Vancomycin Vancomycin Hydrochloride

Reference ID: 3051822 ID: Reference

infections. They do not treat viral infections (e.g., the common cold). When vancomycin is prescribed to treat a treat to prescribed is vancomycin When cold). common the (e.g., infections viral treat not do They infections. bacterial infection, patients should be told that although it is common to feel better early in the course of therapy,

Patients should be counseled that antibacterial drugs including vancomycin should only be used to treat bacterial treat to used be only should vancomycin including drugs antibacterial that counseled be should Patients the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may

Information for Patients for Information (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop

bacteria. resistance and will not be treatable by vancomycin or other antibacterial drugs in the future.

indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant of development the of risk the increases and patient the to benefit provide to unlikely is indication Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued.

Prescribing vancomycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic a or infection bacterial suspected strongly or proven a of absence the in vancomycin Prescribing Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without

intraperitoneal vancomycin. intraperitoneal stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic.

degrees of abdominal pain and fever. This syndrome appears to be short-lived after discontinuation of discontinuation after short-lived be to appears syndrome This fever. and pain abdominal of degrees If this occurs, patients should contact their physician as soon as possible.

To date, this syndrome has ranged from a cloudy dialysate alone to a cloudy dialysate accompanied by variable by accompanied dialysate cloudy a to alone dialysate cloudy a from ranged has syndrome this date, To Drug Interactions

route during continuous ambulatory peritoneal dialysis (CAPD) has resulted in a syndrome of chemical peritonitis. chemical of syndrome a in resulted has (CAPD) dialysis peritoneal ambulatory continuous during route Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and

Reports have revealed that administration of Vancomycin Hydrochloride for Injection, USP by the intraperitoneal the by USP Injection, for Hydrochloride Vancomycin of administration that revealed have Reports histamine-like flushing (see Pediatric Use under PRECAUTIONS) and anaphylactoid reactions (see ADVERSE

by the intraperitoneal route have not been established by adequate and well-controlled trials. well-controlled and adequate by established been not have route intraperitoneal the by REACTIONS).

The safety and efficacy of vancomycin administered by the intrathecal (intralumbar or intraventricular) route or route intraventricular) or (intralumbar intrathecal the by administered vancomycin of efficacy and safety The Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs,

induction. induction. such as amphotericin B, aminoglycosides, bacitracin, polymyxin B, colistin, viomycin, or cisplatin, when indicated,

related events may be minimized by the administration of vancomycin as a 60-minute infusion prior to anesthetic to prior infusion 60-minute a as vancomycin of administration the by minimized be may events related requires careful monitoring.

erythema, urticaria, and pruritus) increases with the concomitant administration of anesthetic agents. Infusion- agents. anesthetic of administration concomitant the with increases pruritus) and urticaria, erythema, Carcinogenesis, Mutagenesis, Impairment of Fertility

There have been reports that the frequency of infusion-related events (including hypotension, flushing, hypotension, (including events infusion-related of frequency the that reports been have There Although no long-term studies in animals have been performed to evaluate carcinogenic potential, no mutagenic

the sites of infusion. of sites the potential of Vancomycin Hydrochloride for Injection, USP was found in standard laboratory tests. No definitive

severity of which can be minimized by administering the drug slowly as a dilute solution (2.5 to 5 g/L) and by rotating by and g/L) 5 to (2.5 solution dilute a as slowly drug the administering by minimized be can which of severity fertility studies have been performed.

tenderness, and necrosis occur with inadvertent extravasation. Thrombophlebitis may occur, the frequency and frequency the occur, may Thrombophlebitis extravasation. inadvertent with occur necrosis and tenderness, Pregnancy: Teratogenic Effects, Category C — Animal reproduction studies have not been conducted with

Vancomycin is irritating to tissue and must be given by a secure intravenous route of administration. Pain, administration. of route intravenous secure a by given be must and tissue to irritating is Vancomycin vancomycin hydrochloride. It is not known whether vancomycin hydrochloride can affect reproduction capacity. In

receiving concomitant drugs that may cause neutropenia should have periodic monitoring of the leukocyte count. count. leukocyte the of monitoring periodic have should neutropenia cause may that drugs concomitant receiving a controlled clinical study, the potential ototoxic and nephrotoxic effects of vancomycin hydrochloride on infants

REACTIONS ). Patients who will undergo prolonged therapy with vancomycin hydrochloride or those who are who those or hydrochloride vancomycin with therapy prolonged undergo will who Patients ). were evaluated when the drug was administered to pregnant women for serious staphylococcal infections

ADVERSE Reversible neutropenia has been reported in patients receiving vancomycin hydrochloride (see (see hydrochloride vancomycin receiving patients in reported been has neutropenia Reversible complicating intravenous drug abuse. Vancomycin hydrochloride was found in cord blood. No sensorineural

Serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity. ototoxicity. of risk the minimize to order in helpful be may function auditory of tests Serial hearing loss or nephrotoxicity attributable to vancomycin was noted. One infant whose mother received

ADMINISTRATION ). ). vancomycin in the third trimester experienced conductive hearing loss that was not attributed to the administration

DOSAGE AND DOSAGE performed and particular care should be taken in following appropriate dosing schedules (see (see schedules dosing appropriate following in taken be should care particular and performed of vancomycin. Because the number of patients treated in this study was limited and vancomycin was administered

patients receiving concomitant therapy with an aminoglycoside, serial monitoring of renal function should be should function renal of monitoring serial aminoglycoside, an with therapy concomitant receiving patients only in the second and third trimesters, it is not known whether vancomycin causes fetal harm. Vancomycin should

In order to minimize the risk of nephrotoxicity when treating patients with underlying renal dysfunction or dysfunction renal underlying with patients treating when nephrotoxicity of risk the minimize to order In be given to a pregnant woman only if clearly needed.

received intravenous vancomycin. intravenous received Nursing Mothers

instances, there have been reports of pseudomembranous colitis due to to due colitis pseudomembranous of reports been have there instances, developing in patients who patients in developing C. difficile difficile C. Vancomycin is excreted in human milk. Caution should be exercised when vancomycin is administered to a nursing

of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken. In rare In taken. be should measures appropriate therapy, during occurs superinfection If essential. is patient the of woman. Because of the potential for adverse events, a decision should be made whether to discontinue nursing or

Prolonged use of vancomycin may result in the overgrowth of nonsusceptible microorganisms. Careful observation Careful microorganisms. nonsusceptible of overgrowth the in result may vancomycin of use Prolonged to discontinue the drug, taking into account the importance of the drug to the mother.

General Pediatric Use PRECAUTIONS In pediatric patients, it may be appropriate to confirm desired vancomycin serum concentrations. Concomitant

administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like

, and surgical evaluation should be instituted as clinically indicated. clinically as instituted be should evaluation surgical and ,

C. difficile C. flushing in pediatric patients (see ADVERSE REACTIONS).

discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of of treatment antibiotic supplementation, protein management, electrolyte and fluid Appropriate discontinued. Geriatric Use

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against against directed not use antibiotic ongoing confirmed, or suspected is CDAD If may need to be to need may

C. difficile C. The natural decrement of glomerular filtration with increasing age may lead to elevated vancomycin serum

administration of antibacterial agents. antibacterial of administration concentrations if dosage is not adjusted. Vancomycin dosage schedules should be adjusted in elderly patients (see

use. Careful medical history is necessary since CDAD has been reported to occur over two months after the after months two over occur to reported been has CDAD since necessary is history medical Careful use. DOSAGE AND ADMINISTRATION). and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic following diarrhea with present who patients all in considered be must CDAD colectomy. require may and

of of cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy antimicrobial to refractory be can infections these as mortality, and morbidity increased cause C. difficile C. ADVERSE REACTIONS

produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains producing Hypertoxin CDAD. of development the to contribute which B and A toxins produces C. difficile C. Infusion-Related Events: During or soon after rapid infusion of vancomycin hydrochloride, patients may develop

Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of of overgrowth to leading colon the of flora normal the alters agents antibacterial with Treatment . C. difficile C. anaphylactoid reactions, including hypotension (see ANIMAL PHARMACOLOGY), wheezing, dyspnea, urticaria, or

including Vancomycin Hydrochloride for Injection, USP, and may range in severity from mild diarrhea to fatal colitis. fatal to diarrhea mild from severity in range may and USP, Injection, for Hydrochloride Vancomycin including pruritus. Rapid infusion may also cause flushing of the upper body (‘‘red neck’’) or pain and muscle spasm of the

associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, antibacterial all nearly of use with reported been has (CDAD) diarrhea associated Clostridium difficile Clostridium chest and back. These reactions usually resolve within 20 minutes but may persist for several hours. Such events

DOSAGE AND ADMINISTRATION AND DOSAGE ). ). and and are infrequent if vancomycin is given by a slow infusion over 60 minutes. In studies of normal volunteers, infusion-

PRECAUTIONS Dosage of vancomycin hydrochloride must be adjusted for patients with renal dysfunction (see (see dysfunction renal with patients for adjusted be must hydrochloride vancomycin of Dosage related events did not occur when vancomycin was administered at a rate of 10 mg/min or less.

by high, prolonged blood concentrations. blood prolonged high, by Nephrotoxicity: Renal failure, principally manifested by increased serum creatinine or BUN concentrations,

should be used with caution in patients with renal insufficiency because the risk of toxicity is appreciably increased appreciably is toxicity of risk the because insufficiency renal with patients in caution with used be should especially in patients administered large doses of vancomycin, has been reported rarely. Rare cases of interstitial

who are receiving concomitant therapy with another ototoxic agent, such as an aminoglycoside. Vancomycin aminoglycoside. an as such agent, ototoxic another with therapy concomitant receiving are who nephritis have been reported. Most of these have occurred in patients who were given aminoglycosides

been reported mostly in patients who have been given excessive doses, who have an underlying hearing loss, or loss, hearing underlying an have who doses, excessive given been have who patients in mostly reported been concomitantly or who had preexisting kidney dysfunction. When vancomycin was discontinued, azotemia resolved

Ototoxicity has occurred in patients receiving vancomycin hydrochloride. It may be transient or permanent. It has It permanent. or transient be may It hydrochloride. vancomycin receiving patients in occurred has Ototoxicity in most patients.

reactions. reactions. Gastrointestinal: Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see

avoid rapid-infusion-related reactions. Stopping the infusion usually results in a prompt cessation of these of cessation prompt a in results usually infusion the Stopping reactions. rapid-infusion-related avoid WARNINGS).

Vancomycin hydochloride should be administered in a dilute solution over a period of not less than 60 minutes to minutes 60 than less not of period a over solution dilute a in administered be should hydochloride Vancomycin Ototoxicity: A few dozen cases of hearing loss associated with vancomycin hydrochloride have been reported.

shock, and, rarely, cardiac arrest. cardiac rarely, and, shock, Most of these patients had kidney dysfunction or a preexisting hearing loss, or were receiving concomitant

Rapid bolus administration (e.g., over several minutes) may be associated with exaggerated hypotension, including hypotension, exaggerated with associated be may minutes) several over (e.g., administration bolus Rapid treatment with an ototoxic drug. Vertigo, dizziness, and tinnitus have been reported rarely. WARNINGS WARNINGS Hematopoietic: Reversible neutropenia, usually starting one week or more after onset of therapy with vancomycin

or after a total dosage of more than 25 g, has been reported for several dozen patients. Neutropenia appears to be

antibiotic. promptly reversible when vancomycin hydrochloride is discontinued. Thrombocytopenia has rarely been reported.

Vancomycin Hydrochloride for Injection, USP is contraindicated in patients with known hypersensitivity to this to hypersensitivity known with patients in contraindicated is USP Injection, for Hydrochloride Vancomycin Although a causal relationship has not been established, reversible agranulocytosis (granulocytes < 500/mm3)

CONTRAINDICATIONS CONTRAINDICATIONS has been reported rarely.

epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. of selection empiric the to contribute may patterns susceptibility and epidemiology Phlebitis: Inflammation at the injection site has been reported.

should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local data, such of absence the In therapy. antibacterial modifying or selecting in considered be should Miscellaneous: Infrequently, patients have been reported to have had anaphylaxis, drug fever, nausea, chills,

suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they available, are information susceptibility and culture When bacteria. susceptible by caused be to suspected eosinophilia, rashes including exfoliative dermatitis, linear IgA bullous dermatosis, Stevens-Johnson syndrome,

antibacterial drugs, vancomycin should be used only to treat or prevent infections that are proven or strongly or proven are that infections prevent or treat to only used be should vancomycin drugs, antibacterial toxic epidermal necrolysis, and vasculitis in association with administration of vancomycin.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of vancomycin and other and vancomycin of effectiveness the maintain and bacteria drug-resistant of development the reduce To Chemical peritonitis has been reported following intraperitoneal administration of vancomycin (see

to determine their susceptibilities to vancomycin hydrochloride. vancomycin to susceptibilities their determine to PRECAUTIONS).

Specimens for bacteriologic cultures should be obtained in order to isolate and identify causative organisms and organisms causative identify and isolate to order in obtained be should cultures bacteriologic for Specimens Post Marketing Reports

both in early-onset prosthetic valve endocarditis caused by by caused endocarditis valve prosthetic early-onset in both or diphtheroids. or

S. epidermidis S. The following adverse reactions have been identified during post-approval use of vancomycin. Because these

Vancomycin hydrochloride has been used successfully in combination with either rifampin, an aminoglycoside, or aminoglycoside, an rifampin, either with combination in successfully used been has hydrochloride Vancomycin reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their

Vancomycin hydrochloride has been reported to be effective for the treatment of diphtheroid endocarditis. diphtheroid of treatment the for effective be to reported been has hydrochloride Vancomycin frequency or establish a causal relationship to the drug exposure.

aminoglycoside. Skin and Subcutaneous Tissue Disorders

), vancomycin hydrochloride has been reported to be effective only in combination with an with combination in only effective be to reported been has hydrochloride vancomycin ),

E. faecalis E. Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) endocarditis caused by by caused endocarditis . For endocarditis caused by enterococci (e.g., (e.g., enterococci by caused endocarditis For . bovis S. or viridans Streptococcus

Vancomycin hydrochloride has been reported to be effective alone or in combination with an aminoglycoside for aminoglycoside an with combination in or alone effective be to reported been has hydrochloride Vancomycin To report SUSPECTED ADVERSE EVENTS, contact FDA at 1-800-FDA-1088 or www.fda.gov.

antibiotics are used as adjuncts to appropriate surgical measures. surgical appropriate to adjuncts as used are antibiotics OVERDOSAGE

tract infections, skin, and skin structure infections. When staphylococcal infections are localized and purulent, and localized are infections staphylococcal When infections. structure skin and skin, infections, tract Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly removed by dialysis.

been documented in other infections due to staphylococci, including septicemia, bone infections, lower respiratory lower infections, bone septicemia, including staphylococci, to due infections other in documented been Hemofiltration and hemoperfusion with polysulfone resin have been reported to result in increased vancomycin

Vancomycin hydrochloride is effective in the treatment of staphylococcal endocarditis. It’s effectiveness has effectiveness It’s endocarditis. staphylococcal of treatment the in effective is hydrochloride Vancomycin clearance.

suspected, but after susceptibility data are available, therapy should be adjusted accordingly. adjusted be should therapy available, are data susceptibility after but suspected, The median lethal intravenous dose is 319 mg/kg in rats and 400 mg/kg in mice.

antimicrobial drugs. Vancomycin is indicated for initial therapy when methicillin-resistant staphylococci are staphylococci methicillin-resistant when therapy initial for indicated is Vancomycin drugs. antimicrobial To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional

cephalosporins, and for infections caused by vancomycin-susceptible organisms that are resistant to other to resistant are that organisms vancomycin-susceptible by caused infections for and cephalosporins, Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians’ Desk

for patients who cannot receive or who have failed to respond to other drugs, including the penicillins or penicillins the including drugs, other to respond to failed have who or receive cannot who patients for Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among

strains of methicillin-resistant (beta-lactam-resistant) staphylococci. It is indicated for penicillin-allergic patients, penicillin-allergic for indicated is It staphylococci. (beta-lactam-resistant) methicillin-resistant of strains drugs, and unusual drug kinetics in your patient.

Vancomycin hydrochloride is indicated for the treatment of serious or severe infections caused by susceptible by caused infections severe or serious of treatment the for indicated is hydrochloride Vancomycin DOSAGE AND ADMINISTRATION

INDICATIONS AND USAGE USAGE AND INDICATIONS Infusion-related events are related to both concentration and rate of administration of vancomycin. Concentrations 2

blood and incubated in 5% CO 5% in incubated and blood of no more than 5 mg/mL and rates of no more than 10 mg/min are recommended in adults (see also age-specific

. . Disk diffusion interpretive criteria applicable only to tests performed using Mueller-Hinton agar with 5% defibrinated sheep defibrinated 5% with agar Mueller-Hinton using performed tests to only applicable criteria interpretive diffusion Disk blood

1 recommendations).

Interpretative criteria applicable only to tests performed using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse lysed 5% to 2 with broth Mueller-Hinton cation-adjusted using performed tests to only applicable criteria Interpretative a In selected patients in need of fluid restriction, a concentration up to 10 mg/mL may be used; use of such higher

concentrations may increase the risk of infusion-related events. Infusion-related events may occur, however, at

20 – 27 – 20 0.5 – 0.12 (49619) Streptococcus pneumoniae Streptococcus any rate or concentration.

a Patients with Normal Renal Function

Adults: The usual daily intravenous dose is 2 g divided either as 500 mg every six hours or 1 g every 12 hours. Each 17 – 21 – 17 applicable Not (25923)

Staphylococcus aureus Staphylococcus dose should be administered at no more than 10 mg/min, or over a period of at least 60 minutes, whichever is longer.

Not applicable Not 2 – 0.5 (29213) Staphylococcus aureus Staphylococcus Other patient factors, such as age or obesity, may call for modification of the usual intravenous daily dose.

Pediatric Patients: The usual intravenous dosage of vancomycin is 10 mg/kg per dose given every six hours. Each

Not applicable Not 4 – 1 (29212)

Enterococcus faecalis Enterococcus dose should be administered over a period of at least 60 minutes. Close monitoring of serum concentrations of Organism (ATTC #) MIC range (mcg/mL) Disk diffusion range (mm) range diffusion Disk (mcg/mL) range MIC #) (ATTC Organism vancomycin is recommended in these patients.

Neonates: In pediatric patients up to the age of 1 month, the total daily intravenous dosage may be lower. In

Table 2. 2. Table Susceptibility Test Quality Control Ranges for Vancomycin for Ranges Control Quality Test Susceptibility

In Vitro In neonates, an initial dose of 15 mg/kg is suggested, followed by 10 mg/kg every 12 hours for neonates in the first

control strains: control week of life and every eight hours thereafter up to the age of one month. Each dose should be administered over

diffusion technique, the 30 mcg vancomycin disk should provide the following zone diameters with the quality the with diameters zone following the provide should disk vancomycin mcg 30 the technique, diffusion 60 minutes. In premature infants, vancomycin clearance decreases as postconceptional age decreases. Therefore,

individuals performing the test. Standard vancomycin powder should provide MIC values provided below. For the For below. provided values MIC provide should powder vancomycin Standard test. the performing individuals longer dosing intervals may be necessary in premature infants. Close monitoring of serum concentrations of

ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the of techniques the and assay, the in used reagents and supplies the of precision and accuracy the ensure vancomycin is recommended in these patients.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to monitor and monitor to microorganisms control laboratory of use the require procedures test susceptibility Standardized Patients with Impaired Renal Function and Elderly Patients

Quality Control Quality Dosage adjustment must be made in patients with impaired renal function. In the elderly, greater dosage reductions

compound in the blood reaches the concentrations usually achievable; other therapy should be selected. be should therapy other achievable; usually concentrations the reaches blood the in compound than expected may be necessary because of decreased renal function. Measurement of vancomycin serum

interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial the if inhibited be to likely not is pathogen the that indicates “Resistant” of report A interpretation. concentrations can be helpful in optimizing therapy, especially in seriously ill patients with changing renal function.

a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in discrepancies major causing from factors technical uncontrolled small prevents which zone buffer a Vancomycin serum concentrations can be determined by use of microbiologic assay, radioimmunoassay,

physiologically concentrated or in situations where high dosage of drug can be used. This category also provides also category This used. be can drug of dosage high where situations in or concentrated physiologically fluorescence polarization immunoassay, fluorescence immunoassay, or high-pressure liquid chromatography.

test should be repeated. This category implies possible clinical applicability in body sites where the drug is drug the where sites body in applicability clinical possible implies category This repeated. be should test If creatinine clearance can be measured or estimated accurately, the dosage for most patients with renal

considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the drugs, feasible clinically alternative, to susceptible fully not is microorganism the if and, equivocal, considered impairment can be calculated using the following table. The dosage of vancomycin per day in mg is about 15 times

blood reaches the concentrations usually achievable. A report of “Intermediate” indicates that the result should be should result the that indicates “Intermediate” of report A achievable. usually concentrations the reaches blood the glomerular filtration rate in mL/min: A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the in compound antimicrobial the if inhibited be to likely is pathogen the that indicates “Susceptible” of report A

2 DOSAGE TABLE FOR VANCOMYCIN

sheep blood and incubated in 5% CO 5% in incubated and blood sheep .

3 IN PATIENTS WITH IMPAIRED RENAL FUNCTION

ted defibrina 5% with agar Mueller-Hinton using method diffusion disk by performed tests to only applicable criteria Interpretative

e (Adapted from Moellering et al)3

with 2 to 5% lysed horse blood horse lysed 5% to 2 with .

1,2 Creatinine Clearance Vancomycin Dose

oth br Mueller-Hinton cationadjusted using method microdilution broth by performed tests to only applicable criteria Interpretative

d mL/min mg/24 h of “Nonsusceptible” should be submitted to a reference laboratory for further testing. further for laboratory reference a to submitted be should “Nonsusceptible” of

tive The current absence of resistant isolates precludes defining results other than “Susceptible”. Isolates yielding results sugges results yielding Isolates “Susceptible”. than other results defining precludes isolates resistant of absence current The 100 1545

procedure based on a dilution method dilution a on based procedure (broth or agar) or equivalent. or agar) or (broth 90 1390

1,2

of inhibition indicates resistance. Those enterococci with intermediate zones of inhibition should be tested by a standardized a by tested be should inhibition of zones intermediate with enterococci Those resistance. indicates inhibition of 80 1235

zone Plates should be held for a full 24 hours and examined using transmitted light. The presence of a haze or any growth within the within growth any or haze a of presence The light. transmitted using examined and hours 24 full a for held be should Plates 70 1080

to detect either ampicillin or penicillin resistance due to ß-lactamase production. ß-lactamase to due resistance penicillin or ampicillin either detect to 60 925

CFU/mL or direct colony growth and a nitrocefin-based substrate should be performed be should substrate nitrocefin-based a and growth colony direct or CFU/mL 10 A ß-lactamase test using an inoculum inoculum an using test ß-lactamase A 50 770 ≥

a 40 620

S. pneumoniae S. 30 465

–– –– 17 –– –– 1 other than than other

≥ ≤ c,e

c,d 20 310

Streptococci 10 155

staphylococci The initial dose should be no less than 15 mg/kg, even in patients with mild to moderate renal insufficiency. –– –– –– 32 16 – 8 4 negative

≥ ≤ The table is not valid for functionally anephric patients. For such patients, an initial dose of 15 mg/kg of body

Coagulase- weight should be given to achieve prompt therapeutic serum concentrations. The dose required to maintain stable

aureus

–– –– –– 16 8 – 4

2 concentrations is 1.9 mg/kg/24 h. In patients with marked renal impairment, it may be more convenient to give

≥ ≤ Staphylococcus maintenance doses of 250 to 1000 mg once every several days rather than administering the drug on a daily basis.

In anuria, a dose of 1000 mg every 7 to 10 days has been recommended.

14 –16 15 17 32 16 – 8 4 Enterococci

≤ ≥ ≥ ≤ b b b a When only the serum creatinine concentration is known, the following formula (based on sex, weight, and age

of the patient) may be used to calculate creatinine clearance. Calculated creatinine clearances (mL/min) are only

(R) (I) (S) (R) (I)

(S) estimates. The creatinine clearance should be measured promptly. Pathogen

Resistant Intermediate Susceptible Resistant Intermediate

Susceptible Men: Weight (kg) x (140 - age in years)

(mm)

(mcg/mL) 72 x serum creatinine concentration (mg/dL)

Disk Diffusion Diameters Diffusion Disk

Minimum Inhibitory Concentrations Inhibitory Minimum Women: 0.85 x above value

Table 1: Susceptibility Test Interpretive Criteria for Vancomycin for Criteria Interpretive Test Susceptibility 1: Table The serum creatinine must represent a steady state of renal function. Otherwise the estimated value for

vancomycin disk should be interpreted according to the following criteria in Table 1. Table in criteria following the to according interpreted be should disk vancomycin creatinine clearance is not valid. Such a calculated clearance is an overestimate of actual clearance in patients

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30-mcg a with test susceptibility single-disk standard the of results providing laboratory the from Reports with conditions: (1) characterized by decreasing renal function, such as shock, severe heart failure, or oliguria;

obtained in the disk test with the MIC for vancomycin. for MIC the with test disk the in obtained (2) in which a normal relationship between muscle mass and total body weight is not present, such as obese

to test the susceptibility of microorganisms to vancomycin. Interpretation involves correlation of the diameter the of correlation involves Interpretation vancomycin. to microorganisms of susceptibility the test to patients or those with liver disease, edema, or ascites; and (3) accompanied by debilitation, malnutrition, or

standardized inoculum concentrations. This procedure uses paper disks impregnated with 30-mcg of vancomycin of 30-mcg with impregnated disks paper uses procedure This concentrations. inoculum standardized inactivity.

susceptibility of bacteria to antimicrobial compounds. One such standardized procedure standardized such One compounds. antimicrobial to bacteria of susceptibility requires the use of use the requires The safety and efficacy of vancomycin administration by the intrathecal (intralumbar or intraventricular) routes

2,3

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the of estimates reproducible provide also diameters zone of measurement require that methods Quantitative have not been established.

Diffusion Techniques Diffusion Intermittent infusion is the recommended method of administration.

values should be interpreted according to the criteria in Table 1. Table in criteria the to according interpreted be should values PREPARATION AND STABILITY

microdilution) or equivalent using standardized inoculum and concentrations of vancomycin powder. The MIC The powder. vancomycin of concentrations and inoculum standardized using equivalent or microdilution) At the time of use, reconstitute the vial with Sterile Water for Injection by adding 10 mL of the diluting solution to

using a standardized procedure. Standardized procedures are based on dilution method dilution on based are procedures Standardized procedure. standardized a using

(broth, agar or agar (broth, the 500-mg vial, 15 mL of the diluting solution to the 750 mg vial, or 20 mL of the diluting solution to the 1-g vial of 1,2

provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC's should be determined be should MIC's The compounds. antimicrobial to bacteria of susceptibility the of estimates provide dry, vancomycin powder. FURTHER DILUTION IS REQUIRED.

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MIC's). These MIC's These (MIC's). concentrations inhibitory minimum antimicrobial determine to used are methods Quantitative After reconstitution with Sterile Water for Injection, the vials may be stored in a refrigerator for 14 days without

Dilution Techniques Dilution significant loss of potency.

in selecting the most effective antimicrobial. effective most the selecting in Reconstituted solutions containing 500 mg of vancomycin must be further diluted with at least 100 mL of diluent.

the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician the aid should reports These pathogens. community-acquired and nosocomial of profile susceptibility the Reconstituted solutions containing 750 mg must be further diluted with at least 150 mL of diluent. Reconstituted

for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe that reports periodic as physician the to areas practice and hospitals local in used drugs antimicrobial for solutions containing 1 g must be further diluted with at least 200 mL of diluent. The desired dose, diluted in this

susceptibility test results test susceptibility vitro in

When available, the clinical microbiology laboratory should provide the results of of results the provide should laboratory microbiology clinical the available, When manner, should be administered by intermittent intravenous infusion over a period of at least 60 minutes.

Susceptibility Test Methods Test Susceptibility Compatibility with Other Drugs and Intravenous Fluids

species Lactobacillus Lactobacillus Solutions that are diluted with 5% Dextrose Injection or 0.9% Sodium Chloride Injection may be refrigerated for

species Actinomyces Actinomyces 14 days without significant loss of potency. Solutions in the vial that are further diluted with the following infusion

Anaerobic Gram-positive bacteria Gram-positive Anaerobic fluids may be stored in a refrigerator for 96 hours:

Streptococcus agalactiae Streptococcus 5% Dextrose Injection, USP

Streptococcus pneumoniae Streptococcus

(including penicillin-resistant strains) penicillin-resistant (including 5% Dextrose and 0.9% Sodium Chloride Injection, USP

Streptococcus pyogenes Streptococcus Lactated Ringer’s Injection, USP

Listeria monocytogenes Listeria Lactated Ringer’s and 5% Dextrose Injection, USP Gram-positive bacteria Gram-positive Normosol®-M and 5% Dextrose

methicillin-resistant strains) in adequate and well-controlled clinical trials. clinical well-controlled and adequate in strains) methicillin-resistant ISOLYTE E

Staphylococci, including including Staphylococci, (including heterogeneous (including epidermidis Staphylococcus and

Staphylococcus aureus Staphylococcus Vancomycin solution has a low pH and may cause chemical or physical instability when it is mixed with other

Enterococci (e.g., (e.g., Enterococci )

Enterococcus faecalis Enterococcus compounds.

Diphtheroids Mixtures of solutions of vancomycin and beta-lactam antibiotics have been shown to be physically incompatible.

Gram-positive bacteria Gram-positive The likelihood of precipitation increases with higher concentrations of vancomycin. It is recommended to

INDICATIONS AND USAGE AND INDICATIONS in clinical infections as described in the the in described as infections clinical in

section. section. adequately flush the intravenous lines between the administration of these antibiotics. It is also recommended to

Vancomycin has been shown to be active against most strains of the following microorganisms, both both microorganisms, following the of strains most against active be to shown been has Vancomycin and

in vitro in dilute solutions of vancomycin to 5 mg/mL or less.

, enterococci, and the viridans group streptococci. streptococci. group viridans the and enterococci, , bovis Streptococcus ,

Staphylococcus aureus Staphylococcus Although intravitreal injection is not an approved route of administration for vancomycin, precipitation has been

The combination of vancomycin and an aminoglycoside acts synergistically synergistically acts aminoglycoside an and vancomycin of combination The against many strains of strains many against

in vitro in reported after intravitreal injection of vancomycin and ceftazidime for endophthalmitis using different syringes and

Synergy needles. The precipitates dissolved gradually, with complete clearing of the vitreous cavity over two months and

mycobacteria, or fungi. fungi. or mycobacteria, with improvement of visual acuity.

between vancomycin and other antibiotics. Vancomycin is not active active not is Vancomycin antibiotics. other and vancomycin between against gram-negative bacilli, gram-negative against

in vitro in Prior to administration, parenteral drug products should be inspected visually for particulate matter and

vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance no is There synthesis. RNA and permeability bacterial-cell-membrane alters vancomycin discoloration prior to administration, whenever solution or container permits.

The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. In addition, In biosynthesis. cell-wall of inhibition from primarily results vancomycin of action bactericidal The HOW SUPPLIED

Microbiology Vancomycin Hydrochloride for Injection, USP is supplied as a sterile powder in single-dose fliptop vials that contain spinal fluid; but, when the meninges are inflamed, penetration into the spinal fluid occurs. fluid spinal the into penetration inflamed, are meninges the when but, fluid; spinal the vancomycin equivalent of either 500 mg, 750 mg, or 1 g.

and in atrial appendage tissue. Vancomycin hydrochloride does not readily diffuse across normal meninges into the into meninges normal across diffuse readily not does hydrochloride Vancomycin tissue. appendage atrial in and NDC Number Fill concentrations are present in pleural, pericardial, ascitic, and synovial fluids; in urine; in peritoneal dialysis fluid; dialysis peritoneal in urine; in fluids; synovial and ascitic, pericardial, pleural, in present are concentrations

concentrations of 10 to 100 mcg/mL. After I.V. administration of vancomycin hydrochloride, inhibitory hydrochloride, vancomycin of administration I.V. After mcg/mL. 100 to 10 of concentrations 0409-4332-01 500 mg

Vancomycin is approximately 55% serum protein bound as measured by ultrafiltration at vancomycin serum vancomycin at ultrafiltration by measured as bound protein serum 55% approximately is Vancomycin 0409-6531-02 750 mg

Total systemic and renal clearance of vancomycin may be reduced in the elderly. the in reduced be may vancomycin of clearance renal and systemic Total 0409-6533-01 1 g

PRECAUTIONS and well-controlled trials (see (see trials well-controlled and

). Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

However, the safety and efficacy of the intraperitoneal use of vancomycin has not been established in adequate in established been not has vancomycin of use intraperitoneal the of efficacy and safety the However, ANIMAL PHARMACOLOGY

concentrations of about 10 mcg/mL are achieved by intraperitoneal injection of 30 mg/kg of vancomycin. vancomycin. of mg/kg 30 of injection intraperitoneal by achieved are mcg/mL 10 about of concentrations In animal studies, hypotension and bradycardia occurred in dogs receiving an intravenous infusion of vancomycin,

dose of vancomycin administered during peritoneal dialysis is absorbed systemically in six hours. Serum hours. six in systemically absorbed is dialysis peritoneal during administered vancomycin of dose 25 mg/kg, at a concentration of 25 mg/mL and an infusion rate of 13.3 mL/min. coefficient is from 0.3 to 0.43 L/kg. There is no apparent metabolism of the drug. About 60% of an intraperitoneal an of 60% About drug. the of metabolism apparent no is There L/kg. 0.43 to 0.3 from is coefficient

slows excretion of vancomycin. In anephric patients, the average half-life of elimination is 7.5 days. The distribution The days. 7.5 is elimination of half-life average the patients, anephric In vancomycin. of excretion slows REFERENCES

Mean plasma clearance is about 0.058 L/kg/hr, and mean renal clearance is about 0.048 L/kg/hr. Renal dysfunction Renal L/kg/hr. 0.048 about is clearance renal mean and L/kg/hr, 0.058 about is clearance plasma Mean 1. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard

In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. glomerular by urine in excreted is vancomycin of dose administered an of 75% about hours, 24 first the In – 8th ed., CLSI document M07-A8. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2009.

The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal renal function. renal normal with subjects in hours 6 to 4 is plasma from vancomycin of half-life elimination mean The 2. Performance Standards for Antimicrobial Susceptibility Testing; 21st Informational Supplement, CLSI document

after a single dose. single a after M100-S21. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2011.

about 10 mcg/mL six hours after infusion. The plasma concentrations during multiple dosing are similar to those to similar are dosing multiple during concentrations plasma The infusion. after hours six mcg/mL 10 about 3. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard – 10th ed., CLSI

mean plasma concentrations of about 19 mcg/mL two hours after infusion, and mean plasma concentrations of concentrations plasma mean and infusion, after hours two mcg/mL 19 about of concentrations plasma mean document M02-A10. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2009.

infused over 30 minutes produces mean plasma concentrations of about 49 mcg/mL at the completion of infusion, of completion the at mcg/mL 49 about of concentrations plasma mean produces minutes 30 over infused 4. Moellering RC, Krogstad DJ, Greenblatt DJ: Vancomycin therapy in patients with impaired renal function: A

concentrations of approximately 8 mcg/mL eleven hours after the end of the infusion. Multiple dosing of 500 mg 500 of dosing Multiple infusion. the of end the after hours eleven mcg/mL 8 approximately of concentrations nomogram for dosage. Ann Inter Med 1981;94:343.

of infusion, mean plasma concentrations of approximately 23 mcg/mL two hours after infusion, and mean plasma mean and infusion, after hours two mcg/mL 23 approximately of concentrations plasma mean infusion, of

60 minutes produces mean plasma concentrations of approximately 63 mcg/mL immediately after the completion the after immediately mcg/mL 63 approximately of concentrations plasma mean produces minutes 60 Revised: 09/2011

In subjects with normal kidney function, multiple intravenous dosing of 1 g of vancomycin (15 mg/kg) infused over infused mg/kg) (15 vancomycin of g 1 of dosing intravenous multiple function, kidney normal with subjects In ®

Vancomycin Hydrochloride for Injection, USP is administered intravenously for therapy of systemic infections. systemic of therapy for intravenously administered is USP Injection, for Hydrochloride Vancomycin ISOLYTE E is a registered trademark of B. Braun

CLINICAL PHARMACOLOGY PHARMACOLOGY CLINICAL

Vancomycin hydrochloride is prepared as a solution and lyophilized in its final container. final its in lyophilized and solution a as prepared is hydrochloride Vancomycin

BEFORE USE BEFORE DOSAGE AND ADMINISTRATION AND DOSAGE (see (see ).

FURTHER DILUTION IS REQUIRED IS DILUTION FURTHER portion should be discarded. When reconstituted with sterile water for injection, injection, for water sterile with reconstituted When discarded. be should portion

bacteriostat and are intended for use only as a single-dose injection. When smaller doses are required, the unused the required, are doses smaller When injection. single-dose a as only use for intended are and bacteriostat

Solutions of vancomycin hydrochloride reconstituted with Sterile Water for Injection, USP contain no contain USP Injection, for Water Sterile with reconstituted hydrochloride vancomycin of Solutions

to dark tan solution with a pH of 4.0 (2.5 to 4.5). This product is oxygen sensitive. oxygen is product This 4.5). to (2.5 4.0 of pH a with solution tan dark to

sodium hydroxide for pH adjustment. When reconstituted with Sterile Water for Injection, USP, it forms a clear, light clear, a forms it USP, Injection, for Water Sterile with reconstituted When adjustment. pH for hydroxide sodium

activity. Vancomycin hydrochloride is a white to tan lyophilized powder. May contain hydrochloric acid and/or acid hydrochloric contain May powder. lyophilized tan to white a is hydrochloride Vancomycin activity.

The vials contain sterile vancomycin hydrochloride equivalent to either 500 mg, 750 mg, or 1 g vancomycin g 1 or mg, 750 mg, 500 either to equivalent hydrochloride vancomycin sterile contain vials The

OH 3 CH

3 HC CH

2 O H N

C HO C

2 C

CH H

H H

NH C

HN O

O C

N C

3 N C

C H

C N

C H OH

• HCI • H H

H C

CI HO

O O

3 CH

3 C H O

OH CH

2 N H O

Vancomycin hydrochloride has the following structural formula: structural following the has hydrochloride Vancomycin

base is equivalent to 0.51 mmol, and 1 g of the base is equivalent to 0.67 mmol. 0.67 to equivalent is base the of g 1 and mmol, 0.51 to equivalent is base

24 9 2 75 66 C • HCl. The molecular weight is 1485.74; 500 mg of the base is equivalent to 0.34 mmol, 750 mg of the of mg 750 mmol, 0.34 to equivalent is base the of mg 500 1485.74; is weight molecular The HCl. • O N Cl H

antibiotic derived from from derived antibiotic ) and has the molecular formula molecular the has and ) orientalis Nocardia (formerly orientalis Amycolatopsis

Vancomycin Hydrochloride for Injection, USP, intravenous, is a chromatographically purified tricyclic glycopeptide tricyclic purified chromatographically a is intravenous, USP, Injection, for Hydrochloride Vancomycin

DESCRIPTION

suspected to be caused by bacteria. by caused be to suspected

For Intravenous Use Use Intravenous For Use Intravenous For Rx only Rx only Rx

Fliptop Vial Fliptop Vial Fliptop

Hydrochloride Hydrochloride Hydrochloride for Injection, USP Injection, for USP Injection, for

Vancomycin Vancomycin Vancomycin EN-2890

EN-2890

Document Name: QEN-2890v3.qxp Name: Document

Last Time Saved: 9/22/11 9:54 AM 9:54 9/22/11 Saved: Time Last PMS Black PMS CODICE INTERNO GRAFIMED / GRAFIMED Internal Code : 10/0129/11

LABEL CHANGE REQUEST NR: LCR-030/11

CLIENTE / Customer : HOSPIRA S.p.A. LISCATE (MI)

BOZZA DEL / Proof date : 10/10/2011

PRODOTTO / Product : VANCOMICINA CLORIDRATO USP

DESCRIZIONE MATERIALE / Material description : ISTRUZIONE

DESTINAZIONE COMMERCIALE / Presentation : VENDITA

MERCATO / Market : USA

CODICE ITEM / Code : K163104B

CODICE LAETUS / Laetus code : I I X (8)

FORMATO POSA STESA / Flat size : 180 mm x 610 mm

FORMATO POSA PIEGATA / Folded size : 180 mm x 44 mm (12 pieghe)

NUMERO FACCIATE / Sides number : 2

CARTA / Paper : 40 g/m2

COLORI / Colors : NERO

FONT - FONT SIZE / Font - Font Size : Univers cond 7,5 pt

NOTE / Notes :

1st draft 2nd draft X 3rd draft 4th draft 5th draft 6th draft 7th draft Date 06/10/2011 Date 07/10/2011 Date 10/10/2011 Date Date Date Date Operator Cirene Operator Cirene Operator Cirene Operator Operator Operator Operator

PAG 1 di 2

Vancomycin Hydrochloride for Injection, USP

Fliptop Vial For Intravenous Use

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

DESCRIPTION Vancomycin Hydrochloride for Injection, USP, intravenous, is a chromatographically purified tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis (formerly Nocardia orientalis) and has the molecular formula C66H75Cl2N9O24 • HCl. The molecular weight is 1485.74; 500 mg of the base is equivalent to 0.34 mmol and 1 g of the base is equivalent to 0.67 mmol. Vancomycin hydrochloride has the following structural formula:

The vials contain sterile vancomycin hydrochloride equivalent to either 500 mg or 1 g vancomycin activity. Vancomycin hydrochloride is a white to tan lyophilized powder. May contain hydrochloric acid and/or sodium hydroxide for pH adjustment. When reconstituted with Sterile Water for Injection, USP, it forms a clear, light to dark tan solution with a pH of 4.0 (2.5 to 4.5). This product is oxygen sensitive. Solutions of vancomycin hydrochloride reconstituted with Sterile Water for Injection, USP contain no bacteriostat and are intended for use only as a single-dose injection. When smaller doses are required, the unused portion should be discarded. When reconstituted with sterile water for injection, FURTHER DILUTION IS REQUIRED BEFORE USE (see DOSAGE AND ADMINISTRATION). Vancomycin hydrochloride is prepared as a solution and lyophilized in its final container.

CLINICAL PHARMACOLOGY Vancomycin Hydrochloride for Injection, USP is administered intravenously for therapy of systemic infections. In subjects with normal kidney function, multiple intravenous dosing of 1 g of vancomycin (15 mg/kg) infused over 60 minutes produces mean plasma concentrations of approximately 63 mcg/mL immediately after the completion of infusion, mean plasma concentrations of approximately 23 mcg/mL two hours after infusion, and mean plasma concentrations of approximately 8 mcg/mL eleven hours after the end of the infusion. Multiple dosing of 500 mg infused over 30 minutes produces mean plasma concentrations of about 49 mcg/mL at the completion of infusion, mean plasma concentrations of about 19 mcg/mL two hours after infusion, and mean plasma concentrations of about 10 mcg/mL six hours after infusion. The plasma concentrations during multiple dosing are similar to those after a single dose. The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal renal function. In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. Mean plasma clearance is about 0.058 L/kg/hr, and mean renal clearance is about 0.048 L/kg/hr. Renal dysfunction slows excretion of vancomycin. In anephric patients, the average half-life of elimination is 7.5 days. The distribution coefficient is from 0.3 to 0.43 L/kg. There is no apparent metabolism of the drug. About 60% of an intraperitoneal dose of vancomycin administered during peritoneal dialysis is absorbed systemically in six hours. Serum concentrations of about 10 mcg/mL are achieved by intraperitoneal injection of 30 mg/kg of vancomycin. However, the safety and efficacy of the intraperitoneal use of vancomycin has not been established in adequate and well-controlled trials (see PRECAUTIONS). Total systemic and renal clearance of vancomycin may be reduced in the elderly. Vancomycin is approximately 55% serum protein bound as measured by ultrafiltration at vancomycin serum concentrations of 10 to 100 mcg/mL. After I.V. administration of vancomycin hydrochloride, inhibitory concentrations are present in pleural, pericardial, ascitic, and synovial fluids; in urine; in peritoneal dialysis fluid; and in atrial appendage tissue. Vancomycin hydrochloride does not readily diffuse across normal meninges into the spinal fluid; but, when the meninges are inflamed, penetration into the spinal fluid occurs. 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. Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi. Synergy The combination of vancomycin and an aminoglycoside acts synergistically in vitro against many strains of Staphylococcus aureus, Streptococcus bovis, enterococci, and the viridans group streptococci. Vancomycin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section. Gram-positive bacteria Diphtheroids Enterococci (e.g., Enterococcus faecalis) Staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis (including heterogeneous methicillin-resistant strains) in adequate and well-controlled clinical trials. Gram-positive bacteria Listeria monocytogenes Streptococcus pyogenes Streptococcus pneumoniae (including penicillin-resistant strains) Streptococcus agalactiae Anaerobic Gram-positive bacteria Actinomyces species Lactobacillus species Susceptibility Test Methods When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial. Dilution Techniques Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MIC's). These MIC's provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC's should be determined using a standardized procedure. Standardized procedures are based on dilution method1,2 (broth, agar or microdilution) or equivalent using standardized inoculum and concentrations of vancomycin powder. The MIC values should be interpreted according to the criteria in Table 1. Diffusion Techniques Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2,3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30-mcg of vancomycin to test the susceptibility of microorganisms to vancomycin. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for vancomycin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30-mcg vancomycin disk should be interpreted according to the following criteria in Table 1.

Table 1: Susceptibility Test Interpretive Criteria for Vancomycin Minimum Inhibitory Concentrations Disk Diffusion Diameters (mcg/mL) (mm) Pathogen Susceptible Intermediate Resistant Susceptible Intermediate Resistant (S) (I) (R) (S) (I) (R) Enterococci a ≤ 4 8 – 16 ≥ 32 ≥ 17b 15 – 16b ≤ 14b Staphylococcus ≤ 2 4 – 8 ≥ 16 –– –– –– aureus Coagulase- negative ≤ 4 8 – 16 ≥ 32 –– –– –– staphylococci Streptococci other than S. ≤ 1c,d –– –– ≥ 17c,e –– –– pneumoniae a A ß-lactamase test using an inoculum ≥ 107 CFU/mL or direct colony growth and a nitrocefin-based substrate should be performed to detect either ampicillin or penicillin resistance due to ß-lactamase production. b Plates should be held for a full 24 hours and examined using transmitted light. The presence of a haze or any growth within the zone of inhibition indicates resistance. Those enterococci with intermediate zones of inhibition should be tested by a standardized procedure based on a dilution method1,2 (broth or agar) or equivalent. c The current absence of resistant isolates precludes defining results other than “Susceptible”. Isolates yielding results suggestive of “Nonsusceptible” should be submitted to a reference laboratory for further testing. d Interpretative criteria applicable only to tests performed by broth microdilution method using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood1,2. e 3 Interpretative criteria applicable only to tests performed by disk diffusion method using Mueller-Hinton agar with 5% defibrinated sheep blood and incubated in 5% CO2 .

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected. Quality Control Standardized susceptibility test procedures require the use of laboratory control microorganisms to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test. Standard vancomycin powder should provide MIC values provided below. For the diffusion technique, the 30 mcg vancomycin disk should provide the following zone diameters with the quality control strains:

Table 2. In Vitro Susceptibility Test Quality Control Ranges for Vancomycin Organism (ATTC #) MIC range (mcg/mL) Disk diffusion range (mm) Enterococcus faecalis (29212) 1 – 4 Not applicable Staphylococcus aureus (29213) 0.5 – 2 Not applicable Staphylococcus aureus (25923) Not applicable 17 – 21 Streptococcus pneumoniae (49619)a 0.12 – 0.5 20 – 27

a Interpretative criteria applicable only to tests performed using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood1. Disk diffusion interpretive criteria applicable only to tests performed using Mueller-Hinton agar with 5% defibrinated sheep blood and incubated in 5% CO2.

INDICATIONS AND USAGE Vancomycin hydrochloride is indicated for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (beta-lactam-resistant) staphylococci. It is indicated for penicillin-allergic patients, for patients who cannot receive or who have failed to respond to other drugs, including the penicillins or cephalosporins, and for infections caused by vancomycin-susceptible organisms that are resistant to other antimicrobial drugs. Vancomycin is indicated for initial therapy when methicillin-resistant staphylococci are suspected, but after susceptibility data are available, therapy should be adjusted accordingly. Vancomycin hydrochloride is effective in the treatment of staphylococcal endocarditis. It’s effectiveness has been documented in other infections due to staphylococci, including septicemia, bone infections, lower respiratory tract infections, skin, and skin structure infections. When staphylococcal infections are localized and purulent, antibiotics are used as adjuncts to appropriate surgical measures. Vancomycin hydrochloride has been reported to be effective alone or in combination with an aminoglycoside for endocarditis caused by Streptococcus viridans or S. bovis. For endocarditis caused by enterococci (e.g., E. faecalis), vancomycin hydrochloride has been reported to be effective only in combination with an aminoglycoside. Vancomycin hydrochloride has been reported to be effective for the treatment of diphtheroid endocarditis. Vancomycin hydrochloride has been used successfully in combination with either rifampin, an aminoglycoside, or both in early-onset prosthetic valve endocarditis caused by S. epidermidis or diphtheroids. Specimens for bacteriologic cultures should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to vancomycin hydrochloride. To reduce the development of drug-resistant bacteria and maintain the effectiveness of vancomycin and other antibacterial drugs, vancomycin 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.

CONTRAINDICATIONS Vancomycin Hydrochloride for Injection, USP is contraindicated in patients with known hypersensitivity to this antibiotic.

WARNINGS Rapid bolus administration (e.g., over several minutes) may be associated with exaggerated hypotension, including shock, and, rarely, cardiac arrest. Vancomycin hydrochloride should be administered in a dilute solution over a period of not less than 60 minutes to avoid rapid-infusion-related reactions. Stopping the infusion usually results in a prompt cessation of these reactions. Ototoxicity has occurred in patients receiving vancomycin hydrochloride. It may be transient or permanent. It has been reported mostly in patients who have been given excessive doses, who have an underlying hearing loss, or who are receiving concomitant therapy with another ototoxic agent, such as an aminoglycoside. Vancomycin should be used with caution in patients with renal insufficiency because the risk of toxicity is appreciably increased by high, prolonged blood concentrations. Dosage of vancomycin hydrochloride must be adjusted for patients with renal dysfunction (see PRECAUTIONS and DOSAGE AND ADMINISTRATION). Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Vancomycin Hydrochloride for Injection, USP, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

PRECAUTIONS General Prolonged use of vancomycin may result in the overgrowth of nonsusceptible microorganisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken. In rare instances, there have been reports of pseudomembranous colitis due to C. difficile developing in patients who received intravenous vancomycin. In order to minimize the risk of nephrotoxicity when treating patients with underlying renal dysfunction or patients receiving concomitant therapy with an aminoglycoside, serial monitoring of renal function should be performed and particular care should be taken in following appropriate dosing schedules (see DOSAGE AND ADMINISTRATION). Serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity. Reversible neutropenia has been reported in patients receiving vancomycin hydrochloride (see ADVERSE REACTIONS). Patients who will undergo prolonged therapy with vancomycin hydrochloride or those who are receiving concomitant drugs that may cause neutropenia should have periodic monitoring of the leukocyte count. Vancomycin is irritating to tissue and must be given by a secure intravenous route of administration. Pain, tenderness, and necrosis occur with inadvertent extravasation. Thrombophlebitis may occur, the frequency and severity of which can be minimized by administering the drug slowly as a dilute solution (2.5 to 5 g/L) and by rotating the sites of infusion. There have been reports that the frequency of infusion-related events (including hypotension, flushing, erythema, urticaria, and pruritus) increases with the concomitant administration of anesthetic agents. Infusion-related events may be minimized by the administration of vancomycin as a 60-minute infusion prior to anesthetic induction.

Approved by : 1 - TESTI / Texts The following item has been 2 - IMPOSTAZIONE GRAFICA / Graphic drawing up checked: 3 - FORMATO / Size 4 - INDICAZIONE DEI COLORI / Color reference 5 - SPECIFICHE TECNICHE / Technical specification

REG. AFFAIRS MARKETING MAINTENANCE/PRODUCTION APPROVED BY Q.A. FOR Item checked: 1 2 3 4 5 Item checked: 1 2 3 4 5 Item checked: 1 2 3 4 5 PRINTING FILM Firma Data Firma Data Firma Data Firma Data Resp. signature Date Resp. signature Date Resp. signature Date Resp. signature Date

Reference ID: 3051822 CODICE INTERNO GRAFIMED / GRAFIMED Internal Code : 10/0129/11

LABEL CHANGE REQUEST NR: LCR-030/11

CLIENTE / Customer : HOSPIRA S.p.A. LISCATE (MI)

BOZZA DEL / Proof date : 10/10/2011

PRODOTTO / Product : VANCOMICINA CLORIDRATO USP

DESCRIZIONE MATERIALE / Material description : ISTRUZIONE

DESTINAZIONE COMMERCIALE / Presentation : VENDITA

MERCATO / Market : USA

CODICE ITEM / Code : K163104B

CODICE LAETUS / Laetus code : I I X (8)

FORMATO POSA STESA / Flat size : 180 mm x 610 mm

FORMATO POSA PIEGATA / Folded size : 180 mm x 44 mm (12 pieghe)

NUMERO FACCIATE / Sides number : 2

CARTA / Paper : 40 g/m2

COLORI / Colors : NERO

FONT - FONT SIZE / Font - Font Size : Univers cond 7,5 pt

NOTE / Notes :

PAG 2 di 2

The safety and efficacy of vancomycin administered by the intrathecal (intralumbar or intraventricular) route or by the intraperitoneal route have not been established by adequate and well-controlled trials. Reports have revealed that administration of Vancomycin Hydrochloride for Injection, USP by the intraperitoneal route during continuous ambulatory peritoneal dialysis (CAPD) has resulted in a syndrome of chemical peritonitis. To date, this syndrome has ranged from a cloudy dialysate alone to a cloudy dialysate accompanied by variable degrees of abdominal pain and fever. This syndrome appears to be short-lived after discontinuation of intraperitoneal vancomycin. Prescribing vancomycin 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. Information for Patients Patients should be counseled that antibacterial drugs including vancomycin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When vancomycin is 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 vancomycin or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible. Drug Interactions Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like flushing (see Pediatric Use under PRECAUTIONS) and anaphylactoid reactions (see ADVERSE REACTIONS). Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs, such as amphotericin B, aminoglycosides, bacitracin, polymyxin B, colistin, viomycin, or cisplatin, when indicated, requires careful monitoring. Carcinogenesis, Mutagenesis, Impairment of Fertility

Although no long-term studies in animals have been performed to evaluate carcinogenic potential, no mutagenic potential of Vancomycin Hydrochloride for Injection, USP was found in standard laboratory tests. No definitive fertility studies have been performed. Pregnancy: Teratogenic Effects–Category C– Animal reproduction studies have not been conducted with vancomycin hydrochloride. It is not known whether vancomycin hydrochloride can affect reproduction capacity. In a controlled clinical study, the potential ototoxic and nephrotoxic effects of vancomycin hydrochloride on infants were evaluated when the drug was administered to pregnant women for serious staphylococcal infections complicating intravenous drug abuse. Vancomycin hydrochloride was found in cord blood. No sensorineural hearing loss or nephrotoxicity attributable to vancomycin was noted. One infant whose mother received vancomycin in the third trimester experienced conductive hearing loss that was not attributed to the administration of vancomycin. Because the number of patients treated in this study was limited and vancomycin was administered only in the second and third trimesters, it is not known whether vancomycin causes fetal harm. Vancomycin should be given to a pregnant woman only if clearly needed. Nursing Mothers Vancomycin is excreted in human milk. Caution should be exercised when vancomycin is administered to a nursing woman. Because of the potential for adverse events, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use In pediatric patients, it may be appropriate to confirm desired vancomycin serum concentrations. Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like flushing in pediatric patients (see ADVERSE REACTIONS). Geriatric Use The natural decrement of glomerular filtration with increasing age may lead to elevated vancomycin serum concentrations if dosage is not adjusted. Vancomycin dosage schedules should be adjusted in elderly patients (see DOSAGE AND ADMINISTRATION).

ADVERSE REACTIONS Infusion-Related Events: During or soon after rapid infusion of vancomycin hydrochloride, patients may develop anaphylactoid reactions, including hypotension (see ANIMAL PHARMACOLOGY), wheezing, dyspnea, urticaria, or pruritus. Rapid infusion may also cause flushing of the upper body (“red neck”) or pain and muscle spasm of the chest and back. These reactions usually resolve within 20 minutes but may persist for several hours. Such events are infrequent if vancomycin is given by a slow infusion over 60 minutes. In studies of normal volunteers, infusion-related events did not occur when vancomycin was administered at a rate of 10 mg/min or less. Nephrotoxicity: Renal failure, principally manifested by increased serum creatinine or BUN concentrations, especially in patients administered large doses of vancomycin, has been reported rarely. Rarely 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 was discontinued, azotemia resolved in most patients. Gastrointestinal: Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see WARNINGS). Ototoxicity: A few dozen cases of hearing loss associated with vancomycin hydrochloride 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 one week or more after onset of therapy with vancomycin or after a total dosage of more than 25 g, has been reported for several dozen patients. Neutropenia appears to be promptly reversible when vancomycin hydrochloride is discontinued. Thrombocytopenia has rarely been reported. Although a causal relationship has not been established, reversible agranulocytosis (granulocytes < 500/mm3) has been reported rarely. Phlebitis: Inflammation at the injection site has been reported. Miscellaneous: Infrequently, patients have been reported to have had anaphylaxis, drug fever, nausea, chills, eosinophilia, rashes including exfoliative dermatitis, linear IgA bullous dermatosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and vasculitis in association with administration of vancomycin. Chemical peritonitis has been reported following intraperitoneal administration of vancomycin (see PRECAUTIONS). Post Marketing Reports The following adverse reactions have been identified during post-approval use of vancomycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to the drug exposure. Skin and Subcutaneous Tissue Disorders Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) To report SUSPECTED ADVERSE EVENTS, contact FDA at 1-800-FDA-1088 or www.fda.gov.

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. The median lethal intravenous dose is 319 mg/kg in rats and 400 mg/kg in mice. 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 Infusion-related events are related to both concentration and rate of administration of vancomycin. Concentrations of no more than 5 mg/mL and rates of no more than 10 mg/min are recommended in adults (see also age-specific recommendations). In selected patients in need of fluid restriction, a concentration up to 10 mg/mL may be used; use of such higher concentrations may increase the risk of infusion-related events. Infusion-related events may occur, however, at any rate or concentration. Patients with Normal Renal Function Adults: The usual daily intravenous dose is 2 g divided either as 500 mg every six hours or 1 g every 12 hours. Each dose should be administered at no more than 10 mg/min, or over a period of at least 60 minutes, whichever is longer. Other patient factors, such as age or obesity, may call for modification of the usual intravenous daily dose. Pediatric Patients: The usual intravenous dosage of vancomycin is 10 mg/kg per dose given every six hours. Each dose should be administered over a period of at least 60 minutes. Close monitoring of serum concentrations of vancomycin may be warranted in these patients. Neonates: In pediatric patients up to the age of 1 month, the total daily intravenous dosage may be lower. In neonates, an initial dose of 15 mg/kg is suggested, followed by 10 mg/kg every 12 hours for neonates in the first week of life and every eight hours thereafter up to the age of one month. Each dose should be administered over 60 minutes. In premature infants, vancomycin clearance decreases as postconceptional age decreases. Therefore, longer dosing intervals may be necessary in premature infants. Close monitoring of serum concentrations of vancomycin is recommended in these patients. Patients with Impaired Renal Function and Elderly Patients Dosage adjustment must be made in patients with impaired renal function. In the elderly, greater dosage reductions than expected may be necessary because of decreased renal function. Measurement of vancomycin serum concentrations can be helpful in optimizing therapy, especially in seriously ill patients with changing renal function. Vancomycin serum concentrations can be determined by use of microbiologic assay, radioimmunoassay, fluorescence polarization immunoassay, fluorescence immunoassay, or high-pressure liquid chromatography. If creatinine clearance can be measured or estimated accurately, the dosage for most patients with renal impairment can be calculated using the following table. The dosage of vancomycin per day in mg is about 15 times the glomerular filtration rate in mL/min:

DOSAGE TABLE FOR VANCOMYCIN IN PATIENTS WITH IMPAIRED RENAL FUNCTION (Adapted from Moellering et al)3

Creatinine Clearance Vancomycin Dose mL/min mg/24 h 100 1545 90 1390 80 1235 70 1080 60 925 50 770 40 620 30 465 20 310 10 155

The initial dose should be no less than 15 mg/kg, even in patients with mild to moderate renal insufficiency. The table is not valid for functionally anephric patients. For such patients, an initial dose of 15 mg/kg of body weight should be given to achieve prompt therapeutic serum concentrations. The dose required to maintain stable concentrations is 1.9 mg/kg/24 h. In patients with marked renal impairment, it may be more convenient to give maintenance doses of 250 to 1000 mg once every several days rather than administering the drug on a daily basis. In anuria, a dose of 1000 mg every 7 to 10 days has been recommended. When only the serum creatinine concentration is known, the following formula (based on sex, weight, and age of the patient) may be used to calculate creatinine clearance. Calculated creatinine clearances (mL/min) are only estimates. The creatinine clearance should be measured promptly.

Men: Weight (kg) x (140 - age in years) 72 x serum creatinine concentration (mg/dL) Women: 0.85 x above value

The serum creatinine must represent a steady state of renal function. Otherwise the estimated value for creatinine clearance is not valid. Such a calculated clearance is an overestimate of actual clearance in patients with conditions: (1) characterized by decreasing renal function, such as shock, severe heart failure, or oliguria; (2) in which a normal relationship between muscle mass and total body weight is not present, such as obese patients or those with liver disease, edema, or ascites; and (3) accompanied by debilitation, malnutrition, or inactivity. The safety and efficacy of vancomycin administration by the intrathecal (intralumbar or intraventricular) routes have not been established. Intermittent infusion is the recommended method of administration.

PREPARATION AND STABILITY At the time of use, reconstitute the vial with Sterile Water for Injection, by adding 10 mL of the diluting solution to the 500-mg vial or 20 mL of the diluting solution to the 1-g vial of dry, vancomycin powder. FURTHER DILUTION IS REQUIRED. After reconstitution with Sterile Water for Injection, the vials may be stored in a refrigerator for 14 days without significant loss of potency. Reconstituted solutions containing 500 mg of vancomycin must be further diluted with at least 100 mL of diluent. Reconstituted solutions containing 1 g must be further diluted with at least 200 mL of diluent. The desired dose, diluted in this manner, should be administered by intermittent intravenous infusion over a period of at least 60 minutes. Compatibility with Other Drugs and Intravenous Fluids Solutions that are diluted with 5% Dextrose Injection or 0.9% Sodium Chloride Injection may be refrigerated for 14 days without significant loss of potency. Solutions in the vial that are further diluted with the following infusion fluids may be stored in a refrigerator for 96 hours: 5% Dextrose Injection, USP 5% Dextrose and 0.9% Sodium Chloride Injection, USP Lactated Ringer’s Injection, USP Lactated Ringer’s and 5% Dextrose Injection, USP Normosol®-M and 5% Dextrose ISOLYTE® E Vancomycin solution has a low pH and may cause chemical or physical instability when it is mixed with other compounds. Mixtures of solutions of vancomycin and beta-lactam antibiotics have been shown to be physically incompatible. The likelihood of precipitation increases with higher concentrations of vancomycin. It is recommended to adequately flush the intravenous lines between the administration of these antibiotics. It is also recommended to dilute solutions of vancomycin to 5 mg/mL or less. Although intravitreal injection is not an approved route of administration for vancomycin, precipitation has been reported after intravitreal injection of vancomycin and ceftazidime for endophthalmitis using different syringes and needles. The precipitates dissolved gradually, with complete clearing of the vitreous cavity over two months and with improvement of visual acuity. Prior to administration, parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution or container permits.

HOW SUPPLIED Vancomycin Hydrochloride for Injection, USP is supplied as a sterile powder in single-dose fliptop vials that contain the vancomycin equivalent of either 500 mg or 1 g. NDC Number Fill 0409-4332-01 500 mg 0409-6533-01 1 g Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

ANIMAL PHARMACOLOGY In animal studies, hypotension and bradycardia occurred in dogs receiving an intravenous infusion of vancomycin, 25 mg/kg, at a concentration of 25 mg/mL and an infusion rate of 13.3 mL/min.

REFERENCES 1. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard – 8th ed., CLSI document M07-A8. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2009. 2. Performance Standards for Antimicrobial Susceptibility Testing; 21st Informational Supplement, CLSI document M100-S21. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2011. 3. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard – 10th ed., CLSI document M02-A10. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2009. 4. Moellering RC, Krogstad DJ, Greenblatt DJ: Vancomycin therapy in patients with impaired renal function: A nomogram for dosage. Ann Inter Med 1981;94:343.

Revised: September, 2011

ISOLYTE® E is a registered trademark of B. Braun

Hospira, Inc., Lake Forest, IL 60045 USA Product of Italy

K163104B

Reference ID: 3051822