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Intravenous Dilution Guidelines

Vancomycin
The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.  PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.

Usual Diluents

D5W, NS
Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate]

Minimizing risk of thrombophlebitis:
* See important points listed further down the page....
Concentration less than or equal to 5 mg/ml
[0 to 500 mg] [100 ml] [ 30 minutes ]
[501-1250 mg] [250 ml] [ 60 minutes ]
[1251-1750mg] [500ml] [ 90 minutes ]
[1751-2250mg] [500 ml] [ 120 minutes ]

(Concentration less than or equal to 2.5 mg/ml )
[Amount of drug] [Infusion volume] [Infusion rate]
[0 to 250 mg] [100 ml] [30 minutes]
[251 - 625 mg] [250 ml] [60 minutes]
[626 - 1250mg] [500ml] [ 90 minutes ]

Minimum Dilutions - Monitor for infusion related reactions
[500-1000mg] [100ml] [60 minutes ]*
[1001-1500mg] [150ml] [60 - 90 minutes - slower rate for upper range ]*
[1251-1750mg] [250ml] [ 90 minutes ]*
[1751-2250mg] [250 ml] [ 120 minutes ]*
*Consider central line

Premixed bagsVancomycin Injection, USP is supplied as a frozen, iso-osmotic, premixed solution in a 100 mL or 200 mL single dose GALAXY plastic container in the following vancomycin-equivalent dose:
Solution: Iso-osmotic
[500 mg ] [100 mL] [ 30 minutes]
[1000 mg ] [200 mL] [ 60 minutes]


Additional support / Important points:
Package Insert Data:
Thrombophlebitis may occur, the frequency and severity of which can be minimized by administering the medicine slowly as a dilute solution (2.5 to 5 mg/ml) and by rotating the sites of infusion.

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. 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.

Important points:
* Consider a central line for long term therapy.
* A peripheral IV site should be monitored for pain, redness or swelling prior to initiating the infusion and every 30 minutes until the completion of the infusion.


Are infusion volumes greater than 250ml required for larger doses??   [IJPC - background info]
Osmolarity:  2 grams of vancomycin added to 100 mL of 0.9% sodium chloride injection has a calculated osmolarity of 348 mOsm/L, however the actual osmolarity using an osmometer is much lower (~ 230) or HYPOTONIC.   Further, vancomycin is very acidic - pH of ~ 3.4 (admixture).  A 20 to 40 fold dilution of the reconstituted vial (1 gram/20 ml) will result in a negligible change in the pH ( ~+ 0.3).  The primary purpose of the dilution is to facilitate a slower administration rate and to reduce the amount of drug present per unit of volume.  For additional guidance, please review data available through the International Journal of Pharmaceutical Compounding:   Direct quote:  "The best method of addressing the pH of vancomycin is that of infusing the drug through a catheter with a tip location in a vessel that will allow for adequate hemodilution. If ideal venous access is not possible, routine rotation of the site and informing the patient of the signs and symptoms of phlebitis are important in preventing morbidity."  Kastango, ES, Hadaway, L. New Perspectives on Vancomycin Use in Homecare,. Part 1. Int J Pharm Compd. 2001; 5: 465-469. 

Stability / Miscellaneous top of page

EXP: 2 DAYS (RT) /14 DAYS(REF)
Label
: Refrigerate.

Serum levels:
Peak: 25 to 40 mcg/ml (Goal: 8x MIC).
Trough: 5 to 15 mcg/ml. Dose by level patient: trough < 15. Note: some sources recommend trough concentrations up to 20 mcg/ml for resistant / severe infections.

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

Stability (Source: Lexi-drugs):
"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."

INDICATIONS AND USAGE
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 hydrochloride 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, and skin and skin-structure infections. When staphylococcal infections are localized and purulent, antibiotics are used as adjuncts to appropriate surgical measures.

Vancomycin hydrochloride has been reported to be effective alone or in combination with an aminoglycoside for endocarditis caused by S. viridans or S. bovis. For endocarditis caused by enterococci (e.g., E. faecalis), vancomycin hydrochloride 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.

The parenteral form of Sterile Vancomycin Hydrochloride may be administered orally for treatment of antibiotic-associated pseudomembranous colitis produced by C. difficile and for staphylococcal enterocolitis. Parenteral administration of vancomycin hydrochloride alone is of unproven benefit for these indications. Vancomycin is not effective by the oral route for other types of infections.

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.

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:

DOSAGE TABLE FOR VANCOMYCIN
IN PATIENTS WITH IMPAIRED RENAL FUNCTION
(Adapted from Moellering et al)
Moellering RC, Krogstad DJ, Greenblatt DJ: Vancomycin therapy in patients with impaired renal function: A nomogram for dosage. Ann Intern Med 1981;94:343.
Creatinine Clearance   Vancomycin Dose
mL/min   mg/24 h
100   1545
90   1390
80   1235
70   1080
60   925
50   770
40   620
30   465
20   310
10   155

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.

Creatinine clearance for males = [140-age (years)]× [body wt (kg)]
72 × [serum creatinine (mg/dL)]
Creatinine clearance for females = [140-age (years)]× [body wt (kg)]× 0.85
72 × [serum creatinine (mg/dL)]


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

Source: [package insert]
Disclaimer
The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.  PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.
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