Vancomycin Hydrochloride Powder for Intravenous (I.V.) Injection
Each 5 mL vial contains:
Vancomycin hydrochloride USP
equivalent to Vancomycin ………………. 250 mg
(As a sterile freeze-dried powder for reconstitution
with 5 mL of sterile water for injection IP)
Each 10 mL vial contains:
Vancomycin hydrochloride USP
equivalent to Vancomycin ………………. 500 mg
(As a sterile freeze-dried powder for reconstitution
with 10 mL of sterile water for injection IP)
Powder for reconstitution and I.V. use only
Vancomycin is a tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis
(formerly Nocardia orientalis). The bactericidal action of vancomycin results primarily from
inhibition of the cell-wall biosynthesis. In addition, vancomycin alters bacterial cell membrane
permeability and RNA synthesis. Vancomycin is not active in vitro against Gram-negative
bacilli, mycobacteria, or fungi. There is no cross-resistance between vancomycin and other
The combination of vancomycin and an aminoglycoside acts synergistically in vitro against
many strains of Staphylococcus aureus, Streptococcus bovis, enterococci and the viridans
Vancomycin has been shown to be active against most strains of the following
microorganisms, both in vitro and in clinical infections:
Aerobic Gram-positive microorganisms
Enterococci (e.g., Enterococcus faecalis)
Staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis (including
heterogeneous methicillin-resistant strains)
Viridans group streptococci
The following in vitro data are available, but their clinical significance is unknown.
Vancomycin exhibits in vitro Minimum inhibitory concentration’s (MIC) of 1 mcg/mL or less
against most (≥90%) strains of streptococci listed below and MIC's of 4 mcg/mL or less
against most (≥ 90%) strains of other listed microorganisms; however, the safety and
effectiveness of vancomycin in treating clinical infections due to these microorganisms have
not been established in adequate and well-controlled clinical trials.
Aerobic Gram-positive microorganisms
Streptococcus pneumoniae (including penicillin-resistant strains)
Anaerobic Gram-positive microorganisms
Vancomycin is not significantly absorbed from the normal gastrointestinal tract and is,
therefore, not effective by the oral route for infections other than staphylococcal enterocolitis
and pseudomembranous colitis due to Clostridium difficile.
In subjects with normal kidney function, multiple I.V. dosing of 1 g of vancomycin (15 mg/kg)
infused over 60 minutes produces mean plasma concentrations as follows: Approximately 63
mcg/mL immediately after the completion of the infusion; approximately 23 mcg/mL, 2 hours
after the infusion; and approximately 8 mcg/mL,11 hours after the end of the infusion.
Multiple dosing of 500 mg infused over 30 minutes produces mean plasma concentrations as
follows: About 49 mcg/mL at the completion of the infusion; about 19 mcg/mL, 2 hours after
the infusion; and about 10 mcg/mL, 6 hours after the infusion. The plasma concentrations
during multiple dosing are similar to those after a single dose.
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
0.058 L/kg/h and mean renal clearance is about 0.048 L/kg/h. Renal dysfunction slows
excretion of vancomycin. In anephric patients, the average half-life of elimination is 7.5 days.
The distribution coefficient is from 0.3 to 0.43 L/kg. There is no apparent metabolism of the
drug. About 60% of an intraperitoneal dose of vancomycin administered during peritoneal
dialysis is absorbed systemically in 6 hours. Serum concentrations of about 10 mcg/mL are
achieved by an intraperitoneal injection of 30 mg/kg of vancomycin. However, the safety and
efficacy of the intraperitoneal use of vancomycin has not been established in adequate and
well-controlled trials.Total systemic and renal clearance of vancomycin may be reduced in
Vancomycin is approximately 55% serum protein-bound, as measured by ultrafiltration at
vancomycin serum concentrations of 10 to 100 mcg/mL. After I.V. administration of
vancomycin, inhibitory concentrations are present in the pleural, pericardial, ascitic and
synovial fluids; in the urine; in the peritoneal dialysis fluid; and in the atrial appendage tissue.
Vancomycin does not readily diffuse across normal meninges into the spinal fluid; but, when
the meninges are inflamed, penetration into the spinal fluid occurs.
VANLID I.V. is indicated for the treatment of serious or severe infections caused by
susceptible strains of methicillin-resistant (betalactam-resistant) staphylococci. It is indicated
for penicillin-allergic patients, for patients who cannot receive or who have failed to respond
to other drugs, including the penicillins or cephalosporins, and for infections caused by
vancomycin-susceptible organisms that are resistant to other antimicrobial drugs. As
vancomycin is an antibiotic to which nearly all strains of staphylococcus remain susceptible, it
should be reserved for those cases where there is a specific indication, to minimize the
chances of resistance emerging. VANLID I.V. is indicated for initial therapy when methicillin-
resistant staphylococci are suspected, but after susceptibility data are available, therapy
should be adjusted accordingly.
Endocarditis, osteomyelitis, lower respiratory tract infections (like pneumonia),
septicaemia, and skin and soft tissue infections caused by Staphylococci.
Vancomycin hydrochloride has been reported to be effective alone or in combination with
an aminoglycoside for endocarditis caused by Streptococcus viridans or S. bovis. For
endocarditis caused by enterococci (e.g. E. faecalis), vancomycin hydrochloride has
been reported to be effective only in combination with an aminoglycoside.
Vancomycin hydrochloride has been reported to be effective for the treatment of
diphtheroid endocarditis. It has also been used successfully in combination with either
rifampin, an aminoglycoside, or both in early-onset prosthetic valve endocarditis caused
by Staphylococcus epidermidis or diphtheroids.
Vancomycin has been used successfully alone as prophylaxis against endocarditis in
patients at risk from dental or surgical procedures.
Specimens for bacteriologic cultures should be obtained in order to isolate and identify
causative organisms and to determine their susceptibilities to vancomycin hydrochloride.
The parenteral form of Sterile vancomycin hydrochloride may be administered orally
for treatment of antibiotic-associated pseudomembranous colitis produced by C. difficile
and for Staphylococcal enterocolitis. Relapse of pseudomembranous colitis is possible
and usually occurs 4 to 21 days after vancomycin is discontinued. Patients appear to
respond to a second course of oral vancomycin. Parenteral administration of vancomycin
hydrochloride alone is of unproven benefit for this indication. Vancomycin hydrochloride is
not effective by the oral route for other types of infection. Intravenous administration may
be used concomitantly if required.
DOSAGE AND ADMINISTRATION
Patients with Normal Renal Function
The usual adult I.V. dose is 500 mg every 6 hours or 1 g every 12 hours, in Sodium Chloride
0.9% solution, Dextrose 5%. Each dose should be administered at no greater than 10
mg/min or over a period of at least 60 minutes, whichever is longer. Other patient factors,
such as age or obesity, may call for modification of the usual I.V. daily dose.
Staphylococcal infections normally respond within 48–72 hours. Duration of therapy depends
on type and severity of infections and patient response. For bacterial endocarditis, the
generally accepted regimen is 500 mg vancomycin I.V. every 6 hours for a minimum of 3
weeks, either alone or in combination with other antibiotics.
Therapeutic range of serum levels
Following multiple intravenous doses, peak serum concentrations, measured 2 hours after
infusion is complete, range from 18-26 mg/litre. Trough levels measured immediately prior to
the next dose should be 5-10 mg/litre. Ototoxicity has been associated with serum drug
levels of 80-100 mg/litre, but this is rarely seen when serum levels are kept at or below 30
Dosage of 125 mg six hourly or 500 mg per day in three or four divided doses for 7 to 10
days has been recommended, although up to 2 g/day have been used in severe cases. The
total daily dosage should not exceed 2 g.
The usual I.V. dosage is 10 mg/kg per dose given every 6 hours (total daily dosage 40 mg/kg
of body weight). Each dose should be administered over a period of at least 60 minutes.
Infants and Neonates
In neonates and young infants, the total daily 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 1 month of age. Each dose should be administered over a period of at
least 60 minutes. In premature infants, vancomycin clearance decreases as postconceptional
age decreases. Therefore, longer dosing intervals may be necessary in premature infants.
Other dosage recommendations are based on post-conceptional or postnatal age. One
dosing nomogram for dosing vancomycin in neonates is illustrated in the following table.
Vancomycin Dosage Guideline for Neonates
PCA (a) Chronological Serum Creatinine Dosage (mg/kg)
30 <7 Refer (c) 15 q24hr
>7 <1.2 10 q12hr
30–36 <14 Refer (c) 10 q12hr
>14 <0.6 10 q8hr
0.7–1.2 10 q12hr
>36 <7 Refer (c) 10 q12hr
>7 <0.6 10 q8hr
0.7–1.2 10 q12hr
(a) PCA = Post-conceptual age (gestational age at birth plus chronological age).
(b) If the serum concentration is >1.2 mg/dL, use an initial dosage of 15 mg/kg every 24
(c) Serum creatinine concentration is not used to determine the dosage for this type of
patient because of its lack of reliability or because of the lack of information.
Close monitoring of serum concentrations of vancomcyin is warranted in these patients.
VANLID I.V. can be administered using 40 mg per kg body weight in three or four divided
doses for 7-10 days. The total daily dose should not exceed 2 g.
Patients with Impaired Renal Function and Elderly Patients
Dosage adjustment must be made in patients with impaired renal function. In premature
infants and the elderly, greater dosage reductions than expected may be necessary because
of decreased renal function.
Accumulation of the drug may occur with prolonged therapy and thus serum concentrations
of vancomycin should be monitored regularly. Vancomycin serum concentrations can be
determined by use of microbiologic assay, radioimmunoassay, fluorescence polarization
immunoassay, fluorescence immunoassay, or high-pressure liquid chromatography.
If creatinine clearance can be measured or estimated accurately, the dosage for most
patients with renal impairment can be calculated using the following table.
The dosage of vancomycin hydrochloride per day in mg is about 15 times the glomerular
filtration rate in mL/min.
Dosage Table for VANLID I.V. in Patients with Impaired Renal Function
Creatinine Clearance VANLID I.V. Dose
mL/min mg/24 hr
The initial dose should be no less than 15 mg/kg, even in patients with mild to moderate renal
The table is not valid for functionally anephric patients. For such patients, an initial dose of 15
mg/kg of body weight should be given to achieve prompt therapeutic serum concentrations.
The dose required to maintain stable concentrations is 1.9 mg/kg/24 hr.
In patients with marked renal impairment, it may be more convenient to give maintenance
doses of 250 to 1,000 mg once every several days rather than administering the medicine on
a daily basis.
In anuria, a dose of 1,000 mg every 7–10 days has been recommended.
In patients on haemodialysis, the drug is not significantly removed by haemodialysis. A dose
of 1 g of vancomycin every seven days produces effective blood levels. Serum levels should
be monitored to avoid drug accumulation and resultant toxicity. The serum half-life ranges
from 120 to 216 hours.
In patients undergoing peritoneal dialysis, the half-life of vancomycin has been reported at
around 18 hours. To prevent undue lowering of serum levels during peritoneal dialysis, an
additional amount of vancomycin could be added to the dialysate in a concentration of 25
microgram per ml.
When only the serum creatinine concentration is known, the following formula (based on sex,
weight, and age of the patient) may be used to calculate creatinine clearance. Calculated
creatinine clearances (mL/min) are only estimates. The creatinine clearance should be
Men Weight (kg) x (140 − age in years)/72 x serum creatinine concentration
Women 0.85 x above value
The serum creatinine must represent a steady state of renal function. Otherwise, the
estimated value for creatinine clearance is not valid. Such a calculated clearance is an
overestimate of actual clearance in patients with the following conditions:
1. Characterized by decreasing renal function, such as shock, severe heart failure, or
2. Where a normal relationship between muscle mass and total body weight is not
present, such as obese patients or those with liver disease, oedema, or ascites.
3. Accompanied by debilitation, malnutrition, or inactivity.
VANLID I.V. is for intravenous infusion and oral use only and not for intramuscular
administration. The safety and efficacy of vancomycin administration by the intrathecal
(intralumbar or intraventricular) routes have not been established.
Reconstitution and Directions for Use
At the time of use, add 10 mL of sterile Water for Injection to a 500 mg vial of VANLID
Powder for I.V. Injection, and add 5 mL of sterile Water for Injection to a 250 mg vial of
VANLID Powder for I.V. Injection. Vials reconstituted in this manner will give a solution of
Reconstituted solutions containing 500 mg VANLID Powder for I.V. Injection must be
diluted with at least 100 mL diluent and reconstituted solutions containing 250 mg VANLID
Powder for I.V. Injection must be diluted with at least 50 mL diluent. 0.9% Sodium Chloride
I.V. Infusion or 5% Dextrose I.V. Infusion are suitable diluents.
The desired dose should be administered by I.V. infusion over a period of 60 minutes or at a
rate of no more than 10 mg/min. Prior to administration, parenteral drug products should be
inspected visually for particulate matter and discolouration whenever the solution and
container permit. After reconstitution, the vials may be stored in a refrigerator for 14 days
without significant loss of potency.
The parenteral form of vancomycin may be administered orally for the treatment of antibiotic-
associated pseudomembranous colitis caused by Clostridium difficile and staphylococcal
enterocolitis. Parenteral administration of vancomycin alone is of unproven benefit in these
indications. Vancomycin is not effective by the oral route for other types of infections. After
initial reconstitution of the vial, the appropriate dose may be diluted in 30 ml of water and
given to the patient to drink. Common flavouring syrups may be added to the solution to
improve the taste for oral administration. The diluted solution may be administered via a
VANLID I.V. is contraindicated in patients with known hypersensitivity to this drug.
WARNINGS AND PRECAUTIONS
Rapid bolus administration (e.g., over several minutes) may be associated with occasional
severe hypotension, including shock and, rarely, cardiac arrest, histamine-like responses and
maculopapular or erythematous rash ("red man's syndrome" or "red neck syndrome").
Vancomycin should be administered over a period of not less than 60 minutes or at a rate not
greater than 10 mg/min to avoid rapid infusion-related reactions. Stopping the infusion
usually results in prompt cessation of these reactions. Slow infusions over one hour are
recommended for infants and children.
Vancomycin should be used with caution in patients with renal impairment because the risk
of toxicity is appreciably increased by high, prolonged blood concentrations. Dosage needs
to be adjusted for patients with renal dysfunction. The concurrent or sequential use of other
nephrotoxic drugs requires careful monitoring and should be avoided, if possible.
Transient or permanent ototoxicity has been reported mostly in patients who have been given
excessive doses, who have an underlying hearing loss, or who are receiving concomitant
therapy with another ototoxic agent, such as an aminoglycoside. Vancomycin should, if
possible, be avoided in patients with previous hearing loss. If used, it is very important that
the dose be adjusted by monitoring the blood concentrations of the drug. Deafness may be
preceded by tinnitus. The elderly are more susceptible to auditory damage. Experience with
other antibiotics suggests that deafness may be progressive despite cessation of treatment.
Clostridium difficile-associated diarrhoea (CDAD) has been reported with the use of nearly all
antibacterial agents, including vancomycin and may range in severity from mild diarrhoea to
fatal colitis. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C.
difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein
supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be
instituted as clinically indicated.
Prolonged use of vancomycin may result in the overgrowth of non-susceptible
microorganisms. Careful observation of the patient is essential. If superinfection occurs
during therapy, appropriate measures should be taken. In rare instances, there have been
reports of pseudomembranous colitis due to C. difficile developing in patients who received
Reversible neutropenia has been reported in patients receiving vancomycin.
Vancomycin is irritating to tissue and must be given by a secure I.V. route of
administration. Pain, tenderness, and necrosis occur with inadvertent extravasation. The
frequency and severity of thrombophlebitis can be minimized if the drug is administered
as a dilute solution (2.5–5 mg/mL) of Dextrose 5% or Normal Saline 0.9% solution by slow
infusion and by rotation of the venous access sites.
There have been reports that the frequency of infusion-related events (including hypotension,
myocardial depression, flushing, erythema, urticaria, and pruritus) increases with the
concomitant administration of anaesthetic agents. During anaesthesia, doses must be well
diluted and administered slowly as a 60-minute infusion prior to anaesthetic induction, along
with close cardiac monitoring. Position changes should be delayed until the infusion is
completed to allow for postural adjustment. The safety and efficacy of vancomycin
administered by the intrathecal (intralumbar or intraventricular) route or by the intraperitoneal
route have not been established by adequate and well-controlled trials.
Reports have revealed that the administration of sterile vancomycin 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 variable degrees of abdominal pain
and fever. This syndrome appears to be short-lived after the discontinuation of
All patients receiving vancomycin should have periodic haematological studies, urine
analysis, liver and renal function tests. Serial tests of auditory function may be helpful in
order to minimize the risk of ototoxicity especially in those aged more than 60 years.
Prescribing vancomycin in the absence of a proven or strongly suspected bacterial infection
or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk
of the development of drug-resistant bacteria.
Patients taking oral vancomycin should be warned of its offensive taste.
Concurrent administration of vancomycin hydrochloride I.V. and anaesthetic agents has been
associated with erythema, histamine-like flushing and anaphylactoid reactions.
Concurrent and/or sequential systemic or topical use of other neurotoxic
and/or nephrotoxic drugs, e.g., amphotericin B, streptomycin, neomycin, gentamicin,
kanamycin, amikacin, tobramycin, bacitracin, polymyxin B, colistin and cisplatin requires
Diuretics such as ethacrynic acid and frusemide may aggravate ototoxicity.
Cholestyramine has been shown to bind vancomycin in vitro. Therefore, if oral vancomycin is
used with cholestyramine, the two drugs should be administered several hours apart.
Please refer DOSAGE AND ADMINISTRATION.
Pregnancy Category C
VANLID I.V. should be given to a pregnant woman only if clearly needed.
Vancomycin is excreted in human milk. Because of the potential for adverse events, a
decision should be made whether to discontinue nursing or to discontinue the drug, taking
into account the importance of the drug to the mother.
In paediatric patients, it may be appropriate to confirm the desired vancomycin serum
concentrations. Concomitant administration of vancomycin and anaesthetic agents has been
associated with erythema and histamine-like flushing in paediatric patients.
The natural decrement of glomerular filtration with increasing age may lead to elevated
vancomycin serum concentrations if the dosage is not adjusted. Vancomycin dosage
schedules should be adjusted in elderly patients (see DOSAGE AND ADMINISTRATION).
During or soon after rapid infusion of vancomycin, patients may develop anaphylactoid
reactions, including hypotension, palpitations, substernal pressure, tachycardia, wheezing,
dyspnoea, urticaria, or pruritus, and rare cases of vasculitis. Rapid infusion may also cause
flushing of the upper body (“red neck”), or pain and muscle spasms of the chest and back.
These reactions usually resolve within 20 minutes but may persist for several hours. Such
events are infrequent if vancomycin is given by a slow infusion over 60 minutes. In studies of
normal volunteers, infusion-related events did not occur when vancomycin was administered
at a rate of 10 mg/min or less.
Renal failure, principally manifested by increased serum creatinine or Blood Urea Nitrogen
(BUN) concentrations, especially in patients administered large doses of vancomycin, has
been reported rarely. Cases of interstitial nephritis have also been reported rarely. Most of
these have occurred in patients who were given aminoglycosides concomitantly or who had
pre-existing kidney dysfunction. When vancomycin was discontinued, azotaemia resolved in
A few dozen cases of hearing loss associated with vancomycin have been reported. Most of
these patients had kidney dysfunction or a pre-existing hearing loss or were receiving
concomitant treatment with an ototoxic drug. Vertigo, dizziness, and tinnitus have been
Reversible neutropenia, usually starting 1 week or more after the onset of therapy with
vancomycin or after a total dosage of more than 25 g, has been reported in several
dozen patients. Neutropenia appears to be promptly reversible when vancomycin is
discontinued. Thrombocytopenia has rarely been reported. Although a causal
relationship has not been established, reversible agranulocytosis (granulocytes
<500/mm3) has been reported rarely.
Inflammation at the injection site has been reported.
Oral doses are extremely unpalatable. In leukaemic patients, oral dosing regimens are
associated with frequent nausea, diarrhoea and occasional vomiting.
Infrequently, patients have been reported to have had anaphylaxis, drug fever, nausea, chills,
eosinophilia, and rashes including exfoliative dermatitis, Stevens-Johnson syndrome and
vasculitis in association with the administration of vancomycin. Tissue irritation and necrosis
occurs after IM injection or extravasation from IV site. Vancomycin has been associated with
the bullous eruption disorders, toxic epidermal necrolysis and linear IgA bullous dermatosis.
If a bullous disorder is suspected, the drug should be discontinued and specialist
dermatological assessment should be carried out.
Chemical peritonitis has been reported following the intraperitoneal administration of
Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly
removed from the blood by haemodialysis or peritoneal dialysis. Haemoperfusion and
haemofiltration with polysulphone resin have been reported to result in increased vancomycin
Vancomycin solution has a low pH that may cause chemical or physical instability when it is
mixed with other compounds.
Vancomycin is chemically incompatible with dexamethasone sodium phosphate, heparin
sodium, methicillin sodium, phenobarbitone sodium and sodium bicarbonate.
Compatibility with I.V. Fluids
Solutions that are diluted with 5% Dextrose Injection or 0.9% Sodium Chloride Injection may
be stored in a refrigerator for 14 days without significant loss of potency.
Solutions that are diluted with the following infusion fluids may be stored in a refrigerator for
5% Dextrose Injection and 0.9% Sodium Chloride Injection, USP
Lactated Ringer’s Injection, USP
Lactated Ringer’s and 5% Dextrose Injection
Normosol (R)-M and 5% Dextrose
Isolyte (R) E
Acetated Ringer’s Injection
Prior to administration, parenteral drug products should be inspected visually for particulate
matter and discolouration whenever the 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 I.V. lines between administrations
of these antibiotics. It is also recommended to dilute solutions of vancomycin to 5 mg/mL or
Although an intra-vitreal injection is not an approved route of administration for vancomycin,
precipitation has been reported after intra-vitreal injection of vancomycin and ceftazidime for
endopthalmitis using different syringes and needles. The precipitates dissolved gradually,
with complete clearing of the vitreous cavity over 2 months and with improvement of visual
STORAGE AND HANDLING INSTRUCTIONS
Prior to reconstitution, store below 25°C.
After reconstitution, the reconstituted solution may be stored in the refrigerator (2o–8oC).
Reconstituted solutions diluted with 5% Dextrose Injection, sterile Water for Injection, or 0.9%
Sodium Chloride Injection are stable for 14 days if kept refrigerated (2o–8oC).
Vancomycin solution is stable for 96 hours under refrigeration when diluted with the following
dilution fluids: 5% Dextrose and 0.9% Sodium Chloride Injection, Lactated Ringer’s Injection,
Lactated Ringer’s and 5% Dextrose Injection, Normosol (R)-M and 5% Dextrose, Isolyte (R)
E, and Acetated Ringer’s Injection.
VANLID 250 …………………………….………………………………available in a vial of 5 mL
VANLID 500 …………………………….………………………………available in a vial of 10 mL
Last updated: December 2010