Consumer medicine information

Vancomycin AN Powder for Injection

Vancomycin

BRAND INFORMATION

Brand name

Vancomycin AN

Active ingredient

Vancomycin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Vancomycin AN Powder for Injection.

What is in this leaflet

This leaflet answers some common questions about this medicine. It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist. All medicines have benefits and risks. Your doctor has weighed the risks of you taking Vancomycin AN against the benefits they expect it will have on you. If you have any concerns about taking this medicine, talk to your doctor or pharmacist. Keep this leaflet with your medicine. You may need to read it again.

What Vancomycin AN is used for

Vancomycin AN is used to treat serious or severe bacterial infections. Your doctor, however, may have prescribed Vancomycin AN for another purpose. Ask your doctor if you have any questions about why Vancomycin AN has been prescribed for you. Vancomycin AN is a broad-spectrum antibiotic and belongs to a glycopeptide group of antibiotics. This medicine works by stopping bacteria from growing and reducing the bacteria's ability to function. Vancomycin AN will not work against infections caused by viruses, such as colds or flu. Vancomycin AN is available only with a doctor's prescription.

Before you are given Vancomycin AN intravenous infusion

When you must not be given it

You have ever had an allergic reaction to medicines containing the active ingredient, vancomycin. Some of the symptoms of an allergic reaction may include rash, itching or hives, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or difficulty in breathing.

Before you are given it

  1. You have, or have ever had, any other health problems or medical conditions, especially kidney damage, hearing problems, blood problems or inflammatory bowel disorders;
  2. You are pregnant or plan to become pregnant. Your doctor will discuss the risks and benefits of taking Vancomycin AN when pregnant;
  3. You are breastfeeding or wish to breastfeed. Your doctor will discuss the risks and benefits of taking Vancomycin AN when breastfeeding;
  4. You are allergic to any other medicines or other substances such as foods, preservatives or dyes. If you have not told your doctor or pharmacist about any of the above, tell them before you start taking or are given Vancomycin ACT.
  5. The packaging is torn or shows any signs of tampering;
  6. The use by date or expiry date printed on the pack has passed. If this medicine is used after the expiry date has passed, it may not work as well.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines you can buy without a prescription from a pharmacy, supermarket or health food shop. Some medicines may be affected by Vancomycin AN or may affect how well Vancomycin AN works.

These include:

  • Some other medicines used to treat infections, such as amicacin, amphotericin, colistin, gentamycin, neomycin and tobramycin;
  • Cisplatin, an anticancer medicine;
  • Some fluid tablets (diuretics) such as ethacrynic acid and frusemide;
  • Anaesthetic agents;
  • Cholestyramine, a powder taken to lower cholesterol levels;
  • Medicine used to relax muscles.

These medicines may be affected by vancomycin, or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines. Your doctor or pharmacist will be able to tell you what to do when using Vancomycin AN or may have more information on medicines to be careful with or avoid while you are being given this medicine.

How to take Vancomycin ACT

Your doctor will tell you how much to take and when to take it. Take Vancomycin AN exactly as directed by your doctor. This may differ from the information contained in this leaflet.

How much to take

Vancomycin AN is administered intravenously under the supervision of a doctor or a nurse. The usual adult daily intravenous dose of vancomycin hydrochloride is either 500 mg every 6 hours or 1000 mg every 12 hours (when in solution). Each dose should be administered at no more than 10 mg/minute or over a period of at least 60 minutes, whichever is the longer. Infusion-related events are related to both the concentration and the rate of administration of vancomycin hydrochloride.

For children the dose varies depending on their age, weight and how sick they are. Your doctor will adjust the amount or frequency of your doses according to the infection being treated and the severity of your condition. If you do not understand the instructions provided, ask your doctor or pharmacist for help.

How long to take Vancomycin Hydrochloride for Intravenous Infusion for

Your doctor will tell you how long you will be treated with Vancomycin AN. Check with your doctor if you are not sure how long you should be taking Vancomycin AN.

While you are taking Vancomycin ACT

Things you must do

If you are being given Vancomycin AN for an infection and your symptoms do not improve within a few days, or if they become worse, tell your doctor.

Tell your doctor if you become pregnant while taking Vancomycin AN. If you are about to start taking a new medicine, tell your doctor or pharmacist that you are taking Vancomycin AN.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Vancomycin AN.

If you are going to have surgery, tell the surgeon and anaesthetist that you are being given this medicine.

Things to be careful of

Be careful driving or operating machinery until you know how vancomycin affects you. This medicine may cause dizziness in some people. If you drink alcohol, dizziness may be worse.

Things you must not do

Do not use Vancomycin AN to treat any other complaints unless your doctor says so. Do not give this medicine to anyone else, even if their symptoms seem similar to yours.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being treated with Vancomycin AN. Vancomycin AN helps most people with bacterial infections, but it may have unwanted side effects in some people. If you are over 65 years of age you may have an increased chance of getting side effects.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects. Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

While you are taking Vancomycin AN

Tell your doctor if you experience any of the following and they worry you: nausea (feeling sick), diarrhoea, vomiting or mild diarrhoea or rashes.

Tell your doctor immediately if you notice any of the following, as you may need urgent medical care:

  • allergic reaction including shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body, rashes, itching or hives on the skin, pain and muscle spasm;
  • a change in the amount or frequency of urine passed;
  • bleeding or bruising more easily than normal, reddish or purplish blotches under the skin;
  • hearing loss, dizziness, ringing in the ears, loss of balance;
  • chest pains or palpitations;
  • redness around the needle site of injection or infusion;
  • severe diarrhoea;
  • fast or irregular heartbeat;
  • chills or fever, which may be accompanied by shivering.

The above list includes serious side effects which may require urgent medical attention. Serious side effects are rare.

After you have finished being given Vancomycin ACT

Tell your doctor immediately if you notice any of the following side effects, particularly if they occur several weeks after treatment with vancomycin:

  • Severe abdominal cramps or stomach cramps;
  • Watery or severe diarrhoea which may also be bloody;
  • Fever, in combination with one or both of the above.

These are serious side effects. You may have a serious condition affecting your bowel. Therefore, you may need urgent medical attention. However, these side effects are rare.

Tell your doctor if you notice anything that is making you feel unwell while you are being given, or soon after you have finished being given Vancomycin AN, even if it is not on this list.

After using Vancomycin AN

Storage

Vancomycin AN will be kept on the ward or in the pharmacy in a cool dry place below 25°C.

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

Disposal

Unused or out dated Vancomycin AN should be disposed of by the standard procedures of the pharmacy at the institution where it is administered.

Product Description

What it looks like

Vancomycin AN is available as a sterile, white to light brown powder in a glass vial. When reconstituted with sterile water for injections, it forms a clear solution. Vancomycin AN is available in two strengths: 500 mg (grey flip-off cap) and 1000 mg (green flip-off cap).

Ingredients

The active ingredient in Vancomycin AN is vancomycin hydrochloride.

Australian registration numbers

Vancomycin AN 500 mg: AUST R 118999

Vancomycin AN 1000 mg: AUST R 119000

Supplier

Vancomycin AN is supplied by:

Medis Pharma Pty Ltd
1002/53 Walker Street
North Sydney NSW 2060 Australia

Date of Preparation: May 2016

Published by MIMS February 2019

BRAND INFORMATION

Brand name

Vancomycin AN

Active ingredient

Vancomycin

Schedule

S4

 

1 Name of Medicine

Vancomycin hydrochloride.

2 Qualitative and Quantitative Composition

Each vial of Vancomycin AN powder for injection contains the 500 mg or 1000 mg of the active ingredient vancomycin hydrochloride.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Vancomycin hydrochloride is a white to light brown powder and is presented in a sterile glass vial. The powder for injection when reconstituted in water forms a clear solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Vancomycin hydrochloride for intravenous infusion is indicated for potentially life-threatening infections, which cannot be treated with another effective, less toxic antimicrobial drug, including the penicillins and cephalosporins.
Vancomycin AN is useful in therapy of severe staphylococcal (including methicillin resistant staphylococcal) infections in patients who cannot receive or who have failed to respond to the penicillins and cephalosporins or who have infections with staphylococci that are resistant to other antibiotics. Once sensitivity data are available, therapy should be adjusted accordingly.
Vancomycin AN is effective alone or in combination with an aminoglycoside for endocarditis caused by Strep. viridans or Strep. bovis. For endocarditis caused by enterococci (e.g. E. faecalis), Vancomycin AN is effective only in combination with an aminoglycoside. Vancomycin AN is effective for the treatment of diphtheroid endocarditis. Vancomycin AN is used in combination with rifampicin, an aminoglycoside, or both in early onset prosthetic valve endocarditis caused by Staph. epidermidis or diphtheroids.
The effectiveness of Vancomycin AN 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 bacteriological cultures should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to Vancomycin AN.

Note for clinicians.

Vancomycin AN should be administered orally for the treatment of Staphylococcal enterocolitis and antibiotic associated pseudo membranous colitis produced by C. difficile. Parenteral administration of vancomycin 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

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/minute 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.

Normal renal function.

Adults.

The usual intravenous dose is 500 mg (in sodium chloride 0.9% injection or glucose 5% in sterile water for injection) every six hours or 1 g every 12 hours. Each dose should be administered at no more than 10 mg/minute 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 48 to 72 hours. The total duration of therapy is determined by the type and severity of the infection and the clinical response of the patient. In staphylococcal endocarditis, therapy for three weeks or longer is recommended.

Children.

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

Infants and neonates.

In neonates and young infants, the total daily intravenous dosage may be lower. An initial dose of 15 mg/kg is suggested, followed by 10 mg/kg every 12 hours in the first week of life and every eight 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.

Impaired renal function and elderly patients.

Dosage adjustment must be made in patients with impaired renal function. In premature infants and 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 microbial 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 Table 1. The Vancomycin AN dose per day in mg is about 15 times the glomerular filtration rate in mL/minute.

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 bodyweight should be given in order to promptly achieve therapeutic serum concentrations. The dose required to maintain stable concentrations is 1.9 mg/kg/24 hours. 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 seven to ten days has been recommended.

Preparation of solution.

At the time of use, add 10 mL sterile water for injection to the vial of dry, sterile Vancomycin AN 500 mg (grey flip-off cap) or 20 mL sterile water for injection to the vial of Vancomycin AN 1000 mg (green flip-off cap). Please note that when the user penetrates the stopper to add water for injection to dissolve vancomycin, the needle's external diameter must not exceed 0.8 mm (21 Gauge). The penetration should be performed at the centre of the stopper and at an angle of 90 degrees in accordance to the surface of the stopper. If this angle deviates from 90 degrees, the needle can cut off part of the bottom edge of the stopper and leave it inside the vial. It is important the needle is not rotated during penetration, as it may act like a knife and cut part of the rubber stopper. Inspect the solution to confirm that it is clear and free of particles. Thereafter, further dilution is required. Intermittent infusion is the preferred method of administration. The solution containing Vancomycin AN 500 mg can be added to 100 to 200 mL of sodium chloride 0.9% injection or glucose 5% in sterile water for injection. The solution containing 1000 mg vancomycin can be added to 200 to 400 mL of sodium chloride 0.9% injection or glucose 5% in sterile water for injection. The desired dose, diluted in this manner to a concentration of 2.38 to 4.55 g/L may be administered by intravenous infusion over a period of at least 60 minutes every 6 or 12 hours.
Continuous infusion (should be used only when intermittent infusion is not feasible). 1 to 2 g vancomycin activity can be added to a sufficiently large volume of sodium chloride 0.9% injection or glucose 5% in sterile water for injection to permit the desired daily dose to be administered slowly by intravenous infusion over a 24 hour period.

Compatibility.

The following diluents are physically and chemically compatible (with Vancomycin AN 4 g/L): glucose 5% solution, glucose 5% and sodium chloride 0.9% solution, sodium chloride 0.9% solution.
To avoid microbial hazards, the solution 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.

Stability of prepared solution.

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

Warning.

Contains no antimicrobial agent (apart from the active ingredient itself). Product is for single use in one patient only. Discard any residue.

4.3 Contraindications

Known hypersensitivity to this antibiotic or other glycopeptides.

4.4 Special Warnings and Precautions for Use

General.

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

Hypersensitivity reactions.

Serious and occasionally fatal hypersensitivity reactions are possible (see Section 4.3 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.

Infusion reactions.

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

Cross-sensitivity reactions.

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

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.

Other.

Concurrent and sequential use of other neurotoxic and/or nephrotoxic antibiotics, particularly etacrynic acid, neuromuscular blocking agents, aminoglycoside antibiotics, polymyxin B, colistin, viomycin and cisplatin requires careful monitoring.
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 (see Section 4.2 Dose and Method of Administration, Compatibility with other drugs and intravenous fluids).
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 (see Section 4.2 Dose and Method of Administration, Compatibility with other drugs and intravenous fluids).

Ototoxicity.

Vancomycin AN should be avoided in patients with previous hearing loss. If it is used in such patients, the dose of Vancomycin AN should be regulated, if possible, by periodic determination of the drug level in the blood. Deafness may be preceded by tinnitus and should be regarded as an indication to discontinue treatment. The elderly is more susceptible to auditory damage. Experience with other antibiotics suggests that deafness may be progressive despite cessation of treatment. Patients with borderline renal function and individuals over the age of 60 years 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.). All patients receiving the drug should have periodic haematological studies, urinalyses, and liver and renal function tests.
Most of the patients who experienced hearing loss had kidney dysfunction, pre-existing hearing loss, or concomitant treatment with an ototoxic drug (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

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.

Prolonged use of Vancomycin AN 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.

Clostridioides difficile-associated disease.

In rare instances, there have been reports of pseudomembranous colitis due to Clostridioides difficile developing in patients who received intravenous vancomycin. C. difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including vancomycin hydrochloride, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use.
Vancomycin AN should be administered orally for the treatment of Staphylococcal enterocolitis and antibiotic associated pseudo membranous colitis produced by C. difficile. Parenteral administration of vancomycin alone is inappropriate for this indication.
Clinically significant serum concentrations have been reported in some patients being treated for active Clostridium difficile induced pseudomembranous colitis after multiple oral doses of vancomycin.

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.

Blood disorders.

Reversible neutropenia has been reported in patients receiving Vancomycin AN (see Section 4.8 Adverse Effects (Undesirable Effects)). Patients undergoing prolonged therapy with Vancomycin AN or who are receiving concomitant drugs, which may cause neutropenia, should have periodic monitoring of the leucocyte 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 in renal impairment.

Because of its ototoxicity and nephrotoxicity, Vancomycin AN should be used with care in patients with renal insufficiency. If it is necessary to use vancomycin parenterally in patients with renal impairment, the dose and/or dose intervals should be adjusted carefully (see Section 4.2 Dose and Method of Administration) and blood level monitored.
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)).

Effect on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concurrent administration of other neurotoxic (e.g. ototoxic) or nephrotoxic drugs, e.g. streptomycin, neomycin, gentamycin, kanamycin, amikacin, amphotericin B, bacitracin, tobramycin, polymyxin B, colistin, cisplatin or piperacillin/tazobactam, requires careful monitoring.
In order to minimise the risk of nephrotoxicity when treating patients with underlying renal dysfunction or those patients receiving concomitant therapy with 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 ethacrynic acid and furosemide may aggravate ototoxicity.
Cholestyramine has been shown to bind vancomycin in vitro. Therefore, if oral vancomycin is used with cholestyramine, the two drugs 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 drugs which may cause neutropenia should have periodic monitoring of the leucocyte count.
There have been reports that the frequency of infusion related events (including hypotension, flushing, erythema, urticaria and pruritus) increases with concomitant administration of anaesthetic agents. Infusion related events may be minimised by the administration of vancomycin at a rate not exceeding 500 milligrams per hour prior to anaesthetic induction.
Vancomycin may enhance neuromuscular blockade produced by drugs 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 reproductive 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 attributable to the administration of vancomycin. As only ten 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 fetal harm. Vancomycin AN should be given to a pregnant woman only if clearly needed and blood levels should be monitored carefully to minimise fetal toxicity.
 Vancomycin is excreted in human milk. Caution should be exercised when vancomycin is administered to a breastfeeding 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)

The incidence of adverse events with a frequency of < 1% (uncommon) include itch, fever, chills, eosinophilia, mild gastrointestinal tract disturbances (oral vancomycin), pain, erythema, thrombophlebitis, nephrotoxicity.
The incidence of adverse events with a frequency of < 0.01% (rare) include anaphylaxis, red man syndrome, superinfection, thrombocytopenia, leucopenia, tinnitus, dizziness, ototoxicity, toxic epidermal necrolysis.

Infusion related events.

During or soon after infusion of vancomycin, patients may develop anaphylactoid reactions including hypotension, bradycardia, cardiogenic shock, cardiac arrest, 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.

Cardiovascular.

Hypotension, palpitations, substernal pressure, tachycardia (see Infusion related events).

Gastrointestinal.

Nausea, vomiting, diarrhoea and pseudomembranous enterocolitis. Oral doses of vancomycin are extremely unpalatable and have been associated with nausea, diarrhoea and occasional vomiting.

Ear and labyrinth disorders.

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

Blood and lymphatic system disorders.

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

Dermatological.

Pruritus at the 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.

Immunological.

Hypersensitivity reactions with chills, nausea, urticaria, fever and rigors. Anaphylactoid reactions have been reported infrequently.

Skin and subcutaneous tissue disorders.

Rashes including exfoliative dermatitis, linear IgA bullous dermatosis, Stevens-Johnson syndrome, toxic epidermal necrolysis and rare cases of vasculitis. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and AGEP (Acute Generalised Exanthematous Pustulosis) have been reported.

Renal and urinary disorders.

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

Vascular disorders.

Phlebitis and vasculitis have been reported.

General.

The use of vancomycin may result in overgrowth of 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 effects 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 to www.tga.gov.au/reporting-problems.

4.9 Overdose

Treatment.

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 overdose, interaction among drugs and unusual drug kinetics in the 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.

The bactericidal action of vancomycin results primarily from inhibition of cell wall synthesis. In addition, vancomycin alters bacterial cell membrane permeability and RNA synthesis. Cross resistance with teicoplanin has been reported. Vancomycin is active against staphylococci, including Staphylococcus aureus and Staph. epidermidis (including heterogeneous methicillin resistant strains); streptococci including Streptococcus pyogenes, Strep. pneumoniae (including penicillin resistant strains), Strep. agalactiae, the viridans group, Strep. bovis, and enterococci (e.g. Enterococcus faecalis); Clostridium difficile (e.g. toxigenic strains implicated in pseudomembranous enterocolitis); and diphtheroids. Other organisms that are susceptible to vancomycin in vitro include Listeria monocytogenes, Lactobacillus sp., Actinomyces sp., Clostridium sp., and Bacillus sp. 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 Staph. aureus, nonenterococcal group D streptococci, enterococci, and Streptococcus sp. (viridans group). The combination of vancomycin and a cephalosporin acts synergistically against some strains of Staph. epidermidis (methicillin resistant). The combination of vancomycin and rifampicin acts with partial synergism against some strains of Staph. aureus and with synergism against Staph. epidermidis. Synergy testing is helpful because the combination of vancomycin and a cephalosporin may act antagonistically against some strains of Staph. epidermidis, and the combination of vancomycin and rifampicin may act antagonistically against some strains of Staph. aureus.

Disc susceptibility tests.

Dilution or diffusion techniques - either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. NCCLS). Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.
A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable; other therapy should be selected.

Note.

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

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Vancomycin AN is poorly absorbed after oral administration; and it is therefore given intravenously for therapy of systemic infections.
In subjects with normal renal function, multiple intravenous dosing of vancomycin 1 g (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 two hours after infusion, and mean plasma concentrations of approximately 8 mg/L eleven 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, mean plasma concentrations of about 19 mg/L two hours after infusion, and mean plasma concentrations of about 10 mg/L six hours after infusion. The plasma concentrations during multiple dosing are similar to those after a single dose.
Although commonly done, measurement of peak plasma levels has not been proven to correlate with either efficacy or toxicity. Monitoring of trough levels is useful in patients with abnormal volumes of distribution or abnormal renal function. Trough levels should be maintained between 10 and 20 mg/L, and sampled immediately before the next dose is administered. Peak levels, when measured, are usually in the range of 25 to 40 mg/L. Levels outside this range suggest abnormal volumes of distribution and dosage adjustments should be considered.
About 60% of an intraperitoneal dose of vancomycin administered during peritoneal dialysis is absorbed systemically in six hours. Serum concentrations of about 10 mg/L are achieved by intraperitoneal injection of vancomycin 30 mg/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.
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.
Measurable serum concentrations of vancomycin may occur in patients treated for active pseudomembranous colitis due to Clostridium difficile.

Distribution.

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.

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/hour, and mean renal clearance is about 0.05 L/kg/hour. Renal dysfunction slows excretion of vancomycin.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Vancomycin AN does not contain any excipients.

6.2 Incompatibilities

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

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 25° C. Protect from light.

6.5 Nature and Contents of Container

Vancomycin AN 500 mg.

Type I clear glass vial containing vancomycin hydrochloride 513 mg (equivalent to vancomycin 500 mg) sealed with a grey flip-off cap. Available in packs of 1, 5 and 10 vials.

Vancomycin AN 1000 mg.

Type I clear glass vial containing vancomycin hydrochloride 1026 mg (equivalent to vancomycin 1000 mg) sealed with a green flip-off cap. Available in packs of 1 and 5 vials.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Vancomycin AN is a chromatographically purified tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis, which is bactericidal against many Gram-positive bacteria.
Molecular formula: C66H75Cl2N9O24.HCl.
Molecular Weight: 1486.

CAS number.

CAS Number: 1404-93-9.

Chemical structure.


7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (S4).

Summary Table of Changes