英文药名: Vancocin (Vancomycin Capsules)

中文药名: 万古霉素胶囊

药品别名
 
稳可信、万刻林、凡可霉素、无菌盐酸万古霉素、Vancocin、VancocinCP、Vancomycin HCl
 
药物剂型
 
1.注射剂（粉)（盐酸)：0.5g，1g；2.胶囊：120mg，250mg。
 
 药理作用
 
万古霉素是由东方链霉菌培养液中所得的一种糖肽类抗生素，盐酸万古霉素为其盐酸盐。其作用机制是以高亲和力结合到敏感细菌细胞壁前体肽聚末端的丙氨酰丙氨酸，阻断构成细菌细胞壁的高分子肽聚糖合成，导致细胞壁缺损而杀灭细菌。此外，它也可能改变细菌细胞膜渗透性，并选择性地抑制RNA的合成。
本药作用特点是对革兰阳性球菌有强大的杀菌作用；口服给药对治疗难辨梭状芽胞杆菌假膜性结肠炎有极好疗效。盐酸万古霉素对化脓性链球菌、肺炎链球菌、金黄色葡萄球菌、表皮葡萄球菌等有较强的抗菌活性；对厌氧链球菌、难辨梭状芽胞杆菌、炭疽杆菌、放线菌、白喉杆菌、淋球菌、绿色链球菌、牛链球菌、粪链球菌等也有一定抗菌作用。本药对多数革兰阴性菌、分枝杆菌属、拟杆菌属、立克次体属、衣原体属或真菌均无效。
 
 药动学
 
盐酸万古霉素胃肠道吸收不良，因此主要通过静脉全身给药。静脉滴注0.5g、1.0g，血药峰浓度分别为10～30mg/L、25～50mg/L。本药分布容积为0.43～1.25L/kg。药物吸收后可广泛分布于全身大多数组织和体液内。其中在血清、胸膜、心包、腹膜、腹腔积液和滑膜液中可达有效抑菌浓度，在尿中浓度较高，但在胆汁中不能达有效抑菌浓度。药物可透过胎盘，也可进入乳汁，但本药不能迅速透过正常血-脑脊液屏障进入脑脊液中，在脑膜发炎时可渗入脑脊液中并达有效抗菌浓度。本药蛋白结合率约为55%。成人半衰期平均为6h(4～11h)，肾功能不全者半衰期可延长至7.5天；小儿半衰期约为2～3h。药物可能经肝脏代谢。给药量中约80%～90%在24h内由肾小球滤过经尿以原形排泄，少量经胆汁排出。血液透析或腹膜透析不能有效清除本药，但血液灌注或血液过滤能有效地将药物从血中清除。
 
 适应证
 
1.本药是肠球菌心内膜炎、棒状杆菌属(类白喉杆菌属)心内膜炎患者在对青霉素类药过敏时的首选用药。
2.口服适用于治疗抗生素相关性假膜性结肠炎经甲硝唑治疗无效者，或多重耐药葡萄球菌小肠结肠炎。
3.静脉给药适用于治疗葡萄球菌(包括甲氧西林耐药菌株和多重耐药菌株)所致心内膜炎、骨髓炎、肺炎、败血症或软组织感染等。
4.静脉给药也适用于治疗对青霉素类或头孢菌素类药过敏，或经上述抗生素治疗无效的严重葡萄球菌所致感染。
静脉给药还可用于治疗对青霉素过敏或不过敏的血液透析患者发生葡萄球菌属所致动、静脉分流感染。
 
 禁忌证
 
对本药过敏者。
 
 注意事项
 
1.慎用：
(1)肾功能不全者；
(2)听力减退或耳聋者；
(3)孕妇：
(4)哺乳期妇女。
2.药物对老人的影响：本药用于年老患者有引起耳毒性与肾毒性的高度危险(听力丧失)。由于老年患者随年龄增长肾功能减退，因此确有指征使用时必须调整剂量。
3.少数患者用药后可出现尿素氮(BUN)升高。
4.长期用药时应定期检查听力；长期用药时应定期监测肾功能及尿液中蛋白、管型、细胞数和尿比重；用药中应注意监测血药浓度，尤其是需延长疗程或有肾功能减退、听力减退、耳聋病史的患者。血药峰浓度不应超过25～40mg/L，谷浓度不应超过5～10mg/L。血药峰浓度高于50mg/L，谷浓度高于10mg/L者为中毒范围。
 
不良反应
 
1.耳毒性：可出现听神经损害、听力减退甚至缺失、耳鸣或耳部饱胀感。在大剂量和长时间应用时尤易发生。
2.肾毒性：主要损害肾小管。早期可有蛋白尿、管型尿、继之出现血尿、尿量或排尿次数显著增多或减少等，严重者可致肾衰竭。在大剂量(血药浓度超过60～100mg/L)和长时间应用时尤易发生。
3.变态反应：快速大剂量静脉给药，少数患者可出现“红颈综合征”。症状有寒战或发热、昏厥、瘙痒、恶心或呕吐、心动过速、皮疹或面潮红；颈根、上身、背、臂等处发红或麻刺感(释放组胺)，偶有低血压和休克样症状。其发生率高于去甲万古霉素和替考拉宁。
4.过敏反应：少数患者用药可出现皮肤瘙痒、药物热等过敏反应症状，偶见过敏性休克。
5.消化系统：口服给药可引起恶心、呕吐等胃肠道症状。
6.其他：肌注或静脉注射时可致注射部位剧烈疼痛，严重者可致血栓性静脉炎。
 
用法用量
 
1.成人：
(1)口服给药：抗生素相关性假膜性结肠炎及难辨梭状芽胞杆菌引起的假膜性结肠炎，经甲硝唑治疗无效者，每次125～500mg，每6小时1次，维持5～10天，每天剂量不宜超过4g。
(2)静脉滴注：
①心瓣膜修补或瓣膜心脏病手术(伴青霉素过敏)前预防：于术前1h静脉滴注1g，8h后重复给药1次；
②全身感染：每6小时静脉滴注7.5mg/kg，或每12小时静脉滴注15mg/kg，对严重的感染患者，可每天静脉滴注3～4g短期应用；③中枢神经系统葡萄球菌感染：最高剂量为每天60mg/kg，分次静脉滴注。
(3)鞘内注射：
①腰椎鞘内给药：每天20mg；
②脑室内滴注：起始量不宜超过5mg，因为在脑脊液内的分布容积相对较小。
(4)肾功能不全时剂量：肾功能减退者给予首次冲击量0.75～1g后，应根据肌酐清除率监测结果调整用药。维持剂量(mg/24h)＝150＋15×患者肌酐清除率。
2.儿童：(1)口服给药：肠道感染可每次10mg/kg，每6小时1次，维持治疗5～10天。(2)静脉滴注：
①心瓣膜修补或瓣膜心脏病手术(伴青霉素过敏)前预防：于术前1h静脉滴注，按20mg/kg，8h后重复给药1次；
②全身感染：婴儿(0～7天)，先用15mg/kg静脉滴注，然后用10mg/kg，每12小时给药1次；婴儿(7天～1个月)，先用15mg/kg静脉滴注，然后用10mg/kg，每8小时给药1次；儿童，每次10mg/kg，每6小时1次，或每次20mg/kg，每12小时1次。
(3)鞘内注射：
①腰椎鞘内给药：新生儿和儿童，每天5～20mg；
②脑室内滴注：起始量不宜超过5mg。
 
药物相应作用
 
1.与氨基糖苷类联用时，对肠球菌有协同抗菌作用。
2.与第三代头孢菌素联用，对金黄色葡萄球菌和肠球菌有协同抗菌作用。
3.与氨基糖苷类合用或先后应用，可增加耳毒性和(或)肾毒性；可能发生听力减退，停药后仍可能继续进展至耳聋，此反应可呈可逆性或永久性。
4.与两性霉素B、杆菌肽(注射)、卷曲霉素、巴龙霉素及多黏菌素类等药物合用或先后应用，可增加耳毒性和(或)肾毒性。
5.与阿司匹林及其他水杨酸盐合用或先后应用，可增加耳毒性和(或)肾毒性。
6.与环孢素合用或先后应用，可增加肾毒性。
7.与依他尼酸注射剂、呋塞米等利尿药合用或先后应用，可增加耳毒性和(或)肾毒性的可能。
8.与琥珀胆碱维库铊等药物合用，可能增强琥珀胆碱维库铊等药物的神经肌肉阻滞作用。
9.与抗组胺药、布克利嗪、赛克力嗪(cyclizine)、吩噻嗪类、噻吨类、曲美苄胺等药合用时，可能掩盖耳鸣、头昏、眩晕等耳毒性症状。
10.与考来烯胺同时口服，因阴离子交换树脂能与其结合，可使药效灭活。11.与麻醉药同用时可增加与输液有关的过敏反应的发生率。 
VANCOCIN^® HCl Capsules

To reduce the development of drug-resistant bacteria and maintain the effectiveness of VANCOCIN® HCl Capsules and other antibacterial drugs, VANCOCIN HCl Capsules should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

This preparation for the treatment of colitis is for oral use only and is not systemically absorbed. VANCOCIN HCl Capsules must be given orally for treatment of staphylococcal entero-colitis and antibiotic-associated pseudo-membranous colitis caused by Clostridium difficile. Orally administered VANCOCIN HCl Capsules are not effective for other types of infection.

Parenteral administration of vancomycin is not effective for treatment of staphylococcal enterocolitis and antibiotic-associated pseudomembranous colitis caused by C. difficile. If parenteral vancomycin therapy is desired, use an intravenous preparation of vancomycin and consult the package insert accompanying that preparation.

DESCRIPTION

VANCOCIN HCl Capsules (Vancomycin Hydrochloride Capsules, USP) contain chromatographically purified vancomycin hydrochloride, a tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis (formerly Nocardia orientalis), which has the chemical formula C66H75Cl2N9O24•HCl. The molecular weight of vancomycin hydrochloride is 1485.73; 500 mg of the base is equivalent to 0.34 mmol.

The capsules contain vancomycin hydrochloride equivalent to 125 mg (0.08 mmol) or 250 mg (0.17 mmol) vancomycin. The capsules also contain F D & C Blue No. 2, gelatin, iron oxide, polyethylene glycol, titanium dioxide, and other inactive ingredients.

Vancomycin hydrochloride has the following structural formula:

CLINICAL PHARMACOLOGY

Vancomycin is poorly absorbed after oral administration. During multiple dosing of 250 mg every 8 hours for 7 doses, fecal concentrations of vancomycin in volunteers exceeded 100 mg/kg in the majority of samples. No blood concentrations were detected and urinary recovery did not exceed 0.76%. Additional data using an oral solution follow. In anephric patients with no inflammatory bowel disease, blood concentrations of vancomycin were barely measurable (0.66 μg/mL) in 2 of 5 subjects who received 2 g of vancomycin HCl for Oral Solution daily for 16 days. No measurable blood concentrations were attained in the other 3 patients. With doses of 2 g daily, very high concentrations of drug can be found in the feces (>3100 mg/kg) and very low concentrations (<1 μg/mL) can be found in the serum of patients with normal renal function who have pseudomembranous colitis. Orally administered vancomycin does not usually enter the systemic circulation even when inflammatory lesions are present. After multiple-dose oral administration of vancomycin, measurable serum concentrations may infrequently occur in patients with active C. difficile-induced pseudomembranous colitis, and, in the presence of renal impairment, the possibility of accumulation exists.

Microbiology

The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other antibiotics.

NOTE: VANCOCIN HCl Capsules are effective only for the infections noted in the INDICATIONS AND USAGE section. The oral form is not effective for any other type of infection.

Vancomycin has been shown to be active against most strains of the following microorganisms in clinical infections as described in the INDICATIONS AND USAGE section.

Aerobic gram-positive microorganisms

Staphylococcus aureus (including methicillin-resistant strains) associated with enterocolitis

Anaerobic gram-positive microorganisms

Clostridium difficile antibiotic-associated pseudomembranous colitis.

INDICATIONS AND USAGE

VANCOCIN HCl Capsules may be administered orally for treatment of enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains) and antibiotic-associated pseudomembranous colitis caused by C. difficile. Parenteral administration of vancomycin is not effective for the above indications; therefore, VANCOCIN HCl Capsules must be given orally for these indications. Orally administered VANCOCIN HCl Capsules are not effective for other types of infection.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of VANCOCIN HCl Capsules and other antibacterial drugs, VANCOCIN HCl Capsules should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

CONTRAINDICATION

VANCOCIN HCl Capsules are contraindicated in patients with known hypersensitivity to vancomycin.

PRECAUTIONS

General

Prescribing VANCOCIN HCl Capsules in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug resistant bacteria.

Clinically significant serum concentrations have been reported in some patients who have taken multiple oral doses of vancomycin for active C. difficile-induced pseudomembranous colitis; therefore, monitoring of serum concentrations may be appropriate in some instances, e.g., in patients with renal insufficiency and/or colitis.

Some patients with inflammatory disorders of the intestinal mucosa may have significant systemic absorption of vancomycin and, therefore, may be at risk for the development of adverse reactions associated with the parenteral administration of vancomycin (see package insert accompanying the intravenous preparation). The risk is greater if renal impairment is present. It should be noted that the total systemic and renal clearances of vancomycin are reduced in the elderly.

Ototoxicity has occurred in patients receiving vancomycin. It may be transient or permanent. It has been reported mostly in patients who have been given excessive intravenous doses, who have an underlying hearing loss, or who are receiving concomitant therapy with another ototoxic agent, such as an aminoglycoside. Serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity.

When patients with underlying renal dysfunction or those receiving concomitant therapy with an aminoglycoside are being treated, serial monitoring of renal function should be performed.

Use of vancomycin may result in the overgrowth of nonsusceptible organisms. If superinfection occurs during therapy, appropriate measures should be taken.

Information for Patients

Patients should be counseled that antibacterial drugs including VANCOCIN HCl Capsules should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When VANCOCIN HCl Capsules are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by VANCOCIN HCl Capsules or other antibacterial drugs in the future.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term carcinogenesis studies in animals have been conducted.

At concentrations up to 1000 μg/mL, vancomycin had no mutagenic effect in vitro in the mouse lymphoma forward mutation assay or the primary rat hepatocyte unscheduled DNA synthesis assay. The concentrations tested in vitro were above the peak plasma vancomycin concentrations of 20 to 40 μg/mL usually achieved in humans after slow infusion of the maximum recommended dose of 1 g. Vancomycin had no mutagenic effect in vivo in the Chinese hamster sister chromatid exchange assay (400 mg/kg IP) or the mouse micronucleus assay (800 mg/kg IP).

No definitive fertility studies have been conducted.

Pregnancy

Teratogenic Effects — Pregnancy Category B — The highest doses of vancomycin tested were not teratogenic in rats given up to 200 mg/kg/day IV (1180 mg/m2 or 1 times the recommended maximum human dose based on mg/m2) or in rabbits given up to 120 mg/kg/day IV (1320 mg/m2 or 1.1 times the recommended maximum human dose based on mg/m2). No effects on fetal weight or development were seen in rats at the highest dose tested or in rabbits given 80 mg/kg/day (880 mg/m2 or 0.74 times the recommended maximum human dose based on mg/m2).

In a controlled clinical study, the potential ototoxic and nephrotoxic effects of vancomycin HCl on infants were evaluated when the drug was administered intravenously to pregnant women for serious staphylococcal infections complicating intravenous drug abuse. Vancomycin was found in cord blood. No sensorineural hearing loss or nephrotoxicity attributable to vancomycin HCl was noted. One infant whose mother received vancomycin HCl in the third trimester experienced conductive hearing loss that was not attributed to the administration of vancomycin HCl. Because the number of patients treated in this study was limited and vancomycin HCl was administered only in the second and third trimesters, it is not known whether vancomycin HCl causes fetal harm. Because animal reproduction studies are not always predictive of human response, VANCOCIN HCl Capsules should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Vancomycin is excreted in human milk based on information obtained with the intravenous administration of vancomycin HCl. However, systemic absorption of vancomycin is very low following oral administration of VANCOCIN HCl Capsules (see CLINICAL PHARMACOLOGY). It is not known whether oral vancomycin is excreted in human milk, as no studies of vancomycin concentration in human milk after oral administration have been done. Caution should be exercised when VANCOCIN HCl Capsules are administered to a nursing woman. Because of the potential for adverse events, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of vancomycin HCl for oral use did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Clinically significant serum concentrations have been reported in some patients who have taken multiple oral doses of vancomycin HCl for active C. difficle-induced pseudomembranous colitis; therefore, monitoring of serum concentrations may be appropriate in some instances, e.g., in patients with renal insufficiency and/or colitis. Some patients with inflammatory disorders of the intestinal mucosa may have significant systemic absorption of vancomycin and, therefore, may be at risk for the development of adverse reactions associated with the parenteral administration of vancomycin. The risk is greater if renal impairment is present. It should be noted that the total systemic and renal clearances of vancomycin are reduced in the elderly (see PRECAUTIONS, General).

ADVERSE REACTIONS

Nephrotoxicity — Rarely, renal failure, principally manifested by increased serum creatinine or BUN concentrations, especially in patients given large doses of intravenously administered vancomycin HCl has been reported. Rare cases of interstitial nephritis have been reported. Most of these have occurred in patients who were given aminoglycosides concomitantly or who had preexisting kidney dysfunction. When vancomycin HCl was discontinued, azotemia resolved in most patients.

Ototoxicity — A few dozen cases of hearing loss associated with intravenously administered vancomycin HCl have been reported. Most of these patients had kidney dysfunction or a preexisting hearing loss or were receiving concomitant treatment with an ototoxic drug. Vertigo, dizziness, and tinnitus have been reported rarely.

Hematopoietic — Reversible neutropenia, usually starting 1 week or more after onset of intravenous therapy with vancomycin HCl or after a total dose of more than 25 g, has been reported for several dozen patients. Neutropenia appears to be promptly reversible when vancomycin HCl is discontinued. Thrombocytopenia has rarely been reported.

Miscellaneous — Infrequently, patients have been reported to have had anaphylaxis, drug fever, chills, nausea, eosinophilia, rashes (including exfoliative dermatitis), Stevens-Johnson syndrome, toxic epidermal necrolysis, and rare cases of vasculitis in association with the administration of vancomycin HCl.

A condition has been reported that is similar to the IV–induced syndrome with symptoms consistent with anaphylactoid reactions, including hypotension, wheezing, dyspnea, urticaria, pruritus, flushing of the upper body (“Red Man Syndrome”), pain and muscle spasm of the chest and back. These reactions usually resolve within 20 minutes but may persist for several hours.

OVERDOSAGE

Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly removed by dialysis. Hemofiltration and hemoperfusion with polysulfone resin have been reported to result in increased vancomycin clearance.

Treatment — To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.

DOSAGE AND ADMINISTRATION

Adults — VANCOCIN HCl Capsules are used in treating antibiotic-associated pseudomembranous colitis caused by C. difficile and staphylococcal enterocolitis. VANCOCIN HCl Capsules are not effective for other types of infections. The usual adult total daily dosage is 500 mg to 2 g administered orally in 3 or 4 divided doses for 7 to 10 days.

Pediatric Patients — The usual daily dosage is 40 mg/kg in 3 or 4 divided doses for 7 to 10 days. The total daily dosage should not exceed 2 g.

HOW SUPPLIED

VANCOCIN HCl Capsules (Vancomycin Hydrochloride Capsules, USP) are available in:

The 125 mg* capsules have an opaque blue cap and opaque brown body imprinted with “3125” on the cap and “VANCOCIN HCL 125 MG” on the body in white ink.