Vd=0.65 l/kg (range: 0.5 to 0.9)


Stability (Lexi):
Vancomycin reconstituted intravenous solutions are stable for 14 days at room temperature or refrigeration.

Stability of parenteral admixture at room temperature (25°C) or refrigeration temperature (4°C): 7 days.

Standard diluent: 500 mg/150 mL D5W; 750 mg/250 mL D5W; 1 g/250 mL D5W.

Minimum volume: Maximum concentration is 5 mg/mL to minimize thrombophlebitis.
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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 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.

Infants and Neonates: In neonates and young infants, the total daily intravenous dosage may be lower. In both neonates and infants, 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. Close monitoring of serum concentrations of vancomycin may be warranted 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 per day in mg is about 15 times the glomerular filtration rate in mL/min: 

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 in order 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 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.

For males: ((140 − age) /( serum creatinine x 72)) (x 0.85 for females) 

The serum creatinine must represent a steady state of renal function or the estimated value for creatinine clearance will not be 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) route have not been assessed.

Intermittent infusion is the recommended method of administration.

PREPARATION AND STABILITY
At the time of use, reconstitute by adding either 10 mL of Sterile Water for Injection to the 500-mg vial or 20 mL of Sterile Water for Injection to the 1-g vial of dry, sterile vancomycin powder. FURTHER DILUTION IS REQUIRED.

After reconstitution with Sterile Water for Injection, 5% Dextrose Injection, or 0.9% Sodium Chloride 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 diluted with at least 100 mL of diluent. Reconstituted solutions containing 1 g must be 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 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, 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 linesbetween 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.

For Oral Administration
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 dosage in pediatric patients 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 patient 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.

HOW SUPPLIED
Sterile Vancomycin Hydrochloride, USP is supplied as a sterilepowder in single-dose fliptop vials that contain the vancomycin equivalent of either 500 mg (List No. 4332) or 1 g (List No. 6533).

Store at controlled room temperature 15° to 30°C (59° to 86°F). [See USP.]

July, 2004
©Hospira 2004 EN-0284
HOSPIRA, INC., LAKE FOREST, IL 60045 USA