匹多莫德口服液-中国
医生用药指南
2017年3月14日，依据2018年3月9日新拟定的中国药品说明书
普利莫®适应症和患者特征
普利莫®批准用于慢性或反复发作的上呼吸道、下呼吸道和尿路感染的辅助治疗。
若患者在近一年内出现6次以上感染，或在过去6个月内出现3次以上感染，则可将其定义为慢性、反复性感染患者。
普利莫®成份
普利莫®活性成份为匹多莫德，一种用作免疫系统调节剂的合成二肽，以及辅料（山梨糖醇，色素等），外观为粉红色口服溶液（全部成分请参见本手册结尾处）。
匹多莫德作用机制：
已证实匹多莫德通过先天性和适应性反免疫应答刺激免疫调节活性。动物和人体受试者的体外研究表明，匹多莫德可增加TLR2蛋白表达、诱导树突状细胞成熟，同时增加促炎分子释放、上调HLA-DR表达，刺激T淋巴细胞增殖并向Th1表型分化、抑制胸腺细胞凋亡和促进吞噬作用（Exposito 2015）。
普利莫®注意事项和禁忌：
年龄:普利莫®批准用于3岁以上儿童和成人。未获得3岁以下或老年人群的充分数据。
过敏：有过敏史的患者应慎用。若已知对山梨糖醇（一种糖）、色素或其他药物成分过敏者，也应慎用。
孕妇和哺乳期妇女用药：尽管动物实验无生殖毒性，与大多数其他药物一样，妊娠三个月内的妇女应避免使用本产品，并/或避免哺乳。
与其他药物合用：若正服用其他免疫系统药物，请慎用。与其他药物的相互作用未见报告。
伴有其他疾病时使用：患有罕见先天性免疫缺陷（高lgE综合征）的患者慎用。
普利莫®剂量：
普利莫®为每瓶400mg的口服溶液。
批准日剂量：儿童为1瓶（每瓶400mg）、每天两次；成年人为2瓶（每瓶400mg）、每天两次。
由于食物会干扰本品的吸收，须空腹服用，用药后过一段时间再进食。
治疗时间超过60天未获得批准。
普利莫®疗效和暴露：
涉及2800多名儿童和成人患者的13项已发表的随机、安慰剂对照临床研究已证实，经普利莫®治疗后，感染的次数和严重程度、抗生素的使用量、解热药的使用量、住院天数和其他反复感染相关参数的减少均有统计学显著性和临床相关性。
在90年代首次批准后，以上结果同样在已发表的超过25项、对照或非对照观察性研究（包括中国在内的2500多名患者）中得到了证实。
在本品获批上市的23个国家中，约有超过300万名患者（其中5/6为儿童）接受过普利莫®治疗。
普利莫®耐受性和安全性：
偶见皮肤过敏反应（皮疹，瘙痒...），偶见消化系统症状（腹泻，腹痛......）和其他已报告的不良反应。
对驾驶或操作机器无影响。
尚无使用本品药物过量的报道，若出现药物过量，催吐，并立即联系医生。
普利莫®药代动力学
本品口服吸收迅速，半衰期（T1/ 2）为4小时。
与禁食状态下给药相比，与食物同时口服时，生物利用度降低50%，血浆浓度到达最大值时晚2小时。
匹多莫德完全经尿液排出。严重的肾功能不全（血浆肌酐浓度5mg/dl），匹多莫德的消除半衰期不超过8〜9小时。尚未进行肝功能不全患者的研究，因为本品几乎完全以原型经尿液排泄。
普利莫®的贮藏：
普利莫®的贮藏无特殊要求。
有效期：请勿在印刷的有效期之后使用本品。
其他普利莫®信息：
普利莫完整处方：匹多莫德，氯化钠，糖精钠，乙二酸四乙酸钠，缓血酸铵，羟甲基苯甲酸钠，羟丙基苯甲酸钠，70%山梨醇溶液，红浆果香精，花青素55，E124，水。
普利莫生产商：多帕药业工业有限公司
普利莫在中国销售代理商：那区地区先锋医药有限公司
指南起草日期：2018年/4月20日
PolimodOral Solution China
Physician’s Information Leaflet
14/March/2017, based on China 09/March/2018 ‘Package insert’
Polimodindication and patient features
Polimodis approved for the adjuvant treatment of chronic upper respiratory tract,lower respiratory tract and urinary infections.
Patientswith more than 6 of these infections in the last year or three infections inthe last 6 months can be defined as chronic, recurrent infections patients.
Polimod composition
Polimodactivemoleculeis pidotimod, asynthetic dipeptide acting as an immune systemmodulator, plus excipients (sorbitol, colorings and others), presented as anoral intake pink liquid solution (please see full composition at the end ofthis leaflet).
Pidotimod mode of action:
Pidotimodhas demonstrated to stimulatethe immunomodulatoryactivity on both innate and adaptive responses. Higher expression of TLR2proteins, induction of dendritic cell maturation accompanied by an increasedrelease of pro-inflammatory molecules, upregulation of the expression ofHLA-DR, stimulation of T lymphocyte proliferation and differentiation toward aTh1 phenotype, inhibition of thymocyte cell death and promotion of phagocytosishave all been demonstrated in in vitro studies in both animal and humansubjects (Exposito 2015).
Polimod prescription precautions and contraindications:
Age:Polimod is approved for use beyond 3 years of age and adults. Not enough dataare available for younger than 3 years of age or elderly people.
Allergies: Patientswith history of allergies should use this product with caution. Allergies topidotimod, sorbitol, colorings or other medication contents (see composition atthe end of the leaflet) should be taken into account if known. Please ask the patientabout his/her allergies history.
Pregnancy andlactation: Although animal experiments have shown that thisproduct does not have any effect on reproduction, women at the first trimesterof pregnancy should avoid of use this product and also avoid lactation.
Use with othermedications: Use with care if other immune system actingmedications are taken. No interaction with other medications has been reported.
Use with other diseases: patients diagnosed with the congenitalimmunodeficiency high lgE syndromeshould use this product with caution.
Polimod dosage:
Polimodis provided as 400 mg bottles of drinkable solution.
Theapproved daily dose is 1 bottle of 400 mg twice a day in children, and two 400mg bottles twice a day in adults.
Foodaffects the absorption of this product, so it should betaken with an emptystomach and there should be an interval between a dose intake and the next meal.
Treatmentlength beyond 60 days is not approved.
Polimod efficacy and exposure:
Polimodhas demonstrated to reduce with statistical significance and clinical relevancethe number and severity of infections, the use of antibiotics, the use of antipyretics,the days of hospitalization and other recurrent infections related parametersin 13 published randomized placebo controlled clinical trials involving > 2800children and adult patients.
Theseresults have been reproduced in more than 25 published observational controlledor uncontrolled studies carried out since its first approval in the ‘90s,involving > 2000 patients, mostly in China.
It isestimated that more than 3 million patients, 5/6 of them children, have beenprescribed Polimod across the 23 countries where the product is approved.
Polimod tolerability and safety:
Occasionalskin allergic reactions (with rash, itching and, rarely, angioedema,…), occasional digestive symptoms (diarrhea, abdominalpain…) and others have been reported.
Noeffect on driving or using machinery has been described.
Inoverdose cases, while no cases have been reported, the conventional methodsshould be used to get the product out of the patients, for example, to inducevomiting.
Polimodpharmacokinetics
The absorption of this product is fast anditshalf-life(T1/2) is 4 hours.
When it is administrated together with food instead offasting conditions the product bioavailability is reduced by half and plasmaconcentrations reach its maximum 2 hours later.
Pidotimod is excreted completely by urine. Patients withsevere renal insufficiency (plasma creatinine ≥ 5mg/dl), the eliminationhalf-life of Pidotimod will increase to 8-9 hours.
Studies have not yet been performed on the patientwith hepatic insufficiency since the product is almost completely excreted byurine.
Conservation of Polimod:
There are nospecial requirements for conservation of Polimod.
Expiry date: Thisproduct should not be used after the printed expiry date.
Other Polimodinformation:
Polipmodfull composition: Pidotimod, Sodium chloride,Sodium saccharin, Sodium edetate, Tromethamine, Sodium ehthyl hydroxybenzoate,Sodium propyl hydroxybenzoate, 70% sorbitaol solution, Wild fruit aroma,Anthocynanin 55, E 124 and water.
Polimodismanufactured by DOPPEL FARMACEUTICI S.R.L.
Polimodis commercialized in China by Naqu Area Pioneer PharmaCo. Ltd.
Date of leaflet approval: 20/April/2018
微信：Pioneer20131105
Stock Code：01345.HK