Vancomycin 1%

Storage And Handling

Vancomycin Injection, USP is supplied as a frozen, iso-osmotic, premixed solution in a 100 mL, 150 mL, or 200 mL single dose GALAXY plastic container (PL 2040) in the following vancomycin doses:

Store at or below -20°C (-4°F).

See DIRECTIONS FOR USE OF Vancomycin Injection, USP in GALAXY plastic container (PL 2040).

The thawed solution in GALAXY plastic container (PL 2040) remains chemically stable for 72 hours at room temperature (25°C/77°F) or for 30 days when stored under refrigeration (5°C/41°F). Do not refreeze. Handle frozen product containers with care. Product containers may be fragile in the frozen state.

REFERENCES

1. Moellering RC, Krogstad DJ, Greenblatt DJ: Vancomycin therapy in patients with impaired renal function: A nomogram for dosage. Ann Inter Med 1981;94:343.

Manufactured by: Baxter Healthcare Corporation, Deerfield, IL 60015 USA Printed in USA. Revised: Dec 2015

Vancomycin 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 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 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 has been reported to be effective only in combination with an aminoglycoside.

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

Vancomycin Injection, USP in the GALAXY plastic container (PL 2040) is intended for intravenous use only.

Vancomycin in the GALAXY Container (PL 2040 Plastic) is not to be administered orally. 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.

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 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)⁴

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 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 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.

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.

Directions For Use Of Vancomycin Injection, USP In GALAXY Plastic Container (PL 2040)

Vancomycin Injection, USP in GALAXY plastic container (PL 2040) is for intravenous administration only.

Storage

Store in a freezer capable of maintaining a temperature at or below -20°C (-4°F).

Thawing of Plastic Containers:

1. Thaw frozen containers at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microwave irradiation. Do not force thaw.
2. Check for minute leaks by squeezing the bag firmly. If leaks are detected, discard solution because sterility may be impaired.
3. Do not add supplemental medication.
4. Visually inspect the container. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Agitate after solution has reached room temperature. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted or if any seals are not intact, the container should be discarded.
5. The thawed solution in GALAXY plastic container (PL 2040) remains chemically stable for 72 hours at room temperature (25°C/77°F) or for 30 days when stored under refrigeration (5°C/41°F).
6. Do not refreeze.

Preparation for Intravenous Administration:

1. Suspend container from eyelet support.
2. Remove protector from outlet port at bottom of container.
3. Attach administration set. Refer to complete directions accompanying set.
4. Use sterile equipment.

Caution: Do not use plastic containers in series connections. Such use could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Vancomycin is contraindicated in patients with known hypersensitivity to this antibiotic. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

WARNINGS

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

Vancomycin should be administered 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.

Ototoxicity has occurred in patients receiving vancomycin. It may be transient or permanent. It has been reported mostly in patients who have been given excessive 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 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 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).

Risk Of High Sodium Load

Each 100mL solution of Vancomycin Injection, USP contains 0.9 g of Sodium Chloride, USP. Avoid use of Vancomycin Injection USP with Sodium Chloride, USP in patients with congestive heart failure, elderly patients and patients requiring restricted sodium intake.

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 (see ADVERSE REACTIONS). Patients who will undergo prolonged therapy with vancomycin 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 slow infusion of the drug 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 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.

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 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 PRECAUTIONS). The potential for toxic effects in pediatric patients from chemicals that may leach from the plastic containers into the single-dose, premixed intravenous preparation has not been determined.

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).

SIDE EFFECTS

Infusion-Related Events

During or soon after rapid infusion of vancomycin, 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. Cases of interstitial nephritis have also been reported rarely. 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 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, Stevens-Johnson syndrome, 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 drug exposure.

Skin And Subcutaneous Tissue Disorders

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)

DRUG INTERACTIONS

Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like flushing (see Usage in Pediatrics 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.

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.

Infusion-Related Events

During or soon after rapid infusion of vancomycin, 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. Cases of interstitial nephritis have also been reported rarely. 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 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, Stevens-Johnson syndrome, 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 drug exposure.

Skin And Subcutaneous Tissue Disorders

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)

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.