Vancomycin

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 grams divided either as 500 mg every 6 hours or 1 gram every 12 hours.

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). [See table below.] 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. [See table below.] 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: characterized by decreasing renal function, such as shock, severe heart failure, or oliguria; 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 accompanied by debilitation, malnutrition, or inactivity.

DOSAGE AND ADMINISTRATION Infusion-related events are related to both the concentration and the rate of administration of vancomycin hydrochloride for injection. Concentrations of no more than 5 mg per 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 per mL may be used; use of such higher concentrations may increase the risk of infusion-related events.

The safety and efficacy of vancomycin hydrochloride for injection administration by the intrathecal (intralumbar or intraventricular) routes have not been established. Intermittent infusion is the recommended method of administration. Compatibility with Other Drugs and Intravenous Fluids The following diluents are physically and chemically compatible (with 4 grams per 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 Normosol ® -M and 5% Dextrose 0.9% Sodium Chloride Injection, USP Isolyte ® E Good professional practice suggests that compounded admixtures should be administered as soon after preparation as is feasible.

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