| 简介：
部份中文喜克馈处方资料（仅供参考）
商品名称：喜克馈
英文名称：Misoprostol Tablets
通用名称：米索前列醇片
适应症
本品用于治疗十二指肠溃疡和胃溃疡，包括关节炎患者由于服用非甾体类抗炎药(NSAID)所引起的十二指肠溃疡和胃溃疡，保障其仍可继续使用NSAID 治疗。本品还可用于预防使用NSAID 所引起的溃疡。
用法用量
成人：
治疗十二指肠溃疡、胃溃疡、及由NSAID 引起的消化性溃疡：
每日0.8mg，在早饭、和/或中饭、晚饭时及睡前(分2 或4 次服用)。即使症状很快得到缓解，开始时治疗应最少持续4 周。大多数患者的溃疡可在4 周内愈合，但如需要疗程可延长至8 周。如有溃疡复发可开始新的疗程。
预防NSAID 引起的消化性溃疡：0.2mg，每日2 次，3 次，或4 次。疗程及用量均根据病情而定。应根据患者的临床状况，剂量个体化。
老年人：
可按常规剂量服用。
肾功能不全患者：
现有资料显示肾功能不全患者无需调整用量。
肝功能不全患者：
本品经全身脂肪酸氧化系统代谢。其代谢和血浆浓度在肝功能不全患者中无明显改变。
儿童
用米索前列醇治疗儿童消化性溃疡或NSAID 引起的消化性溃疡目前尚无评价。
不良反应
将不良反应术语依据发生率进行分类如下：
*腹泻以及腹痛是剂量相关性的，通常发生在治疗早期，一般是自限性的。罕见的严重腹泻导致重度脱水的病例报道。
单次剂量不超过0.2mg 并与食物一起服用，以及若需要服用抗酸剂时，避免使用含镁的抗酸剂，均可降低腹泻发生的风险。
当同时给予非甾体抗炎药（NSAID）时，与喜克馈相关的不良事件的类型相似。
临床试验：
在临床试验中，超过15,000例患者和受试者至少接受过一次剂量的米索前列醇治疗。不良反应主要累及消化系统。
腹泻和腹痛是剂量相关性的，通常发生在治疗早期，一般是自限性的。罕见的严重腹泻导致重度脱水的病例报道。
发生率 ] 1%的不良反应的特征与中短期（持续4-12周时间）以及长期（达1年）临床试验相似。
已经有一些研究证实了长期（超过12周）给予米索前列醇治疗的安全性，在这些研究中患者持续接受米索前列醇治疗达1 年。安全性包括通过胃部活组织检查确定的在胃粘膜形态学方面无不良或者异常的变化。
禁
米索前列醇禁用于以下患者：
－禁用于孕妇或者无法排除妊娠的妇女，或者计划妊娠的妇女，由于在妊娠期间，米索前列醇会增加子宫的张力和收缩，可能引起胎儿不完全或完全流产。妊娠中使用与出生缺陷相关。
－已知对米索前列醇或者本品任何其他成份或者其他前列腺素过敏者。
注意事项
[u]警告：[/u]
有生育能力的妇女在排除妊娠之前不应接受米索前列醇治疗，并且应全面告知其在治疗过程中有效避孕措施的重要性。如果怀疑妊娠，应停止使用本品。
我们建议此类患者仅在下述情况下使用本品：
－采取有效的避孕措施。
－已知本品对妊娠的危险性（参见【禁忌】）。
[u]注意事项：[/u]
接受NSAID 治疗的患者使用米索前列醇，可能发生胃肠道出血、溃疡和穿孔。即使是在无胃肠道症状的情况下，医生以及患者仍需警惕溃疡的发生，并且在适当的条件下，在使用本品之前应进行内镜和活组织检查，以确保上消化道无恶性病变。这些检查以及任何其他临床医生认为有必要的检查均应以合适的间隔时间重复进行，用于随访。
使用米索前列醇治疗后症状缓解，不能排除存在胃部恶性疾病的可能性。
对于有腹泻易发因素如炎症性肠病的患者，为了降低腹泻的风险，应将米索前列醇与食物同服，并且应避免使用含镁的抗酸剂。
对于脱水会导致危险的患者；应该进行密切监测。
临床研究结果表明，在能有效促进胃及十二指肠溃疡愈合的剂量下，本品不会引起低血压。但是，当患者处于低血压可能引起严重并发症的情况下，如脑血管疾病、冠状动脉疾病、或严重的外周血管疾病（包括高血压），应慎用本品。
在健康志愿者和糖尿病患者中，尚未发现本品对糖的代谢有不良影响。
[u]对驾驶车辆和操纵机器能力的影响[/u]
米索前列醇可引起头晕。患者应小心操纵机器或驾驶车辆。
孕妇及哺乳期妇女用药
妊娠期
米索前列醇禁用于妊娠妇女，由于本品可引起子宫收缩，并且与流产、早产、胎儿死亡以及出生缺陷相关。妊娠早期暴露于米索前列醇会导致两种出生缺陷发生风险显著增加；Mobius 综合征，即第6，7 颅神经麻痹，以及末端肢体横向缺陷。其他观察到的缺陷包括关节挛缩。
哺乳期
在母体中，米索前列醇快速代谢为具有生物活性的米索前列醇酸，可经乳汁分泌。正在哺乳的妇女不应使用米索前列醇，因为经乳汁分泌的米索前列醇酸会导致不良反应，如导致母乳喂养的婴儿出现腹泻。
儿童用药
在儿童中的使用尚无评价。
老年用药
在65 岁或以上的患者中的安全性特征与年轻患者相比无显著性差异。
药物相互作用
NSAIDs 与米索前列醇同时使用导致转氨酶水平升高和外周水肿的病例罕见。
本品主要经脂肪酸氧化系统代谢，对肝脏P450 酶系统无不良影响。与安替比林或地西泮联合应用时，未发现具有临床意义的药代动力学相互作用。在多次给予米索前列醇时，观察到普萘洛尔的浓度有一定程度的升高（AUC 平均约上升20 %，Cmax 平均约上升30 %）。大范围的临床研究未发现本品引起的药物间的相互作用。米索前列醇与几种NSAIDs 药物相互作用的研究显示，米索前列醇对布洛芬、双氯芬酸、吡罗昔康、阿司匹林、萘普生或者吲哚美辛的药代动力学无具有临床显著意义的影响。
在米索前列醇治疗期间应避免同时使用含镁的抗酸剂，因为这可能加重米索前列醇引起的腹泻。
药物过量
[u]药物过量的体征与症状[/u]
米索前列醇在人体中的中毒剂量尚不明确。可提示药物过量的临床征象包括镇静、震颤、惊厥、呼吸困难、腹痛、腹泻、发热、心悸、低血压或心动过缓。
[u]药物过量的处理[/u]
由于米索前列醇的代谢与脂肪酸一样，因此透析并不是治疗药物过量的合适方法。发生药物过量时，应根据需要采用标准的支持治疗。
临床研究中，患者可耐受每日1.2mg 剂量，持续3 个月，无明显的不良反应。
药理毒理
本品为天然前列腺素E1 的类似物，能够促进消化性溃疡愈合或缓解症状。本品对胃、十二指肠粘膜的保护作用是通过抑制基础的、刺激性的及夜间胃酸的分泌，减少胃酸的分泌量，降低胃液的蛋白水解酶活性，增加碳酸氢盐和粘液的分泌。
在几倍于临床推荐治疗剂量的单次和多次给药的动物试验中（狗，大鼠，小鼠），毒理学研究结果与已知的前列腺素E 的药理作用一致。主要症状表现为腹泻、呕吐、瞳孔扩大、震颤和高烧。还发现能引起狗，大鼠，小鼠胃粘膜增生。大鼠和狗在用药一年后停药，增生为可逆的。对服药后1 年的患者进行胃的组织学活检，未发现不良的组织改变。对大鼠和兔的生殖、致畸性和围产期前后的毒理学研究无重要的发现。当剂量超过100 倍人用剂量时，发现着床率降低且幼仔的发育延迟。可以得出结论：米索前列醇对生殖无明显影响，无致畸性和胚胎毒性，而且不影响围产期前后大鼠幼仔的发育。
在一组由6个体外分析和1 个体内检测组成的评估致突变可能性的研究中，米索前列醇呈阴性。对大鼠和小鼠的致癌性研究表明其无致癌危险。
药代动力学
本品口服后迅速吸收，30分钟后其活性代谢产物(米索前列醇酸)的血药浓度达峰值。米索前列醇酸的血浆清除半衰期为20－40 分钟。重复给药，每次0.4mg，每日2 次，未发现活性代谢产物在血浆中聚积。
如何提供
Cytotec 100-mcg药片呈白色，圆形，一侧凹陷SEARLE，另一侧凹陷1451; 提供为：
NDC号码
尺寸
0025-1451-60单位使用60瓶
0025-1451-20使用单位的120瓶
0025-1451-34纸箱100单位剂量
Cytotec 200-mcg药片为白色，六角形，上面印有SEARLE，一侧凹陷在线下方1461，另一侧凹陷双胃; 提供为：
NDC号码
尺寸
0025-1461-60单位使用60瓶
0025-1461-31使用单位的100瓶
0025-1461-34 100单位剂量的纸箱
在25°C（77°F）或低于25°C的干燥区域储存。
此产品的标签可能已更新。 有关当前完整的处方信息，请访问www.pfizer.com。
说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4AB12DA7-5731-4E06-BF1C-BC3F2E711F12
CYTOTEC® TABLETS
SCHEDULING STATUS:
S4
PROPRIETARY NAME
(and dosage form):
CYTOTEC® TABLETS
COMPOSITION:
Each CYTOTEC Tablet contains 200 mcg misoprostol.
PHARMACOLOGICAL CLASSIFICATION:
A 11.10 - Medicines acting on the gastrointestinal tract - Special combinations and/or substances.
PHARMACOLOGICAL ACTION:
CYTOTEC (misoprostol) is a synthetic prostaglandin E1 analogue which has gastric antisecretory and mucosal protective properties. The antisecretory activity is mediated by direct action on specific prostaglandin receptors on the surface of gastric parietal cells. The mucosal protective effect against various damaging agents has been demonstrated in humans with doses that inhibit, and doses which minimally affect, acid secretion.
ANTISECRETORY ACTIVITY:
Effect on Acid Secretion: In healthy human subjects, CYTOTEC inhibits daytime and nocturnal basal gastric acid secretion and acid secretion stimulated by histamine, pentagastrin, food, tetragastrin, betazole and coffee. This antisecretory effect is observed up to 5½ hours after CYTOTEC administration.
Effect on Pepsin Secretion and Gastric Fluid Volume: CYTOTEC produces a moderate decrease in pepsin concentration and gastric volume under basal conditions, but not during stimulated conditions.
Effect on Serum Gastrin: CYTOTEC has no persistent effects on fasting levels of, or on postprandial increases in, serum gastrin.
MUCOSAL PROTECTIVE ACTIVITY:
CYTOTEC has properties in animals and humans that strengthen the integrity of the gastroduodenal mucosa! barrier against damaging agents. These include stimulation of duodenal bicarbonate secretion and gastric mucous production. In addition, CYTOTEC maintains mucosal haemodynamics.
OTHER PHARMACOLOGICAL EFFECTS
CYTOTEC has been shown to produce uterine contractions which may endanger pregnancy (see CONTRA-INDICATIONS).
CYTOTEC does not produce clinically significant effects on serum prolactin, gonadotrophins, TSH, GH, thyroxine, cortisol, gastro-intestinal hormones (somatostatin, gastrin, vaso-active intestinal polypeptide and motilin), creatinine, or uric acid, gastric emptying, immunological competence, platelet aggregation, pulmonary function, or the cardiovascular system.
PHARMACOKINETICS:
CYTOTEC is rapidly absorbed following oral administration. Dose-related peak plasma levels of the active metabolite (misoprostol acid) occur after about 30 minutes and thereafter it is eliminated with a plasma half-life of 20-40 minutes.
After an oral dose of radiolabelled CYTOTEC, 73% of the radio-activity was excreted in the urine and 15% was excreted in the faeces. About 56% of the total radio-activity was eliminated in the urine within eight hours after dosing.
CYTOTEC does not accumulate in red blood cells. The serum protein binding of misoprostol acid is not extensive (less than 90%) and is concentration-independent at the therapeutic range.
CYTOTEC is metabolised by fatty-acid oxidizing systems (beta and omega oxidation) which are present in organs throughout the body. Its metabolism and plasma levels are therefore unlikely to be markedly affected in hepatically impaired patients. CYTOTEC does not interfere with hepatic drug-metabolising enzymes nor hepatic blood flow in animals. In multiple-dose human studies. CYTOTEC did not alter the pharmacokinetics or the bio-availability of propranolol; antipyrine or diazepam.
With CYTOTEC no relationship was found between the degree of renal insufficiency and the area under the misoprostol acid concentration-time curves (AUC).
No clinically significant change in the absorption of aspirin, ibuprofen, diclofenac or piroxicam occurred when each of these NSAIDs was given concomitantly with CYTOTEC. CYTOTEC also did not exert any clinically-significant effect on the steady-state blood level or anti-platelet effects of therapeutic doses of aspirin.
CYTOTEC bio-availability was reduced (by 16%) when it was co-administered with high doses of antacid. Administration of CYTOTEC with a high fat content meal did not alter the extent of misoprostol absorption but did reduce the rate of absorption resulting in lower C-max and higher t-max values for misoprostol acid. In healthy elderly subjects over 64 years of age, the AUC for misoprostol acid was slightly increased from that in younger subjects. This was attributed to the reduced clearance probably due partly to decreased volume of distribution and a slight prolongation of elimination t½ of this metabolite in the elderly.
INDICATIONS:
CYTOTEC is indicated for co-administration with non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention of gastric and duodenal ulcers, haemorrhagic lesions and erosions induced by NSAIDs.
CONTRA-INDICATIONS:
CYTOTEC should not be administered to anyone with a known allergy to prostaglandins.
CYTOTEC may endanger pregnancy, and its effect on a developing human foetus is not known. Therefore, CYTOTEC should not be used in pregnant women. Women should be instructed not to become pregnant while taking CYTOTEC. If a woman becomes pregnant while taking CYTOTEC, use of the product should be discontinued.
DOSAGE AND DIRECTIONS FOR USE
For the prevention of gastric ulcers, haemorrhagic lesions and erosions induced by NSAIDs:
A minimum of 200 mcg (one tablet) with food twice daily, together with the prescribed NSAID. Dosage may be increased to 200 mcg three times daily or to a maximum of 200 mcg four times daily, to correspond to the NSAID administration schedule or if indicated by the clinical condition of the patient.
For the prevention of duodenal ulcers induced by NSAIDs:
800 mcg (four tablets) daily in divided doses, with food.
Antacids containing aluminium may be given as needed for relief of pain.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
General:
Symptomatic responses to CYTOTEC do not preclude the presence of gastric malignancy.
Women of childbearing potential should employ adequate contraception (e.g. oral contraceptives or intrauterine devices) while receiving CYTOTEC (see CONTRA-INDICATIONS).
Although it is not known whether CYTOTEC is excreted in human milk, CYTOTEC should not be administered to nursing mothers.
In animals, prostaglandins of the E type have the capacity to produce hypotension through peripheral vasodilation. The results of clinical trials indicate that CYTOTEC does not produce hypotension at dosages of up to 800 mcg per day. However, CYTOTEC should be used with caution in the presence of disease states where hypotension might precipitate severe complications, e.g. cerebral vascular disease or coronary artery disease.
DRUG INTERACTIONS:
In clinical trials there was no evidence of interaction between CYTOTEC and cardiac, gastro-intestinal, pulmonary or CNS drugs (see also PHARMACOKINETICS). Decreased bio-availability of misoprostol acid was observed with high doses of antacid.
Paediatric use: safety and effectiveness in children below the age of 18 years have not been established.
In clinical trials, the most frequent adverse effects were diarrhoea, abdominal pain and loose stools. The events were usually transient and mild to moderate in severity. Diarrhoea, when it occurred, usually developed early in the course of therapy, was self-limiting and required discontinuation of CYTOTEC in the minority of the patients. The incidence of diarrhoea may be minimised by administering CYTOTEC immediately after meals and at bedtime, and by avoiding the use of magnesium-containing antacids. Dose adjustment may also be helpful.
Women who received CYTOTEC during clinical trials reported the following gynaecological disorders: cramps, menorrhagia, menstrual disorder, spotting, dysmenorrhoea.
The following adverse reactions were also reported: nausea, headache, flatulence, dyspepsia, vomiting and constipation.
KNOWN SYMPTOMS OF OVER-DOSAGE AND PARTICULARS OF ITS TREATMENT:
The toxic dose of CYTOTEC in humans has not been determined. Cumulative total daily doses of 1600 mcg have been tolerated with only symptoms of gastro-intestinal discomfort being reported. In animals, the acute toxic effects are similar to those reported for other prostaglandins: relaxation of smooth muscle, respiratory difficulties and depression of the central nervous system. Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnoea, abdominal pain, diarrhoea, fever, palpitations, hypotension and bradycardia. Symptoms should be treated with supportive therapy.
IDENTIFICATION:
CYTOTEC tablets are white, scored, uncoated, flat, hexagonal-shaped tablets, debossed on one side "SEARLE" OVER "1461".
PRESENTATION:
CYTOTEC tablets are supplied in blister packs of 60 or 120 tablets packed in cartons.
STORAGE INSTRUCTIONS:
Store in a dry place below 30°C. Keep out of reach of children.
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