NEW ZEALAND DATA SHEET

VANCOMYCIN

1. Product Name
Vancomycin 500 mg and 1000 mg powder for infusion.

2. Qualitative and Quantitative Composition

Each vial contains 500 mg or 1000 mg of vancomycin base.

3. Pharmaceutical Form
Vancomycin powder for infusion is a white to almost white or slightly pink or yellow freeze-dried
powder which has been prepared in a sterile fashion.

When reconstituted in water, it is a clear solution with a pH of 2.8 – 4.5.

4. Clinical Particulars
4.1 Therapeutic indications
Vancomycin hydrochloride is indicated for potentially life-threatening infections which cannot be
treated with another effective, less toxic antimicrobial drug, including the penicillins and
cephalosporins.

Vancomycin hydrochloride is useful in therapy of severe staphylococcal (including methicillin

resistant staphylococcal) infections in patients who cannot receive or who have failed to respond to
the penicillins and cephalosporins or who have infections with staphylococci that are resistant to
other antibiotics. Once sensitivity data are available, therapy should be adjusted accordingly.

Vancomycin hydrochloride is effective alone or in combination with an aminoglycoside for

endocarditis caused by S. viridans or S. bovis. For endocarditis caused by enterococci (e.g. S.
faecalis), vancomycin hydrochloride is effective only in combination with an aminoglycoside.
Vancomycin hydrochloride is effective for the treatment of diptheroid endocarditis. Vancomycin
hydrochloride is used in combination with rifampicin, an aminoglycoside, or both in early-onset
prosthetic valve endocarditis caused by S. epidermidis or diphtheroids.

The effectiveness of vancomycin has been documented in other infections due to staphylococci
including osteomyelitis, pneumonia, septicaemia and, skin and skin structure infections. When
staphylococcal infections are localised and purulent, antibiotics are used as adjuncts to appropriate
surgical measures.

Specimens for bacteriological cultures should be obtained in order to isolate and identify causative
organisms and to determine their susceptibilities to vancomycin hydrochloride.

Vancomycin hydrochloride should be administered orally for the treatment of staphylococcal

enterocolitis and antibiotic-associated pseudomembranous colitis (produced by C. difficile).
Parenteral administration of vancomycin hydrochloride alone is inappropriate for this indication.

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Vancomycin hydrochloride is not effective by the oral route for other types of infections. For oral
administration the parenteral formulation may be used. Some systemic absorption may occur
following oral administration in patients with pseudo-membranous colitis.

4.2 Dose and method of administration

Dose
Adults
The usual intravenous dose is 500 mg every 6 hours or 1g every 12 hours. A 500 mg dose of
vancomycin hydrochloride should be infused over a period of at least 60 minutes, whereas a 1 g
dose should be administered over a period of at least 2 hours. Vancomycin must not be given by
intramuscular injections (see section 4.4).

Loading dose
The initial dose should be no less than 15 mg/kg, even in patients with mild to moderate renal
insufficiency.

Special populations
Adults with impaired renal function and the elderly
Dosage adjustment must be made in patients with impaired renal function to avoid toxic serum levels.
In the elderly, dosage reduction may be necessary to a greater extent than expected because of
decreasing renal function. Measurement of vancomycin serum concentrations is required to optimise
therapy, especially in seriously ill patients with changing renal function. Vancomycin serum
concentrations may be determined by use of a microbiological assay, a radioimmunoassay, a
fluorescence polarization immunoassay, a fluorescence immunoassay, or high-pressure liquid
chromatography.

For most patients with renal impairment or the elderly, the dosage calculations may be made by
using the following table. The vancomycin dose per day in milligrams is about 15 times the glomerular
filtration rate in ml/minute (see table below).

Dosage table for vancomycin in patients with impaired renal function

Creatinine clearance Vancomycin dose

(ml/min) (mg/24h)
100 1,545
90 1,390
80 1,235
70 1,080
60 925
50 770
40 620
30 465
20 310
10 155

Anephric patients
The table is not valid for functionally anephric patients. For such patients, an initial dose of 15 mg/kg
bodyweight should be given in order to promptly achieve therapeutic serum concentrations. The
dose required to maintain stable concentrations is 1.9 mg/kg/24hours. Since individual maintenance
doses of 250 (250,000 IU) – 1,000 (1000,000 IU) mg are convenient, in patients with marked renal

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impairment, a dose may be given every several days rather than on a daily basis. In anuria, a dose
of 1,000 mg every 7 to 10 days has been recommended.

The majority of patients with infections caused by organisms susceptible to the antibiotic show a
therapeutic response by 48 - 72 hours. The total duration of therapy is determined by the type and
severity of the infection and the clinical response of the patient. In staphylococcal endocarditis,
therapy for three weeks or longer is recommended.

Children
The paediatric dosage of vancomycin is calculated on the basis of 10 mg/kg bodyweight every six
hours after an initial loading dose of 15 mg/kg. Each dose should be administered over a period of
at least 60 minutes.

Infants and neonates

In neonates and young infants, the total daily intravenous dosage may be lower. An initial dose of
15 mg/kg is suggested, followed by 10 mg/kg every 12 hours in the first week of life and every 8
hours thereafter until one month of age. Close monitoring of serum vancomycin concentrations is
mandatory in these patients. Each dose should be administered over a period of at least 60 minutes.

Method of administration
Oral administration
The usual adult total daily dosage for antibiotic associated pseudomembranous colitis produced by
C. difficile is 500 mg to 2 g in 3 or 4 divided doses for 7 to 10 days. The total daily dosage in children
is 40 mg/kg bodyweight in 3 or 4 divided doses. The total daily dosage should not exceed 2 g.

The contents of one 500 mg (500,000 IU) vial may be diluted in 30 ml of distilled or deionised water
and given to the patient to drink, or the diluted material may be administered via nasogastric tube.
Common flavouring syrups may be added to the solution to improve the taste for oral administration.

Reconstituted powder, diluted solution for oral use can be stored for 96 hours at 2°C to 8°C or 24
hours below 25°C.

Preparation of solution for injection

At the time of use, the 500 mg (500,000 IU) vial should be reconstituted with 10 ml of Water for
Injections. The resulting solution contains vancomycin 50 mg/ml. The 1 g (1,000,000 IU) vial should
be reconstituted with 20 ml of Water for Injections. The resulting solution contains vancomycin
50 mg/ml. The reconstituted solution containing 500 mg of vancomycin must be further diluted with
at least 100 ml of Sodium Chloride Intravenous Infusion 0.9% or Glucose Intravenous Infusion 5%.
The reconstituted solution containing 1 g of vancomycin must be further diluted with at least 200 ml
of Sodium Chloride Intravenous Infusion 0.9% or Glucose Intravenous Infusion 5% to a concentration
of not more than 5 mg/ml. The resulting solution should be infused over a period of at least 60
minutes when 500 mg of vancomycin is to be administered, or at least 2 hours when 1 g of
vancomycin is to be given. In selected patients in need of fluid restriction, a concentration of up to
10 mg/ml may be used; use of such higher concentration may increase the risk of infusion related
events. Infusion related events may occur, however, at any rate of concentration.

Displacement volumes
500 mg vial: following reconstitution with 10 ml of Water for Injections, the average displacement
volume is 0.254 ml.

1000 mg vial: following reconstitution with 20 ml of Water for Injections, the average displacement
volume is 0.486 ml.

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Stability of reconstituted solution
Solutions of vancomycin hydrochloride 50 mg/ml (50,000 IU/ml) in Water for Injections do not show
significant loss of potency when stored at 2°C to 8°C for 96 hours.

When diluted to a concentration of either 10 mg/ml or 1 mg/ml with Sodium Chloride Intravenous
Infusion 0.9% or Glucose Intravenous Infusion 5%, vancomycin was chemically stable for 14 days
at 2°C to 8°C.

To reduce microbiological hazard, the infusion should be commenced as soon as practicable after
reconstitution/preparation. If storage is necessary, the solution should be held at 2°C to 8°C for not
more than 24 hours.

4.3 Contraindications
Vancomycin hydrochloride is contraindicated in patients with known hypersensitivity to the active
substance.

4.4 Special warnings and precautions for use

General
Patients with a creatinine clearance <60 mL/minute and all elderly individuals should be given serial
tests of auditory function and of vancomycin blood levels. All patients receiving the drug should
have periodic haematological studies, urine analysis, and renal function tests.

Hypersensitivity reactions
Serious and occasionally fatal hypersensitivity reactions are possible (see section 4.3 and 4.8) In
case of hypersensitivity reactions, treatment with vancomycin must be discontinued immediately and
the adequate emergency measures must be initiated.

Severe cutaneous adverse reactions

Severe Cutaneous Adverse Reactions (SCARs) including Stevens Johnson Syndrome (SJS), toxic
epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and
acute generalised exanthematous pustulosis (AGEP) have been reported in association with
vancomycin treatment (see section 4.8). Patients should be advised to inform their doctor at the first
appearance of rash or any other sign of hypersensitivity.

If a SCAR is suspected, the drug should be discontinued and specialist dermatological assessment
should be carried out.

Infusion reactions
Rapid bolus administration (e.g. over several minutes) may be associated with exaggerated
hypotension, including shock, and, rarely, cardiac arrest, histamine like responses and
maculopapular or erythematous rash (“red neck”).

Vancomycin hydrochloride should be administered in a dilute solution at a rate not exceeding

500 mg/hour to avoid rapid-infusion-related reactions, e.g. hypotension, flushing, erythema, urticaria
and pruritus. Stopping the infusion usually results in a prompt cessation of these reactions (see
sections 4.2 and 4.8).

When given intravenously, toxic serum levels can occur. Vancomycin is excreted fairly rapidly by the
kidney and blood levels increase markedly with decreased renal clearance. During parenteral
therapy, the risk of toxicity and nephrotoxicity appears appreciably increased by high blood
concentrations or prolonged treatment.

Since vancomycin hydrochloride is irritating to tissue and causes drug fever, pain and possibly
necrosis it should never be injected intramuscularly; it must be administered intravenously.

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Pain and thrombophlebitis occur in many patients receiving vancomycin and are occasionally severe.
The frequency and severity of thrombophlebitis can be minimised if the drug is administered in a
volume of at least 200 ml of glucose or saline solution and if the injection sites are rotated.

Use in renal impairment

Because of its nephrotoxicity, vancomycin should be used with care in patients with renal
insufficiency. If it is necessary to use vancomycin parenterally in patients with renal impairment, the
dose and/or dose intervals should be adjusted carefully (see section 4.2) and blood levels monitored.
Serial monitoring of renal function should be performed.

When patients receive concomitant therapy with an aminoglycoside, serial monitoring of renal
function should be performed.

Ototoxicity
Ototoxicity has occurred when serum levels exceeded 80 microgram/ml. It may be transient or
permanent. Deafness may be preceded by tinnitus and should be regarded as an indication to
discontinue treatment. The elderly are more susceptible to auditory damage. Experience with other
antibiotics suggests that deafness may be progressive despite cessation of treatment.

Vancomycin hydrochloride should be avoided (if possible) in patients with previous hearing loss. If it
is used in such patients, the dose of vancomycin should be regulated by periodic determination of
drug levels in the blood. Patients with renal insufficiency and individuals over the age of 60 should
be given serial tests of auditory function and of vancomycin blood levels. All patients receiving the
drug should have periodic hematologic studies, urinalyses, and liver and renal function tests.

Most of the patients who experienced hearing loss had kidney dysfunction, pre-existing hearing loss,
or concomitant treatment with an ototoxic drug (see section 4.5).

Cross-sensitivity reactions
Vancomycin should be used with caution in patients with allergic reactions to teicoplanin, since cross
hypersensitivity, including fatal anaphylactic shock, may occur.

Blood disorders
Reversible neutropenia has been reported in patients receiving vancomycin hydrochloride (see
section 4.8). Patients who will undergo prolonged therapy with vancomycin hydrochloride or those
who are receiving concomitant medicines which may cause neutropenia should have periodic
monitoring of the leukocyte count.

Other routes of administration

The safety and efficacy of vancomycin hydrochloride administration by the intrathecal (intralumbar
or intraventricular) route have not been assessed.

Reports have revealed that administration of sterile vancomycin hydrochloride by the intraperitoneal
route during continuous ambulatory peritoneal dialysis (CAPD) has resulted in a syndrome of
chemical peritonitis. To date, this syndrome has ranged from a cloudy dialysate alone to a cloudy
dialysate accompanied by varying degrees of abdominal pain and fever. This syndrome appears to
be short lived after discontinuation of intraperitoneal vancomycin.

If parenteral and oral vancomycin are administered concomitantly, an additive effect can occur. This
should be taken into consideration when calculating the total dose. In this situation, serum levels of
the antibiotic should be monitored.

Some patients with inflammatory disorders of the intestinal mucosa may have significant systemic
absorption of oral vancomycin and, therefore, may be at risk for the development of adverse
reactions associated with the parenteral administration of vancomycin. The risk is greater if renal

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impairment is present. It should be noted that the total systemic and renal clearances of vancomycin
are reduced in the elderly.

Patients taking oral vancomycin hydrochloride should be warned of its offensive taste.

Use during anaesthesia

In surgical patients the administration of vancomycin should be carefully timed in relation to the
induction of anaesthesia (see section 4.5).

Superinfection
The use of vancomycin hydrochloride may result in the overgrowth of non-susceptible organisms. If
new infections due to bacteria or fungi appear during therapy with this product, appropriate measures
should be taken including withdrawal of vancomycin hydrochloride.

Clostridioides difficile-associated disease

In rare instances there have been reports of pseudomembranous colitis due to Clostridioides difficile
developing in patients who received intravenous vancomycin. C. difficile associated diarrhoea
(CDAD) has been reported with use of nearly all antibacterial agents, including vancomycin
hydrochloride, and may range in severity from mild diarrhoea to fatal colitis. Treatment with
antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin
producing strains of C. difficile cause increased morbidity and mortality, as these infections can be
refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all
patients who present with diarrhoea following antibiotic use. Careful medical history is necessary
since CDAD has been reported to occur over 2 months after the administration of antibacterial
agents.

Other
Concurrent and sequential use of other neurotoxic and/or nephrotoxic antibiotics, particularly
ethacrynic acid, neuromuscular blocking agents, aminoglycoside antibiotics, polymyxin B colistin,
viomycin and cisplatin requires careful monitoring.

Haemorrhagic occlusive retinal vasculitis

Haemorrhagic occlusive retinal vasculitis, including permanent loss of vision, can occur in patients
receiving intracameral or intravitreal administration of vancomycin during or after cataract surgery.
The safety and efficacy of vancomycin administered by the intracameral or the intravitreal route have
not been established by adequate and well-controlled trials and these are not approved routes of
administration for vancomycin. Vancomycin is not indicated for prophylaxis of endophthalmitis.

Use in the elderly

It should be noted that the total systemic and renal clearances of vancomycin are reduced in the
elderly. The natural decrement of glomerular filtration with increasing age may lead to elevated
vancomycin serum concentrations if dosage is not adjusted. Vancomycin dosage schedules should
be adjusted in elderly patients (see section 4.2).

Paediatric use
In premature neonates, infants and children, it is appropriate to confirm vancomycin serum
concentrations. Concomitant administration of vancomycin and anaesthetic agents has been
associated with erythema and histamine like flushing in children (see section 4.8).

Effects on laboratory tests

No data available.

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4.5 Interaction with other medicines and other forms of interaction
Concurrent administration with other neurotoxic (e.g. ototoxic) or nephrotoxic drugs, e.g.
streptomycin, neomycin, gentamicin, kanamycin, amikacin, amphotericin B, bacitracin, tobramycin,
polymyxin B, colistin and cisplatin or piperacillin/tazobactam, requires careful monitoring (see section
4.4).

In order to minimise the risk of nephrotoxicity when treating patients with underlying renal dysfunction
or those patients receiving concomitant therapy with an aminoglycoside, serial monitoring of renal
function should be performed and particular care should be taken in following appropriate dosing
schedules (see section 4.2).

Diuretics such as ethacrynic acid and furosemide may aggravate ototoxicity.

Cholestyramine has been shown to bind vancomycin in vitro. Therefore, if oral vancomycin is used
with cholestyramine, the two medicines should be administered several hours apart.

Reversible neutropenia has been reported in patients receiving vancomycin hydrochloride (see
section 4.8). Patients who are receiving concomitant drugs which may cause neutropenia should
have periodic monitoring of the leukocyte count.

There have been reports that the frequency of infusion related events (including hypotension,
flushing, erythema, urticaria, and pruritus) increases with the concomitant administration of
anaesthetic agents. Infusion related events may be minimised by the administration of vancomycin
at a rate not exceeding 500 mg/hour prior to anaesthetic induction.

Vancomycin may enhance neuromuscular blockade produced by medicines such as

suxamethonium or vecuronium.

4.6 Fertility, pregnancy and lactation

Pregnancy
(Category B21).

Animal reproduction studies have not been conducted with vancomycin hydrochloride. It is not known
whether vancomycin hydrochloride can affect reproduction capacity. In a controlled clinical study,
vancomycin was administered to pregnant women for serious staphylococcal infections complicating
intravenous drug abuse to evaluate potential ototoxic and nephrotoxic effects on the infant.
Vancomycin was found in cord blood. No sensorineural hearing loss or nephrotoxicity attributable to
vancomycin was noted. One infant whose mother received vancomycin in the third trimester
experienced conductive hearing loss that was not attributed to the administration of vancomycin. As
only 10 patients were treated with vancomycin in this study, and administration was only in the
second and third trimesters, it is not known whether vancomycin causes foetal harm. Vancomycin
hydrochloride should be given to a pregnant woman only if clearly needed and blood levels should
be monitored carefully to minimise fetal toxicity.
1Category B2: Drugs which have been taken by only a limited number of pregnant women and
women of childbearing age, without an increase in the frequency of malformation or other direct or
indirect harmful effects on the human foetus having been observed. Studies in animals are
inadequate or may be lacking, but available data show no evidence of an increased occurrence of
foetal damage.

Breast-feeding
Vancomycin hydrochloride is excreted in breast milk but it is not known whether it is harmful to the
newborn. Therefore, it is not recommended for nursing mothers unless the expected benefits
outweigh any potential risk.

Fertility

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No data available. For pre-clinical fertility data refer to section 5.3.

4.7 Effects on ability to drive and use machines

Patients should refrain from driving a vehicle or operating machines since vancomycin hydrochloride
is likely to produce severe adverse effects.

4.8 Undesirable effects

General disorders and administration site conditions
During or soon after infusion of vancomycin hydrochloride, patients may develop anaphylactoid
reactions including hypotension, palpitations, substernal pressure, tachycardia, wheezing,
dyspnoea, urticaria, or pruritus. Severe anaphylactoid reactions require immediate treatment with
adrenaline, corticosteroids and oxygen. Rapid infusion may cause flushing of the upper body (“red
neck”) or pain and muscle spasm of the chest and back. These reactions usually resolve within 20
minutes, but may persist for several hours. Such events are infrequent if vancomycin hydrochloride
is given by a slow infusion at a rate not exceeding 500 mg/hr and at an appropriate dilution.

Pruritus at injection site, generalised flushing, erythematous macular rash with intense pruritus over
face, neck and upper body have occurred after too rapid injection of the drug. Tissue irritation and
necrosis occurs after intramuscular injection or extravasation from the intravenous site. Hypotension,
bradycardia, cardiogenic shock and cardiac arrest have been reported following rapid bolus injection.

Drug fever has also been reported.

Ear and labyrinth disorders

Sensorineural deafness which may be accompanied by tinnitus has occurred but the incidence is
low. Permanent deafness is more likely to occur in patients with compromised auditory or renal
function but reversible deafness has been reported in normal patients. Vertigo and dizziness have
also been reported.

Gastrointestinal
Nausea, vomiting, diarrhoea and pseudomembranous enterocolitis.

Oral doses are extremely unpalatable. In leukaemic patients, oral dosing regimens are associated
with frequent nausea, diarrhoea and occasional vomiting.

Blood and lymphatic system disorders

Some patients have been reported to have developed reversible neutropenia, usually starting one
week or more after onset of therapy with Vancomycin or after a total dose of more than 25 g.
Neutropenia appears to be promptly reversible when vancomycin is discontinued.
Thrombocytopenia has rarely been reported. Eosinophilia and pancytopenia has also been reported.
Although a casual relationship has not been established, reversible agranulocytosis (granulocyte
count less than 500/mm3) has been reported rarely.

Immune system disorders

Anaphylaxis and hypersensitivity reactions with chills, nausea, urticaria, macular rash, fever and
rigors.

Skin and subcutaneous tissue disorders

The types of rashes that can occur include exfoliative dermatitis, Linear IgA bullous dermatosis,
Stevens-Johnson Syndrome, toxic epidermal necrolysis and rare cases of vasculitis. Drug Reaction
with Eosinophilia and Systemic Symptoms (DRESS) and Acute Generalised Exanthematous
Pustulosis (AGEP) have been reported. Anaphylactoid reactions have been reported infrequently
(see General disorders and administration site conditions).

Renal and urinary disorders

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Rarely, renal failure, principally manifested by increased serum creatinine or urea concentrations,
especially in patients given large doses of vancomycin, has been reported. Acute tubular necrosis
and rare cases of interstitial nephritis have been reported. Most of these have occurred in patients
who were given aminoglycosides concomitantly or who had pre-existing kidney dysfunction. When
vancomycin was discontinued, azotemia resolved in most patients. Transient elevations of urea and
granular casts in the urine occasionally occur.

Vascular disorders
Phlebitis and vasculitis have been reported.

General
The use of vancomycin may result in overgrowth of non-susceptible organisms resulting in new
bacterial or fungal infections. If the new infections due to bacteria or fungi appear during therapy with
this product, appropriate measures should be taken.

Chemical peritonitis has been reported following intraperitoneal administration of vancomycin (see
section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows
continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked
to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/.

4.9 Overdose
Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is not effectively
removed by either haemodialysis or peritoneal dialysis. Increased vancomycin clearance has been
reported with highly permeable membranes (polysulfone resin) used in high-flux haemodialysis. At
4 to 6 hours following the onset of high-flux haemodialysis, steady state concentrations of
vancomycin may be reduced by 10 to 15% of the predialysis concentrations. It has also been
reported that haemoperfusion with XAD-4 Resin has been shown to be of benefit.

In managing overdosage, consider the possibility of multiple drug overdoses, interaction among
medicines, and unusual medicine kinetics in your patient.

For further advice on management of overdose please contact the National Poisons Information
Centre (0800 POISON or 0800 764 766).

5. Pharmacological Properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antibacterials for systemic use, ATC code: J01XA01

Mechanism of action
Vancomycin is an amphoteric glycopeptide antimicrobial substance produced by the growth of
certain strains of Nocardia orientalis. It is bactericidal against many gram-positive organisms.
Vancomycin is not chemically related to any of the presently used antimicrobial agents. Vancomycin
hydrochloride is freely soluble in water and insoluble in alcohol.

Vancomycin hydrochloride appears to act by inhibiting the production of bacterial cell wall
mucopeptide. This effect occurs at a site different from that affected by penicillins and produces
immediate inhibition of cell wall synthesis and secondary damage to the cytoplasmic membrane.
There is also evidence that vancomycin alters the permeability of the cell membrane and selectively
inhibits RNA synthesis.

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Microbiology
Vancomycin is active against many gram-positive organisms (see below). Gram-negative bacteria,
mycobacteria and fungi are resistant. Many strains of gram-positive bacteria are sensitive in vitro to
vancomycin concentrations of 0.5 to 5 microgram/ml, but a few Staphylococcus aureus strains
require 10 to 20 microgram/ml for inhibition.

Vancomycin is active against staphylococci, including Staphyloccocus aureus and Staphylococcus

epidermidis (including heterogeneous methicillin-resistant strains); streptococci, including
Streptococcus pyogenes, Streptococcus pneumoniae (including penicillin-resistant strains) ,
Streptococcus agalactiae, the viridans group, Streptococcus bovis, and enterococci (e.g.
Enterococcus faecalis); Clostridium difficile (e.g. toxigenic strains implicated in pseudomembranous
enterocolitis); diphtheroids (e.g. JK corynebacterium). Other organisms that are susceptible to
vancomycin in vitro include Listeria monocytogenes, Lactobacillus species, Actinomyces species,
Clostridioides species, and Bacillus species.

The combination of vancomycin hydrochloride and an aminoglycoside acts synergistically in vitro

against many strains of S. aureus, non-enterococcal group D streptococci, enterococci, and
Streptococcus species (viridans group).

The combination of vancomycin hydrochloride and a cephalosporin acts synergistically against some
strains of S. epidermidis (methicillin-resistant). The combination of vancomycin hydrochloride and
rifampicin acts with partial synergism against some strains of S. aureus and with synergism against
S. epidermidis. Synergy testing is helpful because the combination of vancomycin hydrochloride and
a cephalosporin may act antagonistically against some strains of S. epidermidis, and the combination
of vancomycin hydrochloride and rifampicin may act antagonistically against some strains of S.
aureus.

There is no cross-resistance between vancomycin hydrochloride and other antibiotics.

Susceptibility tests
Dilution or diffusion techniques, either quantitative (MIC) or breakpoint, should be used following a
regularly updated, recognised and standardised method (e.g. NCCLS). Standardised susceptibility
test procedures require the use of laboratory control microorganisms to control the technical aspects
of the laboratory procedures.

A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial
compound in the blood reaches the concentrations usually achievable. A report of "Intermediate"
indicates that the result should be considered equivocal, and if the microorganism is not fully
susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies
possible clinical applicability in body sites where the drug is physiologically concentrated or in
situations where high dosage of drug can be used. This category also provides a buffer zone, which
prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A
report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial
compound in the blood reaches the concentrations usually achievable: other therapy should be
selected.

Note: The prevalence of resistance may vary geographically for selected species and local
information on resistance is desirable, particularly when treating severe infections.

5.2 Pharmacokinetic properties

Absorption
Vancomycin is poorly absorbed by mouth. It is given intravenously for the treatment of systemic
infections. In subjects with normal renal function participating in a multi-dose study 1 g (1,000,000
IU) given over 60 minutes produced mean plasma levels of approximately 63 microgram/ml
immediately after the completion of infusion and mean plasma levels of approximately
23 microgram/ml and approximately 8 microgram/ml at 2 hour and 11 hour respectively, after

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completion of the infusion. Serum levels will be higher in patients with renal impairment, and toxicity
may result.

Distribution
The distribution coefficient is from 0.3 to 0.69 L/kg.

Protein binding is approximately 55% as measured by ultra filtration at vancomycin serum

concentrations of 10 to 100 microgram/ml. Clinically effective concentrations of this antibiotic in the
blood are usually achieved and maintained by its intravenous administration, moreover, inhibitory
concentrations can be demonstrated in pleural, pericardial, ascitic and synovial fluids, in urine, in
peritoneal dialysis fluid, and in atrial appendage tissue. Vancomycin does not readily diffuse across
the meninges into the cerebrospinal fluid.

Measurable serum concentrations of vancomycin may occur in patients treated with oral vancomycin
for active pseudomembranous colitis due to Clostridioides difficile.

Biotransformation
There is no apparent metabolism of the drug.

Elimination
The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal
renal function. In the first 24 hours, about 75% of an administered dose of vancomycin is excreted
in the urine by glomerular filtration. Mean plasma clearance is about 0.06 L/kg/hour, and mean renal
clearance is about 0.05 L/kg/hour. Renal dysfunction slows excretion of vancomycin. In anephric
patients, the average half-life of elimination is 7.5 days.

Vancomycin is not effectively removed by either haemodialysis or peritoneal dialysis; there have
been no reports of vancomycin clearance with haemoperfusion.

Total systemic and renal clearance of vancomycin may be reduced in the elderly.

5.3 Preclinical safety data

Carcinogenicity and mutagenicity
No long-term carcinogenicity studies have been performed using vancomycin in animals. There are
no studies available demonstrating the mutagenic potential of vancomycin.

Impairment of fertility
No definitive fertility studies have been performed.

6. Pharmaceutical Particulars
6.1 List of excipients
Vancomycin does not contain any excipients.

6.2 Incompatibilities
Vancomycin hydrochloride solutions have a low pH and may cause chemical or physical instability
when mixed with other compounds. All parenteral drug products should be inspected visually for
both particulate matter and discolouration prior to administration, whenever solution or container
permits.

6.3 Shelf life

2 years.

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For shelf life after reconstitution see section 4.2.

6.4 Special precautions for storage

Prior to reconstitution, store at or below 25°C.

For storage conditions after reconstitution of the medicine, see section 4.2

6.5 Nature and contents of container

Glass vial with a bromobutyl rubber stopper. Pack sizes of 500 mg or 1000 mg.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused medicine or waste material should be disposed of in accordance with local requirements.

7. Medicines Schedule
Prescription Medicine

8. Sponsor Details
Viatris Ltd
PO Box 11-183
Ellerslie
AUCKLAND
www.viatris.co.nz
Telephone 0800 168 169

9. Date of First Approval

9 Dec 1999

10. Date of Revision of the Text

5 August 2022

Summary Table of Changes

Section Summary of changes

- Updated sponsor logo

4.1 Minor spelling correction

4.4 Added sub-headings.

Moved content within section.

New sections: General, Hypersensitivity reactions, Cross-sensitivity

reactions, Clostridioides difficile-associated disease, Other, Haemorrhagic
occlusive retinal vasculitis

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 Added AGEP to severe cutaneous adverse reactions and histamine like
response to infusion reactions.

Minor editorial changes

4.5 Piperacillin/tazobactam as nephrotoxic drug

4.6 Blood level monitoring to minimise fetal toxicity.

4.8 Updated sub-headings.

Moved content within section.

Added side effects: drug fever, bradycardia, cardiogenic shock, cardiac

arrest, pseudomembranous enterocolitis, anaphylaxis, acute tubular necrosis
and phlebitis.

Added additional side effect in Blood and lymphatic system disorders section
and Skin and subcutaneous tissue disorders section

4.9 Revised wording in overdose.

5.1 Added vancomycin solubility, removed Kirby-Bauer method.

5.2 Minor editorial changes

5.3 Moved Use in children and Use in the elderly to section 4.4

6.1 Allergen statement removed

8 Sponsor details updated

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