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 medication, 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

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doses of 250 (250,000 IU) – 1,000 (1000,000 IU) mg are convenient, in patients with marked renal
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 24 hours
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 vancomycin,
or any other excipients or in patients with previous anaphylaxis or major allergy with other
glycopeptides (see section 4.4).

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 medication
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.

In patients receiving vancomycin over a longer-term period or concurrently with other medications
which may cause neutropenia or agranulocytosis, the leukocyte count should be monitored at regular
intervals.

Severe cutaneous adverse reactions (SCARs)

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), which can be life-threatening or fatal, have
been reported in association with vancomycin treatment (see section 4.8). Most of these reactions
occurred within a few days and up to eight weeks after commencing treatment with vancomycin.
Patients should be advised to inform their doctor at the first appearance of rash or any other sign of
hypersensitivity.

At the time of prescription, patient should be advised of the signs and symptoms and monitored
closely for skin reactions. If a SCAR is suspected, the medication should be discontinued, and
specialist dermatological assessment should be carried out. If the patient has developed a SCAR
with the use of vancomycin, treatment with vancomycin must not be restarted at ay time.

Infusion-related reactions (IRRs)

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

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

500 mg/hour to avoid rapid-infusion-related reactions (IRRs), e.g. hypotension, flushing, erythema,

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urticaria and pruritus. Stopping the infusion usually results in a prompt cessation of these reactions
(see sections 4.2 and 4.8).

The frequency of IRRs (hypotension, flushing, erythema, urticaria and pruritus) increases with the
concomitant administration of anaesthetic agents. This may be reduced by administering the
vancomycin by infusion over at least 60 minutes, before anaesthetic induction.

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.

Administration site related reactions

Pain and thrombophlebitis may occur in many patients receiving vancomycin and are occasionally
severe. The frequency and severity of thrombophlebitis can be minimised if the medication is
administered in a volume of at least 200 ml of glucose or saline solution and if the injection sites are
rotated. The efficacy and safety of vancomycin has not been established for intrathecal, intralumbar
and intraventricular or by intraperitoneal routes of administration. 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.

Use in renal impairment

Because of its ototoxicity and 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, which may be transitory or permanent has been reported in patients with prior deafness,
who have received excessive intravenous doses, when serum levels exceeded 80 microgram/ml, or
who received concomitant treatment with another ototoxic active substance such as an
aminoglycoside. Deafness may be preceded by tinnitus and should be regarded as an indication to
discontinue treatment. Experience with other antibiotics suggests that deafness may be progressive
despite cessation of treatment. Serial test of auditory function may be helpful in order to minimise
the risk of ototoxicity. The elderly are more susceptible to auditory damage. Monitoring of vestibular
and auditory function in the elderly should be carried out during and after 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
medication 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 medication 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 medication (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.

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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 or with C. difficile-induced
pseudomembranous colitis 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 impairment is present. The greater the renal
impairment, the greater the risk of developing the adverse reactions associated with the parenteral
administration of vancomycin. Monitoring of serum vancomycin concentrations of patients with
inflammatory disorders of the intestinal mucosa should be performed. It should be noted that the
total systemic and renal clearances of vancomycin are reduced in the elderly.

Intravenous administration of vancomycin is not effective for the treatment of C. difficile infection.
Vancomycin should be administered orally for this indication.

Testing for C. difficile colonization or toxin is not recommended in children younger than 1 year due
to high rate of asymptomatic colonisation unless severe diarrhoea is present in infants with risk
factors for stasis such as Hirschsprung disease, operated anal atresia or other severe motility
disorders. Alternative aetiologies should always be sought, and C. difficile enterocolitis be proven.

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.
Careful observation of the patient is essential. If new infections due to bacteria or fungi appear during
therapy with this product, appropriate measures should be taken including withdrawal of vancomycin
hydrochloride.

Development of Drug-Resistant Bacteria

Oral vancomycin use increases the chance of vancomycin-resistant Enterococci populations in the
gastrointestinal tract. As a consequence, prudent use of oral vancomycin is advised.

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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. Anti-
diarrhoeic medicinal products must not be given.

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.

Nephrotoxicity
Vancomycin should be used with care in patients with renal insufficiency, including anuria, as the
possibility of developing toxic effects is much higher in the presence of prolonged high blood
concentrations. The risk of toxicity is increased by high blood concentrations or prolonged therapy.

Regular monitoring of the blood levels of vancomycin is indicated in high dose therapy and longer-
term use, particularly in patients with renal dysfunction or impaired faculty of hearing as well as in
concurrent administration of nephrotoxic or ototoxic substances, respectively.

Serial monitoring of renal function should be performed when treating patients with underlying renal
dysfunction or patients receiving concomitant therapy with an aminoglycoside or other nephrotoxic
medications. 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 intracameral or intravitreal use,
including 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 or sequential administration of vancomycin with other neurotoxic (e.g. ototoxic) and/or
nephrotoxic medications (e.g. streptomycin, neomycin, gentamicin, kanamycin, amikacin,
amphotericin B, bacitracin, tobramycin, polymyxin B, colistin and cisplatin or
piperacillin/tazobactam), may potentiate the ototoxicity and/or nephrotoxicity of vancomycin and
consequently 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.

Concomitant administration of vancomycin and anaesthetic agents has been associated with
erythema and histamine-like flushing.

Reversible neutropenia has been reported in patients receiving vancomycin hydrochloride (see
section 4.8). Patients who are receiving concomitant medications 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.

If vancomycin hydrochloride is administered during or immediately after surgery, effects of

concomitantly administered muscle relaxants (e.g. succinylcholine), such as neuromuscular block,
can be enhanced or prolonged.

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 medication 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: Medications 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.

Page 8 of 16
Breastfeeding
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
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 medication. 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. Kounis syndrome has also been reported.

Page 9 of 16
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), Acute Generalised Exanthematous Pustulosis
(AGEP), exanthema and mucosal inflammation, pruritus, urticaria, and Toxic epidermal necrolysis
(TEN) have been reported. Anaphylactoid reactions have been reported infrequently (see General
disorders and administration site conditions).

Renal and urinary disorders

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://pophealth.my.site.com/carmreportnz/s/.

4.9 Overdose
Toxicity due to overdose has been reported. In certain high-risk conditions (e.g. in case of severe
renal impairment) high serum levels and oto- and nephrotoxic effects can occur.

Treatment of overdose includes symptomatic treatment while maintain renal function (i.e. 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 medication 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).

Page 10 of 16
5. Pharmacological Properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antibacterials for systemic use, ATC code: J01XA01

Mechanism of action
Vancomycin is a tricyclic glycopeptide antibiotic that inhibits the synthesis of the cell wall in sensitive
bacteria by binding with high affinity to the D-alanyl-D-alanine terminus of cell wall precursor units.
The medication is slowly bactericidal for dividing microorganisms. In addition, it impairs the
permeability of the bacterial cell membrane and RNA synthesis.

Pharmacokinetic/Pharmacodynamic relationship
Vancomycin displays concentration-independent activity with the area under the concentration curve
(AUC) divided by the minimum inhibitory concentration (MIC) of the target organism as the primary
predictive parameter for efficacy. On basis of in vitro, animal and limited human data, an AUC/MIC
ratio of 400 has been established as a PK/PD target to achieve clinical effectiveness with
vancomycin. To achieve this target when MICs are ≥ 1.0 mg/l, dosing in the upper range and high
trough serum concentrations (15-20 mg/l) are required.

Mechanism of resistance
Acquired resistance to glycopeptides is most common in enterococci and is based on acquisition of
various van gene complexes which modifies the D-alanyl-D-alanine target to D-alanyl-D-lactate or
D-alanyl-D-serine which bind vancomycin poorly. In some countries, increasing cases of resistance
are observed particularly in enterococci; multi-resistant strains of Enterococcus faecium are
especially alarming.

Van genes have rarely been found in Staphylococcus aureus, where changes in cell wall structure
result in “intermediate” susceptibility, which is most commonly heterogeneous. Also, methicillin-
resistant staphylococcus strains (MRSA) with reduced susceptibility for vancomycin were reported.
The reduced susceptibility or resistance to vancomycin in Staphylococcus is not well understood.
Several genetic elements and multiple mutations are required.

There is no cross-resistance between vancomycin and other classes of antibiotics. Cross-resistance

with other glycopeptide antibiotics, such as teicoplanin, does occur. Secondary development of
resistance during therapy is rare.

Synergism
The combination of vancomycin with an aminoglycoside antibiotic has a synergistic effect against
many strains of Staphylococcus aureus, non-enterococcal group D-streptococci, enterococci and
streptococci of the Viridians group. The combination of vancomycin with a cephalosporin has a
synergistic effect against some oxacillin-resistant Staphylococcus epidermidis strains, and the
combination of vancomycin with rifampicin has a synergistic effect against Staphylococcus
epidermidis and a partial synergistic effect against some Staphylococcus aureus strains. As
vancomycin in combination with a cephalosporin may also have an antagonistic effect against some
Staphylococcus epidermidis strains and in combination with rifampicin against some Staphylococcus
aureus strains, preceding synergism testing is useful. Specimens for bacterial cultures should be
obtained in order to isolate and identify the causative organisms and to determine their susceptibility
to vancomycin.

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.

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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 medications, the test should be repeated. This category
implies possible clinical applicability in body sites where the medication is physiologically
concentrated or in situations where high dosage of medication 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 administered intravenously for the treatment of systemic infections. In the case of
patients with normal renal function, intravenous infusion of multiple doses of 1 g vancomycin (15
mg/kg) for 60 minutes produces approximate average plasma concentrations of 50 - 60 mg/L, 20 -
25 mg/L and 5 - 10 mg/L, immediately, 2 hours and 11 hours after completing the infusion,
respectively. The plasma levels obtained after multiple doses are similar to those achieved after a
single dose.

Vancomycin is not usually absorbed into the blood after oral administration. However, absorption
may occur after oral administration in patients with (pseudomembranous) colitis. This may lead to
vancomycin accumulation in patients with co-existing renal impairment.

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Distribution
The volume of distribution is about 60 L/1.73 m2 body surface. At serum concentrations of
vancomycin of 10 mg/l to 100 mg/l, the binding of the medication to plasma proteins is approximately
30 - 55%, measured by ultra-filtration.

Vancomycin diffuses readily across the placenta and is distributed into cord blood. In non-inflamed
meninges, vancomycin passes the blood-brain barrier only to a low extent.

Biotransformation
There is very little metabolism of the medication. After parenteral administration it is excreted almost
completely as microbiologically active substance (approx. 75 - 90% within 24 hours) through
glomerular filtration via the kidneys.

Elimination
The elimination half-life of vancomycin is 4 to 6 hours in patients with normal renal function and 2.2
- 3 hours in children. Plasma clearance is about 0.058 L/kg/h and kidney clearance about 0.048
L/kg/h. In the first 24 hours, approximately 80 % of an administered dose of vancomycin is excreted
in the urine through glomerular filtration.

Renal dysfunction delays the excretion of vancomycin. In anephric patients, the mean half-life is 7.5
days. Due to ototoxicity of vancomycin therapy-adjuvant monitoring of the plasma concentrations is
indicated in such cases.

Biliary excretion is insignificant (less than 5% of a dose). Although the vancomycin is not eliminated
efficiently by haemodialysis or peritoneal dialysis, there have been reports of an increase in
vancomycin clearance with haemoperfusion and hemofiltration.

Linearity/non-linearity
Vancomycin concentration generally increases proportionally with increasing dose. Plasma
concentrations during multiple dose administration are similar to those after the administration of a
single dose.

Characteristics in specific groups

Renal impairment
Vancomycin is primarily cleared by glomerular filtration. In patients with impaired renal function the
terminal elimination half- life of vancomycin is prolonged and the total body clearance is reduced.

Hepatic impairment
Vancomycin pharmacokinetics is not altered in patients with hepatic impairment.

Pregnant women
Significantly increased doses may be required to achieve therapeutic serum concentrations in
pregnant women.

Overweight patients
Vancomycin distribution may be altered in overweight patients due to increases in volume of
distribution, in renal clearance and possible changes in plasma protein binding. In these
subpopulations vancomycin serum concentration were found higher than expected in male healthy
adults.

Paediatric population
Vancomycin PK has shown wide inter-individual variability in preterm and term neonates. In
neonates, after intravenous administration, vancomycin volume of distribution varies between 0.38

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and 0.97 L/kg, similar to adult values, while clearance varies between 0.63 and 1.4 ml/kg/min. Half-
life varies between 3.5 and 10 h and is longer than in adults, reflecting the usual lower values for
clearance in the neonate. In infants and older children, the volume of distribution ranges between
0.26-1.05 L/kg while clearance varies between 0.33-1.87 ml/kg/min.

5.3 Preclinical safety data

Carcinogenicity and mutagenicity
Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology and repeated dose toxicity. Limited data on mutagenic effects are available, they
show no indication of any hazard. Long-term studies in animals regarding a carcinogenic potential
are not available. In teratogenicity studies, where rats and rabbits received doses approximately
corresponding to the human dose based on body surface (mg/m2), no direct or indirect teratogenic
effects were observed.

Impairment of fertility
Animal studies of the use during the perinatal/postnatal period and regarding effects on fertility are
not available.

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 medication products should be inspected visually
for both particulate matter and discolouration prior to administration, whenever solution or container
permits.

Mixtures of solutions of vancomycin and beta-lactam antibiotics have been shown to be physically
incompatible. The likelihood of precipitation increases with higher concentrations of vancomycin. It
is recommended to adequately flush the intravenous lines between the administration of these
antibiotics. It is also recommended to dilute solutions of vancomycin to 5 milligram/mL or less

6.3 Shelf life

2 years.

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 containing 500 mg or 1000 mg.

Not all strengths may be marketed.

6.6 Special precautions for disposal

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

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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

20 May 2024

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Summary Table of Changes

Section Summary of changes

All Update the word “drug” to “medication”.

Minor editorial changes.

Minor formatting changes.

4.4 Updated safety data for hypersensitivity reactions, severe cutaneous adverse
reactions, infusion-related reactions (IRRs), Administration site related
reactions, ototoxicity, other routes of administration, superinfection,
development of drug-resistant bacteria, Clostridioides difficile-associated
disease, nephrotoxicity, and haemorrhagic occlusive retinal vasculitis.

4.5 Additional warning when administering vancomycin with other neurotoxic

and/or nephrotoxic medications.

Addition of warning concomitant administration of vancomycin and

anaesthetic agents.

Addition of warning when administering vancomycin during or immediately

after surgery.

4.8 Addition of exanthema and mucosal inflammation, pruritus, urticaria, and

Toxic epidermal necrolysis (TEN) as potential undesirable effects

Updated ADR reporting site

4.9 Additional information during overdose of vancomycin and treatment for

overdose.

5.1 Updated mechanism of action.

Addition of pharmacokinetic/pharmacodynamic relationship, mechanism of

resistance, synergism.

5.2 Updated whole pharmacokinetic properties section.

Addition of linearity/nonlinearity and characteristics in specific groups

information.

5.3 Updated carcinogenicity, mutagenicity and fertility information.

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