【药品名称】

通用名称：异维A酸软胶囊
英文名称：Isotretinoin Soft Capsules

【成份】

本品主要成份为：异维A酸，又称13-顺式维A酸。

【 适应症 】

适用于重型痤疮,尤其适用于结节囊肿型痤疮，维A酸适用于重型痤疮，尤其适用于结节囊肿型痤疮，亦可用于毛发红糠疹。

【用法用量】

本品应在医生指导下使用，口服治疗痤疮的剂量应因人而异，从0.1～1(mg/kg)/日不等，一般建议开始剂量为0.5(mg/kg)/日，分两次口服。本药为脂溶性，进餐时服药可促进吸收，治疗2～4周后可根据临床效果及不良反应酌情调整剂量。6～8周为一疗程，疗程之间可停药8周，停药后短期内可持续改善症状。

【不良反应】

1.本药的副作用与维生素A过量的临床表现相似，常见的副作用包括口唇及皮肤干燥、唇炎、脱屑、瘙痒、疼痛、皮疹、皮肤脆性增加、掌跖脱皮、瘀斑，还可出现继发感染等。

2.结合膜炎、严重者角膜混浊、视力障碍、视乳头水肿，头痛、头晕、精神症状、抑郁、良性脑压增高。

3.毛发疏松，指甲变软。

4.骨质疏松、肌肉无力、疼痛、胃肠道症状、鼻衄等。

5.妊娠服药可导致自发性流产及胎儿发育畸形。

6.实验室检查可引起血沉快、肝酶升高、血脂升高、血糖升高、血小板下降等。

上述副作用大多为可逆性，停药后可逐渐得到恢复。副作用的轻重与本药的剂量大小、疗程长短及个体耐受性有关。

轻度不良反应可不必停药，或减量使用，重度不良反应应立即停药，并去医院由医师作相应处理。

上述不良反应大多为可逆性，停药后可逐渐得到恢复。

【禁忌】

　　孕妇、哺乳期妇女、肝肾功能不全，维生素A过量及高血脂症患者禁用。

【注意事项】

　　1.本药避免与维生素A及四环素等同时服用;

　　2.育龄期妇女服药前、停药后应作妊娠试验，用药期间及停药后三月内不得献血;

　　3.避免太阳光及UV射线过度照射;

　　4.糖尿病、肥胖症、酗酒及高脂血症、脂质代谢紊乱者慎用;

　　5.治疗初期痤疮症状或许有短暂性加重现象，若无其它异常情况，可在严密观察下继续用药，不宜同时服用其它角质分离剂或表皮剥脱性抗痤疮药;

　　6.必要时可用温和的外用药作辅助性治疗。

【特殊人群用药】

儿童注意事项：

对儿童的安全性尚不清楚。药物过量可发生骨结构的改变，包括儿童骨骺盘早熟融合。

妊娠与哺乳期注意事项：

　　孕妇、哺乳期妇女禁用。

老人注意事项：

肝、肾功能不全者禁用。

【药物相互作用】

1.异维A酸与四环素类抗生素合用，可导致假“脑瘤”产生而引起良性脑压升高，临床表现为伴有头痛的高血压、眩晕和视觉障碍。

2.异维A酸与维生素A同时使用，可产生与维生素A超剂量时相似的症状。

3.异维A酸与卡马西平(Carbamazepine)同时应用，可导致卡马西平的血药浓度下降，与华法林(Warfarin)同时使用，可增强华法林的治疗效果，和甲氨蝶呤(MTX)同时使用，可因MTX的血药浓度增加而增加对肝脏的损害。

【药理作用】

1.药理学：本药的作用机制尚未完全清楚。用于治疗痤疮时具有缩小皮脂腺组织，抑制皮脂腺活性，减少皮脂分泌，减轻上皮细胞角化及毛囊皮脂腺口的角质栓塞，并抑制痤疮丙酸杆菌数的生长繁殖。近来研究还表明本药可调控与痤疮发病机制有关的炎症免疫介质以及选择性地结合维A酸核受体而发挥治疗作用。

2.毒理学：试验表明有严重致畸作用。

【贮藏】

密封，置阴凉处。

Brand name: Isotret Hexal

Active ingredient (generic name): Isotretinoin

Manufacturer: Hexal 

Importer: Behestan Darou

Pharmacotherapeutic group: anti-acne

Pharmaceutical form: 20mg Capsules

Pharmacodynamic:  

The exact mechanism of action of isotretinoin has not yet been elucidated in detail, but it has been established that the improvement observed in the clinical picture of severe acne is associated with suppression of sebaceous gland activity and a histologically demonstrated reduction in the size of the sebaceous glands. Furthermore, a dermal anti-inflammatory effect of isotretinoin has been established.

Hypercornification of the epithelial lining of the pilosebaceous unit leads to shedding of corneocytes into the duct and blockage by keratin and excess sebum. This is followed by formation of a comedone and, eventually, inflammatory lesions. Isotretinoin inhibits proliferation of sebocytes and appears to act in acne by re-setting the orderly program of differentiation. Sebum is a major substrate for the growth of Propionibacterium acnes so that reduced sebum production inhibits bacterial colonisation of the duct.

Pharmacokinetic:

The absorption of isotretinoin from the gastro-intestinal tract is variable and dose-linear over the therapeutic range.

In humans little information is available on the distribution of isotretinoin into tissue.

The major metabolite is 4-oxo-isotretinoin with plasma concentrations at steady state that are 2.5 times higher than those of the parent compound.

After oral administration of radiolabelled isotretinoin approximately equal fractions of the dose were recovered in urine and faeces. Following oral administration of isotretinoin, the terminal elimination half-life of unchanged drug in patients with acne has a mean value of 19 hours. The terminal elimination half-life of 4-oxo-isotretinoin is longer, with a mean value of 29 hours.

 Therapeutic indication:   

Dosage and administration:

The capsules should be taken with food once or twice daily.

Isotretinoin therapy should be started at a dose of 0.5 mg/kg daily. The therapeutic response to isotretinoin and some of the adverse effects are dose-related and vary between patients. This necessitates individual dosage adjustment during therapy. For most patients, the dose ranges from 0.5-1.0 mg/kg per day.

Long-term remission and relapse rates are more closely related to the total dose administered than to either duration of treatment or daily dose. It has been shown that no substantial additional benefit is to be expected beyond a cumulative treatment dose of 120-150 mg/kg. The duration of treatment will depend on the individual daily dose. A treatment course of 8-12 weeks is normally sufficient to achieve remission.

In the majority of patients, complete clearing of the acne is obtained with a single treatment course. In the event of a definite relapse a further course of isotretinoin therapy may be considered using the same daily dose and cumulative treatment dose. As further improvement of the acne can be observed up to 8 weeks after discontinuation of treatment, a further course of treatment should not be considered until at least this period has elapsed.

Adverse reaction:

The following symptoms are the most commonly reported undesirable effects with isotretinoin:

Gram positive (mucocutaneous) bacterial infection, anemia, red blood cell sedimentation rate increased, Thrombocytopenia, neutropenia, allergic skin reaction, anaphylactic reactions, hypersensitivity, suicidal ideation, Lymphadenopathy, diabetes mellitus, depression, headache, blurred vision, cataract, Color blindness, colitis, Ileitis, dry throat, gastrointestinal hemorrhage, hemorrhagic diarrhea and inflammatory bowel disease, Nausea, Pancreatitis

Contraindication:

Isotretinoin is contraindicated in women who are pregnant or breastfeeding.

Isotretinoin is contraindicated in women of childbearing potential unless all of the conditions of the Pregnancy Prevention Program are met.

Isotretinoin is also contraindicated in patients with hepatic insufficiency and excessively elevated blood lipid values.

Pharmacokinetic interactions:

Cases of benign intracranial hypertension (pseudotumor cerebri) have been reported with concomitant use of isotretinoin and tetracyclines. Therefore, concomitant treatment with tetracyclines must be avoided

Special warnings:

Isotretinoin is contraindicated in women of childbearing potential.

Female patients must be provided with comprehensive information on pregnancy prevention and should be referred for contraceptive advice if they are not using effective contraception.

Male patients

The available data suggests that the level of maternal exposure from the semen of the patients receiving isotretinoin is not of sufficient magnitude to be associated with the teratogenic effects of isotretinoin.

Male patients should be reminded that they must not share their medication with anyone, particularly not females.

Additional precautions

Patients should be instructed never to give this medicinal product to another person and to return any unused capsules to their pharmacist at the end of treatment.

Patients should not donate blood during therapy and for 1 month following discontinuation of isotretinoin because of the potential risk to the foetus of a pregnant transfusion recipient.

Educational material

In order to assist prescribers, pharmacists and patients in avoiding foetal exposure to isotretinoin the Marketing Authorisation Holder will provide educational material to reinforce the warnings about the teratogenicity of isotretinoin, to provide advice on contraception before therapy is started and to provide guidance on the need for pregnancy testing.

Full patient information about the teratogenic risk and the strict pregnancy prevention measures as specified in the Pregnancy Prevention Programme should be given by the physician to all patients, both male and female.

Psychiatric disorders

Depression, depression aggravated, aggressive tendencies, mood alterations, psychotic symptoms and, very rarely, suicidal ideation, suicide attempts and suicide have been reported in patients treated with isotretinoin.

Skin and subcutaneous tissues disorders

Acute exacerbation of acne is occasionally seen during the initial period but this subsides with continued treatment, usually within 7-10 days, and usually does not require dose adjustment.

Eye disorders

Dry eyes, corneal opacities, decreased night vision and keratitis usually resolve after discontinuation of therapy. Dry eyes can be helped by the application of a lubricating eye ointment or by the application of tear replacement therapy. Intolerance to contact lenses may occur which may necessitate the patient to wear glasses during treatment.

Hepatobiliary disorders

Liver enzymes should be checked before treatment, 1 month after the start of treatment, and

Lipid Metabolism

Serum lipids (fasting values) should be checked before treatment, 1 month after the start of treatment, and subsequently at 3 monthly intervals unless more frequent monitoring is clinically indicated.

Gastrointestinal disorders

Isotretinoin has been associated with inflammatory bowel disease (inlcuding regional ileitis) in patients without a prior history of intestinal disorders.

High Risk Patients

In patients with diabetes, obesity, alcoholism or a lipid metabolism disorder undergoing treatment with isotretinoin, more frequent checks of serum values for lipids and/or blood glucose may be necessary. Elevated fasting blood sugars have been reported, and new cases of diabetes have been diagnosed during isotretinoin therapy.

Pregnancy and lactation:

Pregnancy is an absolute contraindication to treatment with isotretinoin .If pregnancy does during treatment with isotretinoin or in the month following, there is a great risk of very severe and serious malformation of the foetus.

Isotretinoin is highly lipophilic, therefore the passage of isotretinoin into human milk is very likely. Due to the potential for adverse effects in the mother and exposed child, the use of isotretinoin is contraindicated in nursing mothers.

Storage temperature:   

Room temperature (15-25 C)