Label: VANCOMYCIN HYDROCHLORIDE- vancomycin hydrochloride injection, powder, lyophilized, for solution

  • NDC Code(s): 0409-6531-01, 0409-6534-01, 0409-6535-01
  • Packager: Hospira, Inc.
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated March 20, 2017

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  • SPL UNCLASSIFIED SECTION

    ADD-Vantage™ Vials

    Rx only

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

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  • DESCRIPTION

    Vancomycin Hydrochloride for Injection, USP is a lyophilized powder, for preparing intravenous (IV) infusions, in ADD-Vantage™ vials each containing the equivalent of 500 mg, 750 mg or 1 g vancomycin base. 500 mg of the base are equivalent to 0.34 mmol, 750 mg of the base are equivalent to 0.51 mmol, and 1 g of the base are equivalent to 0.67 mmol. When reconstituted with Sterile Water for Injection to a concentration of 50 mg/mL, the pH of the solution is between 2.5 and 4.5. This product is oxygen sensitive. Vancomycin Hydrochloride for Injection, USP should be administered intravenously in diluted solution (see DOSAGE AND ADMINISTRATION) AFTER RECONSTITUTION FURTHER DILUTION IS REQUIRED BEFORE USE.

    Vancomycin is a tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis (formerly Nocardia orientalis). The chemical name for vancomycin hydrochloride is 3S- [3R*,6S*(S*),7S*,22S*,23R*,26R*,36S*,38aS*]]-3-(2-Amino-2-oxoethyl)-44-[[2-O-(3-amino-2,3,6-trideoxy-3-C-methyl-α-L-lyxo-hexopyranosyl)-ß-D-glucopyranosyl]oxy]-10,19-dichloro-2,3,4,5,6,7,23,24,25,26,36,37,38,38a-tetradecahydro-7,22,28,30,32-pentahydroxy-6-[[4-methyl-2-(methylamino)-1-oxopentyl]amino]-2,5,24,38,39-pentaoxo-22H-8,11:18,21-dietheno-23,36- (iminomethano)-13,16:31,35-dimetheno-1H,16H-[1,6,9]oxadiazacyclohexadecino[4,5- m][10,2,16]-benzoxadiazacyclotetracosine-26-carboxylic acid, monohydrochloride. The molecular formula is C66H75Cl2N9O24 ∙ HCl and the molecular weight is 1,485.74. Vancomycin Hydrochloride has the following structural formula:

    Chemical Structure

    The solutions contain no bacteriostat, antimicrobial agent (except vancomycin) or buffer and are intended for use only as a single-dose injection only with the ADD-Vantage Flexible Diluent Container.

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  • CLINICAL PHARMACOLOGY

    Vancomycin is poorly absorbed after oral administration.

    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 2 hours after infusion, and mean plasma concentrations of approximately 8 mcg/mL 11 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 2 hours after infusion, and mean plasma concentrations of about 10 mcg/mL 6 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/h, and mean renal clearance is about 0.048 L/kg/h. 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 6 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 IV administration of vancomycin, inhibitory concentrations are present in pleural, pericardial, ascitic, and synovial fluids; in urine; in peritoneal dialysis fluid; and in atrial appendage tissue. Vancomycin 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.

    Aerobic gram-positive microorganisms

    Diphtheroids

    Enterococci (e.g., Enterococcus faecalis)

    Staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis (including heterogeneous methicillin-resistant strains)

    Streptococcus bovis

    Viridans group streptococci

    The following in vitro data are available, but their clinical significance is unknown.

    Vancomycin exhibits in vitro MIC's of 1 mcg/mL or less against most (≥90%) strains of streptococci listed below and MIC's of 4 mcg/mL or less against most (≥90%) strains of other listed microorganisms; however, the safety and effectiveness of vancomycin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

    Aerobic gram-positive microorganisms

    Listeria monocytogenes
    Streptococcus pyogenes
    Streptococcus pneumoniae (including penicillin-resistant strains)
    Streptococcus agalactiae

    Anaerobic gram-positive microorganisms

    Actinomyces species
    Lactobacillus species

    Susceptibility Test Methods

    When available, the clinical microbiology laboratory should provide cumulative reports 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 (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method1,2 (broth, agar or microdilution). 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. The zone size should be determined using a standardized test method2,3. This procedure uses paper disks impregnated with 30 mcg of vancomycin to test the susceptibility of microorganisms to vancomycin. The disk diffusion breakpoints are provided in Table 1.

    Table 1: Susceptibility Test Interpretive Criteria for Vancomycin
    Minimum Inhibitory Concentrations
    (mcg/mL)
    Disk Diffusion Diameters
    (mm)
    Pathogen Susceptible
    (S)
    Intermediate
    (I)
    Resistant
    (R)
    Susceptible
    (S)
    Intermediate
    (I)
    Resistant
    (R)
    *
    Isolates with vancomycin MICs of 8 to 16 mcg/mL should be further screened for vancomycin resistance using standardized procedures. 1,2
    Plates should be held for a full 24 hours and examined using transmitted light. Measure the diameter of the zones of complete inhibition (as judged by the unaided eye), including the diameter of the disk. The zone margin should be considered the area showing no obvious, visible growth that can be detected with the unaided eye. Ignore faint growth of tiny colonies that can be detected only with a magnifying lens at the edge of the zone of inhibited growth. Any discernible growth within the zone of inhibition indicates vancomycin resistance. Organisms with intermediate zones should be tested by a standardized dilution method. 1,2
    Dilution testing should be performed to determine the susceptibility of all staphylococcal isolates. Disk diffusion testing is not reliable for testing vancomycin, as it does not differentiate vancomycin-susceptible isolates of S. aureus from vancomycin-intermediate isolates, nor does it differentiate among vancomycin-susceptible, intermediate, and resistant isolates of coagulase-negative staphylococci. 2
    §
    Any S. aureus  isolate for which the vancomycin MIC is ≥ 8 mcg/mL should be sent to a reference laboratory. 2
    Any coagulase-negative Staphylococcus  isolate for which the vancomycin MIC is ≥ 32 mcg/mL should be sent to a reference laboratory. 2
    #
    The rare occurrence of resistant isolates precludes defining any results categories other than "Susceptible". For isolates yielding results suggestive of a nonsusceptible category, organism identification and vancomycin susceptibility test results should be confirmed. If confirmed, isolates should be sent to a reference laboratory. 2
    Þ
    Interpretative criteria applicable only to tests performed by broth microdilution method using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood. 1,2
    ß
    Interpretative criteria applicable only to tests performed by disk diffusion method using Mueller-Hinton agar with 5% defibrinated sheep blood and incubated in 5% CO 2. 3
    Enterococci ≤4 8 to 16* ≥32 ≥17 15 to 16 ≤14
    Staphylococcus aureus,§ ≤2 4 to 8 ≥16 –– –– ––
    Coagulase-negative staphylococci§, ≤4 8 to 16 ≥32 –– –– ––
    Streptococci spp. other than S. pneumoniae ≤1#,Þ –– –– ≥17#,ß –– ––

    A report of "Susceptible" (S) indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentrations usually achievable at the site of infection. A report of "Intermediate" (I) 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" (R) indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentrations usually achievable at the infection site; other therapy should be selected.

    Quality Control

    Standardized susceptibility test procedures require the use of laboratory controls 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 test1,2,3. Standard vancomycin powder should provide the following MIC values noted in Table 2. For the diffusion technique using the 30 mcg vancomycin disk, the criteria in Table 2 should be achieved:

    Table 2. In Vitro Susceptibility Test Quality Control Ranges for Vancomycin
    Organism (ATCC #) MIC range (mcg/mL) Disk diffusion range (mm)
    *
    Quality control strain and interpretive criteria for testing vancomycin susceptibility of enterococci spp.
    Interpretative criteria applicable only to tests performed using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood. 1 Disk diffusion interpretive criteria applicable only to tests performed using Mueller-Hinton agar with 5% defibrinated sheep blood and incubated in 5% CO 2. 2
    Quality control strain and interpretive criteria for testing vancomycin susceptibility of Streptococci spp. other than S. pneumoniae.
    Enterococcus faecalis (29212) 1 to 4 Not applicable
    Staphylococcus aureus (29213) 0.5 to 2 Not applicable
    Staphylococcus aureus (25923)* Not applicable 17 to 21
    Streptococcus pneumoniae (49619), 0.12 to 0.5 20 to 27
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  • INDICATIONS AND USAGE

    Vancomycin hydrochloride for injection is indicated for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (β-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 hydrochloride for injection is indicated for initial therapy when methicillin-resistant staphylococci are suspected, but after susceptibility data are available, therapy should be adjusted accordingly.

    Vancomycin hydrochloride for injection is effective in the treatment of staphylococcal endocarditis. Its 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 for injection has been reported to be effective alone or in combination with an aminoglycoside for endocarditis caused by S. viridans or S. bovis. For endocarditis caused by enterococci (e.g., E. faecalis), vancomycin has been reported to be effective only in combination with an aminoglycoside.

    Vancomycin hydrochloride for injection has been reported to be effective for the treatment of diphtheroid endocarditis. Vancomycin hydrochloride for injection 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.

    To reduce the development of drug-resistant bacteria and maintain the effectiveness of vancomycin hydrochloride for injection and other antibacterial drugs, vancomycin hydrochloride for injection 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.

    The parenteral form of vancomycin hydrochloride may be administered orally for treatment of antibiotic-associated pseudomembranous colitis produced by C. difficile and for staphylococcal enterocolitis. Parenteral administration of vancomycin hydrochloride alone is of unproven benefit for these indications. Vancomycin is not effective by the oral route for other types of infections.

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  • CONTRAINDICATIONS

    Vancomycin hydrochloride for injection is contraindicated in patients with known hypersensitivity to this antibiotic.

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  • WARNINGS

    Infusion Reactions

    Rapid bolus administration (e.g., over several minutes) may be associated with exaggerated hypotension, including shock and rarely cardiac arrest.

    Vancomycin hydrochloride for injection should be administered in a diluted solution over a period of not less than 60 minutes to avoid rapid-infusion-related reactions. Stopping the infusion usually results in prompt cessation of these reactions.

    Nephrotoxicity

    Systemic vancomycin exposure may result in acute kidney injury (AKI). The risk of AKI increases as systemic exposure/serum levels increase. Monitor renal function in all patients, especially patients with underlying renal impairment, patients with co-morbidities that predispose to renal impairment, and patients receiving concomitant therapy with a drug known to be nephrotoxic.

    Ototoxicity

    Ototoxicity has occurred in patients receiving vancomycin hydrochloride for injection. 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 for injection 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, 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.

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  • PRECAUTIONS

    Clinically significant serum concentrations have been reported in some patients being treated for active C. difficile-induced pseudomembranous colitis after multiple oral doses of vancomycin.

    Prolonged use of vancomycin hydrochloride for injection 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 hydrochloride for injection.

    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 for injection (see ADVERSE REACTIONS). Patients who will undergo prolonged therapy with vancomycin hydrochloride for injection or those who are receiving concomitant drugs which may cause neutropenia should have periodic monitoring of the leukocyte count.

    Vancomycin hydrochloride for injection is irritating to tissue and must be given by a secure intravenous route of administration. Pain, tenderness, and necrosis occur with intramuscular (IM) injection of vancomycin hydrochloride for injection or 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 rotation of venous access sites.

    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. 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 sterile vancomycin 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 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 hydrochloride for injection 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.

    Drug Interactions

    Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like flushing (see Pediatric Use - PRECAUTIONS) and anaphylactoid reactions (see ADVERSE REACTIONS).

    Monitor renal function in patients receiving vancomycin and concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs, such as amphotericin B, aminoglycosides, bacitracin, polymixin B, colistin, viomycin, or cisplatin.

    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 was found in standard laboratory tests. No definitive fertility studies have been performed.

    Pregnancy

    Teratogenic Effects

    Pregnancy Category C

    Animal reproduction studies have not been conducted with vancomycin. It is not known whether vancomycin can affect reproduction capacity. In a controlled clinical study, the potential ototoxic and nephrotoxic effects of vancomycin on infants were evaluated when the drug was administered 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 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 hydrochloride for injection is excreted in human milk. Caution should be exercised when vancomycin hydrochloride for injection 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 PRECAUTIONS).

    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).

    Information for Patients

    Patients should be counseled that antibacterial drugs including vancomycin hydrochloride for injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When vancomycin hydrochloride for injection 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 hydrochloride for injection 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.

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  • ADVERSE REACTIONS

    Infusion-Related Events

    During or soon after rapid infusion of vancomycin hydrochloride for injection, 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 hydrochloride for injection is given by a slow infusion over 60 minutes. In studies of normal volunteers, infusion-related events did not occur when vancomycin hydrochloride for injection was administered at a rate of 10 mg/min or less.

    Nephrotoxicity

    Systemic vancomycin exposure may result in acute kidney injury (AKI). The risk of AKI increases as systemic exposure/serum levels increase. Additional risk factors for AKI in patients receiving vancomycin include receipt of concomitant drugs known to be nephrotoxic, in patients with pre-exiting renal impairment, or with co-morbidities that predispose to renal impairment. Interstitial nephritis has also been reported in patients receiving vancomycin.

    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 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 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 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 the administration of vancomycin.

    Chemical peritonitis has been reported following intraperitoneal administration (see PRECAUTIONS).

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  • 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 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.

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  • 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.

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  • DOSAGE AND ADMINISTRATION

    Infusion-related events are related to both the concentration and the 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. An infusion rate of 10 mg/min or less is associated with fewer infusion-related events (see ADVERSE REACTIONS). Infusion-related events may occur, however, at any rate or concentration.

    The use of ADD-Vantage vials of vancomycin hydrochloride is indicated only when doses of 500 mg, 750 mg or 1 g are appropriate. Patient factors, such as renal function and age, are critical in calculating correct dosage regimens (see below). If doses of 500 mg, 750 mg or 1 g are determined to be inappropriate, conventional vials of vancomycin hydrochloride should be used. ADD-VANTAGE VIALS OF VANCOMYCIN HYDROCHLORIDE SHOULD NOT BE USED IN NEONATES, INFANTS, OR PEDIATRIC PATIENTS WHO REQUIRE DOSES OF LESS THAN 500 MG.

    Patients With Normal Renal Function

    Adults

    The usual daily intravenous dose is 2 g divided either as 500 mg every 6 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 6 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 1st week of life and every 8 hours thereafter up to the age of 1 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 premature infants and 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 hydrochloride for injection per day in mg is about 15 times the glomerular filtration rate in mL/min (see following table).

    DOSAGE TABLE FOR VANCOMYCIN IN PATIENTS WITH IMPAIRED RENAL FUNCTION (Adapted from Moellering et al)4
    Creatinine Clearance
    mL/min
    Vancomycin Dose
    mg/24 h
    100 1,545
    90 1,390
    80 1,235
    70 1,080
    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 hr. In patients with marked renal impairment, it may be more convenient to give maintenance doses of 250 to 1,000 mg once every several days rather than administering the drug on a daily basis. In anuria, a dose of 1,000 mg every 7 to 10 days has been recommended. When only serum creatinine 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) × (140 – age in years)]
    72 × serum creatinine concentration (mg/dL)
    Women: 0.85 × 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 in 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

    Vancomycin Hydrochloride ADD-Vantage vials should be used only with approved diluents (5% dextrose injection or 0.9% sodium chloride injection) (see INSTRUCTIONS FOR USE).

    Chemical Stability

    It has been shown that after reconstitution, the admixture solution prepared in either dextrose injection or sodium chloride injection may be stored for 24 hours at room temperature or in a refrigerator for 14 days without significant loss of potency. However, this information is not intended to suggest that it is acceptable practice to administer such an admixture well after the time of preparation. Admixtures should be prepared as close to the time of administration as is reasonable.

    Intermittent infusion is the recommended method of administration.

    The 500 mg ADD-Vantage vial should be joined with at least a 100 mL ADD-Vantage flexible diluent container, the 750 mg and the 1 g ADD-Vantage vial should be joined only to a 250 mL ADD-Vantage flexible diluent container. The desired dose diluted in this manner should be administered by intravenous infusion over a period of at least 60 minutes.

    Compatibility with Intravenous Fluids

    Solutions that are diluted with 5% Dextrose Injection or 0.9% Sodium Chloride Injection may be stored in a refrigerator for 14 days without significant loss of potency. Solutions that are diluted with the following infusion fluids may be stored in a refrigerator for 96 hours:

    5% Dextrose Injection 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 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.

    Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution or container permits.

    For Oral Administration

    NOTE: For information only. ADD-Vantage Vials cannot be used to supply vancomycin for this purpose.

    Oral vancomycin is used in treating antibiotic-associated pseudomembranous colitis caused by C. difficile and for staphylococcal enterocolitis. Vancomycin is not effective by the oral route for other types of infections. The usual adult total daily dosage is 500 mg to 2 g given in 3 or 4 divided doses for 7 to 10 days. The total daily dose in children is 40 mg/kg of body weight in 3 or 4 divided doses for 7 to 10 days. The total daily dosage should not exceed 2 g. The appropriate dose may be diluted in 1 oz of water and given to the patients to drink. Common flavoring syrups may be added to the solution to improve the taste for oral administration. The diluted solution may be administered via a nasogastric tube.

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  • INSTRUCTIONS FOR USE

    To Use Vial in ADD-Vantage Flexible Diluent Container

    To Open:

    Peel overwrap at corner and remove solution container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

    To Assemble Vial and Flexible Diluent Container:
    (Use Aseptic Technique)

    1.
    Remove the protective covers from the top of the vial and the vial port on the diluent container as follows:
    a.
    To remove the breakaway vial cap, swing the pull ring over the top of the vial and pull down far enough to start the opening (See Figure 1.), then pull straight up to remove the cap. (See Figure 2.) NOTE: Do not access vial with syringe.
    Fig. 1 Fig. 2
     
    b.
    To remove the vial port cover, grasp the tab on the pull ring, pull up to break the tie membrane, then pull back to remove the cover. (See Figure 3.)
    2.
    Screw the vial into the vial port until it will go no further. THE VIAL MUST BE SCREWED IN TIGHTLY TO ASSURE A SEAL. This occurs approximately 1/2 turn (180°) after the first audible click. (See Figure 4.) The clicking sound does not assure a seal; the vial must be turned as far as it will go. NOTE: Once vial is seated, do not attempt to remove. (See Figure 4.)
    3.
    Recheck the vial to assure that it is tight by trying to turn it further in the direction of assembly.
    4.
    Label appropriately.
    Fig. 3 Fig. 4

    To Reconstitute the Drug:

    1. Squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial.
    2. With the other hand, push the drug vial down into the container telescoping the walls of the container. Grasp the inner cap of the vial through the walls of the container. (See Figure 5.)
    3. Pull the inner cap from the drug vial. (See Figure 6.) Verify that the rubber stopper has been pulled out, allowing the drug and diluent to mix.
    4. Mix container contents thoroughly and use within the specified time.
    Fig. 5 Fig. 6

    Preparation for Administration:
    (Use Aseptic Technique)

    1. Confirm the activation and admixture of vial contents.
    2. Check for leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired.
    3. Close flow control clamp of administration set.
    4. Remove cover from outlet port at bottom of container.
    5. Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated. NOTE: See full directions on administration set carton.
    6. Lift the free end of the hanger loop on the bottom of the vial, breaking the two tie strings. Bend the loop outward to lock it in the upright position, then suspend container from hanger.
    7. Squeeze and release drip chamber to establish proper fluid level in chamber.
    8. Open flow control clamp and clear air from set. Close clamp.
    9. Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.
    10. Regulate rate of administration with flow control clamp.

    WARNING: Do not use flexible containers in series connections.

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  • HOW SUPPLIED/STORAGE AND HANDLING

    Vancomycin Hydrochloride for Injection, USP is supplied as a sterile powder in single-dose ADD-Vantage vials that contain either 500 mg, 750 mg or 1 g.

    NDC Number Fill Units per Carton
    0409-6534-01 500 mg 10 ADD-Vantage™ Vials
    0409-6531-01 750 mg 10 ADD-Vantage™ Vials
    0409-6535-01 1 g 10 ADD-Vantage™ Vials

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

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  • ANIMAL PHARMACOLOGY

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

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  • REFERENCES

    1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Tenth Edition. CLSI document M07-A10. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500,Wayne, Pennsylvania 19087, USA, 2015.
    2. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational Supplement, CLSI document M100-S25, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500,Wayne, Pennsylvania 19087, USA, 2015.
    3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard – Twelfth Edition. CLSI document M02-A12. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500,Wayne, Pennsylvania 19087, USA, 2015.
    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.
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  • SPL UNCLASSIFIED SECTION

    Hospiral Logo

    Hospira, Inc., Lake Forest, IL 60045 USA

    LAB-0982-1.0
    3/2017

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  • PRINCIPAL DISPLAY PANEL - 750 mg Vial Label

    Single-dose ADD-Vantage™ Vial

    Vancomycin
    Hydrochloride
    for Injection, USP

    750 mg*
    per ADD-Vantage™
    Vial

    For Intravenous Use.

    Hospira, Inc.
    Lake Forest, IL 60045 USA
    Hospira

    PRINCIPAL DISPLAY PANEL - 750 mg Vial Label
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  • PRINCIPAL DISPLAY PANEL - 750 mg Vial Tray

    10 Single-Dose ADD-Vantage™ Vials
    Sterile Powder

    NDC 0409-6531-01
    Rx only

    Vancomycin
    Hydrochloride for Injection, USP

    750 mg* per ADD-Vantage™ Vial

    *Each ADD-Vantage™ Vial contains Vancomycin Hydrochloride equivalent to 750 mg Vancomycin.

    For Intravenous Use.
    MUST BE FURTHER DILUTED BEFORE USE. SEE INSERT.
    Hospira

    PRINCIPAL DISPLAY PANEL - 750 mg Vial Tray
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  • PRINCIPAL DISPLAY PANEL - 1 g Vial Label

    ADD-Vantage™ Vial
    Sterile Powder

    Vancomycin
    Hydrochloride for
    Injection, USP

    For Intravenous Use.

    Equivalent to 1 g Vancomycin

    Hospira, Inc.
    Lake Forest, IL 60045 USA
    Hospira

    PRINCIPAL DISPLAY PANEL - 1 g Vial Label
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  • PRINCIPAL DISPLAY PANEL - 1 g Vial Tray

    ADD-Vantage™ Vial
    Sterile Powder

    10 Units/NDC 0409-6535-01
    Rx only

    Vancomycin
    Hydrochloride for Injection, USP

    For Intravenous Use

    IMPORTANT: Read insert for precautions and directions before use.

    Equivalent to 1 g Vancomycin

    Hospira

    PRINCIPAL DISPLAY PANEL - 1 g Vial Tray
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  • PRINCIPAL DISPLAY PANEL - 500 mg Vial Label

    ADD-Vantage™ Vial
    Sterile Powder

    Vancomycin
    Hydrochloride
    for Injection, USP

    For Intravenous Use.

    Equivalent to 500 mg Vancomycin

    Hospira, Inc., Lake Forest, IL 60045 USA
    Hospira

    PRINCIPAL DISPLAY PANEL - 500 mg Vial Label
    Close
  • PRINCIPAL DISPLAY PANEL - 500 mg Vial Tray

    ADD-Vantage™ Vial
    Sterile Powder

    10 Units/NDC 0409-6534-01
    Rx only

    Vancomycin Hydrochloride
    for Injection, USP

    For Intravenous Use.

    Equivalent to 500 mg Vancomycin

    Important – Read insert for precautions and directions before use.
    Hospira

    PRINCIPAL DISPLAY PANEL - 500 mg Vial Tray
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  • INGREDIENTS AND APPEARANCE
    VANCOMYCIN HYDROCHLORIDE 
    vancomycin hydrochloride injection, powder, lyophilized, for solution
    Product Information
    Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0409-6531
    Route of Administration INTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    VANCOMYCIN HYDROCHLORIDE (UNII: 71WO621TJD) (VANCOMYCIN - UNII:6Q205EH1VU) VANCOMYCIN 750 mg  in 250 mL
    Inactive Ingredients
    Ingredient Name Strength
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    Packaging
    # Item Code Package Description Marketing Start Date Marketing End Date
    1 NDC:0409-6531-01 10 in 1 TRAY 03/23/2012
    1 250 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    ANDA ANDA062933 03/23/2012
    VANCOMYCIN HYDROCHLORIDE 
    vancomycin hydrochloride injection, powder, lyophilized, for solution
    Product Information
    Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0409-6535
    Route of Administration INTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    VANCOMYCIN HYDROCHLORIDE (UNII: 71WO621TJD) (VANCOMYCIN - UNII:6Q205EH1VU) VANCOMYCIN 1 g  in 250 mL
    Inactive Ingredients
    Ingredient Name Strength
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    Packaging
    # Item Code Package Description Marketing Start Date Marketing End Date
    1 NDC:0409-6535-01 10 in 1 TRAY 04/30/2005
    1 250 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    ANDA ANDA062933 04/30/2005
    VANCOMYCIN HYDROCHLORIDE 
    vancomycin hydrochloride injection, powder, lyophilized, for solution
    Product Information
    Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0409-6534
    Route of Administration INTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    VANCOMYCIN HYDROCHLORIDE (UNII: 71WO621TJD) (VANCOMYCIN - UNII:6Q205EH1VU) VANCOMYCIN 500 mg  in 100 mL
    Inactive Ingredients
    Ingredient Name Strength
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    Packaging
    # Item Code Package Description Marketing Start Date Marketing End Date
    1 NDC:0409-6534-01 10 in 1 TRAY 06/16/2005
    1 100 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    ANDA ANDA062931 06/16/2005
    Labeler - Hospira, Inc. (141588017)
    Establishment
    Name Address ID/FEI Business Operations
    Hospira, Inc. 030606222 ANALYSIS(0409-6531, 0409-6534, 0409-6535) , LABEL(0409-6531, 0409-6534, 0409-6535) , MANUFACTURE(0409-6531, 0409-6534, 0409-6535) , PACK(0409-6531, 0409-6534, 0409-6535)
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