Vancomycin Hydrochloride

Administration

Administer orally197 or by slow IV infusion.155 266 267 Should not be given IM;266 267 safety and efficacy of intrathecal† (intralumbar or intraventricular) or intraperitoneal† administration have not been determined.266 267

Given orally as capsules for treatment Clostridium difficile-associated diarrhea and colitis or for treatment of staphylococcal enterocolitis;197 if necessary, the parenteral formulation (500-mg single-use vial) may be diluted and administered orally or by NG tube for treatment of these infections.267

Oral vancomycin is not effective for treatment of systemic infections197 266 267

Oral Administration

Administer orally as capsules.197 Alternatively, an oral solution prepared using the IV preparation of the drug can be given orally or via NG tube.267

Reconstitution

When necessary, an oral solution can be prepared by diluting the appropriate dose of vancomycin powder for IV infusion in 30 mL of water.267 The 500-mg single-use vial should be used to prepare these oral solutions;267 ADD-Vantage vials should not be used.266

IV Infusion

For solution and drug compatibility information, see Compatibility under Stability.

Usually administered by intermittent IV infusion.266 267 Has been administered by continuous IV infusion when intermittent infusions were not feasible.c

Reconstitution and Dilution

Reconstitute powder for IV infusion by adding 10 or 20 mL of sterile water for injection to a vial containing 500 mg or 1 g of vancomycin.267 Further dilute reconstituted solutions containing 500 mg or 1 g with at least 100 mL or at least 200 mL, respectively, of a compatible IV solution.267

Alternatively, ADD-Vantage vials containing 500 mg or 1 g of vancomycin may be reconstituted according to the manufacturer’s directions using 5% dextrose injection or 0.9% sodium chloride injection.266 ADD-Vantage vials should be used only when actual doses of 500 mg or 1 g are appropriate and should not be used in neonates, infants, or young children who require doses <500 mg.266

The pharmacy bulk package is not intended for direct IV infusion; doses of the drug from the reconstituted bulk package must be further diluted in a compatible IV infusion solution prior to administration.157

Thaw the commercially available injection (frozen) at room temperature or in a refrigerator; do not force thaw by immersion in a water bath or by exposure to microwave radiation.155 A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature.155 Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact.155

The thawed injection should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.155

Rate of Administration

Administer by IV infusion over ≥1 hour.266 267

Rapid IV infusion should be avoided and patients monitored closely to detect a hypotensive reaction if it occurs.266 267

Adverse effects may be minimized if infusion rate is ≤10 mg/minute,266 267 but consider that adverse effects associated with vancomycin infusions could occur with any infusion rate.155 247 266 267 (See Infusion Reactions under Cautions.)

If intermittent IV infusion is not feasible, 1–2 g of reconstituted vancomycin may be added to a sufficient volume of 0.9% sodium chloride or 5% dextrose injection to permit administration of the desired daily dosage over a 24-hour period.c

Dosage

Available as vancomycin hydrochloride; dosage expressed in terms of vancomycin.197 266 267

Pediatric Patients

General Dosage for Neonates Systemic Infections IV

AAP states optimal dosage in neonates should be based on serum vancomycin concentrations, especially in those with low birthweight (i.e., <1.5 kg).122

Manufacturer recommends 15 mg/kg initially, followed by 10 mg/kg every 12 hours in neonates <1 week of age and 10 mg/kg every 8 hours in neonates 1 week to 1 month of age.266 267

Neonates <1 week of age: AAP recommends 15 mg/kg every 24 hours in those weighing <1.2 kg, 10–15 mg/kg every 12–18 hours in those weighing 1.2–2 kg, or 10–15 mg/kg every 8–12 hours for those weighing > 2 kg.122

Neonates ≥1 week of age: AAP recommends 15 mg/kg every 24 hours in those weighing <1.2 kg, 10–15 mg/kg every 8–12 hours in those weighing 1.2–2 kg, or 10–15 mg/kg every 6–8 hours in those weighing >2 kg.122

General Pediatric Dosage Systemic Infections IV

10 mg/kg every 6 hours.266 267

Children ≥1 month of age: AAP recommends 40 mg/kg daily given in 3–4 divided doses for mild to moderate infections or 40–60 mg/kg daily given in 4 divided doses for severe infections.122

Endocarditis Treatment of Endocarditis Caused by Staphylococci (Including Oxacillin-resistant Staphylococci) IV

Native valve: 40 mg/kg daily given in 2 or 3 equally divided doses for 6 weeks.265

Prosthetic valve or other prosthetic material: 40 mg/kg daily given in 2 or 3 equally divided doses for ≥6 weeks.265 Given in conjunction with oral or IV rifampin (20 mg/kg daily given in 3 equally divided doses for ≥6 weeks) and IM or IV gentamicin (3 mg/kg daily given in 3 divided doses during first 2 weeks of treatment).265

Treatment of Endocarditis Caused by Viridans Streptococci or S. bovis IV

Native valve: 40 mg/kg daily given in 2 or 3 equally divided doses for 4 weeks.265

Prosthetic valve or other prosthetic material: 40 mg/kg daily given in 2 or 3 equally divided doses for 6 weeks.265

Treatment of Enterococcal Endocarditis IV

Native valve: 40 mg/kg daily given in 2 or 3 equally divided doses for 6 weeks.265 Used in conjunction with IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses for 6 weeks); substitute IM or IV streptomycin (20–30 mg/kg daily given in 2 equally divided doses for 6 weeks) for gentamicin-resistant strains.265

Prosthetic valve or other prosthetic material: 40 mg/kg daily given in 2 or 3 equally divided doses for 6 weeks.265 Used in conjunction with IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses for 6 weeks); substitute IM or IV streptomycin (20–30 mg/kg daily given in 2 equally divided doses for 6 weeks) for gentamicin-resistant strains.265

Culture-negative Endocarditis† IV

Native valve: 40 mg/kg daily given in 2 or 3 equally divided doses in conjunction with oral or IV ciprofloxacin (20–30 mg/kg daily given in 2 equally divided doses) and IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses).265 All 3 drugs should be given for 4–6 weeks.265

Prosthetic valve (≤1 year after valve replacement): 40 mg/kg daily given in 2 or 3 equally divided doses in conjunction with IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses) and oral or IV rifampin (20 mg/kg daily given in 3 equally divided doses).265 Cefepime (150 mg/kg daily given IV in 3 equally divided doses) also may be included.265 Vancomycin, rifampin, and cefepime should be given for 6 weeks; gentamicin should be given only during first 2 weeks of treatment.265

Prevention of Bacterial Endocarditis in Patients Undergoing Certain GU or GI (except Esophageal) Procedures† IV

For moderate-risk patients, 20 mg/kg given IV over 1–2 hours with the infusion completed within 30 minutes prior to start of the procedure.145

For high-risk patients, 20 mg/kg given IV over 1–2 hours with the infusion completed within 30 minutes prior to start of the procedure; given in conjunction with IV or IM gentamicin (1.5 mg/kg given within 30 minutes prior to start of the procedure).145

Meningitis IV

Children ≥1 month of age: AAP and other clinicians recommend 60 mg/kg daily given in 4 divided doses.122 235 236 237

Clostridium difficile-associated Diarrhea and Colitis Oral

40 mg/kg given in 3 or 4 divided doses for 7–10 days.122 156 197

Staphylococcal Enterocolitis Oral

40 mg/kg given in 3 or 4 divided doses for 7–10 days.122 156 197

Adults

General Adult Dosage Treatment of Life-threatening Systemic Infections IV

500 mg every 6 hours or 1 g every 12 hours.266 267

Endocarditis Treatment of Endocarditis Caused by Staphylococci (Including Oxacillin-resistant Staphylococci) IV

Native valve: 30 mg/kg daily given in 2 equally divided doses for 6 weeks.265

Prosthetic valve or other prosthetic material: 30 mg/kg daily given in 2 equally divided doses for ≥6 weeks.265 Given in conjunction with oral or IV rifampin (900 mg daily given in 3 equally divided doses every 8 hours for ≥6 weeks) and IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses during first 2 weeks of treatment).265

Treatment of Endocarditis Caused by Viridans Streptococci or S. bovis IV

Native valve: 30 mg/kg daily given in 2 equally divided doses for 4 weeks.265

Prosthetic valve or other prosthetic material: 30 mg/kg daily given in 2 equally divided doses for 6 weeks.265

Treatment of Enterococcal Endocarditis IV

Native valve: 30 mg/kg daily given in 2 equally divided doses for 6 weeks.265 Given in conjunction with IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses for 6 weeks); substitute IM or IV streptomycin (15 mg/kg daily given in 2 equally divided doses for 6 weeks) for gentamicin-resistant strains.265

Prosthetic valve or other prosthetic material: 30 mg/kg daily given in 2 equally divided doses for 6 weeks.265 Given in conjunction with IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses for 6 weeks); substitute IM or IV streptomycin (15 mg/kg daily given in 2 equally divided doses for 6 weeks) for gentamicin-resistant strains.265

Culture-negative Endocarditis† IV

Native valve: 30 mg/kg daily given in 2 equally divided doses in conjunction with ciprofloxacin (1 g daily given orally in 2 equally divided doses or 800 mg daily given IV in 2 equally divided doses) and IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses).265 All 3 drugs should be given for 4–6 weeks.265

Prosthetic valve (≤1 year after valve replacement): 30 mg/kg daily given in 2 equally divided doses in conjunction with IM or IV gentamicin (3 mg/kg daily given in 3 equally divided doses) and oral or IV rifampin (900 mg daily given in 3 equally divided doses).265 Cefepime (6 g daily given IV in 3 equally divided doses) also may be included.265 Vancomycin, rifampin, and cefepime should be given for 6 weeks; gentamicin should be given only during first 2 weeks of treatment.265

Prevention of Bacterial Endocarditis in Patients Undergoing Certain GU or GI (except Esophageal) Procedures† IV

For moderate-risk patients, 1 g given IV over 1–2 hours with the infusion completed within 30 minutes prior to start of the procedure.145

For high-risk patients, 1 g given IV over 1–2 hours with the infusion completed within 30 minutes prior to start of the procedure; given in conjunction with IV or IM gentamicin (1.5 mg/kg given within 30 minutes prior to start of the procedure).145

Meningitis IV

500 mg every 6 hours or 1 g every 12 hours.266

Osteomyelitis IV

500 mg every 6 hours or 1 g every 12 hours.266

Respiratory Tract Infections IV

500 mg every 6 hours or 1 g every 12 hours.266

Septicemia IV

500 mg every 6 hours or 1 g every 12 hours.266

Skin and Skin Structure Infections IV

500 mg every 6 hours or 1 g every 12 hours.266

Clostridium difficile-associated Diarrhea and Colitis Oral

0.5–2 g daily given in 3 or 4 divided doses for 7–10 days.156 197 Many clinicians recommend 125 mg 4 times daily for 7–10 days.212 215 c

Staphylococcal Enterocolitis Oral

0.5–2 g daily given in 3 or 4 divided doses for 7–10 days.156 197

Prevention of Perinatal Group B Streptococcal (GBS) Infection† IV

1 g every 12 hours beginning at time of labor or rupture of membranes and continued until delivery.158

Perioperative Prophylaxis† Cardiac, Neurosurgical, Orthopedic, Thoracic (Noncardiac), or Vascular Surgery† IV

A single 1-g dose given just prior to the procedure.208

Start infusion 1–2 hours prior to incision to minimize risk of adverse reaction occurring at time of induction of anesthesia and to ensure adequate tissue concentrations at time of incision.208 If surgery is prolonged (>4 hours), additional intraoperative doses may be given every 6–12 hours for duration of the procedure; additional doses also are advisable if substantial blood loss occurs.208 Postoperative doses generally unnecessary and should not be used.208

Prescribing Limits

Pediatric Patients

Maximum 2 g daily.122 235 197 236 237

For treatment of endocarditis, AHA and IDSA state pediatric dosage should not exceed recommended adult dosage.265

Adults

Maximum 2 g daily.265

For treatment of endocarditis, AHA and IDSA recommend maximum 2 g daily unless serum concentrations are inappropriately low.265 These experts recommend dosage be adjusted to obtain peak serum concentrations (1 hour after completion of IV infusion) of 30–45 mcg/mL and trough concentrations of 10–15 mcg/mL.265

Special Populations

Hepatic Impairment

Limited data suggest dosage adjustments not necessary.264

Renal Impairment

Treatment of Systemic Infections IV

Doses and/or frequency of administration must be modified in response to the degree of renal impairment.266 267 c

Various methods of calculating vancomycin dosage for patients with impaired renal function have been proposed and specialized references should be consulted.c

If possible, dosage should be based on serum vancomycin concentrations, especially in seriously ill patients with changing renal function.105 106 266 267 Peak serum concentrations of 30–40 mg/L and trough concentrations <10–20 mg/L generally have been recommended.264 To ensure efficacy and avoid toxicity, trough serum concentrations may be more useful than peak serum concentrations.264

Some clinicians have recommended that 1 g of vancomycin be administered at 12-hour intervals in patients with Scr of <1.5 mg/dL, at 3- to 6-day intervals in patients with Scr of 1.5–5 mg/dL, and at 10- to 14-day intervals in patients with Scr >5 mg/dL.c

Others have recommended that the usual individual dose be administered every 3–10 days in patients with GFR 10–50 mL/minute and every 10 days in patients with GFR <10 mL/minute.116

Geriatric Patients

Cautious dosage selection (usually starting at the low end of the dosing range) because of age-related decreases in renal function.197 266 267 (See Renal Impairment under Dosage and Administration.)

Contraindications

• Hypersensitivity to vancomycin.197 266 267

• Commercially available frozen vancomycin hydrochloride injection in 5% dextrose may be contraindicated in patients with known allergy to corn or corn products.155

Warnings/Precautions

Warnings

Ototoxicity

Ototoxicity, including damage to the auditory branch of the eighth cranial nerve and permanent deafness, vertigo, dizziness, and tinnitus, has been reported.132 134 266 267

Most cases involved patients with renal impairment, patients receiving high dose or prolonged IV therapy, patients with preexisting hearing loss, or those receiving other ototoxic drugs concomitantly.266 267

Ototoxicity usually has been associated with serum or blood vancomycin concentrations of 80–100 mcg/mL, but has occurred with concentrations as low as 25 mcg/mL.132

Ototoxicity may be transient or permanent;155 266 267 deafness may progress despite cessation of therapy.c

Not recommended in patients with previous hearing loss; if use in these patients is considered necessary, reduce dosage.c

Auditory function testing may minimize risk of ototoxicity during vancomycin therapy.155 266 267 In addition, regular determinations of serum or blood vancomycin concentrations is recommended in patients with borderline renal function and in those >60 years of age.c

If tinnitus occurs, discontinue vancomycin.c

Nephrotoxicity

Nephrotoxicity has been reported, including increased BUN or Scr concentrations, presence of hyaline and granular casts and albumin in urine, fatal uremia, and acute interstitial nephritis.132 133 134

Reported most frequently in patients with renal impairment, patients receiving high dose or prolonged IV therapy, or those receiving other nephrotoxic drugs concomitantly.256

Nephrotoxicity usually is associated with serum or blood vancomycin concentrations of 80–100 mcg/mL, but has occurred with concentrations as low as 25 mcg/mL.132

Use with caution in patients with impaired renal function.266 267 Perform urinalysis and renal function tests periodically during therapy.266 267

Infusion Reactions

Rapid IV administration may result in a potentially serious hypotensive reaction.112 118 119 120 136 137 138 139 143 238 244 247

These infusion reactions usually involve a sudden and possibly severe decrease in blood pressure and may be accompanied by flushing and/or a maculopapular or erythematous rash on the face, neck, chest, and upper extremities (“red-man syndrome” or “red-neck syndrome”).112 118 119 120 135 136 137 142 143 Latter manifestations may occur in the absence of hypotension.120 135 136 142 238 244 247 Wheezing, dyspnea, angioedema, urticaria, pruritus, and, rarely, cardiac arrest or seizures may also occur.139 121 138

The reaction usually begin a few minutes after infusion is started, but may not occur until after its completion and usually resolves spontaneously over 1 to several hours after discontinuance.118 120 135 136 143 238 If the hypotensive reaction is severe, antihistamines, corticosteroids, or IV fluids are recommended.118 120 136

To minimize risk of an infusion reaction, administer IV over a period of ≥1 hour using a rate ≤10 mg/minute and monitor patient’s blood pressure.118 119 120 136 155 266 267 Avoid rapid IV administration (e.g., over several minutes).155

Pretreatment with antihistamines may attenuate but not eliminate the risk of infusion reactions.244 136 141 144

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis, urticaria, exfoliative dermatitis, macular rashes, exfoliative dermatitis, and Stevens-Johnson syndrome have been reported.131 266 267

Rapid IV administration may result in anaphylactoid reaction involving hypotension, wheezing, dyspnea, urticaria, or pruritus.266 267 (See Infusion Reactions under Cautions.)

General Precautions

Hematologic Effects

Neutropenia, eosinophilia, and thrombocytopenia have been reported rarely.155 266 267 c Neutropenia may occur ≥7 days after initiation of therapy or after a total dose of >25 g and may be rapidly reversible following discontinuance of the drug.266

Monitor leukocyte counts periodically in patients receiving prolonged therapy and in those receiving concomitant therapy with drugs that may cause neutropenia.155 266 267

Local Reactions

Vancomycin is very irritating to tissues and can cause pain, tenderness, and necrosis if inadvertent extravasation occurs during IV administration.266 267 Thrombophlebitis may occur.266 267 Do not administer by IM injection.266 267

Increased Systemic Absorption

Although not usually appreciably absorbed from GI tract,101 117 266 267 clinically important serum vancomycin concentrations may occur following multiple enteral or oral doses in patients with active C. difficile-associated diarrhea and colitis, particularly those with renal impairment.101 117 266 267 (See Renal Impairment under Cautions.)

Clinically important systemic absorption of vancomycin may occur in some patients receiving oral vancomycin who have inflammatory disorders of intestinal mucosa; this may increase risk of adverse reactions, particularly in those with renal impairment.197 (See Renal Impairment under Cautions.)

Consider monitoring serum vancomycin concentrations in patients with renal impairment and/or colitis.197

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of vancomycin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.155 197

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.155 197 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.155 197

Vancomycin-resistant Enterococci and Staphylococci

Vancomycin-resistant enterococci have been reported with increasing frequency and there are concerns regarding the increased possibility of vancomycin-resistant strains of other gram-positive bacteria (e.g., S. aureus).115 200 217 256 Because vancomycin use is a consistent risk factor for colonization and infection with vancomycin-resistant enterococci, prudent use of the drug is recommended.115 200

CDC recommends that vancomycin be reserved for use in the treatment of serious infections caused by gram-positive bacteria resistant to β-lactam anti-infectives; treatment of gram-positive bacterial infections in patients with severe hypersensitivity to β-lactam anti-infectives; prophylaxis in certain patients at high risk for bacterial endocarditis as recommended by AHA; treatment of C. difficile-associated diarrhea and colitis that is severe or potentially life-threatening or that fails to respond to oral metronidazole; and for perioperative prophylaxis for major surgical procedures involving implantation of prosthetic materials or devices (e.g., cardiac and vascular procedures and total hip replacement) at institutions with a high rate of oxacillin-resistant (methicillin-resistant) S. aureus or S. epidermidis.200

CDC discourages use of vancomycin in all other situations, including treatment of C. difficile-associated colitis when metronidazole would be effective; routine empiric therapy for febrile neutropenic patients; selective decontamination of the GI tract; eradication of colonization with MRSA; routine prophylaxis in patients undergoing surgery; routine prophylaxis in patients undergoing CAPD or hemodialysis; systemic or local (e.g., antibiotic lock) prophylaxis for infection or colonization of indwelling central or peripheral intravascular catheters; routine prophylaxis in very low birthweight neonates; use for topical application or irrigation; use for treatment of infections caused by gram-positive organisms susceptible to β-lactam anti-infectives; and use in response to a single blood culture positive for coagulase-negative staphylococci if other blood cultures drawn in the same time frame are negative (i.e., contamination of the blood culture with skin flora is likely).200

Specific Populations

Pregnancy

Category B with oral administration.197 Category C with IV administration.266 267

Lactation

Distributed in milk following IV administration;266 267 not known whether distributed into milk following oral administration.197 Discontinue nursing or the drug.266 267

Pediatric Use

Safety and efficacy of oral vancomycin not established in pediatric patients.197

Use IV vancomycin with caution in premature neonates and young infants because of renal immaturity and potential for increased serum vancomycin concentrations; close monitoring of serum concentrations recommended.266 267

Geriatric Use

Experience in those ≥65 years of age insufficient to determine whether they respond differently than younger adults.197

Select dosage with caution, usually starting at low end of dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.197 (See Geriatric Patients under Dosage and Administration.)

Risk of increased systemic absorption of vancomycin.197 (See Increased Systemic Absorption under Cautions.)

Serial tests of auditory function and regular determination of serum or blood vancomycin concentrations recommended in patients with borderline renal function and those >60 years of age.c

Renal Impairment

Increased half-life and decreased clearance.104 105 106 155 264 Increased risk of toxicity.266 267 Use with caution and reduce dosage.155 266 267 (See Renal Impairment under Dosage and Administration.)

Careful monitoring of renal function and serum vancomycin concentrations recommended.155 256 (See Renal Impairment under Dosage and Administration.)

Some clinicians recommend monitoring Scr every 3 days in those with stable renal function and as frequently as once daily in those with unstable renal function or when other nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, loop diuretics) are used concomitantly.264 (See Ototoxic and Nephrotoxic Drugs under Interactions.)

Common Adverse Effects

Local effects (pain and thrombophlebitis); infusion reactions; hypersensitivity reactions.c

Absorption

Bioavailability

Not appreciably absorbed from GI tract in most patients; must be given parenterally for treatment of systemic infections.101 117 197 264 266 267

Oral bioavailability usually <5%;264 bioavailability increased in C. difficile-associated diarrhea and colitis and/or in severe renal impairment.101 117 264 266 267

Clinically important serum vancomycin concentrations may occur following multiple enteral or oral doses in some patients being treated for active C. difficile-associated diarrhea and colitis, particularly those with renal impairment.101 117 197 266 267 (See Increased Systemic Absorption under Cautions.)

Special Populations

Serum vancomycin concentrations are higher in patients with renal impairment than in those with normal renal function.197 c

Distribution

Extent

Widely distributed into body tissues and diffuses following IV administration, including pericardial, pleural, ascitic, and synovial fluids.155 266 267 c Small amounts are distributed into bile.102

Does not readily distribute into CSF in the absence of inflammation unless serum concentrations are exceedingly high.155 237 266 267 Low concentrations may be attained in CSF if meninges are inflamed, but negligible amounts detected in CSF in most patients with uninflamed meninges.155 237 The relationship between CSF concentrations and clinical efficacy of vancomycin in the treatment of meningitis is unclear.237

Crosses the placenta and is distributed into cord blood.155

Distributed into milk155 following IV administration;266 267 not known whether distributed into milk following oral administration.197

Plasma Protein Binding

30–60%.103 155 264 266 267

May be decreased to 19–29% in those with hypoalbuminemia (e.g., burn patients, those with end-stage renal disease).264

Elimination

Metabolism

Does not appear to be metabolized.155 264 266 267

Elimination Route

Following oral administration, excreted mainly in feces.197

Following IV administration, 75–90% of a dose eliminated unchanged in urine by glomerular filtration;155 264 266 267 c only small amounts are excreted in bile.c

Removed by hemodialysis;107 108 264 266 267 substantially removed by hemofiltration.127

Only minimally removed by peritoneal dialysis,109 110 123 266 267 including CAPD.124 125 126

Half-life

Adults with normal renal function: 4–7 hours.155 264 266 267 Accumulation tends to occur after 2–3 days of IV administration at 6- or 12-hour intervals.c

Geriatric adults: 12.1 hours.264

Neonates and infants: 6.7 hours in full-term neonates and 4.1 hour in infants ≥1 month but <1 year of age.264

Children 2.5–11 years of age: 5.6 hours.264

Special Populations

Geriatric patients: Renal clearance may be decreased.155 266 267

Renal impairment: Elimination half-life is increased.104 105 106 155 264 266 267 Half-life averages 32.3 hours (range: 10.1–75.1 hours) in patients with Clcr 10–60 mL/minute and 146.7 hours (range: 44.1–406.4 hours) in those with Clcr <10 mL/minute.106

Burn patients: Increased clearance; half-life averages 4 hours.264

• A tricyclic glycopeptide antibiotic obtained from cultures of Amycolatopsis orientalis (formerly Nocardia orientalis).155 197

• Usually bactericidal.266 267

• Binds to the bacterial cell wall and blocks glycopeptide polymerization; inhibits cell wall synthesis and causes damage to the cytoplasmic membrane.266 267 c

• Spectrum of activity includes many gram-positive aerobic and anaerobic bacteria.266 267 c Inactive against gram-negative bacteria, mycobacteria, and fungi.266 267 c

• Gram-positive bacteria: Active against Staphylococci aureus and S. epidermidis (including oxacillin-resistant [methicillin-resistant] strains), S. pyogenes (group A β-hemolytic streptococci), S. pneumoniae (including penicillin-resistant strains), S. agalactiae (group B streptococci), viridans streptococci, nonenterococcal group D streptococci (S. bovis), enterococci (e.g., Enterococcus faecalis), Corynebacterium, and Clostridium (C. difficile).155 266 267 c Also active in vitro against Actinomyces, Bacillus, Lactobacillus, and Listeria monocytogenes.155 266 267

• Resistance reported in enterococci (e.g., E. faecalis, E. faecium, E. gallinarum)169 170 171 172 173 174 175 176 177 200 217 219 222 223 224 225 and staphylococci (e.g., S. haemolyticus, S. epidermidis).114 115 168 200 220 221 226 227 228 229 230 231

Vancomycin Hydrochloride for injection, USP is a white, almost white, or tan lyophilized powder, for preparing intravenous (IV) infusions, in Pharmacy Bulk Package bottles containing the equivalent of 5 g or 10 g vancomycin base. 500 mg of the base are equivalent to 0.34 mmol. When reconstituted with Sterile Water for Injection to a concentration of 50 mg/mL for the 5 g Pharmacy Bulk Package bottle and 100 mg/mL for the 10 g Pharmacy Bulk Package bottle, a clear solution is achieved with the pH of the solution is between 2.5 and 4.5. Vancomycin Hydrochloride for injection, USP should be administered intravenously in diluted solution (see DOSAGE AND ADMINISTRATION). Vancomycin is a tricyclic glycopeptide antibiotic derived from Amycolatopasis orientalis (formerly Nocardia orientals). 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:

A pharmacy bulk package is a container of a sterile preparation for parenteral use that contains many single doses. The contents of this pharmacy bulk package are intended for use by a pharmacy admixture service for addition to suitable parenteral fluids in the preparation of admixtures for intravenous infusion (See DOSAGE AND ADMINISTRATION, Directions for Proper Use of Pharmacy Bulk Package). AFTER RECONSTITUTION, FURTHER DILUTION IS REQUIRED. NOT FOR DIRECT INFUSION.

Vancomycin Hydrochloride for injection, USP 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, USP 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, USP 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, USP 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, USP has been reported to be effective for the treatment of diphtheroid endocarditis. Vancomycin Hydrochloride for injection, USP 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, USP and other antibacterial drugs, Vancomycin Hydrochloride for injection, USP 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 infection.

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.

1. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard – Eighth ed., CLSI document M07-A8. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2009.
2. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-First Informational Supplement, CLSI document M100-S21. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2011.
3. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard – Tenth ed., CLSI document M02-A10. Clinical and Laboratory Standards Institute. Wayne, PA. January, 2009.
4. Moellering RC, Krogstad DJ, Greenblatt DJ: Vancomycin therapy in patients with impaired renal function: A nomogram for dosage. Ann Inter Med 1981;94:343.

Manufactured for:

Lake Zurich, IL 60047

Made in Denmark

www.fresenius-kabi.us

451545

Issued: May 2017

VIAL LABEL

NDC 63323-314-68

Vancomycin Hydrochloride

for Injection, USP

10 grams* per Pharmacy Bulk Package

PHARMACY BULK PACKAGE -
NOT FOR DIRECT INFUSION

For Intravenous Use

AFTER RECONSTITUTION MUST BE FURTHER DILUTED.

NOT TO BE DISPENSED AS A UNIT.

Sterile Lyophilized Powder              Rx only

CARTON

NDC 63323-314-68

Vancomycin Hydrochloride

for Injection, USP

10 grams* per Pharmacy Bulk Package

PHARMACY BULK PACKAGE -

NOT FOR DIRECT INFUSION

For Intravenous Use After Dilution

AFTER RECONSTITUTION MUST BE FURTHER DILUTED.

NOT TO BE DISPENSED AS A UNIT.

Sterile Lyophilized Powder

Rx only

1 bottle

Vancomycin Hydrochloride  Vancomycin Hydrochloride injection, powder, lyophilized, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:63323-314 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Vancomycin Hydrochloride (VANCOMYCIN) VANCOMYCIN 10 g  in 100 mL

Packaging # Item Code Package Description 1 NDC:63323-314-68 1 BOTTLE in 1 CARTON 1 100 mL in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA204125 09/01/2017

Labeler - Fresenius Kabi, LLC (608775388)

Revised: 09/2017   Fresenius Kabi, LLC