Vancocin

Generic Name: Vancomycin Hydrochloride
Class: Glycopeptides
VA Class: AM900
CAS Number: 1404-93-9

Introduction

Antibacterial; tricyclic glycopeptide antibiotic.^{266 267}

Uses for Vancocin

Endocarditis

Treatment of native valve or prosthetic valve endocarditis caused by susceptible Staphylococcus aureus or S. epidermidis, including oxacillin-resistant (methicillin-resistant) strains.^{155 265 266 267} AHA and IDSA recommend vancomycin as drug of choice for treatment of endocarditis caused by oxacillin-resistant staphylococci.²⁶⁵ Also recommended as alternative to nafcillin (or oxacillin) or cefazolin for treatment of endocarditis caused by oxacillin-susceptible staphylococci in patients with immediate-type (anaphylactoid) hypersensitivity to β-lactams.²⁶⁵ May be used alone for native valve endocarditis caused by oxacillin-susceptible staphylococci; used in conjunction with rifampin and gentamicin for endocarditis caused by oxacillin-resistant staphylococci and for prosthetic valve staphylococcal endocarditis.²⁶⁵

Treatment of native valve or prosthetic valve endocarditis caused by viridans streptococci or Streptococcus bovis.^{155 265 266 267} Recommended by AHA and IDSA as an alternative to penicillin G or ceftriaxone for treatment of streptococcal endocarditis in patients with immediate-type (anaphylactoid) hypersensitivity to β-lactams.²⁶⁵

Treatment of native valve or prosthetic valve enterococcal endocarditis; used in conjunction with gentamicin or streptomycin.^{155 265 266 267} Recommended by AHA and IDSA as an alternative to penicillin G or ampicillin for treatment of enterococcal endocarditis in patients with immediate-type (anaphylactoid) hypersensitivity to β-lactams.²⁶⁵

Empiric treatment of culture-negative endocarditis†.²⁶⁵ For culture-negative native valve endocarditis, regimen of ampicillin-sulbactam and gentamicin recommended by AHA and IDSA; regimen of vancomycin, gentamicin, and ciprofloxacin recommended for those unable to tolerate penicillin.²⁶⁵ For culture-negative prosthetic valve endocarditis occurring ≤1 year after valve replacement, regimen of vancomycin, gentamicin, and rifampin recommended; this regimen also should include cefepime if onset of infection is within 2 months of valve replacement.²⁶⁵ Selection of the most appropriate anti-infective regimen is difficult and should be guided by epidemiologic features and clinical course of the infection.²⁶⁵ Consultation with an infectious diseases specialist is recommended.²⁶⁵

Treatment of early-onset prosthetic valve endocarditis caused by Corynebacterium jeikeium (JK group);^{149 266 267 c} used in conjunction with rifampin and/or an aminoglycoside.^c

Prevention of bacterial endocarditis in patients undergoing certain genitourinary and GI (except esophageal) procedures† who have cardiac conditions that put them at moderate or high risk.¹⁴⁵ AHA recommends ampicillin as a drug of choice; vancomycin recommended in those hypersensitive to penicillins.¹⁴⁵ Used alone in penicillin-allergic individuals at moderate risk or in conjunction with gentamicin in those at high risk.¹⁴⁵ Consult most recent AHA recommendations for specific information on which cardiac conditions are associated with high or moderate risk of endocarditis and which procedures require prophylaxis.¹⁴⁵

Meningitis

Treatment of meningitis† caused by S. pneumoniae that are highly resistant to penicillins.^{122 149 235 236 237} .^{122 149 203 204 205 206 235 236 237} For empiric treatment, usually used in conjunction with a third generation cephalosporin (ceftriaxone, cefotaxime) with or without rifampin;^{122 203 204 205 206 235 236 237} vancomycin should be discontinued if the causative organism is found to be susceptible to the cephalosporin.^{235 236 237}

Should not be used alone for treatment of meningitis since effective CSF concentrations may not be attained.^{122 148 235 237}

Osteomyelitis

Treatment of osteomyelitis caused by S. aureus or S. epidermidis, including oxacillin-resistant strains.^{266 267}

Respiratory Tract Infections

Treatment of pneumonia caused by S. aureus or S. epidermidis, including oxacillin-resistant strains.^{266 267}

Treatment of pneumonia caused by S. pneumonia highly resistant to penicillins.^{122 149 235 236 237 266 267} Used alone or in conjunction with a third generation cephalosporin (ceftriaxone, cefotaxime) with or without rifampin.^{122 149 235 236 237}

Septicemia

Treatment of septicemia caused by S. aureus or S. epidermidis, including oxacillin-resistant strains.^{149 155 266 267} Used alone or in conjunction with gentamicin and/or rifampin.¹⁴⁹

Skin and Skin Structure Infections

Treatment of skin and skin structure infections caused by S. aureus or S. epidermidis, including oxacillin-resistant strains.^{155 266 267}

Bacillus Infections

Treatment of infections caused by Bacillus cereus or B. subtilis†.¹⁴⁹ Drug of choice.¹⁴⁹

Capnocytophaga Infections

Treatment of infections caused by Capnocytophaga†.¹⁴⁹

Optimum regimens for treatment of infections caused by Capnocytophaga not identified; some clinicians recommend use of penicillin G or, alternatively, a third generation cephalosporin (cefotaxime, ceftizoxime, ceftriaxone), a carbapenem (imipenem or meropenem), vancomycin, a fluoroquinolone, or clindamycin.¹⁴⁹

Clostridium difficile-associated Diarrhea andColitis

Treatment of Clostridium difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis, C. difficile diarrhea, C. difficile colitis, and pseudomembranous colitis) in seriously ill patients (i.e., with severe or potentially life-threatening colitis) or those who cannot tolerate or do not respond to oral metronidazole.^{122 149 197 198 199 200 211 212 213 214 215 266 267}

Oral metronidazole appears to be as effective as oral vancomycin for treatment of Clostridium difficile-associated diarrhea and colitis.^{172 178 179 180 181 182 183 184 185 193 211 212 213 214 215}

Because of cost considerations^{122 172 178 179 180 181 182 183 184 185 211 212 213 214 215} and concerns about increasing resistance to vancomycin in enterococci and other bacteria (e.g., staphylococci) and the risk of selection of such strains secondary to widespread and/or injudicious use of the drug,^{115 122 169 172 173 174 175 176 189 190 191 192 200} most experts state that oral metronidazole is preferred (unless a resistant strain of C. difficile is suspected or therapy with metronidazole is contraindicated or not tolerated) when anti-infective therapy is indicated for most cases of Clostridium difficile-associated diarrhea and colitis.^{122 149 172 178 179 180 181 182 183 184 185 198 200 211 212 213 214 215}

Oral vancomycin is the drug of choice when anti-infective therapy is indicated for critically ill patients or those who cannot tolerate or do not respond to oral metronidazole.^{122 149 180 181 182 184 193 198 199 200 211 212 213 214 215} (See Vancomycin-resistant Enterococci and Staphylococci under Cautions.)

Has been used to prevent nosocomial outbreaks of Clostridium difficile-associated diarrhea and colitis† in institutionalized patients who asymptomatically harbor the organism.^{186 187 188 194} However, current evidence suggests that the risks of such prophylaxis (e.g., in selecting potentially resistant organisms such as enterococci) outweigh any possible benefit.^{172 177 181 186 188 189 190 192 194} Most experts currently recommend that appropriate enteric and barrier precautions (e.g., isolation of patients, private bathroom facilities, strict hygiene) rather than prophylactic anti-infective therapy be implemented to prevent nosocomial transmission of the organisms.^{177 180 187 188 190 192 193 194 212 213}

Rhodococcus Infections

Treatment of infections caused by Rhodococcus equi†.^{149 240 241 242 243} Optimum regimens not identified; combination regimens usually recommended, including vancomycin given with a fluoroquinolone, rifampin, a carbapenem (imipenem or meropenem), or amikacin.^{149 240 241 242 243}

Staphylococcal Enterocolitis

Treatment of enterocolitis caused by S. aureus (including oxacillin-resistant strains).¹⁹⁹ Considered the drug of choice for staphylococcal enterocolitis because it does not affect the normal coliform bacteria present in the GI tract.^c

Prevention of Perinatal Group B Streptococcal (GBS) Infection

Alternative to penicillin G or ampicillin for prevention of perinatal group B streptococcal (GBS) disease† in penicillin-allergic pregnant women at risk for anaphylaxis with a β-lactam anti-infective when clindamycin or erythromycin cannot be used.^{158 159}

Intrapartum anti-infective prophylaxis to prevent early-onset neonatal GBS disease is administered to women identified as GBS carriers during routine prenatal GBS screening performed at 35–37 weeks during the current pregnancy and to women who have GBS bacteriuria during the current pregnancy, a previous infant with invasive GBS disease, unknown GBS status with delivery at <37 weeks gestation, amniotic membrane rupture for ≥18 hours, or intrapartum temperature of ≥38°C.^{158 159}

Penicillin G is the regimen of choice and ampicillin is the preferred alternative.^{158 159} Cefazolin can be used in penicillin-allergic women who do not have immediate-type penicillin hypersensitivity, but clindamycin or erythromycin are the drugs of choice in penicillin-allergic women at high risk for anaphylaxis.¹⁵⁸

Because S. agalactiae (group B streptococci) with in vitro resistance to clindamycin and erythromycin has been reported with increasing frequency,¹⁵⁸ in vitro susceptibility tests of clinical isolates obtained during GBS prenatal screening is necessary.¹⁵⁸ If in vitro susceptibility testing is not possible, results are unknown, or isolates are found to be resistant to erythromycin or clindamycin, vancomycin should be used for intrapartum prophylaxis in penicillin-allergic women at high risk for anaphylaxis with β-lactams.¹⁵⁸

Perioperative Prophylaxis

Perioperative prophylaxis† to reduce the risk of infection in patients undergoing cardiac surgery (e.g., placement of electrophysiologic devices, ventricular assist devices, ventriculoatrial shunts, arterial patches), neurosurgery (e.g., craniotomy, spinal surgery), orthopedic surgery (e.g., joint replacement, internal fixation of compound or open fractures with nails, plates, screws, or wires), noncardiac thoracic surgery (pulmonary resection, closed-tube thoracostomy for chest trauma with hemothorax or pneumothorax), or vascular surgery (arterial reconstructive surgery involving the abdominal aorta, leg procedures that include a groin incision, lower extremity amputation for ischemia) at institutions where oxacillin-resistant S. epidermidis are frequent causes of postoperative wound infection.²⁰⁸ Also used in these procedures when drugs of first choice (cefazolin, cefuroxime) cannot be used because patient is hypersensitive to β-lactams.²⁰⁸

Routine use of vancomycin for perioperative prophylaxis is not recommended since such use may promote emergence of vancomycin-resistant enterococci or staphylococci.^{200 208 224} (See Vancomycin-resistant Enterococci and Staphylococci under Cautions.)

Empiric Therapy in Febrile Neutropenic Patients

Has been used in conjunction with 1 or 2 other anti-infectives for empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients†.²⁵⁶

Some clinicians suggest that it may be prudent to include vancomycin in an initial empiric regimen in selected patients with clinically suspected serious catheter-related infections (e.g., bacteremia, cellulitis); known colonization with penicillin- and cephalosporin-resistant S. pneumoniae or oxacillin-resistant (methicillin-resistant) S. aureus; initial blood culture results indicating presence of gram-positive bacteria; or hypotension or other evidence of cardiovascular impairment.²⁵⁶

If vancomycin is included in an initial empiric regimen, it should be discontinued within 24–48 hours if results of cultures do not identify gram-positive bacteria susceptible to the drug.²⁵⁶ (See Vancomycin-resistant Enterococci and Staphylococci under Cautions.)

Consult published protocols for the treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of the initial empiric regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients.²⁵⁶ Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also is advised.²⁵⁶

Vancocin Dosage and Administration

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 infections^{197 266 267}

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 S_cr of <1.5 mg/dL, at 3- to 6-day intervals in patients with S_cr of 1.5–5 mg/dL, and at 10- to 14-day intervals in patients with S_cr >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.)

Cautions for Vancocin

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 S_cr 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 S_cr 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

Interactions for Vancocin

Ototoxic and Nephrotoxic Drugs

Concurrent or sequential use with other ototoxic and/or nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, bacitracin, cisplatin, colistin, furosemide, polymyxin B) may result in additive toxicity and should be avoided, if possible.^{155 264 266 267} Monitor renal and auditory function intensely if used concomitantly with an ototoxic and/or nephrotoxic agent.^{155 266 267}

Specific Drugs

Drug	Interaction	Comments
Aminoglycosides	In vitro evidence of synergistic antibacterial activity against S. aureus, nonenterococcal group D streptococci (S. bovis), enterococci, and viridans streptococci155 266 267 Increased risk of ototoxicity and/or nephrotoxicity155 266 267	Used to therapeutic advantage, but consider possible increased risk of ototoxicity and/or nephrotoxicity266 267
Anesthetics	Possible increased risk of anaphylactoid reactions and increased risk of vancomycin infusion reactions in patients receiving anesthetic agents;155 266 267 erythema and histamine-like flushing reported155 266 267	Risk of infusion-related adverse effects may be minimized if vancomycin is given by IV infusion (over ≥1 hour) prior to induction of anesthesia155 266 267

Vancocin Pharmacokinetics

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 Cl_cr 10–60 mL/minute and 146.7 hours (range: 44.1–406.4 hours) in those with Cl_cr <10 mL/minute.¹⁰⁶

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

Stability

Storage

Oral

Capsules

15–30°C.¹⁹⁷

Parenteral

Powder for Infusion

15–30°C.^{266 267}

Following reconstitution with sterile water for injection, solutions prepared in single-use vials are stable for 2 weeks at room temperature; the manufacturers state reconstituted solutions may be stored for 96 hours at 2–8°C without substantial loss of potency.^c

After further dilution to a concentration of 5 mg/mL in 5–30% dextrose injection, solutions are stable when stored in plastic syringes for 24 hours at 4°C and then subsequently for 2 hours at room temperature.¹²⁹

When reconstituted as directed using 5% dextrose injection or 0.9% sodium chloride injection, solutions prepared from ADD-Vantage vials are stable for 24 hours at room temperature or 14 days in a refrigerator.²⁶⁶

Injection (Frozen)

-20° C or lower.¹⁵⁵ After thawing, may be stored for 72 hours at room temperature (25°C) or up to 30 days at 5°C.¹⁵⁵

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Dextran 6% in sodium chloride 0.9%
Dextrose 5% in sodium chloride 0.9%
Dextrose 5 or 10% in water
Ringer’s injection, lactated
Sodium bicarbonate 3.75%
Sodium chloride 0.9%
Sodium lactate (1/6) M

Drug Compatibility

Admixture CompatibilityHID

Compatible
Amikacin sulfate
Atracurium besylate
Calcium gluconate
Cefepime HCl
Cimetidine HCl
Dimenhydrinate
Famotidine
Hydrocortisone sodium succinate
Meropenem
Ofloxacin
Potassium chloride
Ranitidine HCl
Verapamil HCl
Vitamin B complex with C
Incompatible
Amobarbital sodium
Chloramphenicol sodium succinate
Chlorothiazide sodium
Dexamethasone sodium phosphate
Pentobarbital sodium
Phenobarbital sodium
Variable
Aminophylline
Aztreonam
Heparin sodium
Sodium bicarbonate

Y-Site CompatibilityHID

Compatible
Acyclovir sodium
Aldesleukin
Allopurinol sodium
Amifostine
Amiodarone HCl
Atracurium besylate
Clarithromycin
Cyclophosphamide
Dexmedetomidine HCl
Diltiazem HCl
Docetaxel
Doxapram HCl
Doxorubicin HCl liposome injection
Enalaprilat
Esmolol HCl
Etoposide phosphate
Fenoldopam mesylate
Filgrastim
Fluconazole
Fludarabine phosphate
Gallium nitrate
Gemcitabine HCl
Granisetron HCl
Hetastarch in lactated electrolyte injection (Hextend)
Hydromorphone HCl
Labetalol HCl
Levofloxacin
Linezolid
Lorazepam
Magnesium sulfate
Melphalan HCl
Meperidine HCl
Meropenem
Midazolam HCl
Milrinone lactate
Morphine sulfate
Nicardipine HCl
Ondansetron HCl
Paclitaxel
Pancuronium bromide
Premetrexed disodium
Perphenazine
Remifentanil HCl
Sodium bicarbonate
Tacrolimus
Teniposide
Theophylline
Thiotepa
Tolazoline HCl
Vecuronium bromide
Vinorelbine tartrate
Zidovudine
Incompatible
Albumin human
Amphotericin B cholesteryl sulfate complex
Bivalirudin
Drotrecogin alfa (activated)
Heparin sodium
Idarubicin HCl
Lansoprazole
Omeprazole
Variable
Ampicillin sodium
Ampicillin sodium–sulbactam sodium
Aztreonam
Cefepime HCI
Cefotaxime sodium
Cefoxitin sodium
Ceftazidime
Ceftizoxime sodium
Ceftriaxone sodium
Cefuroxime sodium
Foscarnet sodium
Methotrexate sodium
Nafcillin sodium
Piperacillin sodium and tazobactam sodium
Propofol
Sargramostim
Ticarcillin disodium and clavulanate potassium
Warfarin sodium

Actions and SpectrumActions

• 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 Clostricium (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}

Advice to Patients

• Advise patients that antibacterials (including vancomycin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).^{155 197}

• Importance of completing full course of therapy, even if feeling better after a few days.^{155 197}

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with vancomycin or other antibacterials in the future.^{155 197}

• Importance of reporting possible manifestations of adverse effects to the clinician, including ototoxicity, nephrotoxicity, infusion site reactions, and hypersensitivity.^{266 267}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.^{266 267}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{266 267}

• Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Vancomycin Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	125 mg (of vancomycin)	Vancocin HCl Pulvules	ViroPharma
		250 mg (of vancomycin)	Vancocin HCl Pulvules	ViroPharma
Parenteral	For injection	5 g (of vancomycin) pharmacy bulk package	Vancomycin Hydrochloride for Injection	Abraxis, Hospira
		10 g (of vancomycin) pharmacy bulk package	Vancomycin Hydrochloride for Injection	Abraxis
	For injection, for IV infusion	500 mg (of vancomycin)	Vancomycin Hydrochloride for Injection	Abraxis, Hospira
			Vancomycin Hydrochloride Sterile ADD-Vantage	Hospira
		1 g (of vancomycin)	Vancomycin Hydrochloride for Injection	Abraxis, Hospira
			Vancomycin Hydrochloride for Injection ADD-Vantage	Hospira

Vancomycin Hydrochloride in Dextrose

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection (frozen), for IV infusion	5 mg (of vancomycin) per ml (500 mg) in 5% Dextrose	Vancocin HCl in Iso-osmotic Dextrose Injection (Galaxy [Baxter])	Lilly

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Vancocin HCl 125MG Capsules (VIROPHARMA INC): 20/$550.55 or 60/$1591.78

Vancocin HCl 250MG Capsules (VIROPHARMA INC): 20/$915.97 or 60/$2630.13