VANCOMYCIN HYDROCHLORIDE

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Infusion Reactions [see Warnings and Precautions (5.1) ] • Nephrotoxicity [see Warnings and Precautions (5.2) ] • Ototoxicity [see Warnings and Precautions (5.3) ] • Severe Dermatologic Reactions [see Warnings and Precautions (5.4) ] • Clostridioides Difficile -Associated Diarrhea [see Warnings and Precautions (5.5) ] • Hemorrhagic Occlusive Retinal Vasculitis [see Warnings and Precautions (5.6) ] • Neutropenia [see Warnings and Precautions (5.7) ] • Phlebitis and Other Administration Site Reactions [see Warnings and Precautions (5.8) ]. The most common adverse reactions are anaphylaxis, “vancomycin infusion reaction”, acute kidney injury, hearing loss, neutropenia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following adverse reactions associated with the use of vancomycin were identified in clinical trials: Immune System Disorders: Anaphylaxis and “vancomycin infusion reaction” Renal and urinary Disorders: Acute kidney injury and interstitial nephritis Ear and Labyrinth Disorders: Hearing loss, vertigo, and tinnitus Skin and subcutaneous tissue disorders : Rashes including exfoliative dermatitis, and Stevens-Johnson syndrome (SJS) Gastrointestinal Disorders: Clostridioides difficile colitis, nausea Blood and Lymphatic System Disorders: Agranulocytosis, neutropenia, pancytopenia, leukopenia, thrombocytopenia, eosinophilia Cardiac Disorders: Cardiac arrest, chest pain General Disorders and Administration Site Conditions : General discomfort, drug fever, chills, phlebitis, injection site irritation, injection site pain and necrosis following intramuscular injection, chemical peritonitis following intraperitoneal administration (Vancomycin Injection is not approved for intramuscular and intraperitoneal administration) Laboratory Abnormalities: Elevated blood urea nitrogen, elevated serum creatinine Musculoskeletal and connective tissue disorders: Muscle pain Nervous system disorders: Dizziness Respiratory, thoracic and mediastinal disorders: Wheezing, dyspnea Vascular disorders: Hypotension, shock, vasculitis 6.2 Postmarketing Experience The following adverse reactions have been identified during postmarketing use of vancomycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and Subcutaneous Tissue Disorders: Severe dermatologic reactions such as toxic epidermal necrolysis (TEN), Drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear IgA bullous dermatosis (LABD).

4 CONTRAINDICATIONS • Vancomycin Injection is contraindicated in patients with known hypersensitivity to vancomycin. • Solutions containing dextrose including Vancomycin Injection, may be contraindicated in patients with a known allergy to corn or corn products. Hypersensitivity to vancomycin ( 4 )

11 DESCRIPTION Vancomycin Injection USP, in the GALAXY plastic container contains vancomycin, added as Vancomycin Hydrochloride USP. It is a tricyclic glycopeptide antibacterial derived from Amycolatopsis orientalis (formerly Nocardia orientalis ). The chemical name of vancomycin hydrochloride is (Sa)-(3S, 6R, 7R, 22R, 23S, 26S, 36R, 38aR)-44-[[2-O-(3-Amino-2, 3, 6-trideoxy-3-Cmethyl-α-L-lyxo-hexopyranosyl)-β-D-glucopyranosyl]oxy]-3-(carbamoylmethyl)- 10,19dichloro 2,3,4,5,6,7,23,24,25,26,36,37,38,38a-tetradecahydro-7,22,28,30,32-pentahydroxy-6[(2R)-4-methyl-2-(methylamino) valeramido]-2,5,24,38,39-pentaoxo-22H-8,11:18,21-dietheno23, 36-(iminomethano)-13, 16:31, 35-dimetheno-1H, 16H-[l, 6, 9] oxadiazacyclohexadecino [4, 5-m] [10, 2, 16]-benzoxadiazacyclotetracosine-26-carboxylic acid, monohydrochloride. The molecular formula is C 66 H 75 Cl 2 N 9 O 24 ·HCl and the molecular weight is 1,485.71. Vancomycin hydrochloride has the following structural formula: Vancomycin Injection, USP in the GALAXY container is a frozen, iso-osmotic, sterile, nonpyrogenic, premixed single-dose formulation. The composition of Vancomycin Injection, USP, available in the following strengths are: • 500 mg/100 mL (5 mg/mL): containing 500 mg of vancomycin (equivalent to 513 mg of vancomycin hydrochloride); approximately 5 g of dextrose hydrous or 0.9 g of sodium chloride (equivalent to 354 mg total sodium content) • 750 mg/150 mL (5 mg/mL): containing 750 mg of vancomycin (equivalent to 769 mg of vancomycin hydrochloride); approximately 7.5 g of dextrose hydrous or 1.35 g of sodium chloride (equivalent to 531 mg total sodium content) • 1 g/200 mL (5 mg/mL): containing 1 g of vancomycin (equivalent to 1.025 g of vancomycin hydrochloride); approximately 10 g of dextrose hydrous or 1.8 g of sodium chloride (equivalent to 708 mg total sodium content) • 1.25 g/250 mL (5 mg/mL): containing 1.25 g of vancomycin (equivalent to 1.281 g of vancomycin hydrochloride); approximately 12.5 g of dextrose hydrous. • 1.5 g/300 mL (5 mg/mL): containing 1.5 g of vancomycin (equivalent to 1.538 g of vancomycin hydrochloride); approximately 15 g of dextrose hydrous. The pH of the solution may have been adjusted with hydrochloric acid and/or sodium hydroxide. Thawed solutions have a pH in the range of 3.0 to 5.0. After thawing to room temperature, this solution is intended for intravenous use only. This GALAXY container is fabricated from a specially designed multilayer plastic. Solutions are in contact with the polyethylene layer of this container and can leach out certain chemical components of the plastic in very small amounts within the expiration period. The suitability of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies. Vancomycin Structural Formula

2 DOSAGE AND ADMINISTRATION • If a dose of Vancomycin Injection is required that does not equal 500 mg, 750 mg, 1 g, 1.25 g or 1.5 g, this product is not recommended for use and an alternative formulation of vancomycin should be considered. ( 2.1 ) • For Intravenous use only. Do not administer orally. ( 2.1 ). • Administer Vancomycin Injection by intravenous infusion over 60 minutes or greater to reduce the risk of infusion reactions. ( 2.1 ). • Recommended Dosage in Adult Patients with Normal Renal Function: 2 g divided either as 0.5 grams (g) every 6 hours or 1 g every 12 hours. ( 2.2 ) • Recommended Dosage in Pediatric Patients with Normal Renal Function: 10 mg/kg per dose given every 6 hours. ( 2.3 ) • Recommended Dosage in Patients with Renal Impairment: See full prescribing information for recommended doses in patients with renal impairment. ( 2.4 ) • See full prescribing information for further important preparation and administration instructions. ( 2.1 , 2.5 ) 2.1 Important Administration Instructions • If a dose of Vancomycin Injection is required that does not equal 500 mg, 750 mg, 1 g, 1.25 g or 1.5 g, this product is not recommended for use and an alternative formulation of vancomycin should be considered. • Vancomycin Injection is intended for intravenous use only. • Vancomycin Injection is not to be administered orally. • To reduce the risk of infusion related adverse reactions, administer Vancomycin Injection by intravenous infusion over 60 minutes or greater [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . An infusion rate of 10 mg/min or less is associated with fewer infusion-related adverse reactions [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . Infusion related adverse reactions may occur, however, at any rate or concentration. • Drug additives should not be made to this solution. • Vancomycin Injection concentrations of no more than 5 mg/mL are recommended in adults [see Dosage and Administration (2.2) ] . See also age-specific recommendations [see Dosage and Administration (2.3) ]. • Administer Vancomycin by a secure intravenous route of administration to reduce the risk of local irritation and phlebitis reactions [see Warnings and Precautions (5.8) ]. • Administer Vancomycin Injection prior to intravenous anesthetic agents to reduce the risk of infusion related adverse reactions [see Warnings and Precautions (5.1) ]. 2.2 Recommended Dosage in Adult Patients with Normal Renal Function The usual daily intravenous dosage of Vancomycin Injection is 2 grams (g) divided either as 500 mg every 6 hours or 1 g every 12 hours. Administer each dose by intravenous infusion over a period of 60 minutes or greater. Other patient factors, such as age or obesity, may call for modification of the usual intravenous daily dose. The initial daily dose should be no less than 15 mg/kg. 2.3 Recommended Dosage in Pediatric Patients with Normal Renal Function If a dose of Vancomycin Injection is required that does not equal 500 mg, 750 mg, 1 g, 1.25 g or 1.5 g, this product is not recommended for use and an alternative formulation of vancomycin should be considered [see Use in Specific Populations (8.4) ]. Pediatric Patients (Aged 1 Month and Older) The usual intravenous dosage of vancomycin is 10 mg/kg per dose given every 6 hours. Each dose should be administered over a period of at least 60 minutes. Close monitoring of serum concentrations of vancomycin may be warranted in these patients. Pediatric Patients (Younger than 1 Month Old) In pediatric patients up to the age of 1 month, the total daily intravenous dosage may be lower. In neonates, an initial dose of 15 mg/kg is suggested, followed by 10 mg/kg every 12 hours for neonates in the 1 st week of life and every 8 hours thereafter up to the age of 1 month. 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. 2.4 Recommended Dosage in Patients with Renal Impairment Dosage adjustment must be made in patients with renal impairment. The initial dose should be no less than 15 mg/kg in patients with any degree of renal impairment. Measure trough vancomycin serum concentrations to guide therapy, especially in seriously ill patients with changing renal function. For functionally anephric patients, an initial dose of 15 mg/kg of body weight should be given to achieve prompt therapeutic serum concentrations. Measure vancomycin serum concentrations at 24 hours following the first dose to guide further intravenous therapy. 2.5 Administration and Preparation Instructions for Vancomycin Injection Administration Instructions Vancomycin Injection, in GALAXY plastic container is for intravenous administration only. Intermittent infusion is the recommended method of administration. Store the frozen Vancomycin Injection container in a freezer capable of maintaining a temperature at or below -20°C (-4°F) [see How Supplied/Storage and Handling (16) ]. Preparation for Intravenous Administration: Thawing of Plastic Containers 1. Thaw frozen containers at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in waters baths or by microwave irradiation. Do not force thaw. 2. Check for minute leaks by squeezing the bag firmly. If leaks are detected, discard solution because sterility may be impaired. 3. Do not add supplemental medication. 4. Visually inspect the container. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. 5. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Agitate after solution has reached room temperature. 6. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted or if any seals are not intact, discard the container. 7. The thawed solution in GALAXY plastic container remains chemically stable for 72 hours at room temperature (25°C/77°F) or for 30 days when stored under refrigeration (5°C/41°F). 8. Handle frozen product containers with care. Product containers may be fragile in the frozen state. 9. Do not refreeze thawed Vancomycin Injection. Directions for Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. 1. Suspend container from eyelet support. 2. Remove protector from outlet port at bottom of container. 3. Attach administration set. Refer to complete directions accompanying set. 4. Use sterile equipment. Do not use plastic containers in series connections. Such use could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

10 OVERDOSAGE 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. For current information on the management of overdosage, contact the National Poison Control Center at 1-800-222-1222 or www.poison.org.

7 DRUG INTERACTIONS • Anesthetic Agents: Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like flushing. ( 2.1 , 7.1 ) • Piperacillin/Tazobactam: Increased incidence of acute kidney injury in patients receiving concomitant piperacillin/tazobactam and vancomycin as compared to vancomycin alone. Monitor kidney function in patients. ( 7.2 ) 7.1 Anesthetic Agents Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like flushing [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4) ]. 7.2 Piperacillin-Tazobactam Studies have detected an increased incidence of acute kidney injury in patients administered concomitant piperacillin/tazobactam and vancomycin as compared to vancomycin alone. Monitor kidney function in patients receiving concomitant piperacillin/tazobactam and Vancomycin Injection. No pharmacokinetic interactions have been noted between piperacillin/tazobactam and vancomycin. 7.3 Ototoxic and/or Nephrotoxic Drugs Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs with Vancomycin Injection requires more frequent monitoring of renal function.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Vancomycin is an antibacterial drug [see Microbiology (12.4) ]. 12.2 Pharmacodynamics Based on animal models of infection, the antimicrobial activity of vancomycin appears to correlate with the AUC/MIC (area under the concentration-time curve/minimum inhibitory concentration) ratio for certain pathogens, including methicillin resistant Staphylococcus aureus. The principal pharmacokinetic/pharmacodynamic parameter best associated with clinical and microbiological cure has not been elucidated in clinical trials 2,3. 12.3 Pharmacokinetics General Pharmacokinetics 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. Distribution The distribution coefficient is from 0.3 to 0.43 L/kg. 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. Elimination Mean plasma clearance is about 0.058 L/kg/h, and mean renal clearance is about 0.048 L/kg/h. The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal renal function. In anephric patients, the average half-life of elimination is 7.5 days. Total systemic and renal clearance of vancomycin may be reduced in the elderly. Metabolism There is no apparent metabolism of vancomycin. Excretion In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. Renal dysfunction slows excretion of vancomycin. 12.4 Microbiology Mechanism of Action The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. Resistance There is no cross-resistance between vancomycin and other antibacterial(s). Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi. Interaction With Other Antimicrobials The combination of vancomycin and an aminoglycoside acts synergistically in vitro against many isolates of Staphylococcus aureus, Streptococcus gallolyticus (previously known as Streptococcus bovis ), Enterococcus spp, and the viridans group streptococci. Antimicrobial Activity Vancomycin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections [see Indications and Usage section (1) ]. Aerobic bacteria Gram-positive bacteria Corynebacterium spp. Enterococcus spp. (including Enterococcus faecalis ) Staphylococcus aureus (including methicillin-resistant and methicillin-susceptible isolates) Coagulase negative staphylococci (including S. epidermidis and methicillin-resistant isolates) Streptococcus gallolyticus ( previously known as Streptococcus bovis) Viridans group streptococci The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for vancomycin against isolates of similar genus or organism group. However, the efficacy of vancomycin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials. Aerobic bacteria Gram-positive bacteria Listeria monocytogenes Streptococcus pyogenes Streptococcus pneumoniae Streptococcus agalactiae Anaerobic bacteria Gram-positive bacteria Actinomyces spp Lactobacillus spp Susceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

12.1 Mechanism of Action Vancomycin is an antibacterial drug [see Microbiology (12.4) ].

12.2 Pharmacodynamics Based on animal models of infection, the antimicrobial activity of vancomycin appears to correlate with the AUC/MIC (area under the concentration-time curve/minimum inhibitory concentration) ratio for certain pathogens, including methicillin resistant Staphylococcus aureus. The principal pharmacokinetic/pharmacodynamic parameter best associated with clinical and microbiological cure has not been elucidated in clinical trials 2,3.

12.3 Pharmacokinetics General Pharmacokinetics 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. Distribution The distribution coefficient is from 0.3 to 0.43 L/kg. 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. Elimination Mean plasma clearance is about 0.058 L/kg/h, and mean renal clearance is about 0.048 L/kg/h. The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal renal function. In anephric patients, the average half-life of elimination is 7.5 days. Total systemic and renal clearance of vancomycin may be reduced in the elderly. Metabolism There is no apparent metabolism of vancomycin. Excretion In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. Renal dysfunction slows excretion of vancomycin.

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3 DOSAGE FORMS AND STRENGTHS Injection: Vancomycin Injection USP, is a frozen, iso-osmotic, sterile, nonpyrogenic premixed solution available in the following strengths: • 500 mg/100 mL (5 mg/mL); Each 100 mL single-dose GALAXY container contains 500 mg Vancomycin (as Vancomycin hydrochloride) in 5% Dextrose or 0.9% Sodium Chloride. • 750 mg/150 mL (5 mg/mL); Each 150 mL single-dose GALAXY container contains 750 mg Vancomycin (as Vancomycin hydrochloride) in 5% Dextrose or 0.9% Sodium Chloride. • 1 g/200 mL (5 mg/mL); Each 200 mL single-dose GALAXY container contains 1 g Vancomycin (as Vancomycin hydrochloride) in 5% Dextrose or 0.9% Sodium Chloride. • 1.25 g/250 mL (5 mg/mL): Each 250 mL single-dose GALAXY container contains 1.25 g of Vancomycin (as Vancomycin hydrochloride) in 5 % Dextrose. • 1.5 g/300 mL (5 mg/mL): Each 250 mL single-dose GALAXY container contains 1.5 g of Vancomycin (as Vancomycin hydrochloride) in 5 % Dextrose. • Injection: Vancomycin Injection (in 5% Dextrose) 500 mg/100 mL; 750 mg/150 mL; 1 g/200 mL; 1.25 g/250 mL; 1.5 g/300 mL (5 mg/mL) in single-dose GALAXY container. ( 3 ) • Injection: Vancomycin Injection (in 0.9% Sodium Chloride) 500 mg/100 mL; 750 mg/150 mL; 1 g/200 mL (5 mg/mL) in single dose GALAXY container. ( 3 )

VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN DEXTROSE MONOHYDRATE WATER HYDROCHLORIC ACID SODIUM HYDROXIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN DEXTROSE MONOHYDRATE WATER HYDROCHLORIC ACID SODIUM HYDROXIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN DEXTROSE MONOHYDRATE WATER HYDROCHLORIC ACID SODIUM HYDROXIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN SODIUM CHLORIDE WATER HYDROCHLORIC ACID SODIUM HYDROXIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN SODIUM CHLORIDE WATER HYDROCHLORIC ACID SODIUM HYDROXIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN SODIUM CHLORIDE WATER HYDROCHLORIC ACID SODIUM HYDROXIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN DEXTROSE MONOHYDRATE HYDROCHLORIC ACID SODIUM HYDROXIDE WATER VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN HYDROCHLORIDE VANCOMYCIN DEXTROSE MONOHYDRATE HYDROCHLORIC ACID SODIUM HYDROXIDE WATER

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

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term studies in animals have been performed to evaluate carcinogenic potential. No definitive fertility studies have been performed.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term studies in animals have been performed to evaluate carcinogenic potential. No definitive fertility studies have been performed. 13.2 Animal Toxicology and/or Pharmacology In animal studies, hypotension and bradycardia occurred in dogs receiving an intravenous infusion of vancomycin 25 mg/kg, at a concentration of 25 mg/mL and an infusion rate of 13.3 mL/min.

NDA050671

VANCOMYCIN HYDROCHLORIDE

VANCOMYCIN HYDROCHLORIDE

0338-3582

HUMAN PRESCRIPTION DRUG

INTRAVENOUS

12.4 Microbiology Mechanism of Action The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. Resistance There is no cross-resistance between vancomycin and other antibacterial(s). Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi. Interaction With Other Antimicrobials The combination of vancomycin and an aminoglycoside acts synergistically in vitro against many isolates of Staphylococcus aureus, Streptococcus gallolyticus (previously known as Streptococcus bovis ), Enterococcus spp, and the viridans group streptococci. Antimicrobial Activity Vancomycin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections [see Indications and Usage section (1) ]. Aerobic bacteria Gram-positive bacteria Corynebacterium spp. Enterococcus spp. (including Enterococcus faecalis ) Staphylococcus aureus (including methicillin-resistant and methicillin-susceptible isolates) Coagulase negative staphylococci (including S. epidermidis and methicillin-resistant isolates) Streptococcus gallolyticus ( previously known as Streptococcus bovis) Viridans group streptococci The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for vancomycin against isolates of similar genus or organism group. However, the efficacy of vancomycin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials. Aerobic bacteria Gram-positive bacteria Listeria monocytogenes Streptococcus pyogenes Streptococcus pneumoniae Streptococcus agalactiae Anaerobic bacteria Gram-positive bacteria Actinomyces spp Lactobacillus spp Susceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL Container Label NDC 0338-3551-48 Vancomycin Injection, USP in 5% Dextrose 500 mg per 100 mL (5 mg/mL) GALAXY Single-Dose Container Discard unused portion Code 2G3551 Sterile Nonpyrogenic Iso-osmotic Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 5 g Dextrose Hydrous, USP in Water for Injection, USP. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide. Dosage: For intravenous use only. See prescribing information. Cautions: Do not add supplementary medication or additives. Rx Only Store at or below -20°C (-4°F). Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microwave irradiation. Do not force thaw. Thawed solution is stable for 30 days under refrigeration or 72 hours at room temperature. Do not refreeze . PL 2040 Plastic Baxter Logo Baxter and Galaxy are trademarks of Baxter International Inc. Baxter Healthcare Corporation , Deerfield, IL 60015 USA 07-34-74-761 Carton Label Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microware irradiation. Do not force thaw. The thawed solution in GALAXY plastic container (PL 2040) remains chemically stable for 72 hours at room temperature or for 30 days when stored under refrigeration. Do not refreeze. Handle frozen product containers with care. Product containers may be fragile in the frozen state. PL 2040 Plastic 07-04-74-764 Vancomycin Injection, USP in 5% Dextrose 500 mg per 100 mL (5 mg/ mL) Contains 6 Single-Use bags. Each bag contains 100 mL. Iso-osmotic. Store at or below -20°C/-4°F. Rx Only NDC 0338-3551-48 Code 2G3551 *FOR BAR CODE POSITION ONLY (01) 20303383551485 GALAXY Container Sterile Nonpyrogenic Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 5 g Dextrose Hydrous, USP in Water for Injection, USP. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide. Dosage: For intravenous use only. See prescribing information. Cautions: Do not add supplementary medication or additives. Baxter Logo Baxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation , Deerfield, IL 60015 USA Container Label NDC 0338-3552-48 Vancomycin Injection, USP in 5% Dextrose 1 g per 200 mL (5 mg/mL) GALAXY Single-Dose Container Discard unused portion Code 2G3552 Sterile Nonpyrogenic Iso-osmotic Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 5 g Dextrose Hydrous, USP in Water for Injection, USP. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide. Dosage: For intravenous use only. See prescribing information. Cautions: Do not add supplementary medication or additives. Rx Only Store at or below -20°C (-4°F). Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microwave irradiation. Do not force thaw. Thawed solution is stable for 30 days under refrigeration or 72 hours at room temperature. Do not refreeze . PL 2040 Plastic Baxter Logo Baxter and Galaxy are trademarks of Baxter International Inc. Baxter Healthcare Corporation , Deerfield, IL 60015 USA 07-34-74-763 Carton Labels Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microware irradiation. Do not force thaw. The thawed solution in GALAXY plastic container (PL 2040) remains chemically stable for 72 hours at room temperature or for 30 days when stored under refrigeration. Do not refreeze. Handle frozen product containers with care. Product containers may be fragile in the frozen state. PL 2040 Plastic 07-04-74-766 Vancomycin Injection, USP in 5% Dextrose 1 g per 200 mL (5 mg/ mL) Contains 3 Single-Use bags. Each bag contains 200 mL. Iso-osmotic. Store at or below -20°C/-4°F. Rx Only NDC 0338-3552-48 Code 2G3552 *FOR BAR CODE POSITION ONLY (01) 20303383552482 GALAXY Container Sterile Nonpyrogenic Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 5 g Dextrose Hydrous, USP in Water for Injection, USP. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide. Dosage: For intravenous use only. See prescribing information. Cautions: Do not add supplementary medication or additives. Baxter Logo Baxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation , Deerfield, IL 60015 USA Container Label NDC 0338-3580-48 Vancomycin Injection, USP in 5% Dextrose 750 mg per 150 mL (5 mg/mL) GALAXY Single-Dose Container Discard unused portion Code 2G3580 Sterile Nonpyrogenic Iso-osmotic Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 5 g Dextrose Hydrous, USP in Water for Injection, USP. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide. Dosage: For intravenous use only. See prescribing information. Cautions: Do not add supplementary medication or additives. Rx Only Store at or below -20°C (-4°F). Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microwave irradiation. Do not force thaw. Thawed solution is stable for 30 days under refrigeration or 72 hours at room temperature. Do not refreeze . PL 2040 Plastic Baxter Logo Baxter and Galaxy are trademarks of Baxter International Inc. Baxter Healthcare Corporation , Deerfield, IL 60015 USA 07-34-74-762 Carton Labels Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microware irradiation. Do not force thaw. The thawed solution in GALAXY plastic container (PL 2040) remains chemically stable for 72 hours at room temperature or for 30 days when stored under refrigeration. Do not refreeze. Handle frozen product containers with care. Product containers may be fragile in the frozen state. PL 2040 Plastic 07-04-74-765 Vancomycin Injection, USP in 5% Dextrose 750 mg per 150 mL (5 mg/ mL) Contains 3 Single-Use bags. Each bag contains 150 mL. Iso-osmotic. Store at or below -20°C/-4°F. Rx Only NDC 0338-3580-48 Code 2G3580 *FOR BAR CODE POSITION ONLY (01) 20303383580485 GALAXY Container Sterile Nonpyrogenic Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 5 g Dextrose Hydrous, USP in Water for Injection, USP. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide. Dosage: For intravenous use only. See prescribing information. Cautions: Do not add supplementary medication or additives. Baxter Logo Baxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation , Deerfield, IL 60015 USA Container Label NDC 0338-3581-01 Vancomycin Injection, USP in 0.9% Sodium Chloride 500 mg per 100 mL (5 mg/mL) GALAXY Single-Dose Container Discard unused portion Code 2G3590 Sterile Nonpyrogenic Iso-osmotic Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 0.9 g Sodium Chloride, USP in Water for Injection, USP. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide. Dosage: For intravenous use only. See prescribing information. Cautions: Do not add supplementary medication or additives. Rx Only Store at or below -20°C (-4°F). Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microwave irradiation. Do not force thaw. Thawed solution is stable for 30 days under refrigeration or 72 hours at room temperature. Do not refreeze . PL 2040 Plastic Baxter Logo Baxter and Galaxy are trademarks of Baxter International Inc. Baxter Healthcare Corporation , Deerfield, IL 60015 USA 07-34-74-548 Carton Labels Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microware irradiation. Do not force thaw. The thawed solution in GALAXY plastic container (PL 2040) remains chemically stable for 72 hours at room temperature or for 30 days when stored under refrigeration. Do not refreeze. Handle frozen product containers with care. Product containers may be fragile in the frozen state. PL 2040 Plastic 07-04-77-715 Vancomycin Injection, USP in 0.9% Sodium Chloride 500 mg per 100 mL (5 mg/ mL) Contains 6 Single-Dose bags. Each bag contains 100 mL. Iso-osmotic. Store at or below -20°C/-4°F. Rx Only NDC 0338-3581-01 Code 2G3590 *FOR BAR CODE POSITION ONLY (01) 20303383581017 GALAXY Container Sterile Nonpyrogenic Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 0.9 Sodium Chloride, USP in Water for Injection, USP. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide. Dosage: For intravenous use only. See prescribing information. Cautions: Do not add supplementary medication or additives. Baxter Logo Baxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation , Deerfield, IL 60015 USA Container Label NDC 0338-3582-01 Vancomycin Injection, USP in 0.9% Sodium Chloride 750 mg per 150 mL (5 mg/mL) GALAXY Single-Dose Container Discard unused portion Code 2G3591 Sterile Nonpyrogenic Iso-osmotic Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 0.9 g Sodium Chloride, USP in Water for Injection, USP. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide. Dosage: For intravenous use only. See prescribing information. Cautions: Do not add supplementary medication or additives. Rx Only Store at or below -20°C (-4°F). Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microwave irradiation. Do not force thaw. Thawed solution is stable for 30 days under refrigeration or 72 hours at room temperature. Do not refreeze . PL 2040 Plastic Baxter Logo Baxter and Galaxy are trademarks of Baxter International Inc. Baxter Healthcare Corporation , Deerfield, IL 60015 USA 07-34-74-551 Carton Labels Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microware irradiation. Do not force thaw. The thawed solution in GALAXY plastic container (PL 2040) remains chemically stable for 72 hours at room temperature or for 30 days when stored under refrigeration. Do not refreeze. Handle frozen product containers with care. Product containers may be fragile in the frozen state. PL 2040 Plastic 07-04-77-715 Vancomycin Injection, USP in 0.9 Sodium Chloride 750 mg per 150 mL (5 mg/ mL) Contains 3 Single-Dose bags. Each bag contains 150 mL. Iso-osmotic. Store at or below -20°C/-4°F. Rx Only NDC 0338-3582-01 Code 2G3591 *FOR BAR CODE POSITION ONLY (01) 20303383582014 GALAXY Container Sterile Nonpyrogenic Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 0.9 Sodium Chloride, USP in Water for Injection, USP. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide. Dosage: For intravenous use only. See prescribing information. Cautions: Do not add supplementary medication or additives. Baxter Logo Baxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation , Deerfield, IL 60015 USA Container Label NDC 0338-3583-01 Vancomycin Injection, USP in 0.9% Sodium Chloride 1 g per 200 mL (5 mg/mL) GALAXY Single-Dose Container Discard unused portion Code 2G3592 Sterile Nonpyrogenic Iso-osmotic Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 0.9 g Sodium Chloride, USP in Water for Injection, USP. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide. Dosage: For intravenous use only. See prescribing information. Cautions: Do not add supplementary medication or additives. Rx Only Store at or below -20°C (-4°F). Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microwave irradiation. Do not force thaw. Thawed solution is stable for 30 days under refrigeration or 72 hours at room temperature. Do not refreeze . PL 2040 Plastic Baxter Logo Baxter and Galaxy are trademarks of Baxter International Inc. Baxter Healthcare Corporation , Deerfield, IL 60015 USA 07-34-74-553 Carton Labels Thaw at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). Product should not be thawed by immersion in water baths or by microware irradiation. Do not force thaw. The thawed solution in GALAXY plastic container (PL 2040) remains chemically stable for 72 hours at room temperature or for 30 days when stored under refrigeration. Do not refreeze. Handle frozen product containers with care. Product containers may be fragile in the frozen state. PL 2040 Plastic 07-04-77-717 Vancomycin Injection, USP in 0.9 Sodium Chloride 1 g per 200 mL (5 mg/ mL) Contains 3 Single-Dose bags. Each bag contains 200 mL. Iso-osmotic. Store at or below -20°C/-4°F. Rx Only NDC 0338-3583-01 Code 2G3592 *FOR BAR CODE POSITION ONLY (01) 20303383583011 GALAXY Container Sterile Nonpyrogenic Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 0.9 Sodium Chloride, USP in Water for Injection, USP. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide. Dosage: For intravenous use only. See prescribing information. Cautions: Do not add supplementary medication or additives. Baxter Logo Baxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation , Deerfield, IL 60015 USA Container Label NDC 0338-0122-04 1.25 g Vancomycin Injection, USP in 5% Dextrose 1.25 g per 250 mL (5 mg/mL) For Intravenous Infusion Only Single-Dose GALAXY Container Discard Unused Portion Rx Only Sterile Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 5 g Dextrose Hydrous, USP in Water for Injection, USP. Dosage: See prescribing information. Store frozen at or below -20°C /-4°F. Thaw at room temperature 20°C to 25°C (68°F to 77°F) or under refrigeration 2°C to 8°C (36°F to 46°F) and store thawed solution as follows: – Refrigerated Storage: Use within 30 days – Room Temperature Storage: Use within 72 hours Do not force thaw. Do not refreeze the thawed solution. Do not add supplemental medication or additives. Code 2G3557 Baxter Logo Baxter and Galaxy are trademarks of Baxter International Inc. or its subsidiaries. Baxter Healthcare Corporation , Deerfield, IL 60015 USA 07-34-00-1841 *UPC-A BAR CODE POSITION ONLY 309440495057 Carton Label Store frozen at or below -20°C /-4°F. Thaw at room temperature 20 ° C to 25°C (68°F to 77°F) or under refrigeration 2°C to 8°C (36°F to 46°F) and store thawed solution as follows: – Refrigerated Storage: Use within 30 days – Room Temperature Storage: Use within 72 hours Do not force thaw. Do not refreeze the thawed solution Handle frozen product containers with care. Product containers may be fragile in the frozen state. 07-04-00-0961 1.25 g Vancomycin Injection, USP in 5% Dextrose 1.25 g per 250 mL (5 mg/mL) For Intravenous Infusion Only. Contains 2 units of Single-Dose bags. Each bag contains 250 mL. Store at or below -20 ° C/-4 ° F. Rx Only NDC 0338-0122-04 Code 2G3557 *FOR BAR CODE POSITION ONLY (01)00000000000000 GALAXY Container Sterile Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 5 g Dextrose Hydrous, USP in Water for Injection, USP. Dosage: See prescribing information. Do not add supplementary medication or additives. Baxter Logo Baxter and Galaxy are trademarks of Baxter International Inc. or its subsidiaries. Baxter Healthcare Corporation , Deerfield, IL 60015 USA Container Label NDC 0338-0124-04 1.5 g Vancomycin Injection, USP in 5% Dextrose 1.5 g per 300 mL (5 mg/mL) For Intravenous Infusion Only Single-Dose GALAXY Container Discard Unused Portion Rx Only Sterile Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 5 g Dextrose Hydrous, USP in Water for Injection, USP. Dosage: See prescribing information. Store frozen at or below -20°C /-4°F. Thaw at room temperature 20°C to 25°C (68°F to 77°F) or under refrigeration 2°C to 8°C (36°F to 46°F) and store thawed solution as follows: – Refrigerated Storage: Use within 30 days – Room Temperature Storage: Use within 72 hours Do not force thaw. Do not refreeze the thawed solution. Do not add supplemental medication or additives. Code 2G3558 Baxter Logo Baxter and Galaxy are trademarks of Baxter International Inc. or its subsidiaries. Baxter Healthcare Corporation , Deerfield, IL 60015 USA 07-34-00-1842 *UPC-A BAR CODE POSITION ONLY 309440495057 Carton Label Store frozen at or below -20°C /-4°F. Thaw at room temperature 20°C to 25°C (68°F to 77°F) or under refrigeration 2°C to 8°C (36°F to 46°F) and store thawed solution as follows: – Refrigerated Storage: Use within 30 days – Room Temperature Storage: Use within 72 hours Do not force thaw. Do not refreeze the thawed solution Handle frozen product containers with care. Product containers may be fragile in the frozen state. 07-04-00-0962 1.5 g Vancomycin Injection, USP in 5% Dextrose 1.5 g per 300 mL (5 mg/mL) For Intravenous Infusion Only. Contains 2 units of Single-Dose bags. Each bag contains 300 mL. Store at or below -20 ° C/-4 ° F. Rx Only NDC 0338-0124-04 Code 2G3558 *FOR BAR CODE POSITION ONLY (01)00000000000000 GALAXY Container Sterile Each 100 mL contains: Vancomycin Hydrochloride, USP equivalent to 500 mg vancomycin with approx. 5 g Dextrose Hydrous, USP in Water for Injection, USP. Dosage: See prescribing information. Do not add supplementary medication or additives. Baxter Logo Baxter and Galaxy are trademarks of Baxter International Inc. or its subsidiaries. Baxter Healthcare Corporation , Deerfield, IL 60015 USA Vancomycin Representative Container Label NDC 0338-3551-48 Vancomycin Representative Carton Label NDC 0338-3551-48 panel 1 of 3 Vancomycin Representative Carton Label NDC 0338-3551-48 panel 2 of 3 Vancomycin Representative Carton Label NDC 0338-3551-48 panel 3 of 3 Vancomycin Representative Container Label 0338-3552-48 Vancomycin Representative Carton Label 0338-3552-48 panel 1 of 3 Vancomycin Representative Carton Label 0338-3552-48 panel 2 of 3 Vancomycin Representative Carton Label 0338-3552-48 panel 3 of 3 Vancomycin Representative Container Label 0338-3580-48 Vancomycin Representative Carton Label 0338-3580-48 panel 1 of 3 Vancomycin Representative Carton Label 0338-3580-48 panel 2 of 3 Vancomycin Representative Carton Label 0338-3580-48 panel 3 of 3 Vancomycin Representative Container Label 0338-3581-01 Vancomycin Representative Carton Label 0338-3581-01 panel 1 of 3 Vancomycin Representative Carton Label 0338-3581-01 panel 2 of 3 Vancomycin Representative Carton Label 0338-3581-01 panel 3 of 3 Vancomycin Representative Container Label 0338-3582-01 Vancomycin Representative Carton Label 0338-3582-01 panel 1 of 3 Vancomycin Representative Carton Label 0338-3582-01 panel 2 of 3 Vancomycin Representative Carton Label 0338-3582-01 panel 3 of 3 Vancomycin Representative Container Label 0338-3583-01 Vancomycin Representative Carton Label 0338-3583-01 panel 1 of 3 Vancomycin Representative Carton Label 0338-3583-01 panel 2 of 3 Vancomycin Representative Carton Label 0338-3583-01 panel 3 of 3 Vancomycin representative container 0338-0122-04 1 of 2 Vancomycin representative container label - 0338-0122-04 2 of 2 Vancomycin representative carton label - 0338-0122-04 1 of 2 Vancomycin representative carton label - 0338-0122-04 2 of 2 Vancomycin representative container label - 0338-0124-04 1 of 2 Vancomycin representative container label - 0338-0124-04 2 of 2 Vancomycin representative carton label - 0338-0124-04 1 of 2 Vancomycin representative carton label - 0338-0124-04 2 of 2

17 PATIENT COUNSELING INFORMATION Infusion Reactions During or After Intravenous Use Advise patients that generalized skin redness, skin rash, itching, flushing, muscle pain, chest pain, shortness of breath, wheezing, or dizziness may occur during intravenous infusion of Vancomycin Injection. [see Warnings and Precautions (5.1) ]. Acute Kidney Injury Advise patients that Vancomycin Injection can result in kidney damage and that blood tests are required to monitor vancomycin blood levels and kidney function during therapy [see Warnings and Precautions (5.2) ]. Hearing Loss or Balance Problems Advise patients that Vancomycin injection may result in decreased hearing and to report hearing loss or balance problems to their healthcare provider [see Warnings and Precautions (5.3) ]. Severe Dermatologic Reactions Advise patients about the signs and symptoms of serious skin manifestations. Instruct patients to stop Vancomycin Injection immediately and promptly seek medical attention at the first signs or symptoms of skin rash, mucosal lesions and blisters [see Warnings and Precautions (5.4) ]. Diarrhea Diarrhea is a common problem caused by antibacterial drugs, including Vancomycin Injection, which usually ends when the antibacterial drug is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible [see Warnings and Precautions (5.5) ]. Antibacterial Resistance Patients should be counseled that antibacterial drugs including Vancomycin Injection, should only be used to treat bacterial infections. They do not treat viral infections ( e.g. , the common cold). When Vancomycin Injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Vancomycin Injection or other antibacterial drugs in the future. Manufactured by, Packed by, Distributed by: Baxter Healthcare Corporation Deerfield, IL 60015 USA Made in the USA 07-19-03-984 Baxter and Galaxy are trademarks of Baxter International Inc. or its subsidiaries.

15 REFERENCES 1. Byrd RA., Gries CL, Buening M.: Developmental Toxicology Studies of Vancomycin Hydrochloride Administered Intravenously to Rats and Rabbits. Fundam Appl Toxicol 1994; 23: 590-597. 2. Rybak MJ. The pharmacokinetic and pharmacodynamic properties of vancomycin. Clinical Infectious Diseases. 2006;42(Supplement_1): S35-S39. 3. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Clinical Infectious Diseases. 2020;71(6):1361-1364.

8.5 Geriatric Use Vancomycin injection is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection [see Dosage and Administration (2.4) ] , and it may be useful to monitor renal function [see Warnings and Precautions (5.2) ].

8.4 Pediatric Use Vancomycin Injection is indicated in pediatric patients for the treatment of septicemia, infective endocarditis, skin and skin structure infections, bone infections and lower respiratory tract infections for whom appropriate dosing with this formulation can be achieved [see Indications and Usage (1.1 to 1.5 ) and Dosage and Administration (2.1 , 2.3 )]. Because of the limitations of the available strengths and administration requirements (i.e., administration of fractional doses is not recommended) of Vancomycin Injection, and to avoid unintentional overdose, this product is not recommended for use if a dose of Vancomycin Injection that does not equal 500 mg, 750 mg, 1 g, 1.25 g or 1.5 g is required, and an alternative formulation of vancomycin should be considered [see Dosage and Administration (2.1 , 2.3 )]. More severe infusion related reactions related to vancomycin administration may occur in pediatric patients. In pediatric patients, monitor vancomycin serum concentration and renal function when administering Vancomycin injection [see Dosage and Administration (2.3) and Warnings and Precautions (5.2) ]. Concomitant administration of vancomycin and intravenous anesthetic agents has been associated with erythema and histamine-like flushing in all patients including pediatric patients [see Warnings and Precautions (5.1) ].

8.1 Pregnancy Risk Summary Available data over several decades of vancomycin use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . Vancomycin did not show adverse developmental effects when administered intravenously to pregnant rats and rabbits during organogenesis at doses less than or equal to the recommended maximum human dose (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data A published study evaluated hearing loss and nephrotoxicity in infants of 10 pregnant intravenous drug users treated with intravenously administered vancomycin for suspected or documented methicillin-resistant Staphylococcus-aureus (MRSA) in the second or third trimester. The comparison groups were 10 non-intravenous drug-dependent patients who received no treatment, and 10 untreated intravenous drug-dependent patients who served as substance abuse controls. No infant in the vancomycin exposed group had abnormal sensorineural hearing at 3 months of age or nephrotoxicity. A published prospective study assessed outcomes in 55 pregnant women with a positive Group B streptococcus (GBS) culture and a high-risk penicillin allergy with resistance to clindamycin or unknown sensitivity who were administered vancomycin at the time of delivery. Vancomycin dosing ranged from the standard 1 g intravenously every 12 hours to 20 mg/kg intravenous every 8 hours (maximum individual dose 2 g). No major adverse reactions were recorded either in the mothers or their newborns. None of the newborns had sensorineural hearing loss. Neonatal renal function was not examined, but all of the newborns were discharged in good condition. Animal Data Vancomycin did not cause fetal malformations when administered during organogenesis to pregnant rats (gestation days 6 to 15) and rabbits (gestation days 6 to 18) at the equivalent recommended maximum human dose (based on body surface area comparisons) of 200 mg/kg/day IV to rats or 120 mg/kg/day IV to rabbits. No effects on fetal weight or development were seen in rats at the highest dose tested or in rabbits given 80 mg/kg/day (approximately 1 and 0.8 times the recommended maximum human dose based on body surface area, respectively). Maternal toxicity was observed in rats (at doses 120 mg/kg and above) and rabbits (at 80 mg/kg and above). 1

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Available data over several decades of vancomycin use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . Vancomycin did not show adverse developmental effects when administered intravenously to pregnant rats and rabbits during organogenesis at doses less than or equal to the recommended maximum human dose (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data A published study evaluated hearing loss and nephrotoxicity in infants of 10 pregnant intravenous drug users treated with intravenously administered vancomycin for suspected or documented methicillin-resistant Staphylococcus-aureus (MRSA) in the second or third trimester. The comparison groups were 10 non-intravenous drug-dependent patients who received no treatment, and 10 untreated intravenous drug-dependent patients who served as substance abuse controls. No infant in the vancomycin exposed group had abnormal sensorineural hearing at 3 months of age or nephrotoxicity. A published prospective study assessed outcomes in 55 pregnant women with a positive Group B streptococcus (GBS) culture and a high-risk penicillin allergy with resistance to clindamycin or unknown sensitivity who were administered vancomycin at the time of delivery. Vancomycin dosing ranged from the standard 1 g intravenously every 12 hours to 20 mg/kg intravenous every 8 hours (maximum individual dose 2 g). No major adverse reactions were recorded either in the mothers or their newborns. None of the newborns had sensorineural hearing loss. Neonatal renal function was not examined, but all of the newborns were discharged in good condition. Animal Data Vancomycin did not cause fetal malformations when administered during organogenesis to pregnant rats (gestation days 6 to 15) and rabbits (gestation days 6 to 18) at the equivalent recommended maximum human dose (based on body surface area comparisons) of 200 mg/kg/day IV to rats or 120 mg/kg/day IV to rabbits. No effects on fetal weight or development were seen in rats at the highest dose tested or in rabbits given 80 mg/kg/day (approximately 1 and 0.8 times the recommended maximum human dose based on body surface area, respectively). Maternal toxicity was observed in rats (at doses 120 mg/kg and above) and rabbits (at 80 mg/kg and above). 1 8.2 Lactation Risk Summary Vancomycin is present in human milk following intravenous administration, however, there are insufficient data to inform the levels. There are no data on the effects of vancomycin on the breastfed infant or milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for vancomycin and any potential adverse effects on the breastfed infant from vancomycin or from the underlying maternal condition. 8.4 Pediatric Use Vancomycin Injection is indicated in pediatric patients for the treatment of septicemia, infective endocarditis, skin and skin structure infections, bone infections and lower respiratory tract infections for whom appropriate dosing with this formulation can be achieved [see Indications and Usage (1.1 to 1.5 ) and Dosage and Administration (2.1 , 2.3 )]. Because of the limitations of the available strengths and administration requirements (i.e., administration of fractional doses is not recommended) of Vancomycin Injection, and to avoid unintentional overdose, this product is not recommended for use if a dose of Vancomycin Injection that does not equal 500 mg, 750 mg, 1 g, 1.25 g or 1.5 g is required, and an alternative formulation of vancomycin should be considered [see Dosage and Administration (2.1 , 2.3 )]. More severe infusion related reactions related to vancomycin administration may occur in pediatric patients. In pediatric patients, monitor vancomycin serum concentration and renal function when administering Vancomycin injection [see Dosage and Administration (2.3) and Warnings and Precautions (5.2) ]. Concomitant administration of vancomycin and intravenous anesthetic agents has been associated with erythema and histamine-like flushing in all patients including pediatric patients [see Warnings and Precautions (5.1) ]. 8.5 Geriatric Use Vancomycin injection is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection [see Dosage and Administration (2.4) ] , and it may be useful to monitor renal function [see Warnings and Precautions (5.2) ]. 8.6 Renal Impairment Dosage adjustment of Vancomycin Injection must be made in patients with impaired renal function [see Dosage and Administration (2.4) ]. Measure trough vancomycin serum concentrations to guide intravenous therapy, especially in patients with impaired renal function or fluctuating renal function.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Vancomycin Injection, USP is supplied as a frozen, iso-osmotic, premixed solution packaged in a single-dose GALAXY plastic container and is available as follows: Supply Information for Vancomycin Injection, in 5% Dextrose Strength Number of Containers/ Carton NDC 500 mg of vancomycin / 100 mL (5 mg/mL) 12 count 0338-3551-48 750 mg of vancomycin / 150 mL (5 mg/mL) 6 count 0338-3580-48 1 g of vancomycin / 200 mL (5mg/mL) 6 count 0338-3552-48 1.25 g of vancomycin / 250 mL (5 mg/mL) 4 count 0338-0122-04 1.5 g of vancomycin / 300 mL (5 mg/mL) 4 count 0338-0124-04 Supply Information for Vancomycin Injection, in 0.9% Sodium Chloride Strength Number of Containers/ Carton NDC 500 mg of vancomycin / 100 mL (5 mg/mL) 12 count 0338-3581-01 750 mg vancomycin / 150 mL (5 mg/mL) 6 count 0338-3582-01 1 g of vancomycin / 200 mL (5mg/mL) 6 count 0338-3583-01 Storage Store Vancomycin Injection at or below -20°C (-4°F) or Store in a freezer capable of maintaining a temperature at or below -20°C (-4°F). Storage of the thawed solution is described elsewhere in the labeling [see Dosage and Administration (2.5) ] Handling Handle frozen product containers with care. Product containers may be fragile in the frozen state.