Vancomycin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral, as hydrochloride:

Vancocin: 250 mg [contains fd&c blue #2 (indigotine)]

Vancocin HCl: 125 mg [contains fd&c blue #2 (indigotine)]

Generic: 125 mg, 250 mg

Kit, Intravenous, as hydrochloride:

Vancosol Pack: 1 g/100 mL in NaCl 0.9% [DSC]

Solution, Intravenous, as hydrochloride:

Generic: 1000 mg/200 mL (200 mL); 1500 mg/300 mL (300 mL)

Solution, Intravenous, as hydrochloride [preservative free]:

Generic: 500 mg/100 mL (100 mL); 2000 mg/400 mL (400 mL); 1 g/200 mL in Dextrose 5% (200 mL); 1 g/200 mL in NaCl 0.9% (200 mL); 500 mg/100 mL in Dextrose 5% (100 mL); 750 mg/150 mL in Dextrose 5% (150 mL)

Solution Reconstituted, Intravenous [preservative free]:

Generic: 1.25 g (1 ea)

Solution Reconstituted, Intravenous, as hydrochloride:

Generic: 10 g (1 ea)

Solution Reconstituted, Intravenous, as hydrochloride [preservative free]:

Generic: 250 mg (1 ea); 500 mg (1 ea); 750 mg (1 ea); 1 g (1 ea); 1.5 g (1 ea); 5 g (1 ea); 10 g (1 ea); 100 g (1 ea)

Solution Reconstituted, Oral, as hydrochloride:

Firvanq: 25 mg/mL (150 mL, 300 mL); 50 mg/mL (150 mL, 300 mL) [contains fd&c red #40, fd&c yellow #10 (quinoline yellow), sodium benzoate; grape flavor]

Firvanq: 50 mg/mL (150 mL) [contains fd&c red #40, fd&c yellow #10 (quinoline yellow), sodium benzoate; white grape flavor]

Generic: 250 mg/5 mL (80 mL, 150 mL, 300 mL)

Pharmacology

Mechanism of Action

Inhibits bacterial cell wall synthesis by blocking glycopeptide polymerization through binding tightly to D-alanyl-D-alanine portion of cell wall precursor

Pharmacokinetics/Pharmacodynamics

Absorption

Oral: Poor; Intraperitoneal (IP): 60% of an IP dose absorbed in 6 hours; Rectal: significant absorption through inflamed colonic mucosa may occur

Distribution

Distributes widely in body tissue and fluids, except for CSF

V_d:

Neonate, term: 0.57 to 0.69 L/kg (de Hoog 2004)

Neonates, receiving ECMO (mean age: ~39 weeks): Variable; 1.1 L/kg (range: 0.6 to 2.1 L/kg) (Amaker 1996); others have reported lower values: 0.45 ± 0.18 L/kg (Buck 1998), 0.67 ± 0.15 L/kg (Mulla 2005)

Pediatric patients: Median: 0.57 L/kg (range: 0.26 to 1.05 L/kg) (Marsot 2012)

Adults: 0.4 to 1 L/kg (ASHP/IDSA/SIDP [Rybak 2009])

Relative diffusion from blood into CSF: Good only with inflammation (exceeds usual MICs)

Children:

CSF concentrations: 0.2 to 17.3 mcg/mL (de Hoog 2004)

CSF:blood level ratio: Normal meninges: Nil; Inflamed meninges: 7.1% to 68% (de Hoog 2004)

Adults:

Uninflamed meninges: 0 to 4 mcg/mL; serum concentration dependent (ASHP/IDSA/SIDP [Rybak 2009])

Inflamed meninges: 6 to 11 mcg/mL; serum concentration dependent (ASHP/IDSA/SIDP [Rybak 2009])

CSF:serum level ratio: Normal meninges: Nil; Inflamed meninges: ~80% (Shokouhi 2014)

Metabolism

No apparent metabolism

Excretion

Primarily via glomerular filtration; IV: Urine (75% as unchanged drug in the first 24 hours); Oral: Primarily feces

Clearance: presence of malignancy in children is associated with an increase in vancomycin clearance

Neonates: 0.63 to 1.5 mL/minute/kg; dependent on GA and/or PMA (de Hoog 2004)

Neonates, receiving ECMO: ~0.79 mL/minute/kg (Amaker 1996; Buck 1998); others have reported a slightly slower rate: 0.67 mL/minute/kg (Mulla 2005)

Pediatric patients: Median: 1.1 mL/minute/kg (range: 0.33 to 1.87 mL/minute/kg) (Marsot 2012)

Adults: 0.71 to 1.31 mL/minute/kg (de Hoog 2004)

Time to Peak

Serum: IV: Immediately after completion of infusion

Half-Life Elimination

Biphasic: Terminal:

Newborns: 6 to 10 hours

Neonates receiving ECMO: 6.53 ± 2.1 hours (Buck 1998); others have reported longer: 10.4 ± 6.7 hours (Mulla 2005)

Infants and Children 3 months to 4 years: 4 hours

Children and Adolescents >3 years: 2.2 to 3 hours

Adults: 4 to 6 hours; significantly prolonged with renal impairment

End-stage renal disease (ESRD): 7.5 days

Protein Binding

~55%

Use in Specific Populations

Special Populations: Elderly

Total systemic and renal clearance may be reduced.

Use: Labeled Indications

Clostridioides (formerly Clostridium) difficile infection (oral): Treatment of C. difficile infection (CDI)

Endocarditis (injection):

Corynebacteria (diphtheroids): Treatment of diphtheroid endocarditis in combination with either rifampin, an aminoglycoside, or both in early-onset prosthetic valve endocarditis caused by diphtheroids

Enterococcal: Treatment of endocarditis caused by enterococci (eg, Enterococcus faecalis), in combination with an aminoglycoside

Staphylococcal: Treatment of staphylococcal endocarditis

Streptococcal: Treatment of endocarditis due to Streptococcus viridans or Streptococcus bovis, as monotherapy or in combination with an aminoglycoside

Enterocolitis (oral): Treatment of enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains). Note: Staphylococcal enterocolitis is uncommon; the disease and treatment are not well described in the literature (Iwata 2014; Lin 2010).

Staphylococcal infections (injection): Treatment of serious or severe infections (eg, bloodstream infections, bone infections, lower respiratory tract infections, skin and skin structure infections) caused by susceptible strains of methicillin-resistant (beta-lactam-resistant) staphylococci; empiric therapy of infections when methicillin-resistant staphylococci are suspected

Use: Off Label

Catheter-related bloodstream infection, antibiotic lock technique (catheter-salvage therapy)yes

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection, vancomycin antibiotic lock therapy is recommended for patients for whom catheter salvage is the goal, in combination with systemic antimicrobial therapy, especially when peripheral cultures are positive.

Cerebrospinal fluid shunt infectionyes

Based on the IDSA guidelines for health care-associated ventriculitis and meningitis, vancomycin is an effective and recommended systemic therapy (as part of an empiric combination regimen) for treatment of health care-associated ventriculitis and meningitis. Intraventricular administration of vancomycin, as an adjunct to systemic therapy, may be considered in patients with poor response to systemic antimicrobial therapy alone.

Clostridioides (formerly Clostridium) difficile infection (rectal administration)cyes

Rectal administration of vancomycin is recommended in national practice guidelines for the management of fulminant C. difficile infection despite evidence based on case reports/series.

Cystic fibrosis, acute pulmonary exacerbationc

Clinical experience suggests the utility of vancomycin in the treatment of acute pulmonary exacerbations of cystic fibrosis Pettit 2017, Simon 2019.

Diabetic foot infection, moderate to severeyes

Based on the IDSA clinical practice guidelines for the diagnosis and treatment of diabetic foot infections, vancomycin is an effective and recommended treatment in the management of moderate to severe diabetic foot infection.

Endophthalmitis, treatmentc

Data from a limited number of patients studied suggest that intravitreal vancomycin may be beneficial for the treatment of postoperative endophthalmitis Gan 2001. Clinical experience based on data from peer-reviewed scientific literature also suggests the utility of vancomycin in the management of bacterial endophthalmitis Packer 2011.

Intra-abdominal infectionyes

Based on the Surgical Infection Society and IDSA guidelines for diagnosis and management of complicated intra-abdominal infection in adults and children, vancomycin is effective and recommend in patients with intra-abdominal infection due to methicillin-resistant S. aureus (MRSA) or ampicillin-resistant enterococci.

Intracranial abscess (brain abscess, intracranial epidural abscess) or spinal epidural abscesscyes

Based on the IDSA guidelines for the treatment of MRSA infections in adults and children, vancomycin is an effective and recommended agent in the treatment of MRSA infections of the CNS, including brain abscess and spinal epidural abscess. Clinical experience suggests the utility of vancomycin for the treatment of intracranial epidural abscess (Sexton 2019a).

Meningitis, bacterialyes

Based on the IDSA guidelines for the management of bacterial meningitis and for health care-associated ventriculitis and meningitis, vancomycin is an effective and recommended systemic therapy as part of an empiric regimen for treatment of bacterial meningitis when Streptococcus pneumoniae or MRSA is a presumptive pathogen.

Peritonitis, treatment (peritoneal dialysis patients)yes

Based on the International Society for Peritoneal Dialysis (ISPD) peritonitis recommendations, intraperitoneal vancomycin in continuous ambulatory peritoneal dialysis (CAPD) is effective and recommended for empiric treatment of peritonitis caused by gram-positive organisms in CAPD patients.

Prosthetic joint infectionyes

Based on the IDSA guidelines for the management of prosthetic joint infection, vancomycin is effective and recommended for treatment of prosthetic joints infected with staphylococci or Enterococcus spp.

Streptococcus (group B), maternal prophylaxis for prevention of neonatal diseaseyes

Based on the American College of Obstetricians and Gynecologists (ACOG) prevention of group B streptococcal (GBS) early-onset disease in newborns guideline, maternal administration of IV vancomycin is recommended for intrapartum prophylaxis to prevent early-onset GBS disease in the newborn in mothers at high risk for anaphylaxis to penicillin and who have clindamycin-resistant GBS.

Surgical prophylaxisyes

Based on the American Society of Health-System Pharmacists (ASHP) clinical practice guidelines for antimicrobial prophylaxis in surgery, vancomycin given as an alternative antibiotic in patients with beta-lactam allergy requiring surgical prophylaxis is effective and recommended for a number of surgical procedures.

Contraindications

Hypersensitivity to vancomycin or any component of the formulation

Dosage and Administration

Dosing: Adult

Usual dosage range: Note: Initial IV dosing in nonobese patients should be based on actual body weight; subsequent dosing should generally be adjusted based on serum vancomycin concentrations and renal function. Patient-specific pharmacokinetic calculations may be needed to determine appropriate dose and interval in patients expected to have altered pharmacokinetics (eg, morbid obesity, burns, critical illness, unstable renal function, pregnancy, cystic fibrosis). For patients with uncomplicated skin and soft tissue infections who are not obese and have normal renal function, serum trough monitoring is generally not needed (IDSA [Liu 2011]). In adult patients with normal renal function, doses ≥4 g per day are associated with increased toxicity (ASHP/IDSA/SIDP [Rybak 2009]; Lodise 2008).

Oral: Note: Ineffective for treating systemic infections: 125 to 500 mg 4 times daily

IV: Note: Ineffective for treating C. difficile infections: 15 to 20 mg/kg/dose (rounded to the nearest 250 mg; usual maximum: 2 g/dose initially) every 8 to 12 hours (ASHP/IDSA/SIDP [Rybak 2009]). Note: 15 mg/kg/dose (usual maximum: 2 g/dose initially) every 12 hours is a usual starting dose in most nonobese patients with normal renal function; refer to infection-specific dosing (Drew 2019; IDSA [Liu 2011]; Murray 2015).

Loading dose: Complicated infections in seriously ill patients: A loading dose of 25 to 30 mg/kg (based on actual body weight) may be used to rapidly achieve target concentrations (ASHP/IDSA/SIDP [Rybak 2009]; Reardon 2015).

Indication-specific dosing:

Bloodstream infection:

Empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours; adjust dose to obtain a trough concentration of 15 to 20 mcg/mL, an AUC/minimum inhibitory concentration (MIC) of 400 to 600 (ASHP/IDSA/SIDP [Rybak 2009]; Heil 2018; Men 2016; Neely 2018). A loading dose may be considered in seriously ill patients (ASHP/IDSA/SIDP [Rybak 2009]; IDSA [Liu 2011]). Treat uncomplicated S. aureus infection for ≥14 days from first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (IDSA [Liu 2011]; IDSA [Mermel 2009]).

Empiric therapy or pathogen-specific therapy for methicillin-resistant coagulase-negative staphylococci: IV: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours (most patients with normal renal function can be started with 15 mg/kg/dose every 12 hours); adjust dose to obtain a trough concentration of 15 to 20 mcg/mL (Drew 2019). Treat uncomplicated bacteremia for 5 to 7 days from day of first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (IDSA [Mermel 2009]; Tufariello 2019). For catheter-related bloodstream infections, consider antibiotic lock therapy for catheter salvage, in addition to systemic therapy (IDSA [Mermel 2009]).

Antibiotic lock technique (catheter-salvage strategy) (off-label use): Note: For infections caused by susceptible organisms when the catheter cannot be removed; use in addition to systemic antibiotics. Catheter salvage is not recommended for S. aureus (Girand 2019; IDSA [Mermel 2009]).

Intracatheter: Prepare lock solution to final concentration of vancomycin 5 mg/mL; may be combined with heparin. Instill into each lumen of the catheter access port using a volume sufficient to fill the catheter (2 to 5 mL) with a dwell time of up to 72 hours, depending on frequency of catheter use. Withdraw lock solution prior to catheter use; replace with fresh vancomycin lock solution after catheter use. Antibiotic lock therapy is given for the same duration as systemic antibiotics (IDSA [Mermel 2009]; LaPlante 2007).

Cerebrospinal fluid shunt infection (off-label use): As a component of empiric therapy or pathogen-specific therapy (eg, methicillin-resistant S. aureus or coagulase-negative staphylococci):

IV: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours; adjust dose to obtain a trough concentration of 15 to 20 mcg/mL (IDSA [Tunkel 2017]). A loading dose may be considered in seriously ill patients (ASHP/IDSA/SIDP [Rybak 2009]).

Intraventricular (adjunct to systemic therapy; use a preservative-free preparation): 5 to 20 mg/day; some experts recommend adjusting dosage and administration interval based on cerebrospinal fluid (CSF) vancomycin concentrations (goal: 10 to 20 times MIC of causative organism), ventricular size, and daily output from ventricular drain (IDSA [Tunkel 2017]); data for monitoring are limited (Smetana 2018). When intraventricular vancomycin is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in CSF) (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). Note: Intraventricular administration is generally reserved for use in patients who fail parenteral therapy despite removal of CSF shunt or when CSF shunt cannot be removed (Baddour 2019).

Clostridioides (formerly Clostridium) difficile infection: Note: Criteria for disease severity is based on expert opinion and should not replace clinical judgment (IDSA/SHEA [McDonald 2018]).

Oral:

Nonsevere C. difficile infection (supportive clinical data: WBC ≤15,000 cells/mm³ and serum creatinine <1.5 mg/dL):

Initial episode: 125 mg 4 times daily for 10 days (IDSA/SHEA [McDonald 2018])

First recurrence:

If vancomycin was used for initial episode: Pulsed-tapered regimen: 125 mg 4 times daily for 10 to 14 days, then 125 mg twice daily for 7 days, then 125 mg once daily for 7 days, then 125 mg every 2 or 3 days for 2 to 8 weeks (IDSA/SHEA [McDonald 2018])

If metronidazole or fidaxomicin was used for initial episode: 125 mg 4 times daily for 10 days (IDSA/SHEA [McDonald 2018])

Second or subsequent recurrence: Pulsed-tapered regimen as above or 125 mg 4 times daily for 10 days followed by rifaximin (SHEA/IDSA [McDonald 2018])

Severe C. difficile infection (supportive clinical data: WBC >15,000 cells/mm³ and/or serum creatinine ≥1.5 mg/dL): 125 mg 4 times daily (IDSA/SHEA [McDonald 2018])

Fulminant C. difficile infection (supportive clinical data: ileus, megacolon, and/or hypotension/shock): Oral or via nasogastric tube: 500 mg 4 times daily with IV metronidazole; if ileus present, may consider vancomycin retention enema (IDSA/SHEA [McDonald 2018]).

Rectal:

Fulminant C. difficile infection with ileus: Retention enema (off-label route): 500 mg in 100 mL NS; retained for as long as possible and administered every 6 hours. Use in combination with oral vancomycin (if the ileus is partial) or in place of oral vancomycin (if the ileus is complete) plus IV metronidazole. Note: Optimal regimen not established (IDSA/SHEA [McDonald 2018]). Use of rectal vancomycin should be reserved for patients who have not responded to standard therapy and performed by individuals with expertise in administration, as there is risk of colonic perforation (Kelly 2019).

Cystic fibrosis, acute pulmonary exacerbation (off-label use): Empiric or pathogen-directed therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose every 8 hours; adjust dose to obtain trough concentration of 15 to 20 mcg/mL (Pettit 2017; Simon 2019). Duration is usually 10 days to 3 weeks or longer based on clinical response (Flume 2009; Simon 2019).

Diabetic foot infection, moderate to severe (off-label use): Empiric or pathogen-directed therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours; adjust dose to obtain trough concentration of 15 to 20 mcg/mL. For empiric therapy, use as part of an appropriate combination regimen. Duration (which may include appropriate oral step-down therapy) is usually 2 to 4 weeks in the absence of osteomyelitis (IDSA [Lipsky 2012]; Weintrob 2019).

Endocarditis, treatment:

Enterococcus (native or prosthetic valve) (penicillin-resistant strains or patients unable to tolerate beta-lactams): IV: 15 mg/kg/dose (usual maximum: 2 g/dose initially) every 12 hours in combination with gentamicin for 6 weeks; adjust dose to obtain a trough concentration of 10 to 20 mcg/mL (AHA [Baddour 2015]); some experts favor a trough of 15 to 20 mcg/mL (BSAC [Gould 2012]; ESC [Habib 2015]).

S. aureus, methicillin-resistant or methicillin-susceptible (severe-beta lactam hypersensitivity) (alternative agent): IV:

Native valve: 15 mg/kg/dose (usual maximum: 2 g/dose initially) every 12 hours for 6 weeks; adjust dose to obtain a serum trough concentration of 10 to 20 mcg/mL (AHA [Baddour 2015]) or 15 to 20 mg/kg/dose (usual maximum dose: 2 g/dose initially) every 8 to 12 hours for 6 weeks; adjust dose to obtain a trough concentration of 15 to 20 mcg/mL (IDSA [Liu 2011]).

Prosthetic valve: 15 mg/kg/dose (usual maximum: 2 g/dose initially) every 12 hours; adjust dose to obtain a trough concentration of 10 to 20 mcg/mL (AHA [Baddour 2015]) or 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours; adjust dose to obtain a trough concentration of 15 to 20 mcg/mL (IDSA [Liu 2011]). Duration of therapy: At least 6 weeks (combine with rifampin for the entire duration of therapy and gentamicin for the first 2 weeks) (AHA [Baddour 2015]; IDSA [Liu 2011]).

Viridans group streptococci and S. bovis (native or prosthetic valve) (penicillin or ceftriaxone intolerance): IV: 15 mg/kg/dose (usual maximum dose: 2 g/dose initially) every 12 hours for 4 weeks (native valve) or 6 weeks (prosthetic valve); adjust dose to obtain a trough concentration of 10 to 15 mcg/mL (AHA [Baddour 2015]).

Endophthalmitis, treatment (off-label use): Intravitreal: Usual dose: 1 mg per 0.1 mL NS or sterile water injected into vitreum, usually in combination with ceftazidime (Durand 2019; Endophthalmitis Vitrectomy Study Group 1995). A repeat dose(s) may be considered at 24 to 48 hours based on culture result, severity of the infection, and response to treatment (Durand 2019).

Intra-abdominal infection (off-label use): As a component of empiric therapy or pathogen-specific therapy (eg, methicillin-resistant S. aureus): IV: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours; adjust dose to obtain a trough concentration of 15 to 20 mcg/mL (ASHP/IDSA/SIDP [Rybak 2009]; IDSA [Solomkin 2010]).

Intracranial abscess (brain abscess, intracranial epidural abscess) or spinal epidural abscess (off-label use): As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours; adjust dose to obtain a trough concentration of 15 to 20 mcg/mL. A loading dose may be considered in seriously ill patients (ASHP/IDSA/SIDP [Rybak 2009]; IDSA [Liu 2011]). Duration generally ranges from 4 to 8 weeks for brain abscess and spinal epidural abscess and 6 to 8 weeks for intracranial epidural abscess (Bodilsen 2018; Sexton 2019a; Sexton 2019b; Southwick 2019).

Meningitis, bacterial (off-label use): As a component of empiric therapy or pathogen-specific therapy (eg, methicillin-resistant S. aureus or penicillin- and cephalosporin-resistant S. pneumoniae): IV: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours; adjust dose to obtain a trough concentration of 15 to 20 mcg/mL (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]) A loading dose may be considered in seriously ill patients (ASHP/IDSA/SIDP [Rybak 2009]; IDSA [Liu 2011]).

Osteomyelitis: As a component of empiric therapy or pathogen-specific therapy (eg, methicillin-resistant S. aureus): IV: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours (IDSA [Liu 2011]) or 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 12 hours (IDSA [Berbari 2015]); adjust dose to obtain a trough concentration of 15 to 20 mcg/mL. A loading dose may be considered in seriously ill patients (ASHP/IDSA/SIDP [Rybak 2009]). Duration is generally ≥6 weeks; shorter courses are appropriate if the affected bone is completely resected (IDSA [Berbari 2015]; Osmon 2019).

Peritonitis, treatment (peritoneal dialysis patients) (off-label use): Note: Intraperitoneal administration is preferred to IV administration. Adjust dose to obtain a trough concentration between 15 and 20 mcg/mL (ISPD [Li 2016]). Consider a 25% dose increase in patients with significant residual renal function (urine output >100 mL/day) (ISPD [Li 2010]; ISPD [Li 2016]; Mancini 2018; Szeto 2018).

Intermittent (preferred): Intraperitoneal: 15 to 30 mg/kg added to one exchange of dialysate every 5 to 7 days (allow to dwell for ≥6 hours); supplemental doses and more frequent monitoring of serum levels may be needed for patients receiving automated peritoneal dialysis (ISPD [Li 2016]).

Continuous (with every exchange): Intraperitoneal: Loading dose: 30 mg/kg added to first exchange of dialysate; maintenance dose: 1.5 mg/kg/bag for each subsequent exchange of dialysate (Bunke 1983; ISPD [Li 2016]).

Pneumonia: IV:

Community-acquired pneumonia (hospitalized patient): As a component of empiric therapy or pathogen-specific therapy for community-acquired methicillin-resistant S. aureus: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours (ASHP/IDSA/SIDP [Rybak 2009]; IDSA [Liu 2011]; IDSA/ATS [Mandell 2007]); most patients with normal renal function can be started with 15 mg/kg/dose (usual maximum: 2 g/dose initially) every 12 hours. Adjust dose to obtain a trough concentration of 15 to 20 mcg/mL (File 2019). A loading dose may be considered in seriously ill patients (ASHP/IDSA/SIDP [Rybak 2009]; IDSA [Liu 2011]; IDSA/ATS [Mandell 2007]). Note: Duration is for a minimum of 7 days; patients should be afebrile for ≥48 hours and clinically stable prior to discontinuation (IDSA [Liu 2011]; IDSA/ATS [Mandell 2007]).

Hospital-acquired pneumonia or ventilator-associated pneumonia: As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours; adjust dose to obtain a trough concentration of 15 to 20 mcg/mL. A loading dose may be considered in seriously ill patients (ASHP/IDSA/SIDP [Rybak 2009]; IDSA/ATS [Kalil 2016]). Note: Duration is for a minimum of 7 days and varies based on disease severity and response to therapy (IDSA [Liu 2011]; IDSA/ATS [Kalil 2016]).

Prosthetic joint infection (off-label use): IV:

Pathogen-specific therapy for methicillin-resistant or susceptible S. aureus (alternative agent in beta-lactam intolerance): 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours (Berbari 2019; IDSA [Liu 2011]) or 15 mg/kg/dose (usual maximum: 2 g/dose initially) every 12 hours (IDSA [Osmon 2013]); adjust dose to obtain a trough concentration of 15 to 20 mcg/mL (ASHP/IDSA/SIDP [Rybak 2009]). Duration ranges from 2 to 6 weeks depending on prosthesis management, use of rifampin, and other patient-specific factors (IDSA [Osmon 2013]).

Pathogen-specific therapy for Enterococcus spp (penicillin susceptible [alternative agent] or penicillin resistant): 15 mg/kg/dose (usual maximum: 2 g/dose initially) every 12 hours for 4 to 6 weeks (Berbari 2019; IDSA [Osmon 2013]).

Note: In select cases (eg, debridement and retention of prosthesis or one-stage arthroplasty), give oral suppressive antibiotic therapy with an appropriate regimen following completion of initial treatment (Berbari 2019; IDSA [Osmon 2013]).

Sepsis/septic shock: As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours; adjust dose to obtain a trough concentration of 15 to 20 mcg/mL (ASHP/IDSA/SIDP [Rybak 2009]). Administer within 1 hour of identifying sepsis (Rhodes 2017). A loading dose may be considered in seriously ill patients (ASHP/IDSA/SIDP [Rybak 2009]; Rhodes 2017). A duration of therapy of 7 to 10 days is generally adequate for serious infections (Rhodes 2017).

Septic arthritis, without prosthetic material: As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus or coagulase-negative staphylococci: IV: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours; adjust dose to obtain a trough concentration of 15 to 20 mcg/mL (ASHP/IDSA/SIDP [Rybak 2009]; IDSA [Liu 2011]). Most patients with normal renal function can be started with 15 mg/kg/dose (usual maximum: 2 g/dose initially) every 12 hours (Goldenberg 2019). Total treatment duration is 3 to 4 weeks (in the absence of osteomyelitis), including appropriate oral step-down therapy (Goldenberg 2019; IDSA [Liu 2011]); some experts recommend 4 weeks of parenteral therapy for patients with concomitant bacteremia (Goldenberg 2019).

Skin and soft tissue infection (hospitalized patient): As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus: IV: 15 mg/kg/dose (usual maximum: 2 g/dose initially) every 12 hours (IDSA [Stevens 2014]); adjust dose to obtain a trough concentration of 10 to 15 mcg/mL (uncomplicated infection) or 15 to 20 mcg/mL (complicated infection or seriously ill) (ASHP/IDSA/SIDP [Rybak 2009]; IDSA [Liu 2011]; IDSA [Stevens 2014]). Note: For empiric therapy of necrotizing infection, must be used in combination with other agents (IDSA [Stevens 2014]).

Streptococcus (group B), maternal prophylaxis for prevention of neonatal disease (alternative agent) (off-label use): Note: Prophylaxis is reserved for pregnant women with a positive group B streptococcus (GBS) vaginal or rectal screening in late gestation or GBS bacteriuria during the current pregnancy, history of birth of an infant with early-onset GBS disease, and unknown GBS culture status with any of the following: birth <37 0/7 weeks' gestation, intrapartum fever, prolonged rupture of membranes, known GBS positive in a previous pregnancy, or intrapartum nucleic acid amplification testing positive for GBS (ACOG 782 2019).

IV: 20 mg/kg at the onset of labor or prelabor rupture of membranes, then every 8 hours until delivery; maximum single dose: 2 g (ACOG 782 2019). Some experts prefer vancomycin 2 g initially and then 1 g every 12 hours thereafter until delivery (Baker 2019). Note: Vancomycin is reserved for use in penicillin-allergic patients at high risk for anaphylaxis, isolates with resistance to clindamycin, or in the absence of susceptibility data (ACOG 782 2019).

Surgical prophylaxis (in combination with other appropriate agents when coverage for methicillin-resistant S. aureus is indicated or for gram-positive coverage in patients unable to tolerate beta-lactams) (off-label use): IV: 15 mg/kg (usual maximum: 2 g/dose initially) started within 60 to 120 minutes prior to initial surgical incision. Vancomycin doses may be repeated intraoperatively in 2 half-lives (approximately 8 to 12 hours in patients with normal renal function) if procedure is lengthy or if there is excessive blood loss (ASHP/IDSA/SIS/SHEA [Bratzler 2013]). In cases where an extension of prophylaxis is warranted postoperatively, total duration should be ≤24 hours (Anderson 2014). Postoperative prophylaxis is not recommended in clean and clean-contaminated surgeries (CDC [Berrios-Torres 2017]).

Surgical site infection: As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S.aureus: IV: 15 mg/kg/dose (usual maximum: 2 g/dose initially) every 12 hours; adjust dose to obtain trough concentrations of 10 to 15 mcg/mL (uncomplicated infection) or 15 to 20 mcg/mL (complicated infections or seriously ill) (ASHP/IDSA/SIDP [Rybak 2009]; IDSA [Stevens 2014]).

Toxic shock syndrome, staphylococcal: As a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose (usual maximum: 2 g/dose initially) every 8 to 12 hours; adjust dose to obtain a trough concentration of 15 to 20 mcg/mL (ASHP/IDSA/SIDP [Rybak 2009]; Chu 2019). Duration varies based on underlying etiology; 10 to 14 days of treatment is recommended in the absence of bacteremia or other distinct focus of infection (Chu 2019).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Initial dosage recommendations presented, serum concentrations should be monitored and adjusted accordingly. Note: Doses require adjustment in renal impairment. Consider single-dose administration with serum concentration monitoring rather than scheduled dosing in patients with urine output <1 mL/kg/hour or if serum creatinine significantly increases from baseline (eg, doubles). Optimal dose and frequency not established in patients receiving ECMO; available data is very limited and primarily from neonatal experience (Amaker 1996; Buck 1998; Hoie 1990; Mulla 2005). Patient-specific considerations (eg, reason for ECMO) and variability with ECMO procedure itself make extrapolation of pharmacokinetic data and dosing to all patients receiving ECMO difficult; closely monitor serum concentrations and determine individual dosing needs in these patients.

General dosing, susceptible infection: Infants, Children, and Adolescents: IV: 45 to 60 mg/kg/day divided every 6 to 8 hours; dose and frequency should be individualized based on serum concentrations (Red Book [AAP 2018]). Note: Every 6 hour dosing recommended as initial dosage regimen if targeting trough serum concentrations >10 mcg/mL (Benner 2009; Frymoyer 2009) in patients with normal renal function. Close monitoring of serum concentrations and assurance of adequate hydration status is recommended; utilize local antibiogram and protocols for further guidance.

Bacteremia [S. aureus (methicillin-resistant)]: Infants, Children, and Adolescents: IV: 15 mg/kg/dose every 6 hours for 2 to 6 weeks depending on severity (IDSA [Liu 2011])

Bone and joint infection:

Osteomyelitis (S. aureus [methicillin-resistant]): Infants, Children, and Adolescents: IV: 15 mg/kg/dose every 6 hours for a minimum of 4 to 6 weeks (IDSA [Liu 2011])

Septic arthritis (S. aureus [methicillin-resistant]): Infants, Children, and Adolescents: IV: 15 mg/kg/dose every 6 hours for minimum of 3 to 4 weeks (IDSA [Liu 2011])

C. difficile infection:

Manufacturer's labeling: Infants, Children, and Adolescents: Oral: 40 mg/kg/day divided every 6 to 8 hours for 7 to 10 days; maximum daily dose: 2,000 mg/day

Guideline recommendations:

Non-severe infection, initial or first recurrence: Children and Adolescents: Oral: 10 mg/kg/dose 4 times daily for 10 days; maximum dose: 125 mg/dose (IDSA/SHEA [McDonald 2018])

Severe/fulminant infection, initial: Children and Adolescents:

Oral: 10 mg/kg/dose 4 times daily for 10 days; maximum dose: 500 mg/dose; may consider adding IV metronidazole in critically ill patients (IDSA/SHEA [McDonald 2018]). If patient is unable to tolerate oral therapy, may use nasogastric administration (ASID [Trubiano 2016]).

Rectal: Note: Consider use when ileus is present. Limited data available: Rectal enema: 500 mg in 100 mL NS; dose volume is determined by age (IDSA/SHEA [McDonald 2018]); the optimal doses have not been established in pediatric patients; suggested volumes for children: 1 to 3 years: 50 mL; 4 to 9 years: 75 mL; >10 years: 100 mL (ASID [Trubiano 2016]); administer 4 times daily with or without IV metronidazole (IDSA/SHEA [McDonald 2018])

Second or subsequent recurrence: Children and Adolescents: Pulsed-tapered regimen: Oral: 10 mg/kg/dose 4 times daily for 10 to 14 days; then 10 mg/kg/dose twice daily for 7 days, then 10 mg/kg/dose once daily for 7 days, then 10 mg/kg/dose every 2 or 3 days for 2 to 8 weeks; maximum dose: 125 mg/dose (IDSA/SHEA [McDonald 2018])

CNS infection:

Brain abscess, subdural empyema, spinal epidural abscess [S. aureus (methicillin-resistant)]: Infants, Children, and Adolescents: IV: 15 mg/kg/dose every 6 hours for 4 to 6 weeks (some experts combine with rifampin) (IDSA [Liu 2011])

Meningitis: Infants, Children, and Adolescents: IV: 15 mg/kg/dose every 6 hours; Note: Maintain trough serum concentrations of 15 to 20 mcg/mL (IDSA [Tunkel 2004]; IDSA [Tunkel 2017])

S. aureus (methicillin-resistant): Infants, Children, and Adolescents: IV: 15 mg/kg/dose every 6 hours for 2 weeks (some experts combine with rifampin) (IDSA [Liu 2011])

VP-shunt infection, ventriculitis: Limited data available: Infants, Children, and Adolescents: Intrathecal/intraventricular (use a preservative-free preparation): 5 to 20 mg/day; usual dose: 10 or 20 mg/day (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]); due to the smaller CSF volume in infants, some guidelines recommend decreasing the infant dose (IDSA [Tunkel 2017])

Endocarditis, treatment:

Empiric therapy/culture negative: Children and Adolescents: IV 60 mg/kg/day divided every 6 hours; maximum daily dose: 2,000 mg/day; use in combination with other antibiotics for at least 4 weeks; longer duration may be required if prosthetic material is present; dosage should be adjusted to target trough serum concentrations of 10 to 15 mcg/mL; higher trough concentrations (15 to 20 mcg/mL) may be needed if there is a lack of response or if a resistant organism (MIC >1 mcg/mL) is identified (AHA [Baltimore 2015])

Streptococcus (including enterococcus): Children and Adolescents: IV: 40 mg/kg/day divided every 8 to 12 hours for at least 4 to 6 weeks; a longer duration and additional antibiotics may be required depending on organism and presence of prosthetic material; dosage should be adjusted to target trough serum concentrations of 10 to 15 mcg/mL; higher trough concentrations (15 to 20 mcg/mL) may be needed for resistant organisms (MIC >1 mcg/mL) or if there is a lack of response (AHA [Baltimore 2015])

S. aureus:

Non-methicillin resistant: Children and Adolescents: IV: 40 mg/kg/day divided every 8 to 12 hours for at least 4 to 6 weeks; a longer duration and additional antibiotics may be required depending on organism and presence of prosthetic material; dosage should be adjusted to target trough serum concentrations of 10 to 15 mcg/mL; higher trough concentrations (15 to 20 mcg/mL) may be needed for resistant organisms (MIC >1 mcg/mL) or if there is a lack of response (AHA [Baltimore 2015])

Methicillin-resistant:

AHA Guidelines: Children and Adolescents: IV: 40 mg/kg/day divided every 8 to 12 hours for at least 6 weeks; maximum daily dose: 2,000 mg/day; a longer duration may be required depending on the presence of prosthetic material; dosage should be adjusted to target trough serum concentrations of 15 to 20 mcg/mL (AHA [Baltimore 2015])

IDSA Guidelines: Infants, Children, and Adolescents: IV: 60 mg/kg/day divided every 6 hours (IDSA [Liu 2011])

Enterocolitis (S. aureus): Infants, Children, and Adolescents: Oral: 40 mg/kg/day divided every 6 to 8 hours for 7 to 10 days; maximum daily dose: 2,000 mg/day

Intra-abdominal infection, complicated (MRSA): Infants, Children, and Adolescents: IV: 40 mg/kg/day divided every 6 to 8 hours (IDSA [Solomkin 2010])

Peritonitis (peritoneal dialysis) (ISPD [Warady 2012]):

Prophylaxis: Infants, Children, and Adolescents:

Touch contamination of PD line (if known MRSA colonization): Intraperitoneal: 25 mg per liter

High-risk gastrointestinal procedures: Note: Use should be reserved for patients at high risk for MRSA: IV: 10 mg/kg administered 60 to 90 minutes before procedure; maximum dose: 1,000 mg

Treatment: Infants, Children, and Adolescents:

Intermittent: Intraperitoneal: Initial dose: 30 mg/kg in the long dwell; subsequent doses: 15 mg/kg/dose every 3 to 5 days during the long dwell; Note: Increased clearance may occur in patients with residual renal function; subsequent doses should be based on serum concentration obtained 2 to 4 days after the previous dose; redosing should occur when serum concentration <15 mcg/mL.

Continuous: Intraperitoneal: Loading dose: 1,000 mg per liter of dialysate; maintenance dose: 25 mg per liter

Pneumonia:

Community-acquired pneumonia (CAP): Infants >3 months, Children, and Adolescents: IV: 40 to 60 mg/kg/day every 6 to 8 hours; dosing to achieve AUC/MIC >400 has been recommended for treating moderate to severe MRSA infections (IDSA/PIDS [Bradley 2011])

Alternate dosing: S. aureus (methicillin-resistant): Infants, Children, and Adolescents: IV: 60 mg/kg/day divided every 6 hours for 7 to 21 days depending on severity (IDSA [Liu 2011])

Health care-associated pneumonia (HAP), S. aureus (methicillin-resistant): Infants, Children, and Adolescents: IV: 60 mg/kg/day divided every 6 hours for 7 to 21 days depending on severity (IDSA [Liu 2011])

Septic thrombosis of cavernous or dural venous sinus [S. aureus (methicillin-resistant)]: Infants, Children, and Adolescents: IV: 15 mg/kg/dose every 6 hours for 4 to 6 weeks (some experts combine with rifampin) (IDSA [Liu 2011])

Skin and skin structure infections, complicated: [MRSA or S. aureus (methicillin sensitive) in penicillin allergic patients]: Infants, Children, and Adolescents (IDSA [Stevens 2014]):

Non-necrotizing infection: IV: 10 mg/kg/dose every 6 hours

Necrotizing infection: IV: 15 mg/kg/dose every 6 hours. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours.

Alternate dosing: S. aureus (methicillin-resistant): Infants, Children, and Adolescents: IV: 60 mg/kg/day divided every 6 hours for 7 to 14 days (IDSA [Liu 2011])

Surgical (perioperative) prophylaxis: Infants, Children, and Adolescents: IV: 15 mg/kg/dose within 120 minutes prior to surgical incision. May be administered in combination with other antibiotics depending upon the surgical procedure (ASHP/IDSA/SIS/SHEA [Bratzler 2013]).

Reconstitution

IV: Reconstitute 500 mg, 750 mg, and 1 g vials and 5 g bulk vials with a compatible diluent to a final concentration of 50 mg/mL (10 g bulk vials may be reconstituted to a final concentration of 100 mg/mL). Reconstituted solution must be further diluted with at least 100 mL of a compatible diluent per 500 mg of vancomycin prior to parenteral administration.

Intrathecal, intraventricular (off-label route): Vancomycin powder for injection may be diluted to a 2.5, 5, or 10 mg/mL concentration in preservative free 0.9% sodium chloride for administration into the CSF (Ng 2014).

Oral:

Oral solution (Firvanq): Refer to manufacturer's product labeling for reconstitution instructions.

Powder for injection: Reconstitute powder for injection; flavoring syrups may be added to improve taste. See Extemporaneous Preparations section for details. Note: Multiple concentrations described (25 mg/mL, 50 mg/mL); use caution when determining dose volume.

Extemporaneously Prepared

Note: A vancomycin oral solution (25 mg/mL or 50 mg/mL) is commercially available (Firvanq).

Oral Solution

Using a vial of vancomycin powder for injection (reconstituted to 50 mg/mL), add the appropriate volume for the dose to 30 mL of water and administer orally or via NG tube. For oral administration, common flavoring syrups may be added to improve taste.

Vancomycin hydrochloride injection [prescribing information]. Lake Zurich, IL: Fresenius Kabi; February 2018.

25 mg/mL Oral Solution

A vancomycin 25 mg/mL solution in Ora-Sweet and water (1:1) may be prepared by reconstituting vancomycin for injection with sterile water, then dilute with a 1:1 mixture of Ora-Sweet and distilled water to a final concentration of 25 mg/mL; transfer to amber prescription bottle. Stable for 75 days refrigerated or for 26 days at room temperature.

Ensom MH, Decarie D, and Lakhani A, “Stability of Vancomycin 25 mg/mL in Ora-Sweet and Water in Unit-Dose Cups and Plastic Bottles at 4°C and 25°C,” Can J Hosp Pharm 2010, 63(5):366-72.22479004

Administration

Intravenous: Administer vancomycin with a final concentration not to exceed 5 mg/mL by IV intermittent infusion over at least 60 minutes (recommended infusion period of ≥30 minutes for every 500 mg administered [ASHP/IDSA/SIDP {Rybak 2009}]); in adult patients in need of fluid restriction, a concentration up to 10 mg/mL may be used, but risk of infusion-related reactions is increased. Not for IM administration.

If a maculopapular rash appears on the face, neck, trunk, and/or upper extremities (red man syndrome), slow the infusion rate to over 1¹/₂ to 2 hours and increase the dilution volume (Healy 1990; Rybak 1986; Szymusiak-Mutnick 1996). Hypotension, shock, and cardiac arrest (rare) have also been reported with too rapid of infusion. Administration of antihistamines prior to infusion may prevent or minimize this reaction (Rybak 1986; Wilhem 1999).

Irritant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Information conflicts regarding the use of dry cold or dry warm compresses (Hurst 2004; Reynolds 2014); however, dry warm compresses may be of benefit in increasing local blood flow to enhance drug removal from the extravasation site. Intradermal hyaluronidase may be considered for refractory cases (Reynolds 2014).

Hyaluronidase: Intradermal: Inject a total of 1 mL (15 units/mL) as 5 separate 0.2 mL injections (using a tuberculin syringe) along injection site and edematous area (Reynolds 2014).

Antibiotic lock technique (off-label use): Instill prepared vancomycin lock solution into each lumen of the catheter access port using a volume sufficient to fill the catheter (2 to 5 mL) with a dwell time of 48 to 72 hours (dependent on frequency of catheter use). Withdraw lock solution prior to catheter use; replace with fresh vancomycin lock solution after catheter use (IDSA [Mermel 2009]; LaPlante 2007).

Intraventricular (off-label route): Use preservative-free preparations only. May be administered intraventricularly with a final concentration of 2.5 to 10 mg/mL for the treatment of CSF shunt infections. When administered through a ventricular drain, clamp drain for 15 to 60 minutes before opening the drain to allow vancomycin solution to equilibrate in the CSF (IDSA [Tunkel 2004; Tunkel 2017]; Ng 2014).

Intravitreal (off-label route): May administer vancomycin intravitreally with a final concentration of 1 mg/0.1 mL NS or sterile water (Durand 2019; Kelsey 1995).

Oral:

Solution (Firvanq): Shake reconstituted oral solution well before each use.

Injection: Reconstituted powder for injection (not premixed solution) may be diluted and used for oral administration; common flavoring syrups may be added to improve taste. The unflavored, diluted solution may also be administered via nasogastric tube.

Rectal (off-label route): May be administered as a retention enema per rectum (IDSA/SHEA [McDonald 2018]); 500 mg in 100 to 500 mL of NS, volume may depend on length of segment being treated. If sodium chloride causes hyperchloremia could use solution with lower chloride concentration (eg, LR) (ACG [Surawicz 2013]).

Dietary Considerations

May be taken with food.

Storage

Capsules: Store at 15°C to 30°C (59°F to 86°F).

Flexible bags: Store below 25°C (77°F) in the original package. Use within 28 days of removal from aluminum overpouch. Stable at room temperature for 28 days.

Galaxy containers: Store Galaxy containers at or below -20°C (-4°F). Handle frozen product containers with care; may be fragile in the frozen state. Thaw frozen containers at 25°C (77°F) or 5°C (41°F). Do not immerse in water bath or microwave. Thawed solution in remains chemically stable for 72 hours at 25°C (77°F) or for 30 days when stored at 5°C (41°F). Do not refreeze thawed antibiotics.

Oral solution (Firvanq): Store at 2°C to 8°C (36°F to 46°F) prior to and following reconstitution; discard reconstituted solution after 14 days or if appears hazy or contains particulates. Protect from light.

Vials: Store intact vials at 20°C to 25°C (68°F to 77°F). Reconstitute vial using an appropriate diluent; recommendations may vary by product; refer to manufacturer's labeling for choice of diluent and for appropriate storage conditions and timeframes. Prior to administration, further dilution in a compatible solution is required; recommendations may vary by product; refer to manufacturer's labeling for list of compatible solutions and appropriate storage conditions and timeframes.

Pharmacy bulk packages: Store at 20°C to 25°C (68°F to 77°F). Discard pharmacy bulk packages no later than 4 hours after initial closure puncture.

Drug Interactions

Aminoglycosides: Vancomycin may enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bile Acid Sequestrants: May diminish the therapeutic effect of Vancomycin. Management: Avoid concurrent administration of oral vancomycin and bile acid sequestrants when possible. If use of both agents is necessary, consider separating doses by at least 2 hours to minimize the significance of the interaction. Consider therapy modification

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

Colistimethate: Vancomycin may enhance the nephrotoxic effect of Colistimethate. Consider therapy modification

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Neuromuscular-Blocking Agents: Vancomycin may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May increase the serum concentration of Vancomycin. Monitor therapy

Piperacillin: May enhance the nephrotoxic effect of Vancomycin. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Adverse Reactions

Injection:

>10%: Cardiovascular: Hypotension (accompanied by flushing)

1% to 10%:

Cardiovascular: Local phlebitis

Central nervous system: Chills, drug fever

Dermatologic: Skin rash

Hematologic & oncologic: Eosinophilia, neutropenia (reversible)

Frequency not defined: Cardiovascular: Flushing of face and neck (Red man syndrome; may be infusion related)

<1%, postmarketing, and/or case reports: DRESS syndrome (drug rash with eosinophilia and systemic symptoms), ototoxicity (rare; use of other ototoxic agents may increase risk), renal failure (limited data suggesting direct relationship), Stevens-Johnson syndrome, thrombocytopenia, vasculitis

Oral:

>10%: Gastrointestinal: Abdominal pain, dysgeusia (with oral solution), nausea

1% to 10%:

Cardiovascular: Peripheral edema

Central nervous system: Fatigue, headache

Gastrointestinal: Diarrhea, flatulence, vomiting

Genitourinary: Urinary tract infection

Neuromuscular & skeletal: Back pain

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Increased serum creatinine, interstitial nephritis, ototoxicity, renal failure, renal insufficiency, thrombocytopenia, vasculitis

Warnings/Precautions

Concerns related to adverse effects:

• Extravasation and thrombophlebitis: IV vancomycin is an irritant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. Pain, tenderness, and necrosis may occur with extravasation. If thrombophlebitis occurs, slow infusion rates, dilute solution (eg, 2.5 to 5 g/L) and rotate infusion sites.
• Nephrotoxicity: May cause nephrotoxicity although limited data suggest direct causal relationship; usual risk factors include preexisting renal impairment, concomitant nephrotoxic medications, advanced age, dehydration, critically-ill patients, patients with rapidly changing renal function, higher vancomycin serum levels, prolonged exposure, and concomitant piperacillin/tazobactam administration. If multiple sequential (≥2) serum creatinine concentrations demonstrate an increase of 0.5 mg/dL or ≥50% increase from baseline (whichever is greater) in the absence of an alternative explanation, the patient should be identified as having vancomycin-induced nephrotoxicity (ASHP/IDSA/SIDP [Rybak 2009]). Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible. Nephrotoxicity has been reported following treatment with oral vancomycin (typically in patients >65 years of age).
• Neutropenia: Prolonged therapy and use of concomitant drugs that cause neutropenia may increase the risk; monitor leukocyte counts periodically in these patients. Prompt reversal of neutropenia is expected after discontinuation of therapy.
• Ototoxicity: Ototoxicity is rarely associated with monotherapy. Ototoxicity manifests as tinnitus, hearing loss, dizziness, or vertigo. It has been most frequently reported in older patients, patients receiving excessive doses, those who have underlying hearing loss, or those receiving concomitant ototoxic drugs (eg, aminoglycosides). Serial auditory function testing may be helpful to minimize risk. Ototoxicity may be transient or permanent; discontinue treatment if signs of ototoxicity occur.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile infection (CDI); CDI has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Inflammatory bowel disease: Clinically significant serum concentrations have been reported in patients with inflammatory disorders of the intestinal mucosa who have taken oral vancomycin (multiple doses) for the treatment of C. difficile-associated diarrhea. Although use may be warranted, the risk for adverse reactions may be higher in this situation; consider monitoring serum trough concentrations, especially with renal insufficiency, severe colitis, and concurrent enteral vancomycin administration (IDSA/SHEA [McDonald 2018]; Pettit 2015).
• Pregnancy: [US Boxed Warning]: The formulation of vancomycin injection containing the excipients, polyethylene glycol (PEG 400) and N-acetyl D-alanine (NADA), is not recommended for use during pregnancy. PEG 400 and NADA have caused fetal malformations in animal reproduction studies. If use of vancomycin is needed during pregnancy, use other available formulations of vancomycin.
• Renal impairment: Use with caution in patients with renal impairment or those receiving other nephrotoxic or ototoxic drugs; dosage modification required (especially in elderly patients). Accumulation may occur after multiple oral doses of vancomycin in patients with renal impairment; consider monitoring trough concentrations in this circumstance.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Oral vancomycin is only indicated for the treatment of CDI or enterocolitis due to S. aureus and is not effective for systemic infections; parenteral vancomycin is not effective for the treatment of enterocolitis. Prescribing vancomycin in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
• Infusion reactions: Rapid IV administration (eg, over <60 minutes) may result in hypotension, flushing, erythema, urticaria, pruritus, wheezing, dyspnea, and, rarely, cardiac arrest. Reactions usually cease promptly after infusion is stopped. Frequency of infusion reactions may increase with concomitant administration of anesthetics. If used in conjunction with anesthesia, complete the vancomycin infusion prior to anesthesia induction.
• Intraocular administration (off-label route): Hemorrhagic occlusive retinal vasculitis (HORV), including permanent visual loss, has been reported in patients receiving intracameral or intravitreal administration of vancomycin during or after cataract surgery. Safety and efficacy of intraocularly administered vancomycin has not been established; vancomycin is not indicated for prophylaxis of endophthalmitis.
• Intraperitoneal administration (off-label route): Use caution when administering intraperitoneally (IP); in some continuous ambulatory peritoneal dialysis (CAPD) patients, chemical peritonitis (cloudy dialysate, fever, severe abdominal pain) has occurred. Symptoms are self-limited and usually clear after vancomycin discontinuation.

Monitoring Parameters

Intravenous: Periodic renal function tests, CBC, pregnancy test prior to use for formulation containing PEG 400 and NADA excipients, serum trough vancomycin concentrations in select patients (eg, aggressive dosing, life-threatening infection, seriously ill, unstable renal function, concurrent nephrotoxins, prolonged courses)

Suggested frequency of trough vancomycin concentration monitoring for intermittent infusion (ASHP/IDSA/SIDP [Rybak 2009]):

Hemodynamically stable patients: Draw trough concentrations at least once-weekly.

Hemodynamically unstable patients: Draw trough concentrations more frequently or in some instances daily.

Prolonged courses (>3 to 5 days): Draw at least one steady-state trough concentration; repeat as clinically appropriate.

Note: Drawing >1 trough concentration prior to the fourth dose for short course (<3 days) or lower intensity dosing (target trough concentrations <15 mcg/mL) is not recommended. For patients with uncomplicated skin and soft tissue infections who are not obese and have normal renal function, serum trough monitoring is generally not needed (IDSA [Liu 2011]).

Oral/rectal therapy: Serum sample monitoring is not typically required; systemic absorption of enteral vancomycin may occur in patients with mucosal disruption due to colitis, especially in patients with renal failure. Monitoring serum vancomycin levels may be considered for patients with renal failure who have severe colitis and require a prolonged course of enteral vancomycin (IDSA/SHEA [McDonald 2018]; Pettit 2015).

Pregnancy

Pregnancy Considerations

Vancomycin crosses the placenta and can be detected in fetal serum, amniotic fluid, and cord blood (Bourget 1991; Reyes 1989). Adverse fetal effects, including sensorineural hearing loss or nephrotoxicity, have not been reported following maternal use during the second or third trimesters of pregnancy.

The pharmacokinetics of vancomycin may be altered during pregnancy and pregnant patients may need a higher dose of vancomycin. Maternal half-life is unchanged, but the volume of distribution and the total plasma clearance may be increased (Bourget 1991). Individualization of therapy through serum concentration monitoring may be warranted.

Vancomycin is recommended for the treatment of Clostridioides (formerly Clostridium) difficile infections in pregnant women (ACG [Surawicz 2013]). Vancomycin is recommended as an alternative agent to prevent the transmission of group B streptococcal (GBS) disease from mothers to newborns (ACOG 782 2019). In patients colonized with MRSA, vancomycin is recommended as part of the antibiotic regimen for prophylactic use prior to cesarean delivery (ACOG 199 2018).

[US Boxed Warning]: The formulation of vancomycin injection containing the excipients polyethylene glycol (PEG 400) and N-acetyl D-alanine (NADA) is not recommended for use during pregnancy. PEG 400 and NADA have caused fetal malformations in animal reproduction studies. If use of vancomycin is needed during pregnancy, use other available formulations of vancomycin. Pregnancy status should be evaluated in females of reproductive potential prior to using the formulation containing PEG 400 and NADA.

Patient Education

What is this drug used for?

Injection:

• It is used to treat or prevent bacterial infections.

All Oral Products:

• It is used to treat diarrhea caused by a bacterial infection called C diff.
• It is used to treat a type of bowel infection.

Frequently reported side effects of this drug

• Abdominal pain
• Diarrhea
• Passing gas
• Loss of strength and energy
• Back pain
• Headache
• Vomiting
• Nausea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain
• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat
• Flushing
• Painful urination
• Trouble hearing
• Hearing loss
• Shortness of breath
• Wheezing
• Itching
• Muscle pain
• Chest pain
• Dizziness
• Passing out
• Chills
• Sore throat
• Change in balance
• Swelling of arms or legs
• Rash during infusion
• Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools
• Severe injection site redness, edema, pain, or irritation
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.