Get your patient on Vancomycin Hydrochloride

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.

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.

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.

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):

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.

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.

The following diluents are physically and chemically compatible (with 4 g/L vancomycin hydrochloride):

5% Dextrose Injection, USP

5% Dextrose Injection and 0.9% Sodium Chloride Injection, USP

Lactated Ringer’s Injection, USP

5% Dextrose and Lactated Ringer’s Injection

0.9% Sodium Chloride Injection, USP

Good professional practice suggests that compounded admixtures should be administered as soon after preparation as is feasible.

Vancomycin solution has a low pH and may cause physical instability of other compounds.

At the time of use, reconstitute the vials of Vancomycin Hydrochloride for Injection, USP with Sterile Water for Injection to a concentration of 50 mg of vancomycin/mL (see following table for volume of diluent).

After reconstitution, the vials may be stored in a refrigerator for 96 hours without significant loss of potency.

Reconstituted solutions of vancomycin (500 mg/10 mL) must be further diluted in at least 100 mL of a suitable infusion solution. For doses of 1 gram (20 mL), at least 200 mL of solution must be used. The desired dose diluted in this manner should be administered by intermittent IV infusion over a period of at least 60 minutes.

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

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

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.

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

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 2g. 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.

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.

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.

Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see WARNINGS ).

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.

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/mm ³ ) has been reported rarely.

Inflammation at the injection site has been reported.

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 )

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 .

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.

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.

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.

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

Actinomyces species

Lactobacillus species

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.

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 procedure. Standardized procedures are based on dilution method ^1,2 (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 .

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure ^2,3 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 .

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.

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. When tested against appropriate quality control strains, standard vancomycin powder should provide MIC values shown in Table 2 . For the diffusion technique, the 30 mcg vancomycin disk should provide the zone diameters in Table 2 with the quality control strains: