Reconstitution and Administration
Vancomycin hydrochloride is administered by slow IV infusion for the treatment of systemic infections. Vancomycin hydrochloride is given orally as capsules or an oral solution for the treatment of enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains) or for antibiotic-associated pseudomembranous colitis caused by Clostridium difficile; if necessary, the parenteral form of vancomycin HCL also may be administered orally for the treatment of these infections. Vancomycin hydrochloride oral solution or the parenteral formulation also may be administered by nasogastric tube. Orally administered vancomycin isnot effective for treatment of systemic infections. Vancomycin is very irritating to tissue and must not be given IM. Safety and efficacy of intrathecal (intralumbar or intraventricular) or intraperitoneal administration of vancomycin have not been determined.
IV Infusion
Vancomycin hydrochloride powder for injection is reconstituted by adding 10 or 20 mL of sterile water for injection to a vial labeled as containing 500 mg or 1 g of vancomycin, respectively, to provide solutions containing 50 mg of the drug per mL.
For intermittent IV infusion, the reconstituted solutions containing 500 mg or 1 g must be diluted further with at least 100 mL or at least 200 mL, respectively, of a compatible IV solution and administered over a period of at least 1 hour. Alternatively, ADD-Vantage® vials labeled as containing 500 mg or 1 g of vancomycin may be reconstituted according to the manufacturer’s directions and administered over a period of at least 1 hour. ADD-Vantage® vials of the drug should be used only when actual doses of 500 mg or 1 g are appropriate and should not be used in neonates, infants, or young children who require doses of less than 500 mg, in which case the dose should be prepared from a reconstituted solution of the sterile powder.
The pharmacy bulk package is not intended for direct IV infusion; doses of the drug from the reconstituted bulk package must be further diluted in a compatible IV infusion solution prior to administration.
Thawed solutions of the commercially available frozen vancomycin hydrochloride injection in dextrose should be administered by IV infusion only. The commercially available frozen vancomycin hydrochloride in dextrose injections should not be thawed by warming them in a water bath or by exposure to microwave radiation. A precipitate may form while the commercially available injection in dextrose is frozen; however, this usually will dissolve with little or no agitation upon reaching room temperature, and the potency of vancomycin hydrochloride frozen injection is not affected. After thawing at room temperature or under refrigeration, the containers should be checked for minute leaks by firmly squeezing the bag. The injection should be discarded if the container seal or outlet ports are not intact or leaks are found or if the solution is discolored, cloudy, or contains a precipitate.
Additives should not be introduced into the injection container. The injections should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.
Rapid IV administration of vancomycin should be avoided, and patients should be monitored closely during infusion of the drug to detect a hypotensive reaction if it occurs.The frequency and severity of thrombophlebitis can be minimized if vancomycin is administered slowly as a dilute solution (2.-5 mg/mL) and administration sites are frequently rotated. To minimize adverse effects, IV vancomycin should be administered slowly, at a rate not exceeding 10 mg/minute; however, the possibility that adverse effects associated with vancomycin infusion could occur at any infusion rate should be considered
Pretreatment with antihistamines (e.g., diphenhydramine hydrochloride 1 mg/kg IV and cimetidine 4 mg/kg IV) may attenuate but not eliminate the risk of certain adverse effects (e.g., red-man syndrome) associated with rapid IV infusion of vancomycin. When intermittent IV infusion is not feasible, vancomycin may be administered by continuous infusion. In this method, 1-2 g of reconstituted vancomycin may be added to a sufficient volume of 0.9% sodium chloride or 5% dextrose injection to permit administration of the desired daily dosage over a 24-hour period.
Oral Administration
Commercially available vancomycin hydrochloride capsules, powder for oral solution, or the powder for IV administrationcan be used for oral administration. Vancomycin hydrochloride powder for oral solution is reconstituted by adding 115 mL of distilled or deionized water to the container labeled as containing 10 g of the drug to provide a solution containing 500 mg of vancomycin per 6 mL, or by adding 20 mL of distilled or deionized water to the container labeled as containing 1 g of the drug to provide a solution containing 250 mg of vancomycin per 5 mL. The contents should be mixed thoroughly to ensure dissolution.
Alternatively, the contents of one 500-mg vial of vancomycin hydrochloride powder for IV administration may be diluted in 30 mL of water and the appropriate dose administered orally or via a nasogastric tube. For patients who are too ill to receive oral therapy, administration via a long intestinal tube, via enema, or by direct instillation via a colostomy or ileostomy has been suggested.
Dosage
Dosage of vancomycin hydrochloride is expressed in terms of vancomycin. Most patients with infections caused by susceptible organisms show a therapeutic response within 48-72 hours following initiation of IV vancomycin therapy. The total duration of therapy is dependent on the type and severity of infection and the clinical and bacteriologic response of the patient. IV Dosage
General Adult Dosage
For the treatment of potentially life-threatening infections in adults with normal renal function, the usual IV dosage of vancomycin is 500 mg every 6 hours or 1 g every 12 hours.
General Pediatric Dosage
Numerous vancomycin dosage regimens have been suggested for pediatric patients, particularly neonates and young infants. Some clinicians suggest that optimal vancomycin dosage in neonates should be based on serum concentrations of the drug, especially in those with low birthweight (i.e., less than 1.5 kg). For neonates and young infants with normal renal function, the manufacturers recommend an initial IV dose of 15 mg/kg, followed by 10 mg/kg every 12 hours in neonates younger than 8 days of age and 10 mg/kg every 8 hours for infants 8 days to 1 month of age; close monitoring of serum vancomycin concentrations may be warranted in these patients.
The American Academy of Pediatrics (AAP) recommends that neonates younger than 1 week of age receive 10-15 mg/kg of vancomycin every 12-18 hours (for those weighing 2 kg or less) or every 8-12 hours (for those weighing more than 2 kg) and that neonates 1 week of age or older receive 10-15 mg/kg given every 8-12 hours (for those weighing 2 kg or less) or every 6-8 hours (for those weighing more than 2 kg).
The AAP suggests that a dosing interval of every 18-24 hours may be appropriate for very-low-birthweight neonates (i.e., less than 1.2 kg) during the first week of life, and recommend that neonates 4 weeks of age or younger weighing less than 1.2 kg receive 15 mg/kg once every 24 hours.
For older children with normal renal function, the manufacturers recommend an IV dosage of 10 mg/kg every 6 hours. Alternatively, for older children, some clinicians suggest an IV dosage of 1.2 g/m2 daily given in divided doses. The AAP suggests that children 1 month of age or older with mild to moderate infections receive IV vancomycin in a dosage of 40 mg/kg daily given in 3-4 divided doses and that those with severe infections receive 40-60 mg/kg daily given in 4 divided doses.
For the treatment of meningitis in children 1 month of age or older, the AAP and other clinicians recommend that vancomycin be given in a dosage of 60 mg/kg daily (maximum 2 g daily) given in divided doses every 6 hours. For specific information on other pediatric dosage regimens, published protocols and specialized references should be consulted.
Treatment of Bacterial Endocarditis
For the treatment of endocarditis caused by methicillin-resistant (MRSA) or methicillin-susceptible staphylococci in patients with native cardiac valves, the usual dosage of IV vancomycin is 30 mg/kg daily given in 2 equally divided doses (maximum dose 2 g daily unless serum concentrations are monitored) for 4-6 weeks. Patients with methicillin-resistant or methicillin-susceptible staphylococcal endocarditis who have a prosthetic valve or other prosthetic material should receive IV vancomycin in a dosage of 30 mg/kg daily given in 2 or 4 equally divided doses (maximum dose 2 g daily unless serum concentrations are monitored) given for 6 weeks or longer in conjunction with oral rifampin (300 mg every 8 hours given for 6 weeks or longer) and IM or IV gentamicin (1 mg/kg every 8 hours given during the first 2 weeks of vancomycin therapy). For the treatment of endocarditis caused by viridans streptococci or Streptococcus bovis, the usual dosage of IV vancomycin is 30 mg/kg daily given in 2 equally divided doses (maximum dose 2 g daily unless serum concentrations are monitored) for 4 weeks. For the treatment of enterococcal endocarditis, the usual dosage of IV vancomycin is 30 mg/kg daily given in 2 equally divided doses (maximum dose 2 g daily unless serum concentrations of the drug are monitored) for 4-6 weeks given in conjunction with IM or IV gentamicin (1 mg/kg every 8 hours) given for 4-6 weeks.
Prevention of Bacterial Endocarditis
For prevention of enterococcal endocarditis in penicillin-allergic patients at high or moderate risk who are undergoing certain GI, biliary tract, or genitourinary tract surgery or instrumentation (see Uses: Endocarditis), the AHA recommends that adults receive a single 1-g dose of vancomycin and that pediatric patients receive a single 20-mg/kg dose of vancomycin given IV over 1-2 hours with the infusion completed within 30 minutes of the start of the procedure.
While patients with cardiac conditions that put them at moderate risk of enterococcal endocarditis may receive vancomycin alone for prophylaxis, adults and pediatric patients with cardiac conditions that put them at high risk also should receive a single 1.5-mg/kg dose of gentamicin (maximum dose 120 mg) given IM or IV within 30 minutes prior to the start of the procedure. When selecting anti-infectives for the prevention of bacterial endocarditis, the current recommendations published by the AHA should be consulted.
Perioperative Prophylaxis
For perioperative prophylaxis in patients undergoing cardiac surgery (prosthetic valve, coronary artery bypass, other open-heart surgery, pacemaker or defibrillator implant); noncardiac thoracic surgery; vascular surgery (arterial surgery involving the abdominal aorta, a prosthesis, or a groin incision or lower extremity amputation for ischemia); neurosurgery (craniotomy); or orthopedic surgery (total joint replacement, internal fixation of fractures) when a cephalosporin (cefazolin, cefuroxime) cannot be used or when use of vancomycin is considered necessary because of a high incidence of methicillin-resistant staphylococci at the institution, a single 1-g dose of vancomycin should be given IV just prior to the procedure. If surgery is prolonged (more than 4 hours), additional intraoperative doses should be given every 4-8 hours for the duration of the procedure; additional doses also are advisable if substantial blood loss occurs. However, postoperative doses generally are unnecessary and should not be used.
Prevention of Neonatal Group B Streptococcal Disease
If IV vancomycin is used for intrapartum anti-infective prophylaxis for prevention of perinatal group B streptococcal (GBS) disease in women with penicillin hypersensitivity who should not receive a b-lactam anti-infective and should not receive clindamycin and erythromycin because of known or suspected resistance, the CDC recommends that 1 g of vancomycin be given IV every 12 hours until delivery. When indicated, such prophylaxis is initiated at the time of labor or rupture of membranes.
Oral Dosage
Adult Dosage
For the treatment of enterocolitis caused by S. aureus (including methicillin-resistant strains) or C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis, C. difficile diarrhea, C. difficile colitis, and pseudomembranous colitis), the usual adult oral dosage of vancomycin is 0.5-2 g daily given in 3 or 4 divided doses for 7-10 days. However, because clinical and bacteriologic responses in C. difficile-associated diarrhea and colitis generally appear to be similar for the low and high dosages in this range, most clinicians recommend using the lower dosage for cost considerations, unless ileus is impending or the infection is severe (e.g., in critically ill patients)
When vancomycin is indicated for the treatment of C. difficile-associated diarrhea and colitis, many clinicians recommend that oral vancomycin be given in a dosage of 125 mg 4 times daily for 7-10 days; rarely, the drug has been administered for up to 14 days. Pediatric Dosage For the treatment of staphylococcal enterocolitis or antibiotic-associated pseudomembranous colitis in children, the usual oral dosage of vancomycin is 40 mg/kg daily given in 3 or 4 divided doses for 7-10 days. Dosage of oral vancomycin in children should not exceed 2 g daily.
Dosage in Renal Impairment
In patients with impaired renal function, including premature infants and geriatric patients, doses and/or frequency of administration of vancomycin must be modified in response to the degree of impairment, severity of the infection, susceptibility of the causative organism, and serum concentrations of the drug.
Several methods of calculating vancomycin dosage for patients with impaired renal function have been proposed; however, in these patients or patients undergoing hemodialysis or peritoneal dialysis, dosage should generally be based on actual serum concentrations of the drug. In patients with impaired renal function, including geriatric and functionally anephric patients, an initial IV dose of 15 mg/kg should be given.
Subsequent dosage must be based mainly on renal function and serum concentrations of the drug. Clinicians should consult published protocols and specialized references for information on specific methods of dosage adjustment. Some clinicians have recommended that 1 g of vancomycin be administered at 12-hour intervals in patients with serum creatinine concentrations less than 1.5 mg/dL, at 3- to 6-day intervals in patients with serum creatinine of 1.5-5 mg/dL, and at 10- to 14-day intervals in patients with serum creatinine greater than 5 mg/dL.
Others have recommended that the usual individual dose be administered every 3-10 days in patients with glomerular filtration rates of 10-50 mL/minute and every 10 days in patients with glomerular filtration rates less than 10 mL/minute.