VANCOMYCIN HYDROCHLORIDE_- vancomycin hydrochloride_injection, powder, lyophilized, for solution
Function and Efficacy
Vancomycin is an antibacterial drug [see Microbiology ( 12. 4 The pharmacodynamics of vancomycin is unknown. 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 like those after a single dose. Distribution Elimination Metabolism Excretion [see Warnings and Precautions ( 5. 7 Mechanism of Action Resistance in vitro Interaction With Other Antimicrobials in vitro Staphylococcus aureus Streptococcus gallolyticus Streptococcus bovis Antimicrobial Activity in vitro [see Indications and Usage ( 1 Aerobic Gram-Positive Bacteria Corynebacterium Enterococcus spp. (including Enterococcus faecalis Staphylococcus aureus S. epidermidis Streptococcus gallolyticus Streptococcus bovis in vitro in vitro Aerobic Gram-Positive Bacteria Listeria monocytogenes Anaerobic Gram-Positive Bacteria Actinomyces Susceptibility Testing.
Indication
Vancomycin Hydrochloride for Injection is a glycopeptide antibacterial indicated in adult and pediatric patients (neonates and older) for the treatment of: Septicemia ( 1. 1 Infective Endocarditis ( 1. 2 Skin and Skin Structure Infections ( 1. 3 Bone Infections ( 1. 4 Lower Respiratory Tract Infections ( 1. 5 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. 6 Vancomycin Hydrochloride for Injection is indicated in adults and pediatric patients (neonates and older) for the treatment of septicemia due to: Susceptible isolates of methicillin-resistant Staphylococcus aureus Methicillin-susceptible staphylococci in penicillin-allergic patients, or those patients who cannot receive or who have failed to respond to other drugs, including penicillins or cephalosporins. Vancomycin Hydrochloride for Injection is indicated in adults and pediatric patients (neonates and older) for the treatment of infective endocarditis due to: Susceptible isolates of MRSA. Viridans group streptococci Streptococcus gallolyticus Streptococcus bovis Enterococcus Corynebacterium Methicillin-susceptible staphylococci in penicillin-allergic patients, or those patients who cannot receive or who have failed to respond to other drugs, including penicillins or cephalosporins. Vancomycin Hydrochloride for Injection is indicated in adults and pediatric patients (neonates and older) for the treatment of early-onset prosthetic valve endocarditis caused by Staphylococcus epidermidis Vancomycin Hydrochloride for Injection is indicated in adults and pediatric patients (neonates and older) for the treatment of skin and skin structure infections due to: Susceptible isolates of MRSA and coagulase negative staphylococci. Methicillin-susceptible staphylococci in penicillin-allergic patients, or those patients who cannot receive or who have failed to respond to other drugs, including penicillins or cephalosporins. Vancomycin Hydrochloride for Injection is indicated in adults and pediatric patients (neonates and older) for the treatment of bone infections due to: Susceptible isolates of MRSA and coagulase negative staphylococci. Vancomycin Hydrochloride for Injection is indicated in adults and pediatric patients (neonates and older) for the treatment of lower respiratory tract infections due to: Susceptible isolates of MRSA Methicillin-susceptible staphylococci in penicillin-allergic patients, or those patients who cannot receive or who have failed to respond to other drugs, including penicillins or cephalosporins. 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.
Usage and Dosage
Administer Vancomycin Hydrochloride for Injection in a diluted solution over 60 minutes or greater to reduce the risk of infusion reactions. See full prescribing information for further important administration and preparation instructions ( 2. 5 Adult Patients: 2 g divided either as 0. 5 grams (g) every 6 hours or 1 g every 12 hours (2. 2) Pediatric Patients (1 month and older): 10 mg/kg per dose given every 6 hours ( 2. 3 Neonates: See full prescribing information for recommended doses in neonates ( 2. 3 Patients with renal impairment: See full prescribing information for recommended doses in patients with renal impairment ( 2. 4 To reduce the risk of infusion related adverse reactions, administer Vancomycin Hydrochloride for Injection in a diluted solution over 60 minutes or greater [ see Warnings and Precautions ( 5. 1 [see Dosage and Administration ( 2. 2 see Dosage and Administration ( 2. 3 see Warnings and Precautions ( 5. 1 [see Warnings and Precautions ( 5. 8 [see Dosage and Administration ( 2. 5 The usual daily intravenous dose is 2 grams divided either as 500 mg every 6 hours or 1 g every 12 hours. Administer each dose 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. Pediatric Patients (Aged 1 month and older) Neonates (Up to 1 month old) st 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. Vancomycin Hydrochloride for Injection must be reconstituted and further diluted. Reconstitution of the Lyophilized Powder and further dilution Table 1 Volume of Sterile Water for Injection to be Added for Reconstitution and Volume of Infusion Solution to be Used for Further Dilution Vancomycin Strength per Vial Volume of Sterile Water for Injection for reconstitution a Volume of infusion solution b further dilute to a final concentration of 5 mg/mL 750 mg 15 mL 150 mL 1. 25 g 25 mL 250 mL 1. 5 g 30 mL 300 mL a b [see Dosage and Administration ( 2. 6 The following diluents are physically and chemically compatible with 5 g/L vancomycin hydrochloride: Storage of Diluted Solutions: Vancomycin solution has a low pH and may cause chemical or physical instability when it is mixed with other compounds.
Label
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 Clostridioides difficile [see Warnings and Precautions ( 5. 5 Hemorrhagic Occlusive Retinal Vasculitis [see Warnings and Precautions ( 5. 6 Neutropenia [see Warnings and Precautions ( 5. 7 The common adverse reactions are anaphylaxis, “vancomycin infusion reaction”, acute kidney Injury, hearing loss, neutropenia. 1) To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma at (609) 250-7990 or FDA at 1-800-FDA-1088 or www. gov/medwatch. 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. Immune system disorders: [see Warnings and Precautions ( 5. 1 Skin and subcutaneous tissue disorders: [see Warnings and Precautions ( 5. 4 Renal and urinary disorders: Ear and Labyrinth Disorders: Blood and Lymphatic System Disorders: Gastrointestinal Disorders: [see Warnings and Precautions ( 5. 5 Cardiac Disorders: General Disorders and Administration Site Conditions: [see Warnings and Precautions ( 5. 7 Laboratory Abnormalities: Musculoskeletal and connective tissue disorders: Nervous system disorders: Respiratory, thoracic and mediastinal disorders: Vascular disorders: The following adverse reactions have been identified during post approval 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: [see Warnings and Precautions ( 5.
Precautions
Vancomycin Hydrochloride for Injection is contraindicated in patients with known hypersensitivity to vancomycin. Hypersensitivity to vancomycin (4).
Special Population Medication
Risk Summary (see Data (see Data). Data Human Data Staphylococcus-aureus Animal Data Risk Summary Vancomycin Hydrochloride for Injection is indicated in pediatric patients (neonates and older). In pediatric patients, monitor vancomycin serum concentration and renal function when administering Vancomycin Hydrochloride for Injection [see Dosage and Administration ( 2. 2 [see Warnings and Precautions ( 5. 1 Vancomycin Hydrochloride for 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.
Drug Interactions
Anesthetic Agents 2. 1 Piperacillin/Tazobactam 7. 2 Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like flushing [see Warnings and Precautions ( 5. 4 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. No pharmacokinetic interactions have been noted between piperacillin/tazobactam and vancomycin. Concurrent and/or sequential systemic or topical use of other potentially, neurotoxic and/or nephrotoxic drugs requires more frequent monitoring of renal function.
Other Information
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.
NONCLINICAL TOXICOLOGY
Although no long-term studies in animals have been performed to evaluate carcinogenic potential, no mutagenic potential of Vancomycin Hydrochloride for Injection was found in standard laboratory tests. No definitive fertility studies have been performed. 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.
REFERENCES
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.