Last Time Saved: 9/22/11 9:12 AM PMS Black Document Name: QEN-2888v3.qxp EN-2888 EN-2888 Vancomycin Vancomycin Hydrochloride for Injection, USP Hydrochloride for Injection, USP ADD-Vantage™ Vials Rx only ADD-Vantage™ Vials Rx only Hospira, Inc., Lake Forest, IL 60045 USA 60045 IL Forest, Lake Inc., Hospira, To reduce the development of drug-resistant bacteria and maintain the effectiveness of vancomycin and other antibacterial drugs, Printed in USA in Printed vancomycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. DESCRIPTION Vancomycin Hydrochloride for Injection, USP, intravenous, is a chromatographically purified tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis (formerly Nocardia orientalis) and has the molecular formula C66H75Cl2N9O24 • HCl. The molecular weight is 1485.74; 500 mg of the base is equivalent to 0.34 mmol, 750 mg of the base is equivalent to 0.51 mmol, and 1 g of the base is equivalent to 0.67 mmol. Vancomycin Hydrochloride has the following structural formula: OH HO O H2N O OH CH2OH H C O 3 O CH3 CI O O HO CI H C H H H O C H C O H OH • HCI N C O C C H C N C N CH3 O C H C N C O HN H H C NH NH C H CH2 H C H HO C C O C CH2 OH H2N O O HC CH3 OH OH CH3 The ADD-Vantage™ vials contain sterile vancomycin hydrochloride equivalent to either 500 mg, 750 mg, or 1 g vancomycin activity for reconstitution in the ADD-Vantage flexible diluent container containing 5% dextrose injection or 0.9% sodium chloride injection. Vancomycin Hydrochloride is a white to tan lyophilized powder. May contain hydrochloric acid and/or sodium hydroxide for pH adjustment. When reconstituted in water, it forms a clear, light to dark tan solution with a pH of 4.0 (2.5 to 4.5). This product is oxygen sensitive. 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. FURTHER DILUTION IS REQUIRED BEFORE USE (see DOSAGE AND ADMINISTRATION). CLINICAL PHARMACOLOGY Vancomycin Hydrochloride for Injection, USP is administered intravenously for therapy of systemic infections. 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 two hours after infusion, and mean plasma concentrations of approximately 8 mcg/mL Revised: 09/2011 Revised: eleven 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 two hours after infusion, and 1981;94:343. Ann Inter Med Inter Ann mean plasma concentrations of about 10 mcg/mL six hours after infusion. The plasma concentrations during multiple dosing are . 4. Moellering RC, Krogstad DJ, Greenblatt DJ: Vancomycin therapy in patients with impaired renal function: A nomogram for dosage for nomogram A function: renal impaired with patients in therapy Vancomycin DJ: Greenblatt DJ, Krogstad RC, Moellering 4. similar to those after a single dose. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2009. January, PA. Wayne, Institute. Standards Laboratory and Clinical The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal renal function. In the first 3. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard – 10th ed., CLSI document M02-A10. document CLSI ed., 10th – Standard Approved Tests; Susceptibility Disk Antimicrobial for Standards Performance 3. 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. Mean plasma clearance is Clinical and Laboratory Standards Institute. Wayne, PA. January, 2011. January, PA. Wayne, Institute. Standards Laboratory and Clinical about 0.058 L/kg/hr, and mean renal clearance is about 0.048 L/kg/hr. Renal dysfunction slows excretion of vancomycin. In anephric 2. Performance Standards for Antimicrobial Susceptibility Testing; 21st Informational Supplement, CLSI document M100-S21. document CLSI Supplement, Informational 21st Testing; Susceptibility Antimicrobial for Standards Performance 2. 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 document M07-A8. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2009. January, PA. Wayne, Institute. Standards Laboratory and Clinical M07-A8. document metabolism of the drug. About 60% of an intraperitoneal dose of vancomycin administered during peritoneal dialysis is absorbed 1. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard – 8th ed., CLSI ed., 8th – Standard Approved Aerobically; Grow That Bacteria for Tests Susceptibility Antimicrobial Dilution for Methods 1. systemically in six hours. Serum concentrations of about 10 mcg/mL are achieved by intraperitoneal injection of 30 mg/kg of REFERENCES vancomycin. concentration of 25 mg/mL and an infusion rate of 13.3 mL/min. 13.3 of rate infusion an and mg/mL 25 of concentration However, the safety and efficacy of the intraperitoneal use of vancomycin has not been established in adequate and well- In animal studies, hypotension and bradycardia occurred in dogs receiving an intravenous infusion of vancomycin, 25 mg/kg, at a at mg/kg, 25 vancomycin, of infusion intravenous an receiving dogs in occurred bradycardia and hypotension studies, animal In controlled trials (see PRECAUTIONS). ANIMAL PHARMACOLOGY ANIMAL 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 Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Room Controlled USP [See 77°F). to (68 25°C to 20 at Store 10 to 100 mcg/mL. After I.V. administration of vancomycin hydrochloride, inhibitory concentrations are present in pleural, pericardial, ascitic, and synovial fluids; in urine; in peritoneal dialysis fluid; and in atrial appendage tissue. Vancomycin hydrochloride does not 0409-6535-01Vials g 1 ADD-Vantage™ 10 readily diffuse across normal meninges into the spinal fluid; but, when the meninges are inflamed, penetration into the spinal fluid 0409-6531-01Vials mg 750 ADD-Vantage™ 10 occurs. 0409-6534-01Vials mg 500 ADD-Vantage™ 10 Microbiology NDC Number NDC FillCarton per Units The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin alters 500 mg, 750 mg or 1 g. 1 or mg 750 mg, 500 bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other antibiotics. r Vancomycin Hydrochloride for Injection, USP is supplied as a sterile powder in single-dose ADD-Vantage vials that contain eithe contain that vials ADD-Vantage single-dose in powder sterile a as supplied is USP Injection, for Hydrochloride Vancomycin Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi. HOW SUPPLIED HOW Synergy The combination of vancomycin and an aminoglycoside acts synergistically in vitro against many strains of Staphylococcus aureus, WARNING: Do not use flexible containers in series connections. series in containers flexible use not Do WARNING: Streptococcus bovis, enterococci, and the viridans group streptococci. 10. Regulate rate of administration with flow control clamp. control flow with administration of rate Regulate 10. Vancomycin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical 9. Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture. make and prime indwelling, not is device If device. venipuncture to set Attach 9. infections as described in the INDICATIONS AND USAGE section. 8. Open flow control clamp and clear air from set. Close clamp. Close set. from air clear and clamp control flow Open 8. Gram-positive bacteria 7. Squeeze and release drip chamber to establish proper fluid level in chamber. in level fluid proper establish to chamber drip release and Squeeze 7. Diphtheroids the upright position, then suspend container from hanger. from container suspend then position, upright the Enterococci (e.g., Enterococcus faecalis) t in t 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 i lock to outward loop the Bend strings. tie two the breaking vial, the of bottom the on loop hanger the of end free the Lift 6. Staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis (including heterogeneous methicillin-resistant on administration set carton. set administration on strains) in adequate and well-controlled clinical trials. NOTE: See full directions full See 5. Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated. seated. firmly is pin the until motion twisting a with port into set administration of pin piercing Insert 5. Gram-positive bacteria 4. Remove cover from outlet port at bottom of container. of bottom at port outlet from cover Remove 4. Listeria monocytogenes 3. Close flow control clamp of administration set. administration of clamp control flow Close 3. Streptococcus pyogenes 2. Check for leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired. be may sterility as unit discard found, are leaks If firmly. container squeezing by leaks for Check 2. Streptococcus pneumoniae (including penicillin-resistant strains) 1. Confirm the activation and admixture of vial contents.