药品英文名
 
Acrasin
 
药品别名
 
多黏菌素E、哥利迈仙、抗敌素、可立斯丁、可利迈仙、黏杆菌素、Polymyxin E、Colimycine、Colimycin-S、Colistin、Colistinum、Coly-Mycin S、Kangdise、Colistin
 
药物剂型
1.片剂：12.5万U，25万U，50万U，100万U，300万U；
2.注射用黏菌素：100万U；3.黏菌素硫酸盐注射剂(黏菌素硫酸盐1mg相当于3万单位)：50万U。
 
药理作用
 
黏菌素属多黏菌素类。多黏菌素为一复合体，是从产孢子的多黏杆菌培养滤液中分离出的一组抗生素。有A、B、C、D、E五种不同的结构，由不同的菌株产生。
多黏菌素A、C和D毒性较大，已淘汰，临床常用者为多黏菌素B和多黏菌素E。
黏菌素抗菌作用机制主要是作用于细菌细胞膜，使胞内重要物质外漏而起杀菌作用。当本药与细菌细胞膜接触时，其亲水基团与细胞外膜磷脂上的磷酸基形成复合物，而亲脂链则可立即插入膜内脂肪链之间，因而解聚细胞膜结构，导致膜通透性增加，使细菌细胞内的重要物质外漏而造成细胞死亡。
另外，黏菌素进入细菌细胞质后，也影响核质和核糖体的功能。
黏菌素属窄谱抗生素，只对革兰阴性杆菌(变形杆菌属除外)及铜绿假单胞菌具有强大抗菌活性。沙雷菌属、脑膜炎球菌、淋球菌属、布鲁菌属、霍乱埃尔托型以及所有革兰阳性球菌均对黏菌素耐药。
黏菌素抗菌谱包括大肠埃希菌、肠杆菌属、克雷白菌属、铜绿假单胞菌、志贺菌属、沙门菌属、真杆菌属、流感杆菌、百日咳杆菌及除脆弱类杆菌外的其他类杆菌。
 
药动学
 
黏菌素口服很少吸收，皮肤创面也不易吸收。肌内注射后血药浓度也较低。成人肌内注射本药甲烷磺酸盐，2h后达血药峰浓度。儿童单剂肌内注射本药甲烷磺酸盐2.5mg/kg，1～2h后达血药峰浓度，约为5～7mg/L。药物吸收后在肝、脑、心、肌肉和肺组织中有一定的分布(在肺、肾、肝及脑组织中的浓度比多黏菌素B高)，本药分子量相对较大，不易渗入胸腔、关节腔和感染灶内，也难以透入脑脊液中。本药蛋白结合率较低。成人消除半衰期约为6h，儿童消除半衰期约为1.6～2.7h；肾功能不全时，半衰期可延长。药物在体内代谢缓慢，主要经肾脏排泄，肾排泄率可达60%。但给药后12h内仅有0.1%经尿液排出，随后才逐渐增加。连续给药会导致药物在体内蓄积(连续给药尿药浓度可达20～100mg/L)。本药不经胆汁排泄，未排泄药物在体内缓慢灭活。因黏菌素分子量较大，腹膜透析、血液透析难以消除药物。
 
适应证
 
1.适用于治疗对其他抗生素耐药的铜绿假单胞菌和其他革兰阴性杆菌(变形杆菌除外)引起的严重感染。如铜绿色假单胞菌败血症、铜绿色假单胞菌脑膜炎、大肠杆菌性肠炎、泌尿道感染等。
2.口服用于白血病伴中性粒细胞缺乏者的细菌感染预防。
3.口服还可用于肠道手术前准备，以抑制肠道菌群。
4.外用于烧伤和外伤引起的铜绿色假单胞菌局部感染和耳、眼等部位敏感菌所致感染。
 
禁忌证
 
尚不明确。
 
注意事项
 
1.慎用：
(1)孕妇及哺乳期妇女慎用；
(2)肾功能不全者慎用。
2.长期用药时应监测尿常规及肾功能。
 
不良反应
 
黏菌素在常用量下即可出现明显不良反应，总发生率可高达25%。
主要不良反应为肾毒性、神经毒性和变态反应等。
1.肾毒性：肾毒性为本药最突出和最常见的不良反应，发生率约为22.2%(发生率比多黏菌素B低)。肾小管上皮细胞损伤最明显，主要表现为蛋白尿、血尿和管型尿，毒性进一步加重时可出现血清肌酐及尿素氮升高，直至急性肾小管坏死，但停药常可恢复。肾毒性一般发生在用药后4天内，有时停药后肾损害仍能继续加重。
2.神经毒性：轻者表现为头晕、面部麻木和周围神经炎，严重时出现意识混乱、昏迷、共济失调等。也可出现可逆性神经肌肉阻滞，症状发生迅速且无先兆。神经毒性发生时间与肾毒性相似，停药后可消失。
3.过敏反应：少数患者用药后可出现瘙痒、皮疹和药物热等过敏症状，气溶吸入可引起支气管痉挛。.胃肠道反应：口服本药后可出现恶心、呕吐、食欲减退、腹泻等胃肠道症状。
5.局部反应：肌内或静脉给药时可致注射部位疼痛、硬结，严重者可致血栓性静脉炎。
6.其他：用药后偶诱发白细胞减少和肝毒性。
 
用法用量
 
1.成人：
(1)口服给药：每天100万～150万U，分2～3次服用；重症时剂量可加倍；
(2)肌内注射：黏菌素硫酸盐，每天100万～150万U；
(3)静脉滴注：黏菌素硫酸盐，每天100万～150万单位；
(4)鞘内给药：每天1次，每次5mg，共3～4天；以后每次5mg，隔日1次。至少维持到脑脊液培养转阴，糖含量恢复正常2周后；
(5)局部给药：1万～5万U/ml，用氯化钠注射剂溶解，涂于患处；
(6)肾功能不全时剂量：本药的肾毒性与剂量相关，因此，应根据肌酐清除率或血中肌酐水平提示的肾功能情况来调整剂量。①肌酐清除率正常或＞正常80%，每天2.5～3mg/kg；
②肌酐清除率为正常80%至＞正常30%，第1天2.5mg/kg，以后每天1～1.5mg/kg；
③肌酐清除率＜正常30%，第1天2.5mg/kg，以后每2～3天1～1.5mg/kg；
④无尿时，第1天2.5mg/kg，以后每5～7天1mg/kg。
2.儿童：(1)口服给药：每天量2万～3万U/kg，分2～3次服用。(2)肌内注射：多黏菌素E硫酸盐，每天2万～3万U/kg；(3)静脉滴注：多黏菌素E硫酸盐，每天2万～3万U/kg；
(4)鞘内给药：
①对2岁以上儿童：每天1次，每次5mg，共3～4天，以后每次5mg，隔日1次。以上至少维持到脑脊液培养转阴，糖含量恢复正常2周后；
②对2岁以下儿童：每次2mg，每天1次，共3～4天；或2.5mg，隔日1次。以上至少维持到脑脊液培养转阴，糖含量恢复正常2周后；
(5)局部给药：1万～5万u/ml，用氯化钠注射剂溶解，涂于患处。
药物相应作用
 
1.黏菌素与利福平合用呈协同抗菌作用。
2.黏菌素与磺胺类药和(或)TMP联合应用，可增强黏菌素对大肠杆菌、肠杆菌属、肺炎杆菌和铜绿假单胞菌等敏感菌的抗菌作用。且联用时对耐黏菌素的沙雷菌属、变形杆菌属也呈协同抗菌作用。
3.黏菌素与能酸化尿液的药物合用可增强其抗菌活性。
4.黏菌素低浓度时能促进四环素透过真菌细胞膜而抑制其蛋白合成。
5.黏菌素与氨基糖苷类、万古霉素、甲氧西林等同用可增加肾毒性。
6.黏菌素与头孢噻吩同用易发生肾毒性。
7.黏菌素与箭毒、肌肉松弛剂和麻醉药同用可增强其神经肌肉阻滞作用。
 
 专家点评
 
本品为慢效杀菌剂，对生长繁殖期和静止期细菌均有杀菌作用。黏菌素的抗菌谱与多黏菌素B相似，但抗菌活性稍弱于后者 黏菌素副作用;

别名:多黏菌素E、哥利迈仙、抗敌素、可立斯丁、可利迈仙、黏杆菌素、Polymyxin E、Colimycine、Colimycin-S、Colistin、Colistinum、Coly-Mycin S、Kangdise、Colistin;
黏菌素适应症:
1.适用于治疗对其他抗生素耐药的铜绿假单胞菌和其他革兰阴性杆菌(变形杆菌除外)引起的严重感染。如铜绿色假单胞菌败血症、铜绿色假单胞菌脑膜炎、大肠杆菌性肠炎、泌尿道感染等。
2.口服用于白血病伴中性粒细胞缺乏者的细菌感染预防。
3.口服还可用于肠道手术前准备，以抑制肠道菌群。
4.外用于烧伤和外伤引起的铜绿色假单胞菌局部感染和耳、眼等部位敏感菌所致感染。;黏菌素药理学作用:黏菌素属多黏菌素类。多黏菌素为一复合体，是从产孢子的多黏杆菌培养滤液中分离出的一组抗生素。有A、B、C、D、E五种不同的结构，由不同的菌株产生。
多黏菌素A、C和D毒性较大，已淘汰，临床常用者为多黏菌素B和多黏菌素E。
黏菌素抗菌作用机制主要是作用于细菌细胞膜，使胞内重要物质外漏而起杀菌作用。当本药与细菌细胞膜接触时，其亲水基团与细胞外膜磷脂上的磷酸基形成复合物，而亲脂链则可立即插入膜内脂肪链之间，因而解聚细胞膜结构，导致膜通透性增加，使细菌细胞内的重要物质外漏而造成细胞死亡。
另外，黏菌素进入细菌细胞质后，也影响核质和核糖体的功能。
黏菌素属窄谱抗生素，只对革兰阴性杆菌(变形杆菌属除外)及铜绿假单胞菌具有强大抗菌活性。沙雷菌属、脑膜炎球菌、淋球菌属、布鲁菌属、霍乱埃尔托型以及所有革兰阳性球菌均对黏菌素耐药。黏菌素抗菌谱包括大肠埃希菌、肠杆菌属、克雷白菌属、铜绿假单胞菌、志贺菌属、沙门菌属、真杆菌属、流感杆菌、百日咳杆菌及除脆弱类杆菌外的其他类杆菌。

多黏菌素E的其它制剂

COLY-MYCIN S OTIC 5ML
(NEOMY SULF/COLIST SUL/HC/THONZ)

DESCRIPTION

Coly-Mycin®S Otic with Neomycin and Hydrocortisone (colistin sulfate—neomycin sulfate—thonzonium bromide—hydrocortisone acetate otic suspension) is a sterile antibacterial and anti-inflammatory aqueous suspension containing in each mL: Colistin base activity, 3 mg (as the sulfate); Neomycin base activity, 3.3 mg (as the sulfate); Hydrocortisone acetate, 10 mg (1%); Thonzonium bromide, 0.5 mg (0.05%); Polysorbate 80, acetic acid, and sodium acetate in a buffered aqueous vehicle. Thimerosal (mercury derivative), 0.002%, is added as a preservative. It is a nonviscous liquid, buffered at pH 5, for instillation into the canal of the external ear or direct application to the affected aural skin.

The structural formulas of colistin sulfate (mixture of Colistin A & B), neomycin sulfate (mixture of neomycin A, B & C), hydrocortisone acetate ((11β)-21-(acetyloxy)-11,17-dihydroxypregn) methyl]-2 pyrimidinylamino] ethyl]-N,N-dimethyl-1-hexadecanaminium, bromide) are represented below:

CLINICAL PHARMACOLOGY

Colistin sulfate is a polypeptide antibiotic which penetrates into and disrupts the bacterial cell membrane. Neomycin sulfate is an aminoglycoside antibiotic which inhibits protein synthesis, disrupting the normal cycle of ribosomal function. Hydrocortisone acetate is a corticosteroid hormone which is thought to act by regulating the rate of protein synthesis; it controls inflammation, edema, pruritus and other dermal reactions. Cortiscosteroids suppress the inflammatory response to a variety of agents and they may delay healing. Since corticoids may inhibit the body's defense mechanism against infection, a concomitant antimicrobial drug may be used when this inhibition is considered to be clinically significant in a particular case.

The relative potency of corticosteroids depends on the molecular structure, concentration, and release from the vehicle.

Thonzonium bromide is a surface-active agent that promotes tissue contact by dispersion and penetration of the cellular debris and exudate.

Microbiology

Together, colistin sulfate and neomycin sulfate have bactericidal activity against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Aerobic gram-positive microorganisms:

Staphylococcus aureus.

Aerobic gram-negative microorganisms:

Enterobacter aerogenes

Escherichia coli

Klebsiella pneumoniae

Pseudomonas aeruginosa.

Susceptibility Tests

It is not recommended that colistin sulfate or neomycin sulfate be routinely tested and reported by clinical microbiology laboratories.

INDICATIONS AND USAGE

Coly-Mycin®S Otic is indicated for the treatment of superficial bacterial infections of the external auditory canal, caused by organisms susceptible to the action of the antibiotics; and for the treatment of infections of mastoidectomy and fenestration cavities, caused by organisms susceptible to the antibiotics.

CONTRAINDICATIONS

This product is contraindicated in those individuals who have shown hypersensitivity to any of its components.

This product should not be used if the external auditory canal disorder is suspected or known to be due to cutaneous viral infection (e.g., herpes simplex virus or varicella zoster virus).

WARNINGS

Neomycin can induce permanent sensorineural hearing loss due to cochlear damage, mainly destruction of hair cells in the organ of Corti. The risk is greater with prolonged use. Therapy should be limited to 10 consecutive days. (See PRECAUTIONS-General.) Patients being treated with eardrops containing neomycin should be under close clinical observation. Coly-Mycin® S Otic should be used cautiously in any patient with a perforated tympanic membrane.

Neomycin sulfate may cause cutaneous sensitization. A precise incidence of hypersensitivity reactions (primarily skin rash) due to topical neomycin is not known. Discontinue promptly if sensitivity or irritation occurs.

When using neomycin-containing products to control secondary infection in the chronic dermatoses, such as chronic otitis externa or stasis dermatitis, it should be borne in mind that the skin in these conditions is more liable than is normal skin to become sensitized to many substances, including neomycin. The manifestation of sensitization to neomycin is ususally a low-grade reddening with swelling, dry scaling, and itching; it may be manifest simply as a failure to heal. Periodic examination for such signs is advisable, and the patient should be told to discontinue the product if they are observed. These symptoms regress quickly on withdrawing the medication. Neomycin containing applications should be avoided for the patient thereafter.

PRECAUTIONS

General

As with any other antibiotic preparation, prolonged treatment may result in overgrowth of nonsusceptible organisms and fungi. If the infection is not improved after one week, cultures should be repeated to verify the identity of the organism and to determine whether therapy should be changed.

Treatment should not be continued for longer than ten days.

Allergic cross-reactions may occur which could prevent the use of any or all of the aminoglycoside antibiotics for the treatment of future infections.

Information for Patients

Avoid contaminating the dropper with material from the ear, fingers, or other source. This caution is necessary if the sterility of the drops is to be preserved.

If sensitization or irritation occurs, discontinue use immediately and contact your physician.

Do not use in the eyes.

If you prefer to warm the medication before using it, do not heat the suspension above body temperature in order to avoid loss of potency.

SHAKE WELL BEFORE USING.

Laboratory Tests

Systemic effects of excessive levels of hydrocortisone may include a reduction in the number of circulating eosinophils and a decrease in urinary excretion of 17-hydroxycorticosteroids.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal carcinogenicity studies have not been performed with colistin or neomycin, or Coly-Mycin® S Otic. An increased incidence of chromosome aberrations in human lymphocytes has been reported following in vitro exposure to colistin or neomycin.

Fertility studies have not been performed with neomycin, but reports from the scientific literature suggest that it may decrease spermatogenesis in rats. No adverse effects on fertility were observed in male or female rats given intramuscular doses of colistimethate sodium, the methanesulfonate salt of colistin, up to 20 mg/kg (equivalent to 9.3 mg/kg of colistin base). This is approximately 30 times the clinical daily dose based on body surface area, assuming 100% absorption from the ear; however, significant systemic levels of colistin or neomycin would not be anticipated in humans when Coly-Mycin®S Otic is used as directed.

Long term studies in rodents showed no evidence of carcinogenicity attributable to oral administration of corticosteroids. Mutagenicity studies with hydrocortisone were negative. Studies have not been performed to evaluate the effect on fertility of topical corticosteroids.

Pregnancy

Teratogenic Effects

Pregnancy Category C

There are no adequate and well controlled studies of Coly-Mycin®S Otic in pregnant women. It is not known whether Coly-Mycin® S Otic can cause fetal harm when administered to a pregnant woman.

Colistimethate sodium, the methanesulfonate salt of colistin, was not teratogenic in rats or rabbits given intramuscular doses up to 20 mg/kg (equivalent to 9.3 mg/kg of colisitin base, approximately 30 times (rats) or 55 times (rabbits) the clinical daily dose based on body suface area and assuming 100% absorption from the ear). Increased resorptions were observed in rabbits at 20 mg/kg, but not 10 mg/kg (equivalent to 4.15 mg/kg of colistin base). Decreased pup survival at weaning was observed in rats at 20 mg/kg, a maternally toxic dose of colistin, but not 10 mg/kg. Colistin has not been shown to have any adverse effects on the developing embryo or fetus at doses relevant to the amount that will be delivered ototopically at the recommended clinical doses.

Although aminoglycosides can cause congenital deafness in humans if administered during pregnancy, significant systemic levels of neomycin would not be anticipated when Coly-Mycin®S Otic is used as directed.

Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.

Coly-Mycin®S Otic should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Hydrocortisone and colistin sulfate appear in human milk following oral administration of the drugs. Since systemic absorption of these drugs may occur when they are used topically, caution should be exercised when Coly-Mycin®S Otic Suspension is used by a nursing woman.

Pediatric Use

See DOSAGE AND ADMINISTRATION.

The safety and effectiveness of Coly-Mycin® S Otic in infants below one year of age have not been established. The efficacy of Coly-Mycin® S Otic in pediatric patients one year or older in the treatment of superficial bacterial infections of the external auditory canal and for the treatment of infections of mastoidectomy and fenestration cavities has been demonstrated in a controlled clinical trial.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

ADVERSE REACTIONS

Neomycin occasionally causes skin sensitization.

Ototoxicity (see WARNINGS section) and nephrotoxicity have also been reported.

Adverse reactions have occurred with topical use of antibiotic combinations. Exact incidence figures are not available since no denominator of treated patients is available. The reaction occurring most often is allergic sensitization. In one clinical study, using a 20% neomycin patch, neomycin-induced allergic skin reactions occurred in two of 2,175 (0.09%) individuals in the general populaton. In another study the incidence was found to be approximately 1%.

The following local adverse events have been reported with topical corticosteroids, especially under occlusive dressings: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria.

For medical advice about adverse reactions contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact JHP at 1-866-923-2547 or MEDWATCH at 1-800-FDA-1088 (1-800-332-1088) or .

DOSAGE AND ADMINISTRATION

Therapy with this product should be limited to 10 days. (See WARNINGS.)

The external auditory canal should be thoroughly cleansed and dried with a sterile cotton applicator.

When using the calibrated dropper:

For adults, 5 drops of the suspension should be instilled into the affected ear 3 or 4 times daily. For pediatric patients, 4 drops are suggested because of the smaller capacity of the ear canal.

The patient should lie with the affected ear upward and then the drops should be instilled. This position should be maintained for 5 minutes to facilitate penetration of the drops into the ear canal. Repeat, if necessary, for the opposite ear.

If preferred, a cotton wick may be inserted into the canal and then the cotton may be saturated with the suspension. This wick should be kept moist by adding further solution every 4 hours. The wick should be replaced at least once every 24 hours.

HOW SUPPLIED

Coly-Mycin®S Otic is supplied as:

NDC 42023-108-01 ............... 5 mL bottle with dropper

Each mL contains: Colistin sulfate equivalent to 3 mg of colistin base activity, Neomycin sulfate equivalent to 3.3 mg neomycin base activity, Hydrocortisone acetate 10 mg (1%), Thonzonium bromide 0.5 mg (0.05%), and Polysorbate 80 in an aqueous vehicle buffered with acetic acid and sodium acetate. Thimerosal (mercury derivative) 0.002% is added as a preservative.

A sterilized dropper-cap assembly for use on the bottle of suspension is included in the package.

Shake well before using.

Store at 20°–25°C (68°–77°F).

Rx only.

Prescribing Information as of June 2009

Manufactured by: JHP Pharmaceuticals, LLC, Rochester, MI 48307

3000821C

PRINCIPAL DISPLAY PANEL - 5 mL Bottle Label

NDC 42023-108-01

Coly-Mycin® S Otic
with Neomycin and
Hydrocortisone

STERILE

5 mL