Vancotex

Patient Information Leaflet

VANCOTEX 500 mg powder for concentrate for infusion solution for intravenous and oral use
VANCOTEX 1 g powder for concentrate for infusion solution for intravenous and oral use
Vancomycin
Equivalent medicine
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor, hospital pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What VANCOTEX is and what it is used for
2. What you need to know before taking VANCOTEX
3. How to take VANCOTEX
4. Possible side effects
5. How to store VANCOTEX
6. Contents of the pack and other information

1. What VANCOTEX is and what it is used for

VANCOTEX is an antibiotic belonging to a group of antibiotics called "glycopeptides". VANCOTEX works by killing certain bacteria that cause infections.
VANCOTEX powder is reconstituted to form a solution for intravenous infusion or for oral use.
VANCOTEX is used in all age groups via intravenous infusion for the treatment of the following serious infections:

• Skin and underlying tissue infections
• Bone and joint infections
• Lung infection known as "pneumonia"
• Infection of the inner lining of the heart (endocarditis), and to prevent endocarditis in at-risk patients undergoing major surgical procedures
• Central nervous system infection
• Bloodstream infection related to the above-mentioned infections

VANCOTEX is used in adults and children for the treatment of mucosal infections of the small and large intestine with mucosal damage (pseudomembranous colitis) caused by the bacterium Clostridium difficile.

2. What you need to know before using VANCOTEX

Do not use VANCOTEX

• if you are allergic to vancomycin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, hospital pharmacist, or nurse before using VANCOTEX if:

• you have previously had an allergic reaction to the medicine teicoplanin, as this may indicate you are also allergic to VANCOTEX;
• you have a hearing disorder, especially if you are elderly (you may require hearing tests during treatment);
• you have kidney disease (you will need blood and kidney function tests during treatment);
• you are receiving VANCOTEX by intravenous infusion for the treatment of Clostridium difficile-associated diarrhea instead of oral administration;
• you have previously developed a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking vancomycin.

Signs of an allergic reaction to this medicine, including breathing difficulties and chest pain, have been reported with VANCOTEX. Immediately stop taking VANCOTEX and contact your doctor or emergency medical services if you notice any of these symptoms.

Severe skin reactions have been reported during treatment with vancomycin, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Discontinue vancomycin and seek immediate medical attention if you experience any of the symptoms described in section 4.
Serious adverse effects leading to vision loss have been reported following intravitreal injection of vancomycin.

Talk to your doctor, hospital pharmacist, or nurse during treatment with VANCOTEX if:

• you have been receiving VANCOTEX for a prolonged period (you may require liver and kidney blood tests during treatment);
• you develop any skin reaction during treatment;
• you develop severe and persistent diarrhea during or after taking VANCOTEX, and contact your doctor immediately. This may be a sign of intestinal inflammation (pseudomembranous colitis), which can occur following antibiotic treatment.

Children
VANCOTEX should be used with particular caution in premature infants and neonates, as their kidneys are not fully developed and may lead to accumulation of VANCOTEX in the blood. This age group requires blood tests to monitor VANCOTEX levels. Concurrent administration of VANCOTEX and anesthetic agents has been associated with skin flushing (erythema) and allergic reactions in children. Similarly, concomitant use with other medicines such as aminoglycoside antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen), or amphotericin B (a medicine for fungal infections) may increase the risk of kidney damage, and therefore more frequent blood and kidney function tests may be required.

Other medicines and VANCOTEX
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Talk to your doctor before using VANCOTEX if you are taking any of the following medicines:

• Anesthetic agents
• Medicines for the treatment of fungal infections (amphotericin B)
• Medicines for the treatment of cancer (cisplatin)
• Medicines for the treatment of bacterial infections (piperacillin/tazobactam, polymyxin B, colistin, bacitracin, aminoglycosides)
• Medicines used to relieve symptoms of inflammation (NSAIDs, non-steroidal anti-inflammatory drugs)

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before using this medicine.
VANCOTEX should only be administered during pregnancy or breastfeeding if absolutely necessary and under the judgment of your doctor.

Driving and using machines
No adverse effects on the ability to drive or operate machinery are known.

3. How to use VANCOTEX

VANCOTEX will be administered to you by medical staff while you are in hospital. Your doctor will decide
how much of this medicine you should receive each day and how long your treatment will last.
Dosage
The dose administered will depend on:

• your age,
• your body weight,
• the type of infection you have,
• your renal function status,
• your hearing ability,
• other medicines you are taking

Intravenous administration
Adults and adolescents (from 12 years of age)
The dose will be calculated based on your body weight. The usual intravenous infusion dose is 15–20 mg per
kilogram of body weight. It is generally administered every 8–12 hours. In some cases, your doctor may
decide to administer an initial dose of up to 30 mg per kilogram of body weight. The maximum dose
must not exceed 2 g per dose.
Use in children
Children from one month up to less than 12 years of age
The dose will be calculated based on body weight. The usual intravenous infusion dose is 10–15 mg per
kilogram of body weight. It is generally administered every 6 hours.
Preterm neonates and neonates (from 0 to 27 days of age)
Dosing will be calculated based on postmenstrual age [(time elapsed from the first day of the last
menstrual period to birth (gestational age) plus time elapsed after birth (postnatal age)].
Elderly patients, pregnant women, and patients with renal disease, including those on dialysis,
may require a different dose.
Oral administration
For adults and adolescents (from 12 to 18 years of age)
The recommended dose is 125 mg every 6 hours. In some cases, your doctor may decide to prescribe a higher daily dose, up to 500 mg every 6 hours. The maximum daily dose must not exceed 2 g.
If you have previously experienced other episodes (mucosal infections), you may require a different dose and duration of therapy.
Use in children
Neonates, infants, and children under 12 years of age
The recommended dose is 10 mg per kilogram of body weight. It is generally administered every 6 hours.
The maximum daily dose must not exceed 2 g.
Method of administration
Intravenous infusion means that the medicine flows from an infusion bottle or bag through a tube into one of your blood vessels and into your body. Your doctor or nurse will always administer VANCOTEX into the bloodstream and never into the muscle.
VANCOTEX will be administered intravenously over at least 60 minutes.
If administered for the treatment of gastrointestinal disorders (so-called pseudomembranous colitis), the medicine
must be given as an oral solution (you will take the medicine by mouth).
Duration of treatment
The duration of treatment depends on the infection you have and may last for several weeks.
The length of therapy may vary for each patient depending on individual response to treatment.
During treatment, you may need to undergo blood tests; you may be asked to provide urine samples and undergo hearing tests to monitor for possible adverse effects.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop using vancomycin and consult a doctor immediately if you notice any of the following symptoms:

• Flat, red spots, target-shaped or circular, on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital and eye ulcers. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome and toxic epidermal necrolysis).
• Widespread rash, high body temperature and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
• Widespread, red, scaly rash with subcutaneous bumps and blisters accompanied by fever at the beginning of treatment (acute generalized exanthematous pustulosis).
  • Chest pain, which may be a sign of a potentially serious allergic reaction called Kounis syndrome.

VANCOTEX may cause allergic reactions, although severe allergic reactions (anaphylactic shock) are rare. Inform your doctor immediately if you experience sudden wheezing, difficulty breathing, redness of the upper body, rash or itching.
Absorption of VANCOTEX from the gastrointestinal tract is negligible. However, if you have an inflammatory disease of the digestive tract, especially if you also have kidney disease, side effects may occur that are typically seen when VANCOTEX is administered by intravenous infusion.

Common side effects (may affect up to 1 in 10 people):

• Decreased blood pressure
• Shortness of breath, noisy breathing (a high-pitched sound caused by obstruction of airflow in the upper airways)
• Rash and inflammation inside the mouth, itching, itchy rash, hives
• Kidney problems, which may mainly be detected in blood tests
• Redness of the upper body and face, inflammation of a vein
• Increased liver enzymes

Uncommon side effects (may affect up to 1 in 100 people):

• Temporary or permanent hearing loss

Rare side effects (may affect up to 1 in 1,000 people):

• Decrease in white blood cells, red blood cells and platelets (blood cells responsible for clotting)
• Increase in certain white blood cells in the blood
• Loss of balance, ringing in the ears, dizziness
• Inflammation of blood vessels
• Nausea (feeling of disgust)
• Inflammation of the kidneys and kidney failure
• Chest and back muscle pain
• Fever, chills

Very rare side effects (may affect up to 1 in 10,000 people):

• Sudden onset of a severe allergic reaction with blistering or skin peeling. This may be associated with high fever and joint pain.
• Cardiac arrest.
• Inflammation of the intestine causing abdominal pain and diarrhoea, which may contain blood.

Frequency not known (frequency cannot be estimated from the available data):

• Vomiting, diarrhoea
• Confusion, dizziness, loss of energy, swelling, fluid retention, reduced urine output
• Rash with swelling or pain behind the ears, in the neck, groin, under the chin and armpits (swollen lymph nodes), abnormal liver function and blood tests
• Rash with blisters and fever
• Excessive breakdown of red blood cells causing fatigue and pale skin (haemolytic anaemia).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, hospital pharmacist or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store VANCOTEX

Do not store above 25°C.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Expiry".
The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What VANCOTEX 500 mg contains
The active substance is vancomycin. Each vial contains 500 mg of vancomycin (hydrochloride), equivalent to
500,000 IU of vancomycin.
What VANCOTEX 1 g contains
The active substance is vancomycin. Each vial contains 1000 mg of vancomycin (hydrochloride), equivalent to
1,000,000 IU of vancomycin.
Description of the appearance of VANCOTEX and contents of the pack
VANCOTEX 500 mg powder for concentrate for solution for intravenous infusion and oral use
Pack containing 1 vial/10 vials of 500 mg powder
VANCOTEX 1 g powder for concentrate for solution for intravenous infusion and oral use
Pack containing 1 vial of 1 g powder
Marketing Authorization Holder
Pharmatex Italia Srl – Via S. Paolo, 1 – 20121 Milano – Italy
Manufacturer
Fisiopharma srl – Nucleo Industriale – 84020 Palomonte (SA) - Italy
Other sources of information
Medical advice/information
Antibiotics are used to treat bacterial infections. They are ineffective against viral infections.
If your doctor has prescribed antibiotics, they are specifically intended for your current illness.
Despite antibiotic treatment, some bacteria may survive or grow. This phenomenon is called
resistance: some antibiotic treatments become ineffective.
Misuse of antibiotics increases resistance. It may also help bacteria become resistant, thereby delaying
treatment or reducing antibiotic efficacy if the appropriate:

• dosage
• regimen
• duration of treatment is not followed. Consequently, to maintain the effectiveness of this medicine:
  1- Use antibiotics only when prescribed,
  2- Follow instructions strictly,
  3- Do not reuse an antibiotic without a medical prescription, even if you wish to treat a similar illness.

The following information is intended exclusively for physicians or healthcare professionals
Posology and method of administration
Posology
Where appropriate, vancomycin should be administered in combination with other antibacterial agents.
Intravenous administration
The initial dose should be based on total body weight. Subsequent dose adjustments should
be based on serum concentrations to achieve established therapeutic levels. Renal function should
be taken into account for subsequent doses and dosing intervals.
Patients aged 12 years and older
The recommended dose is 15–20 mg/kg body weight every 8–12 hours (should not exceed 2 g per dose).
In seriously ill patients, an initial dose of 25–30 mg/kg body weight may be used to facilitate rapid achievement of the target minimum serum concentration.
Infants and children from one month up to 12 years of age:
The recommended dose is 10–15 mg/kg body weight every 6 hours (see section 4.4).
Term neonates (from birth up to 27 days of age) and preterm neonates (from birth to expected date of delivery plus 27 days)
To establish the dosing regimen for neonates, advice from a physician experienced in neonatal care should be sought.
A possible vancomycin dosing regimen for neonates is shown in the following table (see section 4.4):

PMA: postmenstrual age [(time elapsed from the first day of the last menstrual period to birth (gestational age) plus the time elapsed after birth (postnatal age))].
Perioperative prophylaxis of bacterial endocarditis in all age groups
The recommended dose is an initial dose of 15 mg/kg before induction of anesthesia. Depending on the duration of the procedure, a second dose of vancomycin may be required.
Duration of treatment
The recommended duration of treatment is shown in the table below. In any case, the duration of treatment should be adjusted according to the type and severity of the infection and the individual clinical response.

* Continue until no further debridement is required, the patient has clinically improved, and
the patient has been afebrile for 48–72 hours.
** In the case of prosthetic joint infections, longer durations of oral antibiotic suppression with the indicated antibiotics should be considered.
*** The duration and need for combination therapy depend on the type of valve and infecting organism.

Special populations
Elderly
Lower maintenance doses may be required due to age-related reduction in renal function.

Renal impairment
In pediatric and adult patients with renal impairment, consideration should be given to administering an initial dose followed by monitoring of vancomycin trough serum levels, rather than using a fixed scheduled dosing regimen—particularly in patients with severe renal impairment or those undergoing renal replacement therapy (RRT)—due to the many variable factors that may affect vancomycin levels in these patients.

In patients with mild to moderate renal impairment, the initial dose should not be reduced. In patients with severe renal impairment, prolonging the dosing interval is preferred over administering lower daily doses.

Particular consideration should be given to concomitant administration of medicinal products that may reduce vancomycin clearance and/or potentiate its adverse effects (see section 4.4).

Vancomycin is poorly dialyzable by intermittent hemodialysis. However, the use of high-flux membranes and continuous renal replacement therapy (CRRT) increases vancomycin clearance and generally requires supplemental dosing (usually administered after the hemodialysis session in the case of intermittent hemodialysis).

Adults
Dose adjustments in adult patients may be based on estimated glomerular filtration rate (eGFR) using the following formula:
Men: [Weight (kg) × (140 – age (years))] / [72 × serum creatinine (mg/dL)]
Women: 0.85 × value calculated using the formula above.

The usual initial dose for adult patients is 15–20 mg/kg, which may be administered every 24 hours in patients with creatinine clearance between 20 and 49 mL/min. In patients with severe renal impairment (creatinine clearance <20 mL/min) or those undergoing renal replacement therapy, the appropriate timing and amount of subsequent doses largely depend on the type of RRT and should be based on serum vancomycin trough levels and residual renal function (see section 4.4). Depending on the clinical situation, delaying the next dose to await vancomycin level results may be considered.

In critically ill patients with renal failure, the initial loading dose (25–30 mg/kg) should not be reduced.

Paediatric population
Dose adjustments in paediatric patients aged 1 year and older may be based on estimated glomerular filtration rate (eGFR) using the revised Schwartz formula:
eGFR (mL/min/1.73m²) = (height in cm × 0.413) / serum creatinine (mg/dL)
eGFR (mL/min/1.73m²) = (height in cm × 36.2) / serum creatinine (µmol/L)

For neonates and infants under 1 year of age, expert consultation is required, as the Schwartz formula is not applicable to this population.

Guideline dosage recommendations for the paediatric population are shown in the table below, following the same principles as for adult patients.

* The appropriate timing and amount of subsequent doses largely depend on the mode of RRT and
should be based on serum vancomycin levels obtained prior to dosing and residual renal function.
Depending on the clinical situation, consideration may be given to delaying the next dose
to await the results of vancomycin levels.
Hepatic impairment:
Dosage adjustment is not required in patients with hepatic impairment.
Pregnancy
Significantly increased doses may be required to achieve therapeutic serum concentrations
in pregnant women (see section 4.6).
Obese patients
In obese patients, the initial dose should be individually adjusted according to total body weight as
in non-obese patients.
Oral administration
Patients aged 12 years and older
Treatment of Clostridium difficile infection (CDI)
The recommended dose of vancomycin is 125 mg every 6 hours for 10 days for the first episode of non-
severe CDI. This dose may be increased to 500 mg every 6 hours for 10 days in case of severe disease or
complications. The maximum daily dose should not exceed 2 g.
In patients with multiple recurrences, consideration may be given to treating the current episode of CDI
with vancomycin 125 mg four times daily for 10 days, followed by a gradual dose reduction to 125 mg daily or
a tapered regimen, i.e., 125–500 mg/day every 2–3 days for at least 3 weeks.
Neonates, infants, and children under 12 years of age
The recommended dose of vancomycin is 10 mg/kg orally every 6 hours for 10 days. The maximum daily
dose should not exceed 2 g.
The duration of vancomycin treatment may need to be adjusted according to the clinical course of individual
patients. When possible, the antibiotic suspected of causing CDI should be discontinued. Adequate fluid and
electrolyte replacement should be ensured.
Monitoring of serum vancomycin concentrations
The frequency of therapeutic drug monitoring (TDM) should be individualized based on clinical status and
treatment response, ranging from daily sampling which may be required in some hemodynamically unstable
patients, to at least once weekly in stable patients showing a response to treatment. In patients with normal
renal function, serum vancomycin concentration should be monitored on the second day of treatment, just
before the next dose. In patients on intermittent hemodialysis, vancomycin levels should generally be obtained
before the start of the hemodialysis session.
Serum vancomycin concentration monitoring should be performed after oral administration in patients with
intestinal inflammatory disorders (see section 4.4).
The therapeutic trough level of vancomycin in blood should normally be 10–20 mg/L, depending on the site
of infection and pathogen susceptibility. Minimum levels of 15–20 mg/L are generally recommended by clinical
laboratories to better cover pathogens classified as susceptible with MIC ≥1 mg/L (see sections 4.4 and 5.1).
Model-based methods may be useful in predicting individual dose requirements to achieve adequate AUC.
The model-based approach may be used both for calculating an individualized initial dose and for dose
adjustments based on TDM results (see section 5.1).
Method of administration
Intravenous administration
Vancomycin for intravenous use is generally administered as an intermittent infusion, and the dosing
recommendations presented in this section for intravenous use correspond to this route of administration.
Vancomycin should be administered only as a slow intravenous infusion lasting at least one hour or at a
maximum rate of 10 mg/min (whichever is longer), and must be sufficiently diluted (at least 100 ml for 500 mg or
at least 200 ml for 1000 mg) (see section 4.4).
Patients whose fluid intake must be restricted may also receive a solution of 500 mg/50 ml or 1000 mg/100 ml,
although the risk of infusion-related adverse effects may be increased with these higher concentrations.
For information on solution preparation, see section 6.6.
Continuous infusion of vancomycin may be considered, e.g., in patients with unstable vancomycin clearance.
Oral administration
The contents of one vial (500 mg) may be diluted in approximately 50 ml of water and administered orally or
via a nasogastric tube.
Nephrotoxicity
Vancomycin should be used with caution in patients with renal impairment, including anuria, as the risk of
developing toxic effects is much greater in the presence of prolonged high blood concentrations.
The risk of toxicity is increased by high blood concentrations or prolonged therapy.
Regular monitoring of vancomycin levels is indicated during high-dose therapy and long-term use, particularly
in patients with renal dysfunction or impaired hearing, as well as when administered concomitantly with
nephrotoxic or ototoxic agents (see section 4.2).
Paediatric population
Current intravenous dosing recommendations for the paediatric population, particularly for children under
12 years of age, may result in subtherapeutic vancomycin levels in a high number of children.
However, the safety of higher vancomycin dosing has not been adequately evaluated and doses exceeding
60 mg/kg/day cannot generally be recommended.
Vancomycin should be used with particular caution in premature neonates and young children due to
immature renal function and the potential for increased serum vancomycin concentrations. Serum
vancomycin concentrations should therefore be monitored in these children. Concomitant administration of
vancomycin and anaesthetic agents has been associated with erythema and histamine-like flushing in
children. Similarly, concomitant use with nephrotoxic agents such as aminoglycoside antibiotics, NSAIDs (e.g.
ibuprofen for patent ductus arteriosus closure), or amphotericin B is associated with an increased risk of
nephrotoxicity (see section 4.5), and therefore more frequent monitoring of serum vancomycin levels and renal
function is indicated.
Use in the elderly
The natural decline in glomerular filtration with increasing age may lead to elevated serum vancomycin
concentrations if dosage is not adjusted (see section 4.2).
Pharmacological interactions with anaesthetic agents
Myocardial depression induced by anaesthetics may be enhanced by vancomycin. During anaesthesia, doses
should be well diluted and administered slowly with careful cardiac monitoring. Position changes should be
delayed until the infusion is complete to allow for postural adjustment (see section 4.5).
Pseudomembranous enterocolitis
In case of severe and persistent diarrhoea, pseudomembranous enterocolitis, which may be potentially fatal,
should be considered (see section 4.8). Anti-diarrhoeal agents should not be administered.
Superinfection
Prolonged use of vancomycin may lead to superinfections caused by non-susceptible organisms. Close
clinical observation of the patient is essential. If superinfections occur during therapy, appropriate measures
should be taken.
Oral administration
Intravenous administration of vancomycin is not effective for the treatment of Clostridium difficile infection.
Vancomycin must be administered orally for this indication.
Testing for Clostridium difficile colonization or toxin is not recommended in children under 1 year of age due
to the high rate of asymptomatic colonization, unless severe diarrhoea is present in infants with risk factors for
stasis such as Hirschsprung's disease, operated anal atresia, or other severe motility disorders. Alternative
etiologies should always be investigated and Clostridium difficile enterocolitis should be ruled out.
Potential for systemic absorption
Absorption may be increased in patients with inflammatory disorders of the intestinal mucosa or with
C. difficile-induced pseudomembranous colitis. These patients may be at risk of developing adverse reactions,
especially if concomitant renal impairment is present. The greater the renal impairment, the greater the risk of
developing adverse reactions associated with parenteral vancomycin administration. Serum vancomycin
concentrations should be monitored in patients with inflammatory disorders of the intestinal mucosa.
Nephrotoxicity
Periodic monitoring of renal function should be performed when treating patients with underlying renal
dysfunction or those receiving concomitant therapy with an aminoglycoside or other nephrotoxic drugs.
Ototoxicity
Periodic hearing function tests may be useful to minimize the risk of ototoxicity in patients with pre-existing
hearing loss or those receiving concomitant therapy with an ototoxic agent such as an aminoglycoside.
Pharmacological interactions with anti-motility agents and proton pump inhibitors
Anti-motility agents should be avoided and reconsideration should be given to the use of proton pump
inhibitors.
Development of drug-resistant bacteria
Oral use of vancomycin increases the likelihood of vancomycin-resistant enterococci in the gastrointestinal
tract. Consequently, prudent use of oral vancomycin is advised.
Overdose
Maintenance of glomerular filtration is recommended as supportive measure. Vancomycin is poorly removed
by dialysis.
Increased vancomycin clearance has been achieved through haemofiltration and haemoperfusion with
polysulfonic resin.
In managing overdose, consider the possibility of overdose due to multiple drugs, drug interactions, or unusual
pharmacokinetics in the patient.
Special precautions for disposal and handling
Vancomycin solution has a low pH and may cause physical instability of other compounds. Prior to
administration, parenterally administered drugs should be inspected for particulate matter and/or discoloration
whenever solution and container permit.
Solution preparation
At the time of use, add 10 ml of sterile water for injection to the 500 mg vial or 20 ml of sterile water for
injection to the 1 g vial; a solution of 50 mg/ml is obtained.
Further dilution is required. Read the following instructions:

1. Intermittent intravenous administration (preferred method). The solutions prepared as described above (containing 500 mg and 1 g of vancomycin) are added to 100 ml and 200 ml of 0.9% sodium chloride or 5% dextrose solution, respectively. The intravenous infusion should be administered over at least 60 minutes (see section 4.8) and repeated at 6-hour intervals. Reconstituted and further diluted vancomycin solution with 5% dextrose or 0.9% sodium chloride solution may be stored refrigerated for 14 days without significant loss of potency.

Compatibility with other intravenous fluids
Solutions further diluted with the following infusion fluids may be stored refrigerated for 96 hours:

• 5% dextrose solution and 0.9% sodium chloride solution
• Lactated Ringer's solution
• Lactated Ringer's solution and 5% dextrose solution
• Normosol-M with 5% dextrose
• Isolyte-E solution
• Ringer's acetate solution

2. Continuous infusion (to be used only when intermittent administration is not feasible): add the contents of the vials, prepared as described above, to the volume of 0.9% sodium chloride or 5% dextrose solution required to allow slow intravenous infusion over 24 hours.

Oral administration
The contents of one vial (500 mg) may be diluted in approximately 50 ml of water and administered orally
via a nasogastric tube.