【药品名称】

  通用名称：醋酸去氨加压素口溶片

  商品名称：醋酸去氨加压素片(弥凝)

  英文名称：Desmopressin Acetate Tablets

【主要成份】 醋酸去氨加压素。其化学名为：3-巯基丙酰-酪氨酰-苯丙氨酰-谷氨酰胺酰-天冬酰胺酰-半胱氨酰-脯氨酰-D-精氨酰-甘氨酰胺。

【成 份】

  分子式：C46H64N14O12S2.2(C2H4O2)

   分子量：1189.32

【性 状】 本品为白色片。

【适应症/功能主治】 弥凝用于治疗中枢性尿崩症。服用弥凝后可减少尿液排出，增加尿渗透压，减低血浆渗透压，从而减少尿频和夜尿。 弥凝用于治疗六岁或以上患者的夜间遗尿症。

【规格型号】0.1mg*30s(弥凝)

【用法用量】 剂量因人而异，应区分调整。 治疗中枢性尿崩症：一般成人和儿童的初始适宜剂量为每次0.1毫克，每日三次。再根据患者的疗效调整剂量。根据临床经验，每天的总量在0.2～1.2毫克之间。对多数患者的适宜剂量为每次0.1－0.2毫克，每日三次。 治疗夜间遗尿症：初始适宜剂量为睡前服用0.2毫克，如疗效不显著可增至0.4毫克，连续使用三个月后停用此药至少一周，以便评估是否需要继续治疗。治疗期间须限制饮水，详见“注意事项”。

【不良反应】使用醋酸去氨加压素时若不限制饮水可能会引起水潴留/低钠血症，有/无伴随以下迹象和症状（头痛、恶心/呕吐、血清钠降低、体重增加，更严重者可引起抽搐）。 治疗夜间遗尿症和尿崩症时，常见的不良反应有头疼、腹痛和恶心；罕见皮肤过敏反应、低钠血症和情绪障碍；仅有个别全身过敏反应的报道。

【禁 忌】 醋酸去氨加压素不可用于以下情形： —习惯性或精神性烦渴症患者（尿量超过40毫升/千克/24小时）； —心功能不全或其他疾患需服用利尿剂的患者； —中重度肾功能不全患者（肌酐清除率低于50毫升/分钟）； —抗利尿激素分泌异常综合征（SIADH）患者； —低钠血症患者； —对醋酸去氨加压素或药物的其他成份过敏者。

【注意事项】 急迫性尿失禁患者：器官病变导致的尿频或多尿患者（如良性前列腺增生、尿道感染、膀胱结石/膀胱癌）；烦渴和糖尿病患者不适合用本品治疗。 醋酸去氨加压素片用于治疗夜遗尿时，应在服药前1小时和服药后8小时限制饮水。若治疗时未严格控制饮水将出现水潴留和/或低钠血症及其并发症状（头疼、恶心/呕吐和体重增加，更严重者可引起抽搐），此时应终止治疗直到患者完全康复。 老年人、血钠水平低和24小时尿量多（多于2.8～3.0升）的患者发生低钠血症危险性较高。 在以下情况下，应严格控制饮水并监测患者血钠水平： －与已知可导致抗利尿激素分泌异常综合征（SIADH）的药物（如：三环类抗抑郁剂、选择性血清素再摄取抑制剂、氯丙嗪、卡马西平）合用时， －与非甾体抗炎药（NSAIDs）合用时。 治疗期间，出现体液和/或电解质失衡急性并发症（如：全身感染、发烧和肠胃炎）时，应立即停止治疗。

【儿童用药】醋酸去氨加压素片慎用于年幼患者。

【老年患者用药】临床试验研究显示，65岁以上老年患者用药出现低钠血症的可能性较高。因此，开始治疗时年龄超过65岁的老年人不建议使用本品，尤其在可能导致体液或电解质失衡的情况下。在开始治疗前、开始用药或增加剂量后3天以及治疗医师认为有必要用药时均要检验血清钠水平的患者可考虑使用本品。

【孕妇及哺乳期妇女用药】 孕妇 有限的数据（对53例患尿崩症的孕妇进行的研究）证实，醋酸去氨加压素对孕妇及胎儿/新生儿的健康没有影响。至今仍没有其他相关的流行病学数据。对实验动物的研究不能证明药物对孕妇、胚胎/胎儿形成、分娩和产后阶段具有直接或间接影响。因此孕妇慎用。 哺乳期妇女 经鼻腔给予高剂量醋酸去氨加压素（300微克）后测试母乳，显示醋酸去氨加压素可分泌至乳汁，但婴儿从乳汁吸收的量很少，且低于影响利尿作用所需的量。尚不明确重复给药后醋酸去氨加压素是否在乳汁中蓄积。

【药物相互作用】为避免出现低钠血症，在以下情况下，应严格控制饮水并监测患者血钠水平： －与已知可导致抗利尿激素分泌异常综合征（SIADH）的药物（如：三环类抗抑郁剂、选择性血清素再摄取抑制剂、氯丙嗪、卡马西平）合用时，这类药物可加强抗利尿作用引致体液贮留危险性升高； －与非甾体抗炎药（NSAIDs）合用时，这类药物可能会引起水潴留/低钠血症。 合用洛哌丁胺将导致醋酸去氨加压素的血浆浓度升高三倍，这将增加水潴留/低钠血症的危险。尽管尚未得到证实，但与其它减慢肠运动的药物合用时，可能也会有此作用。 合用二甲硅油可能会降低醋酸去氨加压素的吸收。 人体微粒体的体外研究已证实，醋酸去氨加压素不在肝脏中进行代谢。因此，醋酸去氨加压素与影响肝脏代谢的药物间相互作用的可能性不大。但没有进行过正式的体内药物相互作用的研究。 醋酸去氨加压素的生物利用度在个体内和个体间均存在中度至高度的差异。用药同时或早于用药1.5小时食用脂肪摄入量为27％的标准餐，醋酸去氨加压素的吸收率会降低40％。没有观察到食物对醋酸去氨加压素在药效学方面（尿量或渗透压）的影响。但不排除某些患者同时进食时影响药物作用的可能。

【药物过量】 超量使用会增加水潴留和低钠血症的危险性。 治疗：治疗低钠血症时应依情况而定，可采用以下建议： 对无症状的低钠血症患者，除停用醋酸去氨加压素外应限制饮水；对有症状的患者，应加用滴注等渗或高渗的氯化钠溶液；当体液潴留症状严重（抽搐或神志不清）时，需加服呋塞米。 症状：头痛、恶心、水潴留、低钠血症、少尿、抽搐和肺水肿。

【药理毒理】醋酸去氨加压素为天然精氨盐加压素的结构类似物，系对天然激素的化学结构进行两处改动而得，即1-半胱氨酸脱去氨基和以8-D-精氨酸取代8-L-精氨酸。静脉或皮下给予去氨加压素0.3ug/kg体重，可使血浆中凝血因子VIII(VIII：C)的活力增加2-4倍；也使VonWillebrand因子抗原(VWF：AG)的含量增加，但强并稍小。同时，释放出组织型纤维蛋白溶酶原激活因子(t-PA)。皮下注射的生物利用度约为静脉注射生物利用度的85%，按体重0.3ug/kg给药的最大血药浓度在给药后约 60分钟达到峰值，平均值约为600pg/ml，血浆半衰期3-4小时，止该药含醋酸去氨加压素，与天然激素精氨酸加压素的结构类似。它与精氨酸加压素的区别，主要是对1-半胱氨酸作脱氨基处理和以8-D-精氨酸取代8-L-精氨酸。这些结构改变后，使临床剂量的醋酸去氨加压素的作用时间延长，而不产生加压的副作用。 毒性 若大量饮水，即使使用普通剂量也会引起水中毒。剂量范围从0.3微克/千克（静脉注射给药）到2.4微克/千克（鼻腔内给药），曾导致成人和儿童出现低钠血症和抽搐；另一方面，对5月龄婴儿鼻腔给药40微克或5岁儿童鼻腔给药80微克，均没有影响。对新生婴儿肠外给药4微克，出现少尿症状和体重增加。 临床前安全性资料 醋酸去氨加压素的安全性监测过程和安全性概要未有异常发现。

【药代动力学】口服醋酸去氨加压素的生物利用度在0.08～0.16 %之间。血浆达峰浓度约在1～1.5小时后出现；血浆达峰浓度（Cmax）和血药浓度-时间曲线下面积（AUC值）不随给药剂量成比例增加。分布容积为0.2～0.3升/千克。醋酸去氨加压素不能透过血脑屏障。消除相半衰期平均在2～3小时。 对人体肝微粒体的体外研究显示，醋酸去氨加压素几乎不在肝脏中代谢。因此，醋酸去氨加压素可能不在人体肝脏中进行代谢。 静脉注射后24小时内，尿液中检测到的醋酸去氨加压素为给药量的45％。

【贮 藏】密封。

【包 装】聚乙烯瓶装，30片/瓶。

【有 效 期】36 月

【生产企业】Ferring International Center SA(瑞士)

产品资料  

奧地利因斯布魯克--(美國商業資訊)--新資料已顯示，desmopressin口溶片(MINIRIN® Melt)*治療可改善夜遺尿（尿床）兒童的睡眠模式和心理功能發揮（包括注意力問題和記憶力）。資料同時顯示，尿床對兒童的神經心理功能發揮有不良影響（例如焦慮和社交自尊問題）。1,2上述資料來自於比利時根特大學醫院(University Hospital Ghent)研究人員展開的一項研究，在奧地利因斯布魯克召開的歐洲兒科泌尿科學會(ESPU)第25屆年會上呈報。

該研究結果來自於30個6至16歲的尿床兒童，在desmopressin治療前和治療後6個月進行測評。資料顯示，desmopressin治療6個月後尿床有改善，睡眠中斷有相對的顯著減輕，評估指標是每個睡眠小時的週期性肢體運動（PLMS指數）較少(p<0.001)以及皮質激發減少(p<0.01)。1

此外，尿床兒童經desmopressin治療6個月後心理功能發揮有顯著改善。家長訴稱的注意力問題(p<0.01)以及內化(p<0.05)和外化(p<0.01)兩方面的問題均有顯著減少。此外，生活質素(p<0.01)、執行功能發揮(p<0.01)和聽覺記憶力(p<0.01)均有顯著改善。1

ESPU上呈報的這項研究還提供了一些資料，辨認出尿床兒童存在哪些心理問題，以及當中哪些問題與特定的臨床症狀有關。事實上，該研究中80%的尿床兒童存在至少一項心理、運動或神經系統困難。2兒童的尿床次數與存在社交問題以及焦慮/憂鬱問題之間存在正相關關係。相反，夜尿次數與社交自尊之間存在負相關關係。2

比利時根特大學醫院兒科腎科/泌尿科臨床心理學家Charlotte Van Herzeele對這些結果評論指出：「我們知道尿床對兒童及家庭的生活均有不良影響。但這些新資料提示，這些影響比以往想像的更加深遠，凸顯了家長為子女尋求醫療幫助、並探索可用治療選擇的必要性。」

比利時根特大學醫院兒科睡眠中心的兒童精神科醫生Karlien Dhondt博士說：「兒童最容易罹患尿床的年齡是他們心理和神經認知發育中的關鍵階段。該研究顯示，治療尿床可改善兒童的睡眠品質和心理功能發揮的若干參數。」

5歲兒童中經常尿床的比例可高達16%。3,4 尿床是僅次於敏感症的最常見慢性兒童期病況。5尿床是極為常見的病況，可對兒童造成顯著的心理影響，對兒童家庭造成經濟負擔。6

*Desmopressin含片在全球82個國家獲准用於治療尿床，以若干商品名稱上市銷售，包括MINIRIN®Melt、Desmomelt® 和DDAVP® Melt。

關於本研究

上述資料來自於一項多方法（多導睡眠描記法（監測睡眠）、問卷、臨床訪談、神經心理學測試）、多知情者（詢問兒童、家長和老師）研究，兒童介於6至16歲，轉診至三級醫療，診斷為「單症狀性夜遺尿」（MNE，或簡稱尿床），伴有夜間多尿(NP)。NP的定義是夜間排尿量>同齡人膀胱容量的100%。在desmopressin含片治療啟用之前和治療6個月之後，採用各種不同的衡量指標對兒童進行測評。1,2

關於desmopressin

MINIRIN®(desmopressin)是垂體後葉加壓素的一種人造（合成）形式，垂體後葉加壓素是一種天然抗利尿激素，控制著體內的水平衡。7 Desmopressin的作用機制是與腎臟中的抗利尿激素(V2)受體結合，模擬天然抗利尿激素的效應。此效應可防止過多的水份被濾出血液，從而減少所產生的尿量。8尿床研究顯示，desmopressin長期治療是有效的，耐受性良好，能夠有助於夜遺尿的長期改善。9,10

關於Ferring Pharmaceuticals：

Ferring Pharmaceuticals總部設在瑞士，是一家以研究為導向的專業生物製藥集團，活躍於全球市場。該公司確定、開發並推銷創新產品，涵蓋領域包括生殖健康、泌尿科、腸胃科和內分泌科。Ferring在55個國家擁有自己的營運附屬公司，產品銷售於全球100多個國家

Minirin Melt

Generic Name: Desmopressin acetate
Product Name: Minirin Melt

Indication

Minirin Melt is a medication used to treat primary nocturnal enuresis (bed wetting) in adults and children over 6 years of age whose ability to concentrate urine is normal. Minirin Melt should only be used to treat bed wetting, if management with a bed wetting alarm fails or when a bed wetting alarm is contraindicated or inappropriate.

Minirin Melt may also be used to treat cranial diabetes insipidus, a type of pituitarydisorder characterised by the production of large amounts of urine and constant thirst.

In Australia, the cost of Minirin Melt (120 µg and 240 µg doses) is subsidised under the Government’s Pharmaceutical Benefits Scheme.

Action

Desmopressin, the active ingredient in Minirin Melt, is a synthetic version of the naturally occurring substance called vasopressin which is produced in the pituitary gland.

Vasopressin has several actions in the body including reducing the amount of urine produced by the kidneys. Desmopressin works in the same way as vasopressin.

Dose advice

Dose information

How to take Minirin Melt

The correct dose will be determined by the doctor who prescribes Minirin Melt. Always take the medicine as prescribed by your doctor, even if the dose information on the medicine packet is different. Continue to take the medicine even if you start feeling well. Minirin Melt controls your condition but does not cure it. You must continue to take the medicine or you may become unwell again.

Minirin Melt is a wafer for sublingual administration, which means that when you take them they should be placed under the tongue. Minirin Melt (wafers) are available in Australia in 120 µg and 240 µg doses (a 60 µg dose is available in other countries). Do not give the medicine to anybody else or use it to treat any other health problem.

To remove a wafer from its packet, carefully peel back the foil from one of the blisters, starting in the corner with the arrow. Do not try to push the wafer through the foil backing. Once removed, the wafer should be placed under your tongue. It will dissolve in a few seconds, without water. More detailed instructions about how to take the medicine are provided in the medicine packet.

Bed wetting

Usually you will start by taking 120 µg of Minirin Melt each day at bedtime. The doctor may increase the dose to 240 µg if the starting dose does not effectively treat your condition. Take the medicine every day before going to bed. If you miss a dose, do not take extra medicine to make up for the missed dose. Take your normal dose the following day.

When used as a treatment for bed wetting, Minirin Melt is usually prescribed for up to 3 months. After taking the medicine for periods of 3 months, the doctor will ask you to spend 1 week without taking the medicine. If bed wetting occurs again when you are not taking the medicine, you may be prescribed Minirin Melt for another 3 months. Always attend your scheduled doctor appointments so that your response to the medicine and the need for continued treatment can be assessed.

Dosage for cranial diabetes insipidus

Doses up to 120 µg three times a day may be used. Your doctor will determine how much you need to take, depending on your response to the medicine.

If you forget to take a dose, take it as soon as you remember. Do not take a double dose. Talk to your doctor if you are unsure when to take the following dose.

Fluid restriction

When using Minirin Melt to treat bedwetting, it is important that you restrict your fluid intake. This means that you should limit your fluid intake to a minimum from 1 hour before until 8 hours after taking your daily dose. Over this period, drink no more than a few sips of water or other fluids if needed. In this period, only drink a few sips of water or other fluids if needed- do not drink more than this. At other times of the day, drink fluids normally to prevent dehydration.

When taking Minirin Melt to treat cranial diabetes insipidus, follow your doctor’s instruction on fluid intake. It is important to keep your body fluids in balance.

Overdose

Taking too much Minirin Melt increases the risk of water retention and/or hyponatraemia. If you develop symptoms of these conditions, which include headache, drowsiness, confusion, rapid weight gain, nausea and vomiting and convulsions, stop taking the medicine immediately and consult your doctor or call the Poisons Information Hotline (telephone number in Australia is 13 11 26).

If you have any queries about the correct way to use Minirin Melt, please ask your doctor.

Contraindications

Minirin Melt should not be used under certain conditions. Tell your doctor if you:

· Have an allergy to desmopressin (the active ingredient) or any excipients (inactive ingredients) in the product, or any other medicine or food;

· Drink large quantities of water: A higher fluid intake at bedtime when taking Minirin Melt can increase the chance of fluid overload. Restrict or limit fluid intake from 1 hour before until 8 hours after taking Minirin Melt. Drinking too much water can lead to complications including water retention and/or hyponatraemia (a condition characterised by lack of salts in the blood). These conditions may occur with or without accompanying warning signs and symptoms (such as headache, nausea and vomiting, weight gain and convulsions);

· Have heart problems characterised by shortness of breath and swelling of the lower legs and feet as a result of fluid accumulation;

· Have kidney problems that cause you to pass small amounts of urine or no urine;

· Have low levels of sodium in your blood, a condition known as hyponatraemia;

· Have a condition called syndrome of inappropriate anti-diuretic hormone secretion (SIADH), which causes you to secrete too much anti-diuretic hormone (ADH).

Precautions

Special care needs to be taken before you can start using Minirin Melt. Tell your doctor if you:

· Have an allergy to desmopressin (the active ingredient in Minirin Melt) or any other medicines, foods, preservatives or dyes;

· Have a fluid imbalance in your body, which means that you have too much or too little water your body;

· Develop water retention and/or hyponatraemia, which may or may not cause signs and symptoms including headache, nausea and vomiting, weight gain and convulsions. If you develop these signs and symptoms whilst taking Minirin Melt, stop taking the medicine immediately and see your doctor;

· Have a condition affecting your bladder;

· Have a condition affecting how much urine you produce, including multiple sclerosis and urge incontinence (a sudden urge to urinate);

· Have diabetes mellitus;

· Have a condition which affects your kidneys;

· Have a condition affecting your heart;

· Have low blood pressure;

· Have cystic fibrosis;

· Have low blood sodium levels (hyponatraemia);

· Have a disease which affects the way your blood clots;

· Have a fluid or electrolyte imbalance which may arise due to systemic infection, gastroenteritis, fever or syndrome of inappropriate anti-diuretic hormone secretion;

· Take a medicine called a diuretic;

· Take a medicine called loperamide, which is used to treat diarrhoea;

· Take medicines called non-steroidal anti-inflammatory drugs (NSAIDs), which are used to relieve pain and inflammation;

· Take tricyclic antidepressants;

· Take selective serotonin reuptake inhibitors;

· Take chlorpromazine or carbamazepine;

Other medications

If you are taking Minirin Melt, tell your doctor, pharmacist or other healthcare professional before starting any new medicines. Tell the surgeon or anaesthetist that you are taking Minirin Melt before you are sedated to have surgery.

Pregnancy

Minirin Melt is a Pregnancy Category B2 medication. You should not use Minirin Melt if you are pregnant unless your doctor has specifically told you that you should. Studies have not been conducted to determine whether the medicine is safe when used during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant whilst taking Minirin Melt so that they can discuss the risks and benefits of using the drug during pregnancy.

Breastfeeding

You should not use Minirin Melt if you are breastfeeding. The medicine is passed into your breastmilk. Studies have not been done to determine whether or not the medicine is safe when used during breastfeeding.

Children

Minirin Melt can be used by children 6 years of age and older for the treatment of bedwetting. Children should be closely observed when they are taking the medicine to ensure they take the correct dose. They should also be monitored to ensure that they restrict their fluid intake.

Minirin Melt can also be used by children to treat cranial diabetes insipidus.

Storage

Minirin Melt should be stored below 25°C, in the original packaging and protected from moisture and light. Do not take the medicine if it has passed its expiry date or if the packaging shows signs of tampering. Return damaged or expired medicines to your pharmacy.

Schedule

Minirin (Melt) is a Schedule S4 (prescription only) medication.1

Common side effects

All medicines can have side effects. Most commonly the side effects are minor; however, some can be more serious. Usually the benefits of taking a medication outweigh the associated side effects. Your doctor would have considered these side effects before starting you on Minirin Melt.

Without concomitant reduction of fluid intake, there is a risk of water retention/hyponatraemia when taking Minirin Melt with or without accompanying warning signs and symptoms (headache, nausea/vomiting, decreased sodium, weight gain and, in severe cases, convulsions). Elderly people (older than 60 years) have an increased risk, as do those taking higher doses of the medicine.

In clinical studies, the following side effects have occurred at least once in individuals using Minirin Melt to treat cranial diabetes insipidus:

· Cold;

· Headache;

· Weight gain (due to increased fluid retention);

· Dizziness;

· Sore throat;

· Depressed mood.

The following side effects of Minirin Melt have been observed in patients treated for diabetes insipidus and/or primary nocturnal enuresis (bed wetting).

Very common side effects

Very common side effects are those that occur in more than 10% of people given Minirin Melt. These include:

· N/A

Common side effects

Common side effects are those that occur in 1–10% of people given Minirin Melt. These include:

· Headache;

· Abdominal pain;

· Nausea.

Uncommon side effects

Side effects that occur in less than 1% of people given Minirin Melt are considered uncommon. People do not necessarily experience any of these side effects, so do not become alarmed by this list:

· N/A

Rare side effects

Rare side effects are those that occur in 0.01–0.1% of people given Minirin Melt. These include:

· N/A 

Very rare side effects

Very rare side effects are those that occur in less than 0.01% of people given Minirin Melt. These include:

· Hyponatraemia (a condition characterised by lack of salts in the blood). See Precautions for more information).

After Minirin Tablets were made available, there have been isolated occurrences of allergic skin reactions and more severe general allergic reactions, visual abnormalities and very rare cases of emotional disturbances in children.

If you experience any of the listed side effects, or any other symptoms that appear abnormal or unusual, please tell your doctor.