cessation. It is recommended that the dose be reduced for the last 2 to 4 weeks of therapy. The rate of tapering should be patient-specific and the patient should be monitored by the treating physician during this period.

The capsules should be swallowed whole with water, and not chewed, broken or crushed before being swallowed.

PHARMACEUTICAL INFORMATION

Drug Substance

ASTRAZENECA
Generic Name for ENTOCORT EC
Budesonide (micronized) 3mg; e-c granules in caps.
Legal Classification:
Rx
Pharmacological Class for ENTOCORT EC
Steroid.
Manufacturer of ENTOCORT EC
AstraZeneca Pharmaceuticals
      
Indications for ENTOCORT EC
Mild to moderate Crohn's disease of the ileum and/or ascending colon: to treat and to maintain clinical remission for up to 3 months.
      
Adult dose for ENTOCORT EC

Swallow whole. Treatment: 9mg once daily in the AM for up to 8 weeks; may repeat an 8-week course. Maintenance of remission: 6mg once daily for up to 3 months. Taper other systemic steroids when transferring to budesonide.

Children's dosing for ENTOCORT EC
Not recommended.
Warnings/Precautions for ENTOCORT EC
Systemic fungal, viral, or mycobacterial infections. Live vaccines.
Hypertension. Diabetes. Osteoporosis. Peptic ulcer. Glaucoma. Cataracts.
If exposed to chickenpox or measles, consider prophylactic passive immune therapy. Supplement with more steroids in physiologic stress. Caution when transferring from steroids with high systemic availability. Monitor for hypercorticism in moderate to severe liver disease; consider reducing dose. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended.
Interactions for ENTOCORT EC
Avoid grapefruit juice. Systemic effects may be potentiated by CYP3A4
inhibitors (eg, ketoconazole, ritonavir, erythromycin); consider reducing
budesonide dose. Drug release characteristics may be affected by drugs that affect gastrointestinal pH.
Adverse Reactions for ENTOCORT EC
Headache, infection, sinusitis, nausea, arthralgia, hypercorticism (eg, acne,bruising, face edema,hirsutism).
      
How is ENTOCORT EC supplied?
Caps—100

      
Related Disease:
Colorectal disorders
Crohn's disease
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原产地英文商品名:
ENTOCORT EC CAPSULE SR 24H 3MG/CAP 100CAPS/BOTTLE
原产地英文药品名:
BUDESONIDE
中文参考商品译名:
ENTOCORT EC 24小时缓释胶囊 3毫克/胶囊 100胶囊/瓶
中文参考药品译名:
布地奈德
生产厂家中文参考译名:
阿斯利康
生产厂家英文名: