Vancomycin Hydrochloride for Injection, USP

ADD-Vantage^® Vials

Rx only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of vancomycin hydrochloride for injection and other antibacterial drugs, vancomycin hydrochloride for injection, should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Vancomycin hydrochloride for injection, USP is a lyophilized powder, for preparing intravenous (IV) infusions, in ADD-Vantage^® vials each containing the equivalent of 500 mg, 750 mg or 1 g vancomycin base. 500 mg of the base are equivalent to 0.34 mmol, 750 mg of the base are equivalent to 0.51 mmol, and 1 g of the base are equivalent to 0.67 mmol. When reconstituted with Sterile Water for Injection to a concentration of 50 mg/mL, the pH of the solution is between 2.5 and 4.5. This product is oxygen sensitive. Vancomycin Hydrochloride for Injection, USP should be administered intravenously in diluted solution (see DOSAGE AND ADMINISTRATION).

Vancomycin is a tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis (formerly Nocardia orientalis). The chemical name for vancomycin hydrochloride is 3S- [3R*,6S*(S*),7S*,22S*,23R*,26R*,36S*,38aS*]]-3-(2-Amino-2-oxoethyl)-44-[[2-O-(3-amino-2,3,6-trideoxy-3-C-methyl-α-L-lyxo-hexopyranosyl)-ß-D-glucopyranosyl]oxy]-10,19-dichloro-2,3,4,5,6,7,23,24,25,26,36,37,38,38a-tetradecahydro-7,22,28,30,32-pentahydroxy-6-[[4-methyl-2-(methylamino)-1-oxopentyl]amino]-2,5,24,38,39-pentaoxo-22H-8,11:18,21-dietheno-23,36- (iminomethano)-13,16:31,35-dimetheno-1H,16H-[1,6,9]oxadiazacyclohexadecino[4,5- m][10,2,16]-benzoxadiazacyclotetracosine-26-carboxylic acid, monohydrochloride. The molecular formula is C₆₆H₇₅Cl₂N₉O₂₄ ∙ HCl and the molecular weight is 1,485.74. Vancomycin Hydrochloride has the following structural formula:

The solutions contain no bacteriostat, antimicrobial agent (except vancomycin) or buffer and are intended for use only as a single-dose injection only with the ADD-Vantage Flexible Diluent Container.

Vancomycin is poorly absorbed after oral administration.

In subjects with normal kidney function, multiple intravenous dosing of 1 g of vancomycin (15 mg/kg) infused over 60 minutes produces mean plasma concentrations of approximately 63 mcg/mL immediately after the completion of infusion, mean plasma concentrations of approximately 23 mcg/mL 2 hours after infusion, and mean plasma concentrations of approximately 8 mcg/mL 11 hours after the end of the infusion. Multiple dosing of 500 mg infused over 30 minutes produces mean plasma concentrations of about 49 mcg/mL at the completion of infusion, mean plasma concentrations of about 19 mcg/mL 2 hours after infusion, and mean plasma concentrations of about 10 mcg/mL 6 hours after infusion. The plasma concentrations during multiple dosing are similar to those after a single dose.

The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal renal function. In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. Mean plasma clearance is about 0.058 L/kg/h, and mean renal clearance is about 0.048 L/kg/h. Renal dysfunction slows excretion of vancomycin. In anephric patients, the average half-life of elimination is 7.5 days. The distribution coefficient is from 0.3 to 0.43 L/kg. There is no apparent metabolism of the drug. About 60% of an intraperitoneal dose of vancomycin administered during peritoneal dialysis is absorbed systemically in 6 hours. Serum concentrations of about 10 mcg/mL are achieved by intraperitoneal injection of 30 mg/kg of vancomycin. However, the safety and efficacy of the intraperitoneal use of vancomycin has not been established in adequate and well-controlled trials (see PRECAUTIONS).

Total systemic and renal clearance of vancomycin may be reduced in the elderly. Vancomycin is approximately 55% serum protein bound as measured by ultrafiltration at vancomycin serum concentrations of 10 to 100 mcg/mL. After IV administration of vancomycin, inhibitory concentrations are present in pleural, pericardial, ascitic, and synovial fluids; in urine; in peritoneal dialysis fluid; and in atrial appendage tissue. Vancomycin does not readily diffuse across normal meninges into the spinal fluid; but, when the meninges are inflamed, penetration into the spinal fluid occurs.

Vancomycin hydrochloride for injection is indicated for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (β-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 hydrochloride for injection is indicated for initial therapy when methicillin-resistant staphylococci are suspected, but after susceptibility data are available, therapy should be adjusted accordingly.

Vancomycin hydrochloride for injection 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, skin and skin structure infections. When staphylococcal infections are localized and purulent, antibiotics are used as adjuncts to appropriate surgical measures.

Vancomycin hydrochloride for injection 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 has been reported to be effective only in combination with an aminoglycoside.

Vancomycin hydrochloride for injection has been reported to be effective for the treatment of diphtheroid endocarditis. Vancomycin hydrochloride for injection 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.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of vancomycin hydrochloride for injection and other antibacterial drugs, vancomycin hydrochloride for injection 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.

The parenteral form of 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.

Vancomycin hydrochloride for injection is contraindicated in patients with known hypersensitivity to this antibiotic.

Clinically significant serum concentrations have been reported in some patients being treated for active C. difficile-induced pseudomembranous colitis after multiple oral doses of vancomycin.

Prolonged use of vancomycin hydrochloride for injection may result in the overgrowth of nonsusceptible microorganisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken. In rare instances, there have been reports of pseudomembranous colitis due to C. difficile developing in patients who received intravenous vancomycin hydrochloride for injection.

Serial tests of auditory function may be helpful in order to minimize the risk of ototoxicity.

Reversible neutropenia has been reported in patients receiving vancomycin hydrochloride for injection (see ADVERSE REACTIONS). Patients who will undergo prolonged therapy with vancomycin hydrochloride for injection or those who are receiving concomitant drugs which may cause neutropenia should have periodic monitoring of the leukocyte count.

Vancomycin hydrochloride for injection is irritating to tissue and must be given by a secure IV route of administration. Pain, tenderness, and necrosis occur with intramuscular (IM) injection of vancomycin hydrochloride for injection or with inadvertent extravasation. Thrombophlebitis may occur, the frequency and severity of which can be minimized by administering the drug slowly as a dilute solution (2.5 to 5 g/L) and by rotation of venous access sites.

There have been reports that the frequency of infusion-related events (including hypotension, flushing, erythema, urticaria, and pruritus) increases with the concomitant administration of anesthetic agents. Infusion-related events may be minimized by the administration of vancomycin as a 60-minute infusion prior to anesthetic induction. The safety and efficacy of vancomycin administered by the intrathecal (intralumbar or intraventricular) route or by the intraperitoneal route have not been established by adequate and well-controlled trials.

Reports have revealed that administration of sterile vancomycin by the intraperitoneal route during continuous ambulatory peritoneal dialysis (CAPD) has resulted in a syndrome of chemical peritonitis. To date, this syndrome has ranged from cloudy dialysate alone to a cloudy dialysate accompanied by variable degrees of abdominal pain and fever. This syndrome appears to be short-lived after discontinuation of intraperitoneal vancomycin.

Prescribing vancomycin hydrochloride for injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly removed by dialysis. Hemofiltration and hemoperfusion with polysulfone resin have been reported to result in increased vancomycin clearance. The median lethal intravenous dose is 319 mg/kg in rats and 400 mg/kg in mice.

To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.

Infusion-related events are related to both the concentration and the 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. 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.

The use of ADD-Vantage vials of vancomycin hydrochloride is indicated only when doses of 500 mg, 750 mg or 1 g are appropriate. Patient factors, such as renal function and age, are critical in calculating correct dosage regimens (see below). If doses of 500 mg, 750 mg or 1 g are determined to be inappropriate, conventional vials of vancomycin hydrochloride should be used. ADD-VANTAGE VIALS OF VANCOMYCIN HYDROCHLORIDE SHOULD NOT BE USED IN NEONATES, INFANTS, OR PEDIATRIC PATIENTS WHO REQUIRE DOSES OF LESS THAN 500 MG.

To Use Vial in ADD-Vantage Flexible Diluent Container

To Open:

Peel overwrap at corner and remove solution container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

To Assemble Vial and Flexible Diluent Container:

(Use Aseptic Technique)

1. 1.Remove the protective covers from the top of the vial and the vial port on the diluent container as follows:
   1. 1.To remove the breakaway vial cap, swing the pull ring over the top of the vial and pull down far enough to start the opening (See Figure 1.), then pull straight up to remove the cap. (See Figure 2.) NOTE: Do not access vial with syringe.

Figure 1

Figure 2

• • 2.To remove the vial port cover, grasp the tab on the pull ring, pull up to break the tie membrane, then pull back to remove the cover. (See Figure 3.)
• 2.Screw the vial into the vial port until it will go no further. THE VIAL MUST BE SCREWED IN TIGHTLY TO ASSURE A SEAL. This occurs approximately 1/2 turn (180°) after the first audible click. (See Figure 4.) The clicking sound does not assure a seal; the vial must be turned as far as it will go. NOTE: Once vial is seated, do not attempt to remove. (See Figure 4.)
• 3.Recheck the vial to assure that it is tight by trying to turn it further in the direction of assembly.
• 4.Label appropriately.

Figure 3

Figure 4

To Reconstitute the Drug:

1. 1.Squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial.
2. 2.With the other hand, push the drug vial down into the container telescoping the walls of the container. Grasp the inner cap of the vial through the walls of the container. (See Figure 5.)
3. 3.Pull the inner cap from the drug vial. (See Figure 6.) Verify that the rubber stopper has been pulled out, allowing the drug and diluent to mix.
4. 4.Mix container contents thoroughly and use within the specified time.

Figure 5

Figure 6

Preparation for Administration:

(Use Aseptic Technique)

1. 1.Confirm the activation and admixture of vial contents.
2. 2.Check for leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired.
3. 3.Close flow control clamp of administration set.
4. 4.Remove cover from outlet port at bottom of container.
5. 5.Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated. NOTE: See full directions on administration set carton.
6. 6.Lift the free end of the hanger loop on the bottom of the vial, breaking the two tie strings. Bend the loop outward to lock it in the upright position, then suspend container from hanger.
7. 7.Squeeze and release drip chamber to establish proper fluid level in chamber.
8. 8.Open flow control clamp and clear air from set. Close clamp.
9. 9.Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.
10. 10.Regulate rate of administration with flow control clamp.

WARNING: Do not use flexible containers in series connections.

Vancomycin Hydrochloride for Injection, USP is supplied as a sterile powder in single-dose ADD-Vantage vials that contain either 500 mg, 750 mg or 1 g.

In animal studies, hypotension and bradycardia occurred in dogs receiving an intravenous infusion of vancomycin hydrochloride 25 mg/kg, at a concentration of 25 mg/mL and an infusion rate of 13.3 mL/min.

1. Moellering RC, Krogstad DJ, Greenblatt DJ: Vancomycin therapy in patients with impaired renal function: A nomogram for dosage. Ann Inter Med 1981;94:343.

Distributed by Hospira, Inc., Lake Forest, IL 60045 USA

LAB-0982-8.0

Revised: 10/2021

Single-dose ADD-Vantage^® Vial

Vancomycin
Hydrochloride
for Injection, USP

Equivalent to 750 mg/vial Vancomycin

For Intravenous Use.

Distributed by Hospira, Inc.
Lake Forest, IL 60045 USA

Hospira

10 Single-Dose ADD-Vantage^® Vials
Sterile Powder

Rx only
NDC 0409-6531-01
Contains 10 of NDC 0409-6531-11

Vancomycin
Hydrochloride for Injection, USP

Equivalent to 750 mg/vial Vancomycin

For Intravenous Use.

MUST BE FURTHER DILUTED BEFORE USE. SEE INSERT.

Hospira

Single-dose
ADD-Vantage^® Vial

Vancomycin
Hydrochloride for
Injection, USP

For Intravenous Use.

Equivalent to 1 g/vial Vancomycin

Distributed by Hospira, Inc.
Lake Forest, IL 60045 USA

Hospira

10 Single-dose ADD-Vantage^® Vials
Sterile Powder

Rx only
NDC 0409-6535-01
Contains 10 of NDC 0409-6535-11

Vancomycin
Hydrochloride for Injection, USP

For Intravenous Use

IMPORTANT: Read insert for precautions and directions before use.

Equivalent to 1 g/vial Vancomycin

Hospira

Single-dose ADD-Vantage^® Vial
Sterile Powder

Vancomycin
Hydrochloride
for Injection, USP

For Intravenous Use.

Equivalent to 500 mg/vial Vancomycin

Distributed by
Hospira, Inc., Lake Forest, IL 60045 USA

Hospira

10 Single-dose ADD-Vantage^® Vials
Sterile Powder

Rx only
NDC 0409-6534-01
Contains 10 of NDC 0409-6534-11

Vancomycin Hydrochloride
for Injection, USP

For Intravenous Use.

Equivalent to 500 mg/vial Vancomycin

Important – Read insert for precautions and directions before use.

Hospira