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تعداد ایتم قابل مشاهده باقیمانده : 4 مورد

Vancomycin: Drug information

Vancomycin: Drug information
(For additional information see "Vancomycin: Patient drug information" and see "Vancomycin: Pediatric drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
ALERT: US Boxed Warning
Risk of embryo-fetal toxicity due to excipients:

A formulation of vancomycin injection contains the excipients polyethylene glycol (PEG 400) and N-acetyl D-alanine (NADA), which resulted in fetal malformations in animal reproduction studies at dose exposures approximately 8 and 32 times, respectively, higher than the exposures at the human equivalent dose. If use of vancomycin is needed during the first or second trimester of pregnancy, use other available formulations of vancomycin.

Brand Names: US
  • Firvanq;
  • Vancocin;
  • Vancocin HCl;
  • Vancosol Pack [DSC]
Brand Names: Canada
  • JAMP Vancomycin;
  • JAMP-Vancomycin;
  • PMS-Vancomycin;
  • Vancocin;
  • Vancomycin HCl
Pharmacologic Category
  • Glycopeptide
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 therapeutic monitoring. Trough monitoring has traditionally been used for therapeutic monitoring; however, for serious methicillin-resistant S. aureus (MRSA) infections (eg, bacteremia, infective endocarditis, meningitis, osteomyelitis, pneumonia, sepsis), AUC monitoring is preferred (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). For patients with uncomplicated skin and soft tissue infections who are not obese and have normal renal function, therapeutic monitoring is generally not needed (IDSA [Liu 2011]). Risk of toxicity (eg, acute kidney injury) increases as a function of trough concentration, especially when trough is maintained above 15 to 20 mg/L; recent data suggest risk increases along the vancomycin AUC continuum, especially when daily AUC exceeds 650 to 1,300 mg•h/L (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

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

IV: Note: Ineffective for treating C. difficile infections.

Intermittent infusion: 15 to 20 mg/kg/dose (rounded to the nearest 250 mg) every 8 to 12 hours initially; for serious MRSA infections (eg, bacteremia, infective endocarditis, meningitis, osteomyelitis, pneumonia, sepsis), adjust based on therapeutic monitoring to achieve a target AUC/minimum inhibitory concentration (MIC) determined by broth microdilution (MICBMD) ratio of 400 to 600 (assuming a vancomycin MICBMD of 1 mg/L; see "Reference Range" for more information). Trough-only monitoring (target trough: 15 to 20 mg/L) is no longer recommended in patients with serious MRSA infections (ASHP/IDSA/PIDS/SIDP [Rybak 2020]), but may be needed in nonserious MRSA or non-MRSA infections. Early and frequent monitoring for dosage adjustments is recommended, especially when empiric doses exceed 4 g/day (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Loading dose: Seriously ill patients with documented/suspected MRSA infection: A loading dose of 20 to 35 mg/kg (based on actual body weight; maximum: 3 g/dose) may be considered to rapidly achieve target concentrations. After administration of the loading dose, the initiation of the maintenance dose should occur at the next dosing interval (eg, for a prescribed interval of every 8 hours, initiate the maintenance dose 8 hours after the start of the loading dose) (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Continuous infusion: Note: May be considered for critically ill patients who are unable to achieve AUC target with intermittent infusion dosing. Loading dose: 15 to 20 mg/kg, followed by a maintenance continuous infusion dose of 30 to 40 mg/kg/day (up to 60 mg/kg/day) to achieve a target steady state concentration of 20 to 25 mg/L (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Indication-specific dosing:

Bloodstream infection:

Empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). A loading dose may be considered in seriously ill patients (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; 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 every 8 to 12 hours initially; adjust based on therapeutic monitoring. 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 2020). 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 2.5 to 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 every 8 to 12 hours initially; adjust based on therapeutic monitoring (IDSA [Tunkel 2017]). A loading dose may be considered in seriously ill patients (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

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 d ifficile infection, prophylaxis (off-label use):

Note: For patients with a recent history of C. difficile infection (CDI) who subsequently require systemic antibiotics. Some experts reserve for patients who are older (≥65 years of age) or are significantly immunocompromised who have been hospitalized with severe CDI in the past 3 months (ACG [Kelly 2021b]); other experts consider use for any patients with CDI in the prior 12 months (Kelly 2021a).

Oral: 125 mg once daily; continue for 5 to 7 days after completion of systemic antibiotics (ACG [Kelly 2021b]; Kelly 2021a).

Clostridioides d ifficile infection, treatment:

Note: Criteria for disease severity is based on expert opinion and should not replace clinical judgment. There is no role for vancomycin doses other than 125 mg and 500 mg (ACG [Kelly 2021b]; IDSA/SHEA [McDonald 2018]).

Initial, nonfulminant infection: Oral: 125 mg 4 times daily (ACG [Kelly 2021b]; IDSA/SHEA [McDonald 2018]). Usual duration is 10 days. If delayed response to treatment, a longer duration (eg, up to 14 days) may be considered (IDSA/SHEA [McDonald 2018]). If antibiotic(s) for a primary infection are essential, some experts extend CDI treatment one week beyond other antibiotic(s) (Kelly 2021a).

Recurrent, nonfulminant infection: Note: Regimen selection depends on prior treatment (ACG [Kelly 2021b]; IDSA/SHEA [McDonald 2018]).

Oral: 125 mg 4 times daily (IDSA/SHEA [McDonald 2018]). Some experts reserve for patients who did not receive vancomycin for the initial episode (IDSA/SHEA [McDonald 2018]). Usual duration is 10 days. If delayed response to treatment, a longer duration (eg, up to 14 days) may be considered (IDSA/SHEA [McDonald 2018]). If antibiotic(s) for a primary infection are essential, some experts extend CDI treatment one week beyond other antibiotic(s) (Kelly 2021a).

Pulsed-tapered regimen: Oral: 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 (ACG [Kelly 2021b]; IDSA/SHEA [McDonald 2018]).

Combination regimen with rifaximin: Note: Rifaximin resistance may be a concern; some experts avoid in patients who have previously received rifamycins, and others do not routinely recommend this regimen (ACG [Kelly 2021b]; Kelly 2021a).

Oral: 125 mg 4 times daily for 10 days followed by rifaximin (IDSA/SHEA [McDonald 2018]).

Fulminant infection (ie, ileus, megacolon, and/or hypotension/shock): Oral or via nasogastric tube: 500 mg 4 times daily with IV metronidazole; if ileus is present, may consider vancomycin retention enema (ACG [Kelly 2021b]; IDSA/SHEA [McDonald 2018]). Usual duration is 10 days. If delayed response to treatment, a longer duration (eg, up to 14 days) may be considered (IDSA/SHEA [McDonald 2018]). If antibiotic(s) for a primary infection are essential, some experts extend CDI treatment one week beyond other antibiotic(s) (Kelly 2021a).

Fulminant infection with ileus: Rectal retention enema (off-label route): 500 mg in 100 mL NS; retained for as long as possible and replaced 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 2021a). Usual duration is 10 days. If delayed response to treatment, a longer duration (eg, up to 14 days) may be considered (IDSA/SHEA [McDonald 2018]). If antibiotic(s) for a primary infection are essential, some experts extend CDI treatment one week beyond other antibiotic(s) (Kelly 2021a).

Cystic fibrosis, acute pulmonary exacerbation, moderate to severe (off-label use): Empiric or pathogen-directed therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose every 8 hours initially; adjust based on therapeutic monitoring (Pettit 2017; Simon 2020). Duration is usually 10 days to 3 weeks or longer based on clinical response (Flume 2009; Simon 2020).

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 every 8 to 12 hours initially; adjust based on therapeutic monitoring (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). 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 every 12 hours initially; adjust to obtain a trough concentration of 10 to 20 mg/L (AHA [Baddour 2015]); some experts favor a trough of 15 to 20 mg/L (BSAC [Gould 2012]; ESC [Habib 2015]). Administer in combination with gentamicin for 6 weeks (AHA [Baddour 2015]).

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

Native valve: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (AHA [Baddour 2015]; ASHP/IDSA/PIDS/SIDP [Rybak 2020]). A loading dose may be considered in seriously ill patients (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). Duration of therapy is 6 weeks (AHA [Baddour 2015]).

Prosthetic valve: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (AHA [Baddour 2015]; ASHP/IDSA/PIDS/SIDP [Rybak 2020]). A loading dose may be considered in seriously ill patients (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). Duration of therapy is 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 every 12 hours initially; adjust based on therapeutic monitoring. Duration of therapy is 4 weeks (native valve) or 6 weeks (prosthetic valve) (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 2020; 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 2020).

Intra-abdominal infection, health care–associated (off-label use): Empiric or pathogen-directed therapy for Enterococcus spp. in high-risk patients (eg, postoperative infection or health careassociated infection in patients with prior use of antibiotics that select for Enterococcus, immunocompromising condition, valvular heart disease, or prosthetic intravascular material): IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; SIS/IDSA [Solomkin 2010]). Use as part of an appropriate combination regimen (Barshak 2021; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]). Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Sawyer 2015; SIS [Mazuski 2017]).

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 every 8 to 12 hours initially; adjust based on therapeutic monitoring. A loading dose may be considered in seriously ill patients (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; 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 2021; Sexton 2019b; Southwick 2020).

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 every 8 to 12 hours initially; adjust based on therapeutic monitoring (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). A loading dose may be considered in seriously ill patients (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; 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 every 8 to 12 hours initially (IDSA [Berbari 2015]; IDSA [Liu 2011]); adjust based on therapeutic monitoring. A loading dose may be considered in seriously ill patients (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). 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 to obtain a trough concentration between 15 and 20 mg/L (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, as a component of empiric therapy or pathogen-specific therapy for methicillin-resistant S. aureus: IV: 15 to 20 mg/kg/dose every 8 to 12 hours initially; adjust based on therapeutic monitoring (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; IDSA [Liu 2011]; IDSA/ATS [Metlay 2019]). A loading dose may be considered in seriously ill patients (ASHP/IDSA/PIDS/SIDP [Rybak 2009]; IDSA [Liu 2011]). Note: Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days. When used for empiric therapy, give as part of an appropriate combination regimen (IDSA/ATS [Metlay 2019]; IDSA/ATS [Kalil 2016]; IDSA [Liu 2011]).

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 every 8 to 12 hours initially (Berbari 2019; IDSA [Liu 2011]; IDSA [Osmon 2013]); adjust based on therapeutic monitoring. A loading dose may be considered in seriously ill patients (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). 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 every 12 hours initially; adjust based on therapeutic monitoring. Duration: 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 every 8 to 12 hours; adjust based on therapeutic monitoring (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). A loading dose is recommended; administer within 1 hour of suspected or confirmed sepsis (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; SCCM [Rhodes 2017]). Usual duration of therapy is dependent on underlying source, but is typically 7 to 10 days or longer, depending on clinical response (SCCM [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 every 8 to 12 hours initially; adjust dose on therapeutic monitoring. A loading dose may be considered in seriously ill patients (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). Total treatment duration is 3 to 4 weeks (in the absence of osteomyelitis), including appropriate oral step-down therapy (Goldenberg 2020; IDSA [Liu 2011]); some experts recommend 4 weeks of parenteral therapy for patients with concomitant bacteremia (Goldenberg 2020).

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 every 12 hours initially (IDSA [Stevens 2014]). For patients with uncomplicated skin and soft tissue infections who are not obese and have normal renal function, therapeutic monitoring is generally not needed; for complicated or severe infections, adjust based on therapeutic monitoring (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 patients 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 797 2020).

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 797 2020). Some experts prefer vancomycin 2 g initially and then 1 g every 12 hours thereafter until delivery (Baker 2020). 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 797 2020).

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 [Anderson 2020]) 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 every 12 hours initially; adjust based on therapeutic monitoring (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; 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 every 8 to 12 hours initially; adjust based on therapeutic monitoring (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Chu 2021). A loading dose may be considered in seriously ill patients (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). 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 2021).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Oral: There are no dosage adjustments provided in the manufacturer's labeling. However, dosage adjustment unlikely due to low systemic absorption.

IV:

Note: Initial IV dosing in nonobese patients should be based on actual body weight; subsequent dosing should generally be adjusted based on therapeutic monitoring. Trough monitoring has traditionally been used for therapeutic monitoring; however, for serious methicillin-resistant S. aureus (MRSA) infections (eg, bacteremia, infective endocarditis, meningitis, osteomyelitis, pneumonia, sepsis), AUC monitoring is preferred (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). A ratio of AUC over 24 hours to minimum inhibitory concentration (AUC/MIC) of ≥400 is the primary pharmacokinetic/pharmacodynamic predictor of vancomycin efficacy in serious MRSA infections (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Holmes 2013; Kullar 2011). Serum concentration monitoring should be conducted within the first 48 hours of therapy for patients with suspected or documented serious infections due to MRSA, with subsequent dosing adjusted to maintain AUC/MIC between 400 to 600 in order to maximize efficacy and minimize risk of vancomycin nephrotoxicity (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Moise-Broder 2004; Suzuki 2012; Zasowski 2017).

Altered kidney function:

Intermittent infusion: Note: The following table provides general recommendations (expert opinion derived from ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Golightly 2013). Refer to institution-specific policies and procedures for more detailed guidance.

Vancomycin Initial Dose Adjustments in Altered Kidney Function

CrCl (mL/minute)

Suggested loading dose (when applicable)a

Suggested initial maintenance dose

Suggested dosing interval

aLoading doses recommended in critically ill patients with suspected/documented serious MRSA infections. A loading dose of up to 35 mg/kg may be considered in critically ill patients with sepsis. Obese patients usually require 20 to 25 mg/kg loading doses. Maximum recommended loading dose is 3 g (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

bMonitor vancomycin serum concentrations more frequently, especially early on in therapy, to achieve target concentrations as these patients may have unstable or less predictable drug clearance. Care should be taken not to administer maintenance doses when serum concentrations remain >20 mg/L (Golightly 2013; expert opinion).

>90 to <130

25 to 30 mg/kg

15 to 20 mg/kg

8 to 12 hours

50 to 90

20 to 25 mg/kg

15 to 20 mg/kg

12 hours

15 to <50

20 to 25 mg/kg

10 to 15 mg/kg

24 hours

<15b

20 to 25 mg/kg

10 to 15 mg/kg

48 to 72 hours

Continuous infusion:

Loading dose: Administer an appropriate loading dose (eg, 15 to 20 mg/kg) (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Baptista 2014; Pea 2009); higher loading doses may be considered in critically ill patients with sepsis (Cristallini 2016; Ocampos-Martinez 2012); also refer to institution-specific policies and procedures.

Maintenance dose: Various protocols have been developed (Baptista 2014; Cristallini 2016; Ocampos-Martinez 2012; Pea 2009; Spadaro 2015); recommendations may vary based on the population studied. The following is an example protocol (Cristallini 2016), and doses should be adjusted to achieve a target steady state concentration of 20 to 25 mg/L (ASHP/IDSA/PIDS/SIDP [Rybak 2020]); also refer to institution-specific policies and procedures.

CrCl >80 to 119 mL/minute: 30 mg/kg administered over 24 hours.

CrCl >50 to 80 mL/minute: 25 mg/kg administered over 24 hours.

CrCl 25 to 50 mL/minute:14 mg/kg administered over 24 hours.

CrCl <25 mL/minute: 7 mg/kg administered over 24 hours.

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post-trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010).

Intermittent infusion: Loading dose (when applicable): 25 to 35 mg/kg (expert opinion) followed by 15 to 20 mg/kg every 8 hours depending on degree of augmented kidney function; some patients may require more frequent dosing (eg, 15 mg/kg every 6 hours) to attain target concentrations (Kim 2016; Lin Wu 2015; expert opinion); utilize frequent serum concentration monitoring.

Continuous infusion:

Loading dose: Administer an appropriate loading dose (eg, 15 to 20 mg/kg) (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Baptista 2014; Pea 2009); higher loading doses (eg, 25 mg/kg) have been used in some protocols and may vary based on population studied (Cristallini 2016; Vu 2019); also refer to institution-specific policies and procedures.

Maintenance dose: 40 to 60 mg/kg/day depending on degree of augmented kidney function with frequent serum concentration monitoring; adjust to achieve a target steady state concentration of 20 to 25 mg/L (Baptista 2014; Cristallini 2016; Pea 2009; Schmelzer 2013; Vu 2019; expert opinion).

Hemodialysis, intermittent (thrice weekly): Dialyzable (25% to 40% depending on dialyzer permeability) (Lucksiri 2002; Nyman 2018; Scott 1997).

Vancomycin Dosing Depending on Dose Timing and Dialyzer Permeabilitya

Dose timing and dialyzer permeability

Vancomycin doseb

aASHP/IDSA/PIDS/SIDP [Rybak 2020]

bInitial recommended loading/maintenance doses. The optimal pharmacokinetic/pharmacodynamic target in this population is unknown, but targeting predialysis concentrations of 15 to 20 mg/L are likely to achieve AUCs of 400 to 600 mg•hour/L (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Crew 2015). Predialysis serum concentrations should be obtained no less than weekly and should determine subsequent dosing (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

cThrice-weekly dose administration. Typically, patients may require ~25% larger doses for the 3-day interdialytic period (eg, Friday to Monday) to maintain sufficient vancomycin exposure on the third day.

Dose given after dialysis ends

Low permeability (low flux)

Loading dose: 25 mg/kg

Maintenance dose: 7.5 mg/kgc

High permeability (high flux)

Loading dose: 25 mg/kg

Maintenance dose: 10 mg/kgc

Dose given during last hours of dialysis (intradialytic)

Low permeability (low flux)

Loading dose: 30 mg/kg

Maintenance dose: 7.5 to 10 mg/kgc

High permeability (high flux)

Loading dose: 35 mg/kg

Maintenance dose: 10 to 15 mg/kgc

Peritoneal dialysis:

Loading dose: 20 to 25 mg/kg (expert opinion). A vancomycin serum concentration should be obtained ~48 to 72 hours after the loading dose, and subsequent doses (usually 10 to 15 mg/kg) should be administered based on attainment of goal serum concentrations (expert opinion). Doses may vary based on infection site and severity, as well as the presence or absence of residual renal function. Some experts use maintenance doses of up to 20 mg/kg/dose (Drew 2019).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response and adverse reactions due to drug accumulation is important.

Loading dose: 20 to 25 mg/kg followed by 7.5 to 10 mg/kg every 12 hours with more frequent serum concentration monitoring (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). In patients with suspected or confirmed serious MRSA infections, dose adjustments should be made based on AUC monitoring occurring in the first 24 to 48 hours of therapy (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions due to drug accumulation is important.

Loading dose (administer even if PIRRT is occurring): 20 to 25 mg/kg, followed by 15 mg/kg after each PIRRT session ends (or during the final 60 to 90 minutes of the session) with more frequent serum concentration monitoring (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). In patients with suspected or confirmed serious MRSA infections, dose adjustments should be made based on AUC monitoring occurring in the first 24 to 48 hours of therapy (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Dosing: Hepatic Impairment: Adult

Oral: There are no dosage adjustments provided in the manufacturer’s labeling. However, dosage adjustment unlikely due to low systemic absorption.

IV: There are no dosage adjustments provided in the manufacturer’s labeling. However, degrees of hepatic dysfunction do not affect the pharmacokinetics of vancomycin (Marti 1996).

Dosing: Pediatric

(For additional information see "Vancomycin: Pediatric drug information")

Note: For IV dosing, initial dosage recommendations for patients with normal kidney function presented; doses should be adjusted based on serum concentration monitoring; 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. Dosing presented in mg/kg/dose and mg/kg/day; routes of administration may vary (eg, IV, oral, intrathecal, intracatheter, intraperitoneal, rectal); use caution.

Optimal dose and frequency not established in patients receiving extracorporeal membrane oxygenation (ECMO); available data are limited (Amaker 1996; Buck 1998; Hoie 1990; Moffett 2018; Mulla 2005; Zylbersztajn 2018). 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: Initial: 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 2021]). Note: Based on adult data, an AUC24 target of 400 mg•hour/L is recommended in patients with serious methicillin-resistant S. aureus (MRSA) infections; specific dosing recommendations may be higher when targeting this range (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). See "MRSA infection, serious; treatment".

In general, monitoring of serum concentrations and assurance of adequate hydration status is recommended; utilize local antibiogram and protocols for further guidance.

Antibiotic lock therapy; catheter salvage: Limited data available: Optimal dose not established:

Note: For infections caused by susceptible organisms when the vascular catheter cannot be removed; use in addition to systemic antibiotics. Catheter salvage not effective in all cases; removal of catheter is recommended for infections with S. aureus (Hecht 2020; IDSA [Mermel 2009]; Wolf 2014). Dosing regimens variable; consider age and size of patient and catheter size (including number of lumens) when determining dose due to potential for lock to be delivered intravenously.

Infants, Children, and Adolescents: Intracatheter: Usual concentrations of lock solution: 2 to 5 mg/mL of vancomycin with or without heparin additive; most common concentrations reported: vancomycin 2 mg/mL, 2.5 mg/mL, or 5 mg/mL; refer to institutional protocol if available (Denaburg 2013; IDSA [Mermel 2009]; Tsai 2015). Concentrations described in literature range from 0.025 to 10 mg/mL with or without heparin or citrate (Justo 2014); a vancomycin concentration of 5 mg/mL has been shown to be more efficacious than 1 mg/mL when biofilm present (Lee 2006). Instill into each lumen of the catheter access port using a volume sufficient to fill the catheter, with a dwell time of ideally ≥8 to 12 hours and 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 (Denaburg 2013; IDSA [Mermel 2009]; Justo 2014; Tsai 2015). Note: If heparin is utilized in the lock solution, the dose used should not approach therapeutic unit/kg dose.

C. difficile infection; treatment:

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]).

Endocarditis, treatment: Note: Dosage adjustment to target trough serum concentrations of 10 to 15 mg/L is recommended in pediatric endocarditis by the AHA (AHA [Baltimore 2015]). Dosage adjustment to target AUC24 of 400 mg•hour/L has been recommended in the treatment of proven or suspected MRSA infections based on adult data (ASHP/IDSA/SIDP/PIDS [Rybak 2020]).

Empiric therapy/culture negative: Children and Adolescents: IV: Initial: 60 mg/kg/day divided every 6 hours; initial maximum daily dose: 2,000 mg/day; use in combination with other antibiotics for at least 4 to 6 weeks; longer duration may be required if prosthetic material is present or in cases of recurrent endocarditis (AHA [Baltimore 2015]).

Streptococcus (including enterococcus): Children and Adolescents: IV: Initial: 40 mg/kg/day divided every 8 to 12 hours; initial maximum daily dose: 2,000 mg/day; treat for at least 4 to 6 weeks; a longer duration and additional antibiotics may be required depending on organism and presence of prosthetic material (AHA [Baltimore 2015]).

S. aureus:

Non-methicillin resistant: Children and Adolescents: IV: Initial: 40 mg/kg/day divided every 8 to 12 hours; initial maximum daily dose: 2,000 mg/day; treat for at least 4 to 6 weeks; a longer duration and additional antibiotics may be required depending on organism and presence of prosthetic material (AHA [Baltimore 2015]).

Methicillin-resistant: Children and Adolescents: IV: Initial: 40 mg/kg/day divided every 8 to 12 hours for at least 6 weeks; usual initial maximum daily dose: 2,000 mg/day (AHA [Baltimore 2015]); however, higher initial doses have been recommended for patients with serious MRSA infection with normal renal function, though dosing based on studies and models that were not specific to endocarditis (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). See "MRSA infection, serious; treatment".

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.

Meningitis, including health care-associated meningitis: Infants, Children, and Adolescents: IV: Initial: 15 mg/kg/dose every 6 hours (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). Higher initial doses have been recommended for patients with serious MRSA infection with normal renal function, though dosing based on studies and models that were not specific to meningitis (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). See "MRSA infection, serious; treatment".

MRSA infection, serious; treatment:

Note: Doses should be adjusted based on patient-specific serum concentrations to a target AUC24 of 400 mg•hour/L, but potentially up to 600 mg•hour/L, based on adult data. In pediatric patients, an AUC24 of ≥400 mg•hour/L has been associated with trough concentrations of 7 to 10 mg/L, though trough concentrations do not clearly predict AUC on an individual level and trough-only monitoring is not recommended (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Frymoyer 2013; Le 2013). Some studies have indicated that doses on the lower end of the range (ie, 60 mg/kg/day divided every 6 hours) will achieve target AUC24 in most children (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Frymoyer 2013). To minimize risk of acute kidney injury, maintain AUC24 <800 mg•hour/L and trough <15 mg/L. For obese patients, start with a one-time loading dose of 20 mg/kg (based on total body weight), then start maintenance dosing (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Infants ≥3 months and Children <12 years: IV: Initial: 60 to 80 mg/kg/day in divided doses every 6 hours; initial maximum daily dose: 3,600 mg/day.

Children ≥12 years and Adolescents: IV: Initial: 60 to 70 mg/kg/day in divided doses every 6 to 8 hours; initial maximum daily dose: 3,600 mg/day.

Peritonitis (peritoneal dialysis) (ISPD [Warady 2012]): Limited data available:

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: Infants >3 months, Children, and Adolescents: IV: Initial: 40 to 60 mg/kg/day in divided doses every 6 to 8 hours; (IDSA/PIDS [Bradley 2011]). Note: Higher doses may be necessary when treating MRSA infections; doses should be adjusted based on patient-specific serum concentrations to a target AUC24 of 400 mg•hour/L (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). See "MRSA infection, serious; treatment".

Skin and skin structure infections, complicated: Note: Duration of treatment should be individualized and is dependent on severity of infection, adequacy of source control, and clinical improvement. For necrotizing fasciitis, continue treatment until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours.

Necrotizing infections, mixed (non-MRSA): Infants, Children, and Adolescents: IV: Initial: 10 to 13 mg/kg/dose every 8 hours (IDSA [Stevens 2014]).

Serious MRSA infection, including necrotizing infection and pyomyositis: Note: Dosage adjustment to target AUC24 of 400 mg•hour/L recommended for serious MRSA infections based on adult data. A loading dose of 20 mg/kg (based on total body weight) is recommended in obese patients (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Infants ≥3 months and Children <12 years: IV: Initial: 60 mg/kg/day in divided doses every 6 hours; maximum daily dose: 3,600 mg/day (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; IDSA [Stevens 2014]). Based on pharmacokinetic modeling studies, doses up to 80 mg/kg/day may be necessary to achieve target AUC24 (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Children ≥12 years and Adolescents: IV: Initial: 60 mg/kg/day in divided doses every 6 to 8 hours; maximum daily dose: 3,600 mg/day (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; IDSA [Stevens 2014]). Based on pharmacokinetic modeling studies, doses up to 70 mg/kg/day may be necessary to achieve target AUC24 (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

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]).

Ventriculitis (including health care-associated ventriculitis and cerebrospinal fluid [CSF] shunt infections):

Infants, Children, and Adolescents: Limited data available: Intraventricular or intrathecal: 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; adult dosage recommendations are based on ventricle size (IDSA [Tunkel 2017]).

Continuous infusion dosing: Limited data available; optimal dosing unknown:

Infants, Children, and Adolescents: IV: Loading dose: 10 to 15 mg/kg/dose administered over 1 to 2 hours, followed by maintenance infusion of 40 to 60 mg/kg/day; adjust dose to achieve target serum concentration (Berthaud 2019; Genuini 2018; Girand 2020; Guilhaumou 2016; Hurst 2019; McKamy 2012). Note: Required dose to achieve target concentration varies significantly between patients and depending on age, renal function, and target concentration; total daily doses of 30 to 110 mg/kg/day have been reported (Berthaud 2019; Hurst 2019). Pediatric patients with cancer or who are critically ill may require higher doses to achieve target concentrations (Genuini 2018; Guilhaumou 2016). Note: When transitioning from intermittent to continuous infusion, an initial loading dose may not be required; the total daily dose will likely need reduced depending on patient-specific factors, concentrations achieved during intermittent dosing, and clinical considerations (Hurst 2019).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

Oral: There are no dosage adjustments provided in manufacturer's labeling; however, dosage adjustment unlikely due to low systemic absorption.

IV: Note: Vancomycin levels should be monitored in patients with any renal impairment:

Infants, Children, and Adolescents: The following adjustments have been recommended (Aronoff 2007): Note: Renally-adjusted dose recommendations are based on intravenous doses of 10 mg/kg/dose every 6 hours or 15 mg/kg/dose every 8 hours.

GFR 30 to 50 mL/minute/1.73 m2: 10 mg/kg/dose every 12 hours.

GFR 10 to 29 mL/minute/1.73 m2: 10 mg/kg/dose every 18 to 24 hours.

GFR <10 mL/minute/1.73 m2: 10 mg/kg/dose; redose based on serum concentrations.

Intermittent hemodialysis: 10 mg/kg/dose; redose based on serum concentrations.

Peritoneal dialysis (PD): 10 mg/kg/dose; redose based on serum concentrations.

Continuous renal replacement therapy (CRRT): 10 mg/kg/dose every 12 to 24 hours; monitor serum concentrations.

Dosing: Hepatic Impairment: Pediatric

Oral: There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely needed due to low systemic absorption.

IV: There are no dosage adjustments provided in the manufacturer's labeling; however, degrees of hepatic dysfunction do not affect the pharmacokinetics of vancomycin (Marti 1996).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Obesity: Adult

The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Principles of body weight dosing:

Note: Vancomycin is a hydrophilic antimicrobial with a low to medium Vd and clearance (CL) that is proportional to glomerular filtration rate. Vancomycin Vd correlates with actual body weight (ABW), but does not increase proportionately with increasing body size (Hong 2015) and has been reported to be lower in morbid obesity compared to individuals who are not obese (0.3 to 0.5 L/kg vs 0.68 L/kg) (Adane 2015; Bauer 1998; Hong 2015). Since vancomycin loading doses are dependent on Vd, lower loading doses are generally needed in patients with obesity and the dose can be capped once a threshold dose is reached (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). Vancomycin CL can be estimated by variables used to estimate kidney function. Estimated vancomycin CL in patients with obesity is ~6 L/hour and rarely exceeds 9 L/hour. The empiric maintenance daily dose can be calculated by an estimate of CL and the AUC/minimum inhibitory concentration (MIC) target of 400 to 600 (ASHP/IDSA/PIDS/SIDP [Rybak 2020]). Using a targeted AUC approach may reduce the total daily dose (TDD) of vancomycin versus a target trough concentration; lower TDD may reduce the risk of acute kidney injury (Covvey 2020; Langton 2019). Optimal dosing and monitoring regimens are uncertain; refer to institutional protocol.

Example of dosing regimen:

IV:

Loading dose: Note: Consider utilizing a loading dose when rapid attainment of target concentrations is necessary (eg, sepsis, documented/suspected methicillin-resistant S. aureus infection) (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Initial: 20 to 25 mg/kg using actual body weight; maximum loading dose: 3 g. After administration of the loading dose, initiate maintenance dose at the next dosing interval (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Maintenance dose: Use actual body weight and the following CL equations to calculate a maintenance dose; empiric maintenance doses >4.5g/day are unlikely to be necessary (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Crass 2018). Note: If vancomycin therapy is continued, individualize vancomycin dose using early Bayesian approach (ie, two-serum concentrations within first 24 to 48 hours) to achieve target AUC (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

1. Calculate estimated vancomycin CL (Crass 2018).

Estimate CL (L/hour): 9.656 – [0.078 × age] – [2.009 × SCr] + [0.04 × ABW0.75] + [1.09 × sex].

Where adult age is in years; SCr is serum creatinine in mg/dL; ABW is actual body weight in kg scaled to an exponent of 0.75; and sex is 1 if male and 0 if female.

2. Calculate empiric vancomycin maintenance regimen (Crass 2018).

Estimate daily dose (rounded to nearest 250 mg): Estimated CL (L/hour) × 500 mg•hour/L.

Where 500 mg•hour/L is the mid-range AUC target selected for an MIC of 1 mg/L. When the vancomycin CL is estimated to be ≤3 L/hour, administer the dose every 24 hours or divide the daily dose every 12 hours. If CL is estimated to be >3 L/hour, divide the daily dose and administer every 12 hours (expert opinion).

Dosage Forms: US

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: 750 mg/150 mL (150 mL); 1000 mg/200 mL (200 mL); 1250 mg/250 mL (250 mL); 1500 mg/300 mL (300 mL); 1750 mg/350 mL (350 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: 500 mg (1 ea); 1 g (1 ea); 1.5 g (1 ea); 10 g (1 ea)

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

Generic: 250 mg (1 ea); 500 mg (1 ea); 750 mg (1 ea); 1000 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, 300 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)

Generic Equivalent Available: US

Yes

Dosage Forms Considerations

First-Vancomycin oral solution and Vancomycin+SyrSpend SF oral suspension are compounding kits. Refer to manufacturer’s labeling for compounding instructions.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as hydrochloride:

Vancocin: 125 mg, 250 mg [contains fd&c blue #2 (indigotine)]

Generic: 125 mg, 250 mg

Solution, Intravenous, as hydrochloride:

Generic: 1 g/200 mL in NaCl 0.9% (200 mL)

Solution Reconstituted, Intravenous, as hydrochloride:

Generic: 500 mg (1 ea, 10 mL); 1000 mg (1 ea); 1 g (1 ea, 20 mL, 30 mL); 5 g (1 ea); 10 g (1 ea)

Administration: Adult

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 (vancomycin flushing syndrome [formerly “red man syndrome”]), slow the infusion rate to over 11/2 to 2 hours and increase the dilution volume (Austin 2020; 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 2020; 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]).

Administration: Pediatric

Oral:

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

Powder for 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.

Parenteral:

IV:

Intermittent: Administer intermittent IV infusion over 60 minutes. Vancomycin flushing syndrome (formerly "red man syndrome") may occur if the infusion is too rapid. It is not an allergic reaction, but may be characterized by hypotension and/or a maculopapular rash appearing on the face, neck, trunk, and/or upper extremities; if this should occur, slow the infusion rate to administer dose over 90 to 120 minutes (Healy 1990; PIDS 2021; Szymusiak-Mutnick 1996) and increase the dilution volume; the reaction usually dissipates in 30 to 60 minutes; administration of antihistamines just before the infusion may also prevent or minimize this reaction.

Continuous: Administer over 24 hours (Girand 2020; Hurst 2019).

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

Intrathecal/Intraventricular: Use preservative-free preparations only. Administer as diluted solution (1 to 10 mg/mL) over 1 to 2 minutes (Al-Jeraisy 2004; Cook 2009; Parasuraman 2018; Pfausler 1997). When administered through a ventricular drain, clamp drain for 15 to 60 minutes to allow vancomycin solution to equilibrate in the cerebrospinal fluid (CSF) (IDSA [Tunkel 2017]).

Intracatheter (vascular); antibiotic lock technique: Instill prepared vancomycin lock solution into each lumen of the catheter access port using a volume sufficient to fill the catheter with a dwell time of ≥8 to 12 hours and up 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 (Denaburg 2013; IDSA [Mermel 2009]; Justo 2014).

Rectal: Instill vancomycin enema solution via rectal foley; retain for 1 hour. In pediatric patients the optimal doses have not been established; suggested volumes for pediatric patients: 1 to 3 years of age: 50 mL; 4 to 9 years of age: 75 mL; >10 years of age: 100 mL (ASID [Trubiano 2016]).

Use: Labeled Indications

Clostridioides difficile infection, treatment (oral): Treatment of C. difficile infection (CDI) in adults and pediatric patients <18 years of age.

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) in adults and pediatric patients <18 years of age. 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: Adult

Catheter-related bloodstream infection, antibiotic lock technique (catheter-salvage therapy); Cerebrospinal fluid shunt infection; Clostridioides difficile infection, prophylaxis; Clostridioides difficile infection, treatment (rectal administration); Cystic fibrosis, acute pulmonary exacerbation; Diabetic foot infection, moderate to severe; Endophthalmitis, treatment; Intra-abdominal infection, health care–associated; Intracranial abscess (brain abscess, intracranial epidural abscess) or spinal epidural abscess; Meningitis, bacterial; Peritonitis, treatment (peritoneal dialysis patients); Prosthetic joint infection; Streptococcus (group B), maternal prophylaxis for prevention of neonatal disease; Surgical prophylaxis

Medication Safety Issues
Sound-alike/look-alike issues:

IV vancomycin may be confused with INVanz

Vancomycin may be confused with clindamycin, gentamicin, tobramycin, valACYclovir, vecuronium, Vibramycin

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication (intrathecal administration) among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions (Significant): Considerations
Anaphylaxis

Vancomycin may rarely cause life-threatening immune-mediated anaphylaxis, which may present as generalized and extensive pruritus and/or erythema of skin, respiratory distress, bronchospasm, hypoxia, and hypotension. Clinical presentation is similar to vancomycin flushing syndrome (a nonimmune-mediated anaphylactoid infusion-related reaction; formerly called “red man syndrome”), making it difficult for clinicians to distinguish between the 2 reactions (Ref).

Mechanism: Non-dose-related; immunologic; IgE-mediated with specific antibodies formed against a drug allergen following initial exposure (immunologically mediated) or result in direct mast cell stimulation (Ref). IgE binding and cross-linking of the high affinity IgE receptor (FcεRI) on the surface of mast cells causes release of histamine and other mediators that can result in urticaria, flushing, airway obstruction, hypotension, and tachycardia (Ref).

Onset: Rapid; IgE-mediated reactions generally occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). In a systematic review analyzing 7 case reports of vancomycin-induced anaphylaxis, the median time to onset of signs/symptoms was 2 minutes (range: 1 to 35 minutes) (Ref).

Risk factors:

• Previous exposure to vancomycin (necessary for IgE-mediated anaphylaxis) (Ref)

Clostridioides difficile infection

Although oral vancomycin is used for the treatment of Clostridioides difficile infection (CDI), Clostridioides difficile-associated diarrhea and Clostridioides difficile colitis have been reported with intravenous vancomycin (Ref). Clinical symptoms range from mild diarrhea to life-threatening colitis, toxic megacolon, and sepsis. In patients with severe CDI, frequent symptoms include watery diarrhea, abdominal pain, fever, nausea, anorexia, and malaise (Ref).

Mechanism: Non-dose-related; antibiotics disrupt the indigenous gut microbiota which promotes C. difficile spore germination, growth, and toxin production, leading to epithelial damage and colitis (Ref).

Onset: Varied; may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref).

Risk factors:

• Antibiotic exposure (highest risk factor); antibiotics most frequently associated with C. difficile include clindamycin, fluoroquinolones, and third-/fourth-generation cephalosporins (Ref)

• Long durations in a hospital or other health care setting (recent or current) (Ref)

• Advanced age (Ref)

• Immunocompromised conditions or a serious underlying condition (Ref)

• GI surgery/manipulation (Ref)

• Antiulcer medications, such as proton pump inhibitors and H2 blockers (suggested risk factors) (Ref)

• Chemotherapy (suggested risk factor) (Ref)

Drug-induced immune thrombocytopenia

Drug-induced immune thrombocytopenia (DITP) has been associated with use. Vancomycin-induced ITP has been associated with severe bleeding characterized by petechial hemorrhages, ecchymoses, and oozing from the buccal mucosa. Rarely, acutely-ill patients have experienced gross hematuria, lower GI hemorrhage, intrapulmonary hemorrhage, and excessive bleeding from venipuncture sites (Ref).

Mechanism: Non-dose-related; immunologic; platelet-reactive antibodies of the IgG class, the IgM class, or both, have been detected in patients with thrombocytopenia while receiving vancomycin. These antibodies reacted with platelets only in the presence of vancomycin, suggesting that the mechanism is similar to quinine-induced thrombocytopenia rather than a hapten-specific antibody (Ref).

Onset: Varied; DITP; typically occurs within 1 to 2 weeks after initiating therapy or longer in patients with intermittent exposure (Ref). In case reports, the mean time to platelet nadir count was ~8 days following first exposure. However, there are rare case reports describing a rapid onset (within 24 hours) of acute severe thrombocytopenia, primarily in settings of reexposure to vancomycin (Ref).

Hypersensitivity reactions (delayed)

Maculopapular rash and severe cutaneous adverse reactions (SCARs), including drug rash with eosinophilia and systemic symptoms (DRESS), toxic epidermal necrosis (TEN), Stevens-Johnson syndrome (SJS), and acute generalized exanthematous pustulosis (AGEP), have occurred rarely with use and may be life-threatening (Ref). In addition, vancomycin-induced dermatologic disorder (linear IgA bullous dermatosis [LABD]) has been reported rarely and clinical presentation may mimic TEN, making it difficult to distinguish (Ref). Other reactions include erythema multiforme, exfoliative dermatitis, and hypersensitivity angiitis (Ref).

Mechanism: Non-dose-related; immunologic. Delayed hypersensitivity reactions are mediated by T-cells or antibodies other than IgE (eg, IgG-mediated, such as some cytopenias) (Ref). SCARs are delayed type IV hypersensitivity reactions involving a T-cell mediated drug-specific immune response (Ref). The mechanism behind vancomycin-induced LABD is unknown; LABD is a rare immune-mediated blistering disorder resulting in linear deposition of IgA at the basement membrane zone (Ref).

Onset: Delayed; type IV reactions are delayed hypersensitivity reactions that typically occur days to weeks after drug exposure but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref). DRESS usually does not develop until after 2 weeks of administration (Ref). In a systematic case review, a median onset of 9 days and 21 days was observed for SJS/TEN and DRESS, respectively (Ref). In vancomycin-induced LABD, lesions typically appear 1 to 15 days after the first vancomycin dose (Ref); a median latency of 7 days was observed in a systematic review (Ref).

Risk factors:

• Patients with end-stage renal disease (suggested risk factor) (Ref)

• In DRESS, a strong association was observed for patients with the HLA-A*32:01 allele in a study involving predominantly European ancestry (Ref)

• Cross-reactivity with teicoplanin (Ref)

Infusion-related reaction (vancomycin flushing syndrome [formerly “red man syndrome”])

An infusion-related reaction, referred to as vancomycin flushing syndrome (formerly “red man syndrome”), which is a non-IgE-mediated drug reaction most often characterized by an erythematous rash, generalized flushing, and pruritus, may occur. Severe reactions, which are uncommon, may also include hypotension, chest pain, and dyspnea. Rarely, RMS may be life-threatening and cause severe hypotension and cardiac arrest or cardiovascular collapse. Clinical presentation can be similar to IgE-mediated anaphylaxis making it difficult for clinicians to distinguish between the 2 reactions (Ref). Reactions usually cease promptly after infusion is stopped.

Mechanism: Non-IgE-mediated drug reaction caused by histamine release from mast cells and basophils found in the skin, lung, GI tract, myocardium, and vascular system (Ref). The mast cell receptor MRGPRX2 has also been identified as a cause of non-IgE-mediated drug reactions (Ref).

Onset: Rapid; usually occurs 4 to 10 minutes after the start of the infusion with the first dose but may also occur at any time (Ref).

Risk factors:

• Typically caused by rapid IV infusion (<1 hour) of large doses (Ref)

• Concomitant medications that also induce histamine release including ciprofloxacin; barbiturates; opioids (except fentanyl which rarely induces histamine); certain neuromuscular antagonists (atracurium, cisatracurium, doxacurium, mivacurium, succinylcholine, tubocurarine); propofol; plasma expanders (dextran, polygeline); and radiocontrast agents (Ref).

Nephrotoxicity

Systemic exposure is associated with nephrotoxicity (usually reversible), which may result in acute kidney injury (or acute renal failure), predominantly occurring in patients with multiple risk factors (Ref). Cases of systemic absorption and nephrotoxicity with oral vancomycin have been reported (Ref).

Mechanism: Non-dose-related; most commonly attributed to acute tubular necrosis (or renal tubular necrosis), resulting from direct oxidative stress on proximal tubule cells or obstructive tubular cast formation. In addition, acute interstitial nephritis has also been described, characterized by tubular and interstitial inflammation, resulting from an immunologically mediated (non-IgE) process (Ref).

Onset: Intermediate; usually occurs 5 to 7 days and up to 14 days following monotherapy (Ref). Acute interstitial nephritis was observed at a median onset of 26 days in a systematic case review (Ref).

Risk factors:

• Vancomycin exposure (trough levels ≥15 mg/L, larger AUC [>650 to 1,300 mg-h/L], high daily doses [>4 g/day]) (Ref)

• Duration of therapy >7 days (Ref)

• Obesity (Ref)

• Preexisting kidney dysfunction (Ref)

• Critical illness (Ref)

• Concurrent nephrotoxin therapy or concurrent prolonged use of piperacillin/tazobactam (Ref)

• Older adults >65 years:

• Parenteral: Less commonly associated risk factor (Ref)

• Oral: Increases the risk of systemic absorption from oral vancomycin

Neutropenia/pancytopenia

Neutropenia (severe) and agranulocytosis have been observed in numerous case reports and case series; in some cases, drug fever also accompanied the neutropenia (Ref). Reversible pancytopenia has also been reported in case reports (Ref).

Mechanism: Non-dose-related; available data suggest a peripheral mechanism mediated by antibodies and direct toxicity to the bone marrow (Ref).

Onset: Varied; usually occurs after 7 to 12 days of treatment, with most cases occurring after 20 days (Ref). However, 1 case report described an onset of 8 weeks following discontinuation of a 3-week course, and then upon rechallenge, neutropenia recurred 3 days following reinitiation (Ref).

Risk factors:

• Prolonged exposure (ie, >7 days) (Ref)

• Teicoplanin: In patients experiencing neutropenia who were switched to teicoplanin (another glycopeptide), 50% of these patients also developed teicoplanin-induced neutropenia (Ref)

Ototoxicity

Vancomycin is infrequently associated with ototoxicity, manifested as tinnitus, sensorineural hearing loss, dizziness, or vertigo; some cases have reported irreversible hearing loss (Ref). Of note, vancomycin has not been found to be ototoxic in animal models (Ref).

Mechanism: Non-dose-related; proposed to be via direct damage to the auditory branch of the eighth cranial nerve, although data are conflicting and unclear if ototoxicity is directly attributable to vancomycin or to other confounding factors (Ref).

Risk factors:

• Older adults (Ref)

• Coadministration with ototoxic agents (eg, aminoglycosides) (Ref)

• Kidney dysfunction (potential risk factor) (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

IV:

Frequency not defined:

Cardiovascular: Chest pain, flushing, hypotension, shock, vasculitis

Dermatologic: Bullous dermatitis, erythema of skin, exfoliative dermatitis (Forrence 1990), pruritus, Stevens-Johnson syndrome (Lin 2014)

Hematologic & oncologic: Agranulocytosis (di Fonzo 2018), eosinophilia, leukopenia, thrombocytopenia

Hypersensitivity: Hypersensitivity reaction (Kupstaite 2010)

Local: Injection site phlebitis, irritation at injection site, pain at injection site

Nervous system: Chills, dizziness, malaise, vertigo

Neuromuscular & skeletal: Myalgia

Otic: Hearing loss (Klibanov 2003), ototoxicity (Forouzesh 2009), tinnitus (Traber 1981)

Renal: Increased blood urea nitrogen (Bergman 1988), increased serum creatinine, interstitial nephritis (Bergman 1988), renal tubular necrosis (Shah-Khan 2011)

Respiratory: Dyspnea, wheezing

Miscellaneous: Fever (Smith 1999)

Postmarketing:

Cardiovascular: Hypersensitivity angiitis (rare: <1%) (Pingili 2017)

Dermatologic: Acute generalized exanthematous pustulosis (rare: <1%) (Mawri 2015), dermatologic disorder (linear IgA bullous dermatosis) (rare: <1%) (Tashima 2014), erythema multiforme (rare: <1%) (Khicher 2019), maculopapular rash (Marik 1997), toxic epidermal necrolysis (rare: <1%) (Changela 2013)

Gastrointestinal: Clostridioides difficile associated diarrhea (rare: <1%) (Hecht 1989), Clostridioides difficile colitis (rare: <1%) (Hecht 1989), peritonitis (following intraperitoneal administration during CAPD) (Freiman 1992)

Hematologic & oncologic: Henoch-Schonlein purpura (Min 2017), immune thrombocytopenia (Al Jafar 2015; Mohammadi 2017), neutropenia (reversible) (literature suggests an incidence ranging from 2% to 12%) (Black 2011; di Fonzo 2018), pancytopenia (rare: <1%) (Carmichael 1986)

Hypersensitivity: Anaphylaxis (rare: <1%) (Anne 1994), fixed drug eruption (Gilmore 2004), infusion-related reaction (vancomycin flushing syndrome [formerly “red man syndrome”]; literature suggests an incidence ranging from 4% to as high as 47%) (Alvarez-Arango 2021; Austin 2020; Symons 1985; Wazny 2001)

Immunologic: Drug reaction with eosinophilia and systemic symptoms (rare: <1%) (Cacoub 2011)

Renal: Acute kidney injury (Sawada 2018), nephrotoxicity (common: ≥10%) (Lodise 2009)

Oral:

>10%:

Endocrine & metabolic: Hypokalemia (13%)

Gastrointestinal: Abdominal pain (15%), nausea (17%)

1% to 10%:

Cardiovascular: Peripheral edema (6%)

Gastrointestinal: Diarrhea (9%), flatulence (8%), vomiting (9%)

Genitourinary: Urinary tract infection (8%)

Nervous system: Fatigue (5%), headache (7%)

Neuromuscular & skeletal: Back pain (6%)

Renal: Nephrotoxicity (5%)

Miscellaneous: Fever (9%)

Frequency not defined:

Cardiovascular: Hypotension

Gastrointestinal: Clostridioides difficile colitis, constipation

Hematologic & oncologic: Anemia

Nervous system: Depression, insomnia

Renal: Increased serum creatinine, renal failure syndrome, renal insufficiency

Postmarketing:

Cardiovascular: Vasculitis

Dermatologic: Acute generalized exanthematous pustulosis, dermatologic disorder (linear IgA bullous dermatosis) (Tashima 2014), exfoliative dermatitis (rare: <1%) (Forrence 1990), pruritus, skin rash, Stevens-Johnson syndrome (rare: <1%) (An 2011), toxic epidermal necrolysis (rare: <1%) (An 2011), urticaria

Hematologic & oncologic: Eosinophilia, thrombocytopenia

Hypersensitivity: Anaphylaxis, flushing (vancomycin flushing syndrome [formerly “red man syndrome”]; case report following systemic absorption) (Arroyo-Mercado 2019), nonimmune anaphylaxis

Immunologic: Drug reaction with eosinophilia and systemic symptoms (Cacoub 2011)

Nervous system: Chills, dizziness, drug fever, pain, vertigo

Neuromuscular & skeletal: Muscle spasm (chest and back)

Otic: Tinnitus

Respiratory: Dyspnea, wheezing

Contraindications

Hypersensitivity to vancomycin or any component of the formulation

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.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection.

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 in patients with renal insufficiency, severe colitis, and a prolonged course (IDSA/SHEA [McDonald 2018]; Pettit 2015).

• Renal impairment: Use with caution in patients with renal impairment or those receiving other nephrotoxic drugs; dosage modification required and close monitoring is recommended in patients with preexisting renal impairment and those at high risk for renal impairment. Accumulation may occur after multiple oral doses of vancomycin in patients with renal impairment; consider monitoring serum concentrations in this circumstance.

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.

• 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.

• 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.

Metabolism/Transport Effects

None known.

Drug Interactions

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

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

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: 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. Risk D: 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. Risk X: Avoid combination

Colistimethate: Vancomycin may enhance the nephrotoxic effect of Colistimethate. Management: Avoid coadministration of colistimethate and vancomycin whenever possible due to the potential for additive or synergistic nephrotoxicity. If coadministration cannot be avoided, closely monitor renal function. Risk D: Consider therapy modification

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

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

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

Piperacillin: May enhance the nephrotoxic effect of Vancomycin. Risk C: 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. Risk D: Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

Reproductive Considerations

Pregnancy status should be evaluated in patients who may become pregnant prior to using the IV formulation containing the excipients polyethylene glycol (PEG 400) and N-acetyl D-alanine (NADA).

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 mild, moderate, or severe Clostridioides difficile infections in pregnant patients. Standard doses should be used (ACG [Surawicz 2013]).

Vancomycin is recommended as an alternative option to prevent the transmission of group B streptococcal (GBS) disease from mothers to newborns. Untreated asymptomatic GBS disease can result in maternal urinary tract infection, intraamniotic infection, endometritis, preterm labor, and/or stillbirth. Vertical transmission from the mother can cause sepsis, pneumonia, or meningitis in the newborn. Vancomycin IV is recommended for use in women who are at high risk for anaphylaxis to penicillin (or whose risk is unknown), and the GBS isolate is resistant to clindamycin. Dose and rate of infusion should be based on maternal weight and renal function, similar to nonpregnant patients (ACOG 797 2020).

In patients known to be colonized with methicillin-resistant S. aureus (MRSA), a single dose of vancomycin is recommended as part of the antibiotic regimen for prophylactic use prior to cesarean delivery. Monotherapy with vancomycin does not provide sufficient coverage for cesarean delivery surgical prophylaxis (ACOG 199 2018).

Based on limited data, vancomycin is considered likely compatible with pregnancy when used for the treatment of airway diseases, such as cystic fibrosis (ERS/TSANZ [Middleton 2020]).

The formulation of vancomycin injection containing the excipients polyethylene glycol (PEG 400) and N-acetyl D-alanine (NADA) has caused fetal malformations in animal reproduction studies. If use of vancomycin is needed during the first or second trimesters of pregnancy, use other available formulations of vancomycin.

Breast-Feeding Considerations

Vancomycin is present in breast milk following IV administration.

Information related to the presence of vancomycin in breast milk is available from a mother who received vancomycin 1 g IV every 12 hours during pregnancy and for at least 1 week prior to sampling. Vancomycin 12.7 mcg/mL was detected in breast milk 4 hours after a maternal dose (Reyes 1989).

Vancomycin exhibits minimal oral absorption; therefore, the amount available to pass into the milk would be limited following oral administration and unlikely to provide clinically relevant exposure to an infant exposed via breast milk.

In general, antibiotics that are present in breast milk may cause non-dose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush or diarrhea (WHO 2002).

Vancomycin is recommended for the treatment of Clostridioides difficile infections in breastfeeding women (ACG [Surawicz 2013]) and is considered compatible with breastfeeding when used for the treatment of airway diseases, such as cystic fibrosis (ERS/TSANZ [Middleton 2020]). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Dietary Considerations

May be taken with food.

Monitoring Parameters

IV: Periodic renal function tests, CBC, pregnancy test prior to use for formulation containing PEG 400 and NADA excipients, serial auditory function testing may be helpful to minimize risk of ototoxicity, serum trough vancomycin concentrations in select patients (eg, aggressive dosing, life-threatening infection, seriously ill, unstable renal function, concurrent nephrotoxins, prolonged courses).

AUC monitoring: Frequency of AUC monitoring should be based on clinical judgement; frequent or daily monitoring may be appropriate for hemodynamically unstable patients; hemodynamically stable patients may only require once-weekly monitoring (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Trough monitoring:

Hemodynamically stable patients: Draw trough concentrations at least once weekly (ASHP/IDSA/SIDP [Rybak 2009]).

Hemodynamically unstable patients: Draw trough concentrations more frequently or in some instances daily (ASHP/IDSA/SIDP [Rybak 2009]).

Prolonged courses (>3 to 5 days): Draw at least one steady-state trough concentration; repeat as clinically appropriate (ASHP/IDSA/SIDP [Rybak 2009]).

Note: Drawing >1 trough concentration prior to the fourth dose for short course (<3 days) or lower intensity dosing (target trough concentrations <15 mg/L) 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).

Reference Range

IV:

Timing of serum samples:

First-order pharmacokinetic analytic equations or Bayesian software to estimate AUC: Requires collection of 2 serum concentrations, postdistributional peak concentration (Cmax) drawn 1 to 2 hours after infusion and trough concentration (Cmin) drawn at the end of the dosing interval. It is preferable that a near steady-state postdistributional peak and trough concentration within the same dosing interval (if possible) are used with the equation-based method. Bayesian-derived AUC monitoring does not require steady-state serum concentrations (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Trough monitoring: Draw trough concentration just before the administration of a dose at steady-state conditions. Steady-state conditions generally occur approximately after the third dose; therefore, may begin monitoring vancomycin trough concentrations before the fourth dose (usually within 1 hour of administration). More specific recommendations for timing of serum samples may be found in "Monitoring Parameters" (Alvarez 2016; ASHP/IDSA/SIDP [Rybak 2009]).

Target concentrations:

Intermittent infusion:

AUC/minimum inhibitory concentration determined by broth microdilution (MICBMD): 400 to 600, assuming MICBMD of 1 mg/L. When MICBMD is >1 mg/L, probability of attaining an AUC/MIC target of ≥400 is low with conventional dosing; higher doses may risk unnecessary toxicity. When MICBMD is <1 mg/L, decreasing the dose to achieve the AUC/MIC target is not recommended (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Trough: 10 to 20 mg/L; target within this range depends on site and severity of infection, as well as clinical response. For pathogens with a minimum inhibitory concentration (MIC) ≤1 mg/L, the minimum trough concentration should be 15 mg/L to meet target AUC/MIC of ≥400. For complicated infections (eg, bacteremia, endocarditis, osteomyelitis, meningitis, and hospital-acquired pneumonia caused by S. aureus) or infections associated with severe sepsis or septic shock, trough concentrations of 15 to 20 mg/L are recommended to improve penetration and improve clinical outcomes (ASHP/IDSA/SIDP [Rybak 2009]; Liu 2011; Rhodes 2017). The American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guidelines for hospital-acquired pneumonia and the IDSA meningitis guidelines also recommend trough concentrations of 15 to 20 mg/L (Kalil 2016; Tunkel 2004; Tunkel 2017).

Continuous infusion: Target steady-state concentration: 20 to 25 mg/L (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Concentrations associated with toxicity: Serum concentration >80 mg/L.

Intraventricular (off-label route): Limited data available (IDSA [Tunkel 2004; Tunkel 2017]; Smetana 2018): Prior to administration of the next intraventricular dose, withdraw a sample of cerebrospinal fluid (CSF). This trough CSF concentration divided by the vancomycin MIC for the isolated bacterial pathogen (inhibitory quotient) should exceed 10 to 20.

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

Pharmacodynamics and Pharmacokinetics

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

Distribution: Distributes widely in body tissue and fluids, except for CSF.

Vd:

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

Infants: 0.56 L/kg (Rainkie 2015).

Children ≤6 years of age: 0.61 L/kg (Rainkie 2015).

Children >6 years of age: 0.47 L/kg (Rainkie 2015).

Adolescents: 0.49 L/kg (Rainkie 2015).

Adults: 0.4 to 1 L/kg (ASHP/IDSA/SIDP [Rybak 2009]); 0.3 to 0.5 L/kg in patients who are morbidly obese (Adane 2015; Bauer 1998; Hong 2015).

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

Children:

CSF concentrations: 0.2 to 17.3 mg/L (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 mg/L; serum concentration dependent (ASHP/IDSA/SIDP [Rybak 2009]).

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

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

Protein binding: ~55%.

Metabolism: No apparent metabolism.

Half-life elimination: Biphasic: Terminal:

Preterm neonates (GA: 32 to 34 weeks); PNA ~3 to 5 days: 5.9 to 9.8 hours (Schaad 1980).

Term neonates; PNA ~2 to 3 days: 6.7 hours (Schaad 1980).

Infants: 2.8 hours (Rainkie 2015).

Children <6 years of age: 2.4 hours (Rainkie 2015).

Children ≥6 years of age: 2.9 hours (Rainkie 2015).

Adolescents: 3.2 hours (Rainkie 2015).

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

End-stage renal disease: 7.5 days.

Time to peak, serum: IV: Immediately after completion of infusion.

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).

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

Adults: 1.6 to 6.2 L/hour (Matzke 1984); patients who are obese: ~6 L/hour (rarely exceeds 9 L/hour) (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Pharmacodynamics and Pharmacokinetics: Additional Considerations

Pediatric: Extracorporeal membrane oxygenation (ECMO): Reported pharmacokinetic parameters in pediatric patients receiving ECMO vary widely based on ECMO circuitry/filters, age, weight, kidney function, and underlying diseases. In general, volume of distribution may be increased and clearance may be increased or decreased; reported parameters vary significantly; elimination half-life appears to be dependent upon renal function (Amaker 1996; Buck 1998; Cies 2017; Moffett 2018; Mulla 2005; Zylbersztajn 2018).

Geriatric: Total systemic and renal clearance may be reduced.

Anti-infective considerations:

Parameters associated with efficacy: Note: Ratios, including the minimum inhibitory concentration (MIC), depend upon the methodology used; MIC determined by E-test is typically 1.5 to 2 times MIC determined by broth microdilution (ASHP/IDSA/PIDS/SIDP [Rybak 2020]).

Staphylococcus aureus: AUC/MICBMD ≥400 mg•hour/L (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Kullar 2011; Lodise 2014; Moise-Broder 2004); specific cutoff for efficacy has varied slightly between studies.

Enterococcus spp.: AUC/MICEtest ≥389 (Jumah 2018).

Parameters associated with toxicity: Nephrotoxicity: AUC ≥600 to 650 mg•hour/L; risk continues to increase along AUC continuum (Aljefri 2019; ASHP/IDSA/PIDS/SIDP [Rybak 2020]; Fiorito 2018; Le 2015; Lodise 2020); Cmin ≥15 mg/L (ASHP/IDSA/PIDS/SIDP [Rybak 2020]; van Hal 2013).

Postantibiotic effect: A short postantibiotic effect has been observed in E. faecalis (0.5 to 1 hour) and S. aureus (0.6 to 2 hours); slightly longer in S. epidermidis (4.3 to 6.5 hours) (Hanberger 1991; Löwdin 1998).

Pricing: US

Capsules (Vancocin HCl Oral)

125 mg (per each): $103.35

Capsules (Vancocin Oral)

250 mg (per each): $190.55

Capsules (Vancomycin HCl Oral)

125 mg (per each): $31.31

250 mg (per each): $57.72

Solution (Vancomycin HCl in Dextrose Intravenous)

1GM/200ML 5% (per mL): $0.16

500 mg/100 mL 5% (per mL): $0.09

750MG/150ML 5% (per mL): $0.10

Solution (Vancomycin HCl in NaCl Intravenous)

1GM/200ML 0.9% (per mL): $0.14

500 mg/100 mL 0.9% (per mL): $0.09

750MG/150ML 0.9% (per mL): $0.10

Solution (Vancomycin HCl Intravenous)

500 mg/100 mL (per mL): $0.11

750 mg/150 mL (per mL): $0.10

1000 mg/200 mL (per mL): $0.10

1250 mg/250 mL (per mL): $0.09

1500MG/300ML (per mL): $0.09

1750MG/350ML (per mL): $0.09

2000MG/400ML (per mL): $0.08

Solution (reconstituted) (Firvanq Oral)

25 mg/mL (per mL): $0.86

50 mg/mL (per mL): $1.14

Solution (reconstituted) (Vancomycin HCl Intravenous)

1 g (per each): $4.14 - $24.90

1.25 g (per each): $24.12

1.5 g (per each): $28.93 - $28.94

5 g (per each): $19.72 - $107.24

10 g (per each): $39.18 - $258.10

100 g (per each): $600.00

250 mg (per each): $4.81

500 mg (per each): $2.96 - $12.89

750 mg (per each): $9.10 - $13.23

1000 mg (per each): $7.19

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Aekovan (PH);
  • Alvarcin (CR, DO, GT, HN, NI, PA, SV);
  • Celovan (HK);
  • Citerin (MX);
  • Covan (BD);
  • Covancin (IN);
  • Cytovan (IN);
  • Dhacocin (MY, SG);
  • Edicin (BG, CZ, EE, RO, RU, SK, TH, TR, UA);
  • Estavam (MX);
  • Forstaf (IN);
  • Icoplax (AR, PE);
  • Kovan (CL);
  • Levovanox (IT);
  • Mersa (PH);
  • Normedia (SE);
  • Riveran (AR, PE);
  • Vacsol (MX);
  • Vagran (VE);
  • Vamysin (BE);
  • Vanauras (MX);
  • Vanaurus (CR, DO, EC, GT, HN, NI, PA, SV);
  • Vancard (BD);
  • Vancep (ID);
  • Vancin (BD);
  • Vancin-S (TH);
  • Vanco-SAAR (DE);
  • Vanco-Teva (IL);
  • Vancoavenir (IL);
  • Vancobac (BD);
  • Vancobact (EG);
  • Vancocid (TH);
  • Vancocin (AE, AT, AU, BB, BG, HU, IE, JO, LB, LK, MT, NL, RU, SA, SI, VN, ZA);
  • Vancocin CP (CN, IN, MX, PK, TW);
  • Vancocin HCl (BF, BJ, CH, CI, DK, ET, GB, GH, GM, GN, HK, KE, LR, MA, ML, MR, MU, MW, NE, NG, PH, SC, SD, SE, SL, SN, TN, TW, TZ, UG, ZM, ZW);
  • Vancocina (IT);
  • Vancocine (FR);
  • Vancodex (ID);
  • Vancoled (AE, KR, KW, VN);
  • Vancolon (AE, BH, EG, ET, KW, LB, PH, QA, SA);
  • Vancomax (PE, PY);
  • Vancomet (PH);
  • Vanconix (BD);
  • Vancorin (TR);
  • Vancorus (RU);
  • Vancosam (LK);
  • Vancosan (BR, FI, IS, LT, LV);
  • Vancotech (LK);
  • Vancotek (AR);
  • Vancotex (MY);
  • Vancotrat (BR);
  • Vancox (MX);
  • Vancozin (EG, KR);
  • Vanlyo (TW);
  • Vanmicira (CZ);
  • Vantocil (ID);
  • Varedet (AR, PE, PY, UY);
  • Vivocin (MY);
  • Voncon (GR);
  • Vondem (GR);
  • Voxin (GR)


For country abbreviations used in Lexicomp (show table)

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