Consumer medicine information

Vancomycin JUNO

Vancomycin

BRAND INFORMATION

Brand name

Vancomycin Juno

Active ingredient

Vancomycin

Schedule

SUMMARY CMI

VANCOMYCIN JUNO

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using VANCOMYCIN JUNO?

VANCOMYCIN JUNO contains the active ingredient vancomycin hydrochloride. Vancomycin is an antibiotic used to treat serious infections caused by bacteria (germs). These infections may occur in different parts of the body. Vancomycin can also be used orally to treat serious infections involving the bowel.

For more information, see Section 1. Why am I using VANCOMYCIN JUNO? in the full CMI.

2. What should I know before I use VANCOMYCIN JUNO?

Do not use if you have ever had an allergic reaction to vancomycin or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use VANCOMYCIN JUNO? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with vancomycin and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use VANCOMYCIN JUNO?

Your doctor will decide the appropriate dose for you.
A doctor or nurse will usually prepare and administer the injection or infusion.
Follow all instructions given to you by your doctor and pharmacist.

More instructions can be found in Section 4. How do I use VANCOMYCIN JUNO? in the full CMI.

5. What should I know while using VANCOMYCIN JUNO?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using vancomycin.
Things you should not do	Do not take any anti-diarrhoeal medicine without first checking with your doctor.
Driving or using machines	Be careful before you drive or use any machines or tools until you know how vancomycin affects you. Vancomycin may cause dizziness in some people.
Drinking alcohol	Tell your doctor if you drink alcohol. Alcohol may increase the side effects of some medicines.
Looking after your medicine	This medicine will generally be stored in the pharmacy or on the ward (below 25°C and protected from light).

For more information, see Section 5. What should I know while using VANCOMYCIN JUNO? in the full CMI.

6. Are there any side effects?

Side effects of this medicine may include stomach ache, nausea, chills, diarrhoea, vomiting, injection site reactions, hearing problems, kidney problems, dizziness, irregular or fast heartbeat, chest tightness, wheezing, breathlessness, rash or severe skin reactions, increased bleeding/bruising, upper body redness or pain/spasm of the chest and back, skin blisters/bleeding (lips, eyes, mouth, nose or genitals) or high fever.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

VANCOMYCIN JUNO

Active ingredient(s): vancomycin hydrochloride

Consumer Medicine Information (CMI)

This leaflet provides important information about using VANCOMYCIN JUNO. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using VANCOMYCIN JUNO.

Where to find information in this leaflet:

1. Why am I using VANCOMYCIN JUNO?
2. What should I know before I use VANCOMYCIN JUNO?
3. What if I am taking other medicines?
4. How do I use VANCOMYCIN JUNO?
5. What should I know while using VANCOMYCIN JUNO?
6. Are there any side effects?
7. Product details

1. Why am I using VANCOMYCIN JUNO?

VANCOMYCIN JUNO contains the active ingredient vancomycin hydrochloride. Vancomycin is an antibiotic. It works by killing the bacteria causing the infection.

VANCOMYCIN JUNO is used:

to treat serious infections caused by bacteria (germs).
These infections may occur in different parts of the body.
orally, to treat serious infections involving the bowel.

2. What should I know before I use VANCOMYCIN JUNO?

Warnings

Do not use VANCOMYCIN JUNO if:

you are allergic to vancomycin or similar antibiotics e.g. teicoplanin
you are allergic to any of the ingredients listed at the end of this leaflet.

Check with your doctor if you:

you are allergic to any other medicines, foods, dyes or preservatives
have any other medical conditions, in particular kidney or liver disease or inflammatory bowel disorders, or if you have suffered from hearing problems
take any medicines for any other condition.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant. Your doctor can discuss with you the benefits and risks involved.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Vancomycin is not recommended for use while breastfeeding as it is found in breast milk.

Elderly patients or patients with pre-existing kidney disease

Elderly patients or those with a pre-existing kidney condition may be more sensitive to the effects or side effects of this medicine.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

These include:

some other medicines used to treat infections, such as amikacin, amphotericin, bacitracin, colistin, piperacillin/tazobactam, gentamicin, neomycin and tobramycin
cisplatin, an anticancer medicine
some fluid tablets (diuretics), such as etacrynic acid and furosemide (frusemide)
anaesthetic agents
cholestyramine, a powder taken to lower cholesterol levels
suxamethonium or vecuronium, medicines used to relax muscles.

Some medicines may affect the way other medicines work.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these could affect vancomycin.

4. How do I use VANCOMYCIN JUNO?

How much to take / use

Your doctor will decide what dose of VANCOMYCIN JUNO you will be given, depending on your infection and other factors such as your age and weight.
If given orally, the dose for adults is 500 mg to 2 g given in 3 or 4 divided doses for 7 to 10 days. The total daily dosage in children is 40 mg/kg of body weight in 3 or 4 divided doses. The total dose for children should not exceed 2 grams per day.
Your doctor will decide for how long you will be given this medicine. This will depend on the severity of the infection being treated.

When to take / use VANCOMYCIN JUNO

For most infections, VANCOMYCIN JUNO is usually given in divided doses throughout the day.

How to use VANCOMYCIN JUNO

Intravenously

VANCOMYCIN JUNO is a sterile powder which is dissolved and diluted with suitable sterile fluids. It is given as a slow injection into a vein, known as a continuous infusion or a ‘drip’.

It will take at least 60 minutes for the solution containing your dose of VANCOMYCIN JUNO to be infused into your vein.

Your doctor or nurse will prepare the infusion of VANCOMYCIN JUNO for you.

Orally

VANCOMYCIN JUNO may also be given as an oral solution to treat serious infections involving the bowel.

Your doctor or pharmacist may use flavouring to improve the taste of the solution.

If you use too much VANCOMYCIN JUNO

As VANCOMYCIN JUNO is given to you in hospital under the supervision of your doctor, it is very unlikely that you will receive an overdose. Symptoms of a vancomycin overdose include the effects listed below in the ‘Side Effects’ section but are usually of a more severe nature.

5. What should I know while using VANCOMYCIN JUNO?

Things you should do

Remind any doctor, dentist or pharmacist you visit that you are using vancomycin.
If you are going to have surgery, tell the surgeon or anaesthetist that you are being given this medicine. It may affect other medicines used during surgery.

Things you should not do

Do not take any anti-diarrhoeal medicine without first checking with your doctor.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how VANCOMYCIN JUNO affects you.

Vancomycin may cause dizziness in some people. If this occurs, do not drive, operate machinery or do anything else that could be dangerous. If you drink alcohol, dizziness may be worse.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may increase the side effects of some medicines.

Looking after your medicine

VANCOMYCIN JUNO will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light, where the temperature stays below 25°C.

Getting rid of any unwanted medicine

Any unwanted medicine will be disposed of in a safe manner by your doctor, nurse or pharmacist.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor, nurse or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effects	What to do
stomach ache nausea, vomiting or mild diarrhoea dizziness chills irritation at the injection site	Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects

What to do

severe pain, warmth, itching, redness of the skin at the injection site
severe blisters and bleeding in the lips, eyes, mouth, nose and genitals
severe flaking or peeling of the skin
fluid-filled blisters that are located along creases in the skin which may be itchy
severe skin reaction starting with painful red areas, then large blisters and end with peeling layers of skin, accompanied by fever and chills, aching muscles and generally feeling unwell
rash with small puss-filled blisters that may be accompanied by a fever
pain, swelling and redness along a vein which is extremely tender when touched
itchy spots accompanied by fever and feeling unwell
signs of an allergic reaction, such as chest pain, shortness of breath, wheezing, coughing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin
bleeding or bruising more easily than normal
flushing/redness of the upper body or pain and muscle spasm of the chest and back
chills or fever, which may be accompanied by shivering
fever, loss of appetite, weight loss, fatigue, general aches and pains
severe and constant abdominal pain, fever, inability to break wind or pass stools, nausea and vomiting, shock
fast, slow or irregular heart beat, heart palpitations
dizziness and lightheadedness, fast pulse rate, white skin, sweating, restlessness, loss of consciousness; heart attack
ringing in the ears (tinnitus) or hearing loss, deafness, dizziness or problems with your balance
diarrhoea, usually with blood and mucus, stomach pain, fever
frequent infections such as fever, severe chills, sore throat or mouth ulcers; tiredness, being short of breath and looking pale
little or no urine, drowsiness, nausea, vomiting, breathlessness, kidney disease
other infections.

Call your doctor or nurse straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Side effects after treatment

Side effects after treatment	What to do
severe stomach cramps or pain severe, watery or bloody diarrhoea fever, in combination with one of the above.	Tell your doctor immediately, particularly if these occur several weeks after stopping treatment.

Tell your doctor, nurse or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What VANCOMYCIN JUNO contains

Active ingredient (main ingredient)	Vancomycin hydrochloride
Other ingredients (inactive ingredients)	None
Potential allergens	VANCOMYCIN JUNO does not contain lactose, sucrose, tartrazine or any other azo dyes.

Do not take this medicine if you are allergic to any of these ingredients.

What VANCOMYCIN JUNO looks like

Vancomycin JUNO is available in two strengths:

500 mg (Aust R 407963)
1 g (Aust R 407964)

It is an off white to light beige powder in a glass vial with a rubber stopper.

Who distributes VANCOMYCIN JUNO

Juno Pharmaceuticals Pty Ltd
15-17 Chapel Street
Cremorne VIC 3121

This leaflet was prepared in May 2024.

Published by MIMS July 2024

BRAND INFORMATION

Brand name

Vancomycin Juno

Active ingredient

Vancomycin

Schedule

1 Name of Medicine

Vancomycin hydrochloride.

2 Qualitative and Quantitative Composition

Vancomycin Juno is available as sterile vials containing vancomycin hydrochloride equivalent to either 500 mg (500,000 IU) or 1 g (1,000,000 IU) of vancomycin activity.
No excipients are included in the formulation.

3 Pharmaceutical Form

Powder for injection.
An off white to light beige homogenous freeze-dried cake. When reconstituted in water, it is a clear solution with a pH range of 2.5 to 4.5.

4 Clinical Particulars

4.1 Therapeutic Indications

Vancomycin Juno is indicated in potentially life-threatening infections which cannot be treated with another effective, less toxic antimicrobial drug, including the penicillins and cephalosporins.
Vancomycin Juno is useful in therapy of severe staphylococcal (including methicillin-resistant staphylococcal) infections in patients who cannot receive or who 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 Juno 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. E. faecalis), Vancomycin Juno is effective only in combination with an aminoglycoside. Vancomycin Juno is effective for the treatment of diphtheroid endocarditis. Vancomycin Juno is used in combination with rifampin, an aminoglycoside, or both in early-onset prosthetic valve endocarditis caused by S. epidermidis or diphtheroids.
The effectiveness of Vancomycin Juno has been documented in other infections due to staphylococci including osteomyelitis, pneumonia, septicaemia, and soft tissue infections. When staphylococcal infections are localised and purulent, antibiotics are used as adjuncts to appropriate surgical measures.
Specimens for bacteriologic cultures should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to Vancomycin Juno.
Vancomycin Juno should be administered orally for the treatment of Staphylococcal enterocolitis and antibiotic associated pseudomembranous colitis produced by C. difficile. Parenteral administration of Vancomycin Juno alone is inappropriate for this indication. Vancomycin 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 pseudomembranous colitis.

4.2 Dose and Method of Administration

Product is for single use in one patient only. Discard any residue.
Vancomycin should be administered intravenously in dilute solution.
Infusion-related events are related to both concentration and rate of administration of vancomycin. Concentrations of no more than 5 mg/mL and rates of no more than 10 mg/min are recommended in adults (see also age specific recommendations). In selected patients in need of fluid restriction, a concentration up to 10 mg/mL may be used; use of such higher concentrations may increase the risk of infusion-related events. Infusion-related events may occur, however, at any rate or concentration.

Patients with normal renal function.

Adults.

The usual intravenous dose is 500 mg (in 0.9 percent sodium chloride injection or 5 percent glucose in sterile water for injection) every six hours or 1 g every twelve hours. Each dose should be administered at no more 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 daily dose.
The majority of patients with infections caused by organisms susceptible to the antibiotic show a therapeutic response by forty-eight to seventy-two 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 Juno is calculated on the basis of 10 mg/kg of body weight 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. Each dose should be administered over 60 minutes. Close monitoring of serum vancomycin concentrations is mandatory in these patients.

Patients with impaired renal function and elderly patients.

Dosage adjustment must be made in patients with impaired renal function. In premature infants and 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 microbiologic assay, a radioimmunoassay, a fluorescence polarisation 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 Juno dose per day in mg is about 15 times the glomerular filtration rate in mL/min. (See Table 1).

Loading dose.

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

Anephric patients.

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 in order to promptly achieve therapeutic serum concentrations. The dose required to maintain stable concentrations is 1.9 mg/kg/24 h. Since individual maintenance doses of 250 to 1000 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 1000 mg every 7 to 10 days has been recommended.

Preparation of solution.

At the time of use, add 10 mL of sterile water for injection to the vial of dry, sterile Vancomycin Juno, 500 mg or 20 mL of sterile water for injection to the vial of Vancomycin Juno, 1 g.
Further dilution is required, read instructions which follow:
a. Intermittent infusion is the preferred method of administration. The solution containing 500 mg (500,000 IU) vancomycin activity can be added to 100-200 mL of 0.9 percent sodium chloride injection or 5 percent glucose in sterile water for injection. The solution containing 1 g (1,000,000 IU) vancomycin activity can be added to 200-400 mL of 0.9 percent sodium chloride injection or 5 percent glucose in sterile water for injection. The desired dose, diluted in this manner to a concentration of 2.38-4.55 g per L may be administered by intravenous infusion over a period of at least 60 minutes every 6 or 12 hours.
b. Continuous infusion (should be used only when intermittent infusion is not feasible). One to 2 g (1,000,000 to 2,000,000 IU) vancomycin activity can be added to a sufficiently large volume of 0.9 percent sodium chloride injection or 5 percent glucose in sterile water for injection to permit the desired daily dose to be administered slowly by intravenous infusion over a twenty-four hour period.

Compatibility with other drugs and intravenous fluids.

The following diluents are physically and chemically compatible (with 4 g/L vancomycin):
5% glucose solution;
5% glucose and 0.9% sodium chloride solution;
0.9% sodium chloride solution.
To avoid microbiological hazards, the solutions should be used as soon as possible after preparation.
Vancomycin solution has a low pH that may cause chemical or physical instability when it is mixed with other compounds. Parenteral drug products should be inspected visually for 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 mg/mL or less.
Although intravitreal injection is not an approved route of administration for vancomycin, precipitation has also been reported after intravitreal injection of vancomycin and ceftazidime for endophthalmitis using different syringes and needles.

For oral administration.

The usual adult total daily dosage for antibiotic-associated pseudomembranous colitis produced by C. difficile and Staphylococcal enterocolitis is 500 mg to 2 g given in 3 or 4 divided doses for 7 to 10 days. The total daily dosage in children is 40 mg/kg of body weight in 3 or 4 divided doses. The total daily dosage should not exceed 2 g. The appropriate dose 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.

Stability of prepared solution.

After reconstitution with water for injection, 5% glucose injection or 0.9% sodium chloride injection, the solution may be stored in a refrigerator for 24 hours without significant loss of potency. To reduce microbiological hazards, the solution should be used as soon as practicable after reconstitution.

4.3 Contraindications

Vancomycin Juno is contraindicated in patients with known hypersensitivity to vancomycin, any of the excipients, or other glycopeptides.

4.4 Special Warnings and Precautions for Use

General.

All patients receiving the drug should have periodic haematological studies, urinanalyses, and liver and renal function tests.

Hypersensitivity reactions.

Serious and occasionally fatal hypersensitivity reactions are possible (see Section 4.3 Contraindications; Section 4.8 Adverse Effects (Undesirable Effects)). In case of hypersensitivity reactions, treatment with vancomycin must be discontinued immediately and the adequate emergency measures must be initiated.

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP) have been reported in association with vancomycin treatment (see Section 4.8 Adverse Effects (Undesirable Effects)). Patients should be advised to inform their doctor at the first appearance of rash or any other sign of hypersensitivity.
If a SCAR is suspected, the drug should be discontinued and specialist dermatological assessment should be carried out.

Infusion reactions.

Bolus administration (e.g. over several minutes) may be associated with exaggerated hypotension, including shock, and rarely, cardiac arrest, histamine like responses and maculopapular or erythematous rash ("red neck").
Vancomycin Juno should be administered in a dilute solution over a period of not less than 60 minutes to avoid rapid-infusion-related reactions. Stopping the infusion usually results in a prompt cessation of these reactions (see Section 4.2 Dose and Method of Administration; Section 4.8 Adverse Effects (Undesirable Effects)).
Complications of occasional severe hypotension, histamine like responses and rash can be avoided by slow administration of the recommended dilute solutions over at least one hour for both adults and children.
When given intravenously, toxic serum levels can occur. Vancomycin is excreted fairly rapidly by the kidney and blood levels increase markedly with decreased renal clearance. During parenteral therapy, the risk of toxicity and nephrotoxicity appears appreciably increased by high blood concentrations or prolonged treatment.
Since vancomycin is irritating to tissue and causes drug fever, pain and possibly necrosis, it should never be injected intramuscularly; it must be administered intravenously.
Pain and thrombophlebitis occur in many patients receiving vancomycin and are occasionally severe. The frequency and severity of thrombophlebitis can be minimised if the drug is administered in a volume of at least 200 mL of glucose or saline solution and if the sites of injection are rotated.

Ototoxicity.

Ototoxicity has occurred. It may be transient or permanent. Deafness may be preceded by tinnitus and should be regarded as an indication to discontinue treatment. The elderly are more susceptible to auditory damage. Experience with other antibiotics suggests that deafness may be progressive despite cessation of treatment.
Vancomycin should be avoided in patients with previous hearing loss. If it is used in such patients, the dose of vancomycin should be regulated, if possible by periodic determination of the drug level in the blood.
Most of the patients who experienced hearing loss had kidney dysfunction, pre-existing hearing loss, or concomitant treatment with an ototoxic drug (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Cross-sensitivity reactions.

Vancomycin should not be used in patients allergic to teicoplanin, since cross-sensitivity, including fatal anaphylactic shock, may occur (see Section 4.3 Contraindications).

Blood disorders.

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

Other routes of administration.

Neither the safety nor the efficacy of vancomycin administration by the intrathecal or intraventricular routes have been studied. Vancomycin should not be administered by these routes.
Reports have revealed that administration of sterile vancomycin hydrochloride by the intraperitoneal route during continuous ambulatory peritoneal dialysis (CAPD) has resulted in a syndrome of chemical peritonitis. To date, this syndrome has ranged from a cloudy dialysate alone to a cloudy dialysate accompanied by varying degrees of abdominal pain and fever. This syndrome appears to be short lived after discontinuation of intraperitoneal vancomycin.
If parenteral and oral vancomycin are administered concomitantly, an additive effect can occur. This should be taken into consideration when calculating the total dose. In this situation, serum levels of the antibiotic should be monitored.
Some patients with inflammatory disorders of the intestinal mucosa may have significant systemic absorption of oral vancomycin and, therefore, may be at risk for the development of adverse effects associated with the parenteral administration of vancomycin. The risk is greater if renal impairment is present.
Patients taking oral vancomycin 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 Interactions with Other Medicines and Other Forms of Interactions).

Superinfection.

Clinically significant serum concentrations have been reported in some patients being treated for active C. difficile-induced pseudomembranous colitis after multiple oral doses of vancomycin.
Prolonged use of vancomycin may result in the overgrowth of nonsusceptible organisms.
Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken including withdrawal of vancomycin. In rare instances, there have been reports of pseudomembranous colitis due to C. difficile developing in patients who received intravenous vancomycin. C. difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including vancomycin hydrochloride, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use.

Haemorrhagic occlusive retinal vasculitis.

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

Other.

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

Use in renal impairment.

Because of its ototoxicity and nephrotoxicity, vancomycin should be used with care in patients with renal insufficiency. The risk of toxicity is appreciably increased by high blood concentrations or prolonged therapy. If it is necessary to use vancomycin in such patients, blood levels should be monitored and appropriate dosage modifications made.
Patients with borderline renal function and individuals over the age of sixty should be given serial tests of auditory function and of vancomycin blood levels.
(Vancomycin serum levels may be determined by use of the modified Rammelkamp serial twofold dilution technique with streptococcus C203 as the indicator organism.)
When patients receive concomitant therapy with an aminoglycoside, serial monitoring of renal function should be performed.

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 Dose and Method of Administration).

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 Adverse Effects (Undesirable Effects)).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concurrent and/or sequential systemic or topical use of other potentially neurotoxic (e.g. ototoxic) and/or nephrotoxic drugs, such as amphotericin B, aminoglycosides (streptomycin, neomycin, gentamicin, kanamycin, amikacin, tobramycin) bacitracin, polymyxin B, colistin, viomycin, or piperacillin/tazobactam or cisplatin, requires careful monitoring (see Section 4.4 Special Warnings and Precautions for Use).
In animal studies designed to evaluate nephrotoxicity in the rat, renal impairment occurred with high serum concentrations of vancomycin alone and with lower concentrations when vancomycin was administered with an aminoglycoside. Combining vancomycin with a loop diuretic in the rat model did not potentiate the renal impairment that occurred with vancomycin alone. 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 in order to minimise the risk of nephrotoxicity.
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 Dose and Method of Administration).
Diuretics such as etacrynic acid and furosemide (frusemide) may aggravate ototoxicity.
Cholestyramine has been shown to bind vancomycin in vitro. Therefore, if oral vancomycin is used with cholestyramine, the two medicines should be administered several hours apart.
Reversible neutropenia has been reported in patients receiving vancomycin hydrochloride (see Section 4.8 Adverse Effects (Undesirable Effects)). Patients who are receiving concomitant medicines 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 Juno as a 60-minute infusion prior to anaesthetic induction.
Vancomycin may enhance neuromuscular blockade produced by medicines such as suxamethonium or vecuronium.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B2)
Animal reproduction studies have not been conducted with vancomycin. It is also not known whether vancomycin can affect reproduction capacity. In a controlled clinical study, vancomycin was administered to pregnant women for serious staphylococcal infections complicating intravenous drug abuse to evaluate potential ototoxic and nephrotoxic effects on the infant. Vancomycin was found in cord blood. No sensorineural hearing loss or nephrotoxicity attributable to vancomycin was noted. One infant whose mother received vancomycin in the third trimester experienced conductive hearing loss that was not attributed to the administration of vancomycin. As only 10 patients were treated with vancomycin in this study, and administration was only in the second and third trimesters, it is not known whether vancomycin causes foetal harm. Vancomycin should be given to a pregnant woman only if clearly needed.
Vancomycin hydrochloride is excreted in human milk. Caution should be exercised when vancomycin hydrochloride is administered to a lactating woman. Because of the potential for adverse events, a decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Infusion-related events.

During or soon after infusion of vancomycin, 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. In animal studies, hypotension and bradycardia occurred in animals given large doses of vancomycin at high concentrations and rates. Such events are infrequent if vancomycin is given by a slow infusion over 60 minutes and at a sufficient dilution. In a study using multiple infusion rates, infusion-related events were not reported by the 4 volunteers administered vancomycin hydrochloride at a rate of 10 mg/min or less.
Pruritus at injection site, generalised flushing, erythematous macular rash with intense pruritus over face, neck and upper body have occurred after too rapid injection of the drug. Tissue irritation and necrosis occurs after intramuscular injection or extravasation from the intravenous site. Hypotension, bradycardia, cardiogenic shock and cardiac arrest have been reported following rapid bolus injection.
Drug fever has also been reported.

Gastrointestinal.

Nausea, vomiting, diarrhoea and pseudomembranous enterocolitis.
Oral doses of vancomycin are extremely unpalatable and have been associated with nausea, diarrhoea and occasional vomiting. In leukaemic patients, oral dosing regimens are associated with frequent nausea, diarrhoea and occasional vomiting.

Renal and urinary disorders.

Rarely, renal failure, principally manifested by increased serum creatinine or urea concentrations, especially in patients given large doses of vancomycin hydrochloride, 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 preexisting kidney dysfunction. When vancomycin was discontinued, uraemia resolved in most patients.
Transient elevations of urea and granular casts in the urine occasionally occur.

Ototoxicity.

There have been reports of hearing loss associated with vancomycin. Most of these patients had kidney dysfunction, preexisting hearing loss, or concomitant treatment with an ototoxic drug. Vertigo, dizziness, and tinnitus have also been reported rarely.
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.

Haematological.

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 has also been reported. Although a causal relationship has not been established, reversible agranulocytosis (granulocyte count less than 500/mm³) has been reported rarely.

Liver function.

Elevation of liver transaminases.

Vascular disorders.

Inflammation at the injection site (phlebitis and vasculitis) has been reported.

Immunological and skin/subcutaneous tissue disorders.

Hypersensitivity reactions with chills, nausea, urticaria, rashes, including exfoliative dermatitis, linear IgA bullous dermatosis; Stevens-Johnson syndrome, toxic epidermal necrolysis and rare cases of vasculitis, fever and rigors. Anaphylactoid reactions have been reported infrequently. Kounis syndrome has also been reported.
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and AGEP (Acute Generalised Exanthematous Pustulosis) have been reported. DRESS is a serious, potentially life-threatening adverse drug reaction with distinct feature. Prompt recognition along with drug withdrawal is essential for improved prognosis. DRESS is characterized by severe drug eruption accompanied by high fever, erythematous rash and inflammation of internal organs.

General.

The use of vancomycin may result in overgrowth of nonsusceptible organisms. If 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 Special Warnings and Precautions for Use).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly removed by dialysis. Haemoperfusion with Amberlite resin XAD-4 has been reported to be of limited benefit. Haemofiltration and haemoperfusion with polysulfone resin have been reported to result in increased vancomycin clearance.
In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology.

Vancomycin is a chromatographically purified tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis (formerly Nocardia orientalis) which is bactericidal against many gram-positive bacteria.
The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin alters bacterial cell membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other antibiotics. Vancomycin is active against staphylococci, including Staphylococcus 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 [formerly Streptococcus faecalis]); C. difficile (e.g. toxigenic strains implicated in pseudomembranous enterocolitis); and diphtheroids. The following in vitro data are available, but their clinical significance is unknown. Other organisms that are susceptible to vancomycin in vitro include Listeria monocytogenes, Lactobacillus species, Actinomyces species, Clostridium species, and Bacillus species. (See Table 2).

Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi.

Synergy.

The combination of vancomycin and an aminoglycoside acts synergistically in vitro against many strains of S. aureus, nonenterococcal group D streptococci, enterococci, and Streptococcus sp. (viridans group). The combination of vancomycin and a cephalosporin acts synergistically against some strains of S. epidermidis (methicillin-resistant). The combination of vancomycin and rifampin 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 and a cephalosporin may act antagonistically against some strains of S. epidermidis, and the combination of vancomycin and rifampin may act antagonistically against some strains of S. aureus.

Disc susceptibility tests.

Quantitative methods that require measurement of zone diameters give the most precise estimates of antibiotic susceptibility. The Bauer- Kirby-Sherris-Turck Method has been recommended for use with discs for testing susceptibility to vancomycin. Results of standard single-dose susceptibility tests with a 30 microgram vancomycin hydrochloride disc should be interpreted according to the following criteria. Susceptible organisms produce zones greater than or equal to 12 mm, indicating that the test organism is likely to respond to therapy. Organisms that produce zones of 10 or 11 mm are considered to be of intermediate susceptibility. Organisms in this category are likely to respond if the infection is confined to tissues or fluids in which high antibiotic concentrations are attained. Resistant organisms produce zones of 9 mm or less, indicating that other therapy should be selected. With a standardised dilution method, a bacterial isolate may be considered susceptible if the MIC value for vancomycin is 4 mg/L or less. Organisms are considered resistant to vancomycin if the MIC is greater than or equal to 16 mg/L. Organisms having an MIC value of less than 16 mg/L but greater than 4 mg/L are considered to be of intermediate susceptibility.
Standardised procedures require the use of laboratory control organisms. The 30 microgram vancomycin disc should give zone diameters between 15 and 19 mm for S. aureus ATCC 25923. As with the standard diffusion methods, dilution procedures require the use of laboratory control organisms. Standard vancomycin powder should give MIC values in the range of 0.5 mg/L to 2.0 mg/L for S. aureus ATCC 29213. For E. faecalis ATCC 29212, the MIC range should be 1.0 to 4.0 mg/L.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Vancomycin is poorly absorbed after oral administration; it is given intravenously for therapy of systemic infections.
Measurable serum concentrations of vancomycin may occur in patients treated for active pseudomembranous colitis due to Clostridium difficile.

Distribution.

In subjects with normal kidney function, multiple intravenous dosing of 1 g of vancomycin (15 mg/kg) infused over 60 minutes produces mean plasma concentrations of approximately 63 mg/L immediately at the completion of infusion, mean plasma concentrations of approximately 23 mg/L 2 hours after infusion, and mean plasma concentrations of approximately 8 mg/L 11 hours after the end of the infusion. Multiple dosing of 500 mg infused over 30 minutes produces mean plasma concentrations of about 49 mg/L at the completion of infusion, and mean plasma concentrations of about 19 mg/L 2 hours after infusion, and mean plasma concentrations of about 10 mg/L 6 hours after infusion. The plasma concentrations during multiple dosing are similar to those after a single dose.
Protein binding is approximately 55% as measured by ultrafiltration at vancomycin serum concentrations of 10 to 100 mg/L. Clinically effective concentrations of this antibiotic in the blood are usually achieved and maintained by its intravenous administration, moreover, inhibitory concentrations can be demonstrated in pleural, pericardial, ascitic and synovial fluids, in urine, in peritoneal dialysis fluid, and in atrial appendage tissue. This antibiotic does not readily diffuse across the meninges into the cerebrospinal fluid.
About 60% of an intraperitoneal dose of vancomycin administered during peritoneal dialysis is absorbed systemically in 6 hours. Serum concentrations of about 10 mg/L are achieved by intraperitoneal injection of 30 mg/kg of vancomycin.

Metabolism.

There is no apparent metabolism of the drug.

Excretion.

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 urine by glomerular filtration. Mean plasma clearance is about 0.06 L/kg/hr, and mean renal clearance is about 0.05 L/kg/hr. 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 0.69 L/kg.
Although vancomycin is not effectively removed by either haemodialysis or peritoneal dialysis; there have been reports of increased vancomycin clearance with haemoperfusion and haemofiltration.
Total systemic and renal clearance of vancomycin may be reduced in the elderly.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

No excipients are included in the formulation.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Prior to reconstitution: store below 25°C. Keep the vial in the outer carton in order to protect from light.

6.5 Nature and Contents of Container

Vancomycin Juno (vancomycin hydrochloride) 500 mg (500,000 IU) vancomycin activity, 13.5 mL size, bromobutyl rubber-stoppered glass vials, with aluminium caps and polypropylene flip off caps. Available in packs of 1 vial and packs of 10 vials.
Vancomycin Juno (vancomycin hydrochloride) 1 g (1,000,000 IU) vancomycin activity, 26 mL size, bromobutyl rubber-stoppered glass vials, with aluminium caps and polypropylene flip off caps. Available in packs of 1 vial and packs of 10 vials.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

The following structure of vancomycin hydrochloride has been confirmed by X-ray diffraction:

CAS number.

1404-93-9
Vancomycin has the chemical formula C₆₆H₇₅Cl₂N₉O₂₄.HCl.
The formula weight is 1449; 500 mg of the base is equivalent to 0.35 mmol.

7 Medicine Schedule (Poisons Standard)

Prescription only medicine (S4).

Service Unavailable

Consumer medicine information

Vancomycin JUNO

Vancomycin

Keep track of your medicines

BRAND INFORMATION