Consumer medicine information

Vancomycin Alphapharm

Vancomycin

BRAND INFORMATION

Brand name

Vancomycin Alphapharm

Active ingredient

Vancomycin

Schedule

SUMMARY CMI

VANCOMYCIN ALPHAPHARM

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 healthcare professional.

1. Why am I being treated with VANCOMYCIN ALPHAPHARM?

VANCOMYCIN ALPHAPHARM contains the active ingredient vancomycin hydrochloride. Vancomycin is used to treat severe bacterial infections. For more information, see Section 1. Why am I using VANCOMYCIN ALPHAPHARM? in the full CMI.

2. What should I know before being treated with VANCOMYCIN ALPHAPHARM?

Do not start treatment if you/your child have ever had an allergic reaction to vancomycin, other antibiotics that are the same type, or any of the ingredients listed at the end of the CMI. Your doctor will know which antibiotics are the same type. Talk to your doctor if you/your child have had any allergic reaction to any antibiotic; have kidney or hearing problems, have inflammatory bowel disorders; take any other medicines; or are pregnant, plan to become pregnant or are breastfeeding. 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. For more information, see Section 2. What should I know before I use VANCOMYCIN ALPHAPHARM? 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 is VANCOMYCIN ALPHAPHARM given?

The doctor will decide how much vancomycin is needed. It will depend on factors such as the type of infection, age and bodyweight and if you/your child have kidney problems. More instructions can be found in Section 4. How do I use VANCOMYCIN ALPHAPHARM? in the full CMI.

5. What should I know while being treated with VANCOMYCIN ALPHAPHARM?

Things you should do	Tell your healthcare professional immediately if you develop a rash or any other sign of allergic reaction (shortness of breath, wheezing or difficulty breathing, swelling of the lips, face, throat, tongue or other parts of the body, rash, itching or hives on the skin)
Things you should not do	You/your child should not be treated with vancomycin if you/your child have had an allergic reaction to vancomycin, the same type of antibiotics as vancomycin, or any of the other ingredients listed in Section 7. Product details. Your doctor will know which antibiotics are the same type as vancomycin.
Driving or using machines	Be careful before you drive a car or operate machinery until you know how vancomycin affects you. Vancomycin may cause dizziness in some people.
Looking after your medicine	Store in original carton at below 25°C until ready for use.

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

6. Are there any side effects?

Side effects of this medicine may include allergic reactions (chest pain, shortness of breath, wheezing or difficulty breathing, swelling of the lips, face, throat, tongue or other parts of the body, rash, itching or hives on the skin); rash or severe skin reaction that may be accompanied with a fever; severe stomach or abdominal cramps; nausea or vomiting, appetite loss, weight loss; fatigue, general aches and pains, pale skin; severe blisters and bleeding in the lips, eyes, mouth, nose or genitals; vertigo, dizziness, ringing in the ears or hearing loss; pain and irritation at the injection site; extremely tender, swelling and redness along a vein; fast, slow or irregular heartbeat, heart attack, drowsiness, loss of consciousness, sweating, restlessness; upper body flushing, chest and backpain and muscle spasm; watery and severe diarrhoea which may also be bloody; fever, chills, other infections; bruising more than usual; kidney problems, little or no urine.

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 ALPHAPHARM

Active ingredient: Vancomycin hydrochloride

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

1. Why am I being treated with VANCOMYCIN ALPHAPHARM?
2. What should I know before being treated with VANCOMYCIN ALPHAPHARM?
3. What if I am taking other medicines?
4. How is VANCOMYCIN ALPHAPHARM given?
5. What should I know while being treated with VANCOMYCIN ALPHAPHARM?
6. Are there any side effects?
7. Product details

1. Why am I being treated with VANCOMYCIN ALPHAPHARM?

VANCOMYCIN ALPHAPHARM contains the active ingredient vancomycin hydrochloride. VANCOMYCIN ALPHAPHARM is a glycopeptide antibiotic use to treat severe bacterial infections.

2. What should I know before being treated with VANCOMYCIN ALPHAPHARM?

Warnings

You/your child should not be given VANCOMYCIN ALPHAPHARM if you/your child are:

allergic to vancomycin, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine.
allergic to or have previously had a severe allergic reaction to similar antibiotics as VANCOMYCIN ALPHAPHARM. Your doctor will know which antibiotics are the same type as VANCOMYCIN ALPHAPHARM.

Check with your doctor if you/your child:

have kidney problems
have hearing problems
have inflammatory bowel disorders
are taking 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.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor can discuss with you the risks and benefits involved.

3. What if I am taking other medicines?

Tell your healthcare professional 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.

Some medicines may interfere with VANCOMYCIN ALPHAPHARM and affect how it works.

These include:

some other antibiotic medicines used to treat infections, such as aminoglycoside antibiotics (e.g. amikacin, gentamicin, neomycin and tobramycin), cephalosporin antibiotics (e.g. cefalexin, cefalotin, cefazolin, cefoxitin, cefuroxime, cefamandole, cefaclor, cefotaxime, ceftazidime, ceftriaxone, cefepime, ceftaroline, fosamil, ceftolozane), colistin, colistimethate sodium, capreomycin, piperacillin/tazobactam, clindamycin, ethambutol hydrochloride, and sulfadiazine
amphotericin B, a medicine used to treat fungal infections
medicine used to control and treat viral injections e.g. elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide, tenofovir alafenamide, adefovir dipivoxil, emtricitabine with tenofovir alafenamide, and cidofovir
ciclosporin or tacrolimus, medicine used to suppress the immune system after organ transplants, severe rheumatoid arthritis, severe psoriasis, atopic dermatitis (skin allergies), and dry eye disease
sulfasalazine, medicine used to treat inflammatory bowel diseases such as ulcerative colitis and Crohn's disease, and rheumatoid arthritis.
some medicines used to treat pain and inflammation such as naproxen, ketorolac trometamol, flurbiprofen, and methoxyflurane
etoricoxib, a medicine used to treat osteoarthritis, gout attacks, and relieve short-term pain
medicines used to treat certain cancers, including cisplatin, carmustine, cyclophosphamide mitomycin, Mycobacterium bovis (Bacillus Calmette and Guerin (BCG) strain, and teicoplanin
antithyroid medicines (e.g. propylthiouracil and carbimazole)
clozapine, medicine used mainly in the treatment of schizophrenia
fluid tablets (diuretics), such as furosemide (frusemide) and bumetanide
anaesthetic agents, e.g. halothane, isoflurane, desflurane, sevoflurane, thiopental, fentanyl, alfentanil, ketamine, propofol, nitrous oxide, and esketamine
colestyramine, a powder taken to lower cholesterol levels
medicines used to relax muscles, such as suxamethonium, vecuronium, pancuronium, atracurium, cisatracurium, rocuronium bromide, mivacurium chloride, and botulinum toxin.

Check with your healthcare professional if you are not sure about what medicines, vitamins or supplements you are taking and if these affect VANCOMYCIN ALPHAPHARM.

4. How is VANCOMYCIN ALPHAPHARM given?

How much will be given?

The doctor will decide what dose of VANCOMYCIN ALPHAPHARM is needed depending on certain factors such as the type of infection, age, bodyweight, and if you/your child have kidney problems.

How long will VANCOMYCIN ALPHAPHARM need to be given?

A course of treatment depends on the type, severity of the infection and how you/your child responds. The doctor will decide how many days you will need treatment with VANCOMYCIN ALPHAPHARM. VANCOMYCIN ALPHAPHARM should be used

How is VANCOMYCIN ALPHAPHARM given?

VANCOMYCIN ALPHAPHARM is given as either an injection into a vein or my mouth, depending on the infection. Vancomycin has an offensive taste.

If too much VANCOMYCIN ALPHAPHARM is given

As VANCOMYCIN ALPHAPHARM is generally given to you in hospital under the supervision of your healthcare professional, it is very unlikely that you will receive an overdose. Symptoms of a vancomycin overdose include the effects listed below in Section 6. Are there any side effects?

You should immediately:

phone the Poisons Information Centre
(Australia telephone 13 11 26) for advice, or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while being treated with VANCOMYCIN ALPHAPHARM?

Things you should do

Remind any doctors, nurses, dentists and pharmacists you see that you/your child are being given VANCOMYCIN ALPHAPHARM.
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.
If you become pregnant soon after being given vancomycin, tell your doctor.

Tell your healthcare professional straight away if you/ your child:

get severe diarrhoea, severe abdominal or stomach cramps
get a fever, in combination with one of all of the above.

Do this even if it occurs several weeks after VANCOMYCIN ALPHAPHARM has been stopped.

Diarrhoea may be caused by a serious condition affecting the bowel. You or your child may need urgent medical care.

Driving or using machines

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

VANCOMYCIN ALPHAPHARM may cause dizziness in some people.

Looking after your medicine

VANCOMYCIN ALPHAPHARM will be stored in the pharmacy or on the ward. The injection is kept in a cool, dry place away from moisture, heat or sunlight, where the temperature stays below 25°C. The expiry date will be checked that it has not passed.

6. Are there any side effects?

All medicines can have side effects. If you/your child 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 healthcare professional if you have any further questions about side effects.

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

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

Tell your healthcare professional 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 healthcare professional 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 ALPHAPHARM contains

Active ingredient (main ingredient)	Vancomycin hydrochloride
Other ingredients (inactive ingredients)	hydrochloric acid sodium hydroxide

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

What VANCOMYCIN ALPHAPHARM looks like

VANCOMYCIN ALPHAPHARM is a white to off-white powder, which will be dissolved to a clear solution before it is given to you.

VANCOMYCIN ALPHAPHARM is available in the following strengths:

VANCOMYCIN ALPHAPHARM 500 mg (as hydrochloride) powder for Injection Vial AUST R 153438
VANCOMYCIN ALPHAPHARM 1 g (as hydrochloride) powder for Injection Vial AUST R 153439

Sponsor

Alphapharm Pty Ltd trading as ALPHAPHARM
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.ALPHAPHARM.com.au
Phone: 1800 274 276

This leaflet was prepared in May 2023.

VANCOMYCIN ALPHAPHARM_cmi\May23/00

Published by MIMS June 2023

BRAND INFORMATION

Brand name

Vancomycin Alphapharm

Active ingredient

Vancomycin

Schedule

1 Name of Medicine

Vancomycin hydrochloride.

2 Qualitative and Quantitative Composition

Vancomycin Alphapharm 500 mg.

Each vial contains 500 mg (500,000 IU) of vancomycin (as hydrochloride).

Vancomycin Alphapharm 1000 mg.

Each vial contains 1000 mg (1,000,000 IU) of vancomycin (as hydrochloride).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for injection. White to almost white or slightly pink or yellow freeze dried powder.

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 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 is effective alone or in combination with an aminoglycoside for endocarditis caused by S. viridans or S. bovis. For endocarditis caused by enterococci (e.g. S. faecalis), vancomycin is effective only in combination with an aminoglycoside. Vancomycin is effective for the treatment of diphtheroid endocarditis. Vancomycin is used in combination with rifampicin, an aminoglycoside, or both in early onset prosthetic valve endocarditis caused by S. epidermidis or diphtheroids.
The effectiveness of vancomycin has been documented in other infections due to Staphylococci including osteomyelitis, pneumonia, septicaemia and, skin and skin structure infections. When staphylococcal infections are localised and purulent, antibiotics are used as adjuncts to appropriate surgical measures.
Specimens for bacteriological cultures should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to vancomycin.
Vancomycin should be administered orally for the treatment of staphylococcal enterocolitis and antibiotic associated pseudomembranous 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

Vancomycin hydrochloride for intravenous infusion is a lyophilized powder for reconstitution. When reconstituted in water, it is a clear solution with a pH of 2.8 to 4.5. It should be administered intravenously in dilute solution.
This product is for single use in one patient only. Discard any residue.
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 of 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 every 6 hours or 1000 mg every 12 hours. A 500 mg dose of vancomycin should be infused over a period of at least 60 minutes, whereas a 1000 mg dose should be administered over a period of at least two hours. Vancomycin must not be given by intramuscular injections (see Section 4.4 Special Warnings and Precautions for Use).
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.

Adults with impaired renal function and the elderly.

Dosage adjustment must be made in patients with impaired renal function to avoid toxic serum levels. In the elderly, dosage reduction may be necessary to a greater extent than expected because of decreasing renal function. Measurement of vancomycin serum concentrations is required to optimise therapy, especially in seriously ill patients with changing renal function. Vancomycin serum concentrations may be determined by use of a microbiological assay, a radioimmunoassay, a fluorescence 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 dose per day in mg is about 15 times the glomerular filtration rate in mL/minute (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.

Table 1 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 (250,000 IU) to 1,000 (1,000,000 IU) mg are convenient, in patients with marked renal impairment, a dose may be given every several days rather than on a daily basis. In anuria, a dose of 1,000 mg every seven to ten days has been recommended.
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 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 twelve hours in the first week of life and every eight hours thereafter until one month of age. Close monitoring of serum vancomycin concentrations is mandatory in these patients. Each dose should be administered over a period of at least 60 minutes.

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 three or four divided doses for 7 to 10 days. The total daily dosage in children is 40 mg/kg bodyweight in three or four divided doses. The total daily dosage should not exceed 2 g.
After initial reconstitution of the vial 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.

Preparation of solution for injection.

At the time of use, the 500 mg (500,000 IU) vial should be reconstituted with 10 mL of water for injections. The resulting solution contains vancomycin 50 mg/mL. The 1000 mg (1,000,000 IU) vial should be reconstituted with 20 mL of water for injections. The resulting solution contains vancomycin 50 mg/mL. The reconstituted solution containing 500 mg of vancomycin must be further diluted with at least 100 mL of sodium chloride intravenous infusion 0.9% or glucose intravenous infusion 5%. The reconstituted solution containing 1000 mg of vancomycin must be further diluted with at least 200 mL of sodium chloride intravenous infusion 0.9% or glucose intravenous infusion 5%. The resulting solution should be infused over a period of at least 60 minutes when 500 mg of vancomycin is to be administered, or at least 2 hours when 1000 mg of vancomycin is to be given. In selected patients in need of fluid restriction, a concentration of up to 10 mg/mL may be used; use of such higher concentration may increase the risk of infusion related events. Infusion related events may occur, however, at any rate of concentration.

4.3 Contraindications

Vancomycin is contraindicated in patients with known hypersensitivity to vancomycin or any of the excipients 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 functions and of vancomycin blood levels. All patients receiving the drug should have periodic haematological studies, urine analysis, and renal functional 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.

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 should be administered in a dilute solution at a rate not exceeding 500 milligram/hour to avoid rapid infusion related reactions, e.g. hypotension, flushing, erythema, urticaria and pruritus. 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)).
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 injection sites are rotated.

Use in renal impairment.

Because of its ototoxicity and nephrotoxicity, vancomycin should be used with care in patients with renal insufficiency. If it is necessary to use vancomycin parenterally in patients with renal impairment, the dose and/or dose intervals should be adjusted carefully (see Section 4.2 Dose and Method of Administration) and blood levels monitored. Serial monitoring of renal function should be performed.
When patients receive concomitant therapy with an aminoglycoside, serial monitoring of renal function should be performed.

Ototoxicity.

Ototoxicity has occurred when serum levels exceeded 80 microgram/mL. 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 (if possible) in patients with previous hearing loss. If it is used in such patients, the dose of vancomycin should be regulated by periodic determination of drug levels in the blood. Patients with renal insufficiency and individuals over the age of 60 should be given serial tests of auditory function and of vancomycin blood levels. All patients receiving the drug should have periodic hematologic studies, urinalyses, and liver and renal function tests.
Most of the patients who experienced hearing loss had kidney dysfunction, pre-existing hearing loss, or concomitant treatment with an ototoxic drug (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

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.

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.

The safety and efficacy of vancomycin administration by the intrathecal (intralumbar or intraventricular) route have not been assessed.
Reports have revealed that administration of sterile vancomycin hydrochloride by the intraperitoneal route during continuous ambulatory peritoneal dialysis (CAPD) has resulted in a syndrome of chemical peritonitis. To date, this syndrome has ranged from a cloudy dialysate alone to a cloudy dialysate accompanied by varying degrees of abdominal pain and fever. This syndrome appears to be short lived after discontinuation of intraperitoneal vancomycin.
If parenteral and oral vancomycin are administered concomitantly, an additive effect can occur. This should be taken into consideration when calculating the total dose. In this situation, serum levels of the antibiotic should be monitored.
Some patients with inflammatory disorders of the intestinal mucosa 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.

The use of vancomycin may result in overgrowth of non-susceptible organisms. If new infections due to bacteria or fungi appear during therapy with this product, appropriate measures should be taken including withdrawal of vancomycin.

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. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.

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.

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.

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 administration with other neurotoxic (e.g. ototoxic) or nephrotoxic drugs e.g. streptomycin, neomycin, gentamicin, kanamycin, amikacin, amphotericin B, bacitracin, tobramycin, polymyxin B, colistin, cisplatin or piperacillin/tazobactam, requires careful monitoring (see Section 4.4 Special Warnings and Precautions for Use).
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.
Colestyramine has been shown to bind vancomycin in vitro. Therefore, if oral vancomycin is used with colestyramine, 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 at a rate not exceeding 500 milligram/hour 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 definitive fertility studies have been performed.
(Category B2)
Animal reproduction studies have not been conducted with vancomycin hydrochloride. It is not known whether vancomycin hydrochloride can affect reproduction capacity. In a controlled clinical study, vancomycin was administered to pregnant women for serious staphylococcal infections complicating intravenous 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 fetal harm. Vancomycin hydrochloride for intravenous infusion 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 breast milk but it is not known whether it is harmful to the newborn. Therefore, it is not recommended for nursing mothers unless the expected benefits outweigh any potential risk.

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)

General disorders and administration site conditions.

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 (epinephrine), corticosteroids and oxygen. Rapid infusion may cause flushing of the upper body ("red neck") or pain and muscle spasm of the chest and back. These reactions usually resolve within 20 minutes, but may persist for several hours. Such events are infrequent if vancomycin is given by a slow infusion at a rate not exceeding 500 milligram/hour and at an appropriate dilution.
Pruritus at injection site, generalised flushing, erythematous macular rash with intense pruritus over face, neck and upper body have occurred after too rapid injection of the 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.

Ear and labyrinth disorders.

Sensorineural deafness which may be accompanied by tinnitus has occurred but the incidence is low. Permanent deafness is more likely to occur in patients with compromised auditory or renal function but reversible deafness has been reported in normal patients. Vertigo and dizziness have also been reported.

Gastrointestinal disorders.

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

Blood and lymphatic system disorders.

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

Immune system disorders.

Anaphylaxis and hypersensitivity reactions with chills, nausea, urticaria, macular rash, fever and rigors. Kounis syndrome has also been reported.

Skin and subcutaneous tissue disorders.

The types of rashes that can occur include exfoliative dermatitis, Linear IgA bullous dermatosis, Stevens-Johnson syndrome, toxic epidermal necrolysis and rare cases of vasculitis.
Drug reaction with eosinophilia and systemic symptoms (DRESS) and AGEP (acute generalised exanthematous pustulosis) have been reported. Anaphylactoid reactions have been reported infrequently (see General disorders and administration site conditions).

Renal and urinary disorders.

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

Vascular disorders.

Phlebitis and vasculitis have been reported.

General.

The use of vancomycin may result in overgrowth of non-susceptible organisms resulting in new bacterial or fungal infections. If the new infections due to bacteria or fungi appear during therapy with this product, appropriate measures should be taken.
Chemical peritonitis has been reported following intraperitoneal administration of vancomycin (see Section 4.4 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 www.tga.gov.au/reporting-problems.

4.9 Overdose

Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is not effectively removed by either haemodialysis or peritoneal dialysis. Increased vancomycin clearance has been reported with highly permeable membranes (polysulfone resin) used in high-flux haemodialysis. At 4 to 6 hours following the onset of high-flux haemodialysis, steady state concentrations of vancomycin may be reduced by 10 to 15% of the predialysis concentrations. It has also been reported that haemoperfusion with XAD-4 Resin has been shown to be of benefit.
In managing overdosage, consider the possibility of multiple drug overdoses, interaction among medicines, 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.

Vancomycin is an amphoteric glycopeptide antimicrobial substance produced by the growth of certain strains of Amycolatopsis orientalis (formerly Nocardia orientalis). It is bactericidal against many gram-positive organisms. Vancomycin is not chemically related to any of the presently used antimicrobial agents. Vancomycin hydrochloride is freely soluble in water and insoluble in alcohol.

Microbiology.

Vancomycin is active against many gram-positive organisms (see below). Gram-negative bacteria, mycobacteria and fungi are resistant. Many strains of gram-positive bacteria are sensitive in vitro to vancomycin concentrations of 0.5 to 5 microgram/mL, but a few Staph. aureus strains require 10 to 20 microgram/mL for inhibition.
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); Clostridioides difficile (e.g. toxigenic strains implicated in pseudomembranous enterocolitis); diphtheroids (e.g. JK corynebacterium). Other organisms that are susceptible to vancomycin in vitro include Listeria monocytogenes, Lactobacillus species, Actinomyces species, Clostridioides species, and Bacillus species.
The combination of vancomycin and an aminoglycoside acts synergistically in vitro against many strains of S. aureus, nonenterococcal group D Streptococci, Enterococci, and Streptococcus species (viridans group).
The combination of vancomycin and a cephalosporin acts synergistically against some strains of S. epidermidis (methicillin resistant). The combination of vancomycin and rifampicin acts with partial synergism against some strains of S. aureus and with synergism against S. epidermidis. Synergy testing is helpful because the combination of vancomycin and a cephalosporin may act antagonistically against some strains of S. epidermidis, and the combination of vancomycin and rifampicin may act antagonistically against some strains of S. aureus.
Vancomycin appears to act by inhibiting the production of bacterial cell wall mucopeptide. This effect occurs at a site different from that affected by penicillins and produces immediate inhibition of cell wall synthesis and secondary damage to the cytoplasmic membrane. There is also evidence that vancomycin alters the permeability of the cell membrane and selectively inhibits RNA synthesis.
There is no cross resistance between vancomycin and other antibiotics.

Susceptibility tests.

Dilution or diffusion techniques, either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. NCCLS). Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.
A report of "susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "intermediate" indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible 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 concentrations usually achievable: other therapy should be selected.
Note: The prevalence of resistance may vary geographically for selected species and local information on resistance is desirable, particularly when treating severe infections.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Vancomycin is poorly absorbed by mouth. It is given intravenously for the treatment of systemic infections. In subjects with normal renal function participating in a multi-dose study, 1000 mg (1,000,000 IU) given over 60 minutes produced mean plasma levels of approximately 63 microgram/L immediately after the completion of infusion, and mean plasma levels of approximately 23 microgram/L and approximately 8 microgram/L at 2 hours and 11 hours respectively, after completion of the infusion. Serum levels will be higher in patients with renal impairment, and toxicity may result.

Distribution.

Protein binding is approximately 55% as measured by ultrafiltration at vancomycin serum concentrations of 10 to 100 microgram/mL. 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. Vancomycin does not readily diffuse across the meninges into the cerebrospinal fluid.
Measurable serum concentrations of vancomycin may occur in patients treated with oral vancomycin for active pseudomembranous colitis due to Clostridioides difficile.

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 the 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. 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.
Vancomycin is not effectively removed by either haemodialysis or peritoneal dialysis; there have been no reports of vancomycin clearance with haemoperfusion.
Total systemic and renal clearance of vancomycin may be reduced in the elderly.

5.3 Preclinical Safety Data

Genotoxicity.

There are no studies available demonstrating the mutagenic potential of vancomycin.

Carcinogenicity.

No long term carcinogenicity studies have been performed using vancomycin in animals.

6 Pharmaceutical Particulars

6.1 List of Excipients

Hydrochloric acid, nitrogen and water for injections.

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. 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.

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

Store below 25°C in original container. Protect from light.
Also see Section 4.2 Dose and Method of Administration, Stability of prepared solution.

6.5 Nature and Contents of Container

The injections are packaged in a clear type II glass vial with a bromobutyl stopper - packs of 1 vial/carton.

Australian register of therapeutic goods (ARTG).

AUST R 153438 - Vancomycin Alphapharm 500 mg vancomycin (as hydrochloride) powder for injection vial.
AUST R 153439 - Vancomycin Alphapharm 1000 mg vancomycin (as hydrochloride) powder for injection vial.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

Molecular Formula: C₆₆H₇₅Cl₂N₉O₂₄,HCl.
Molecular Weight: 1485.7.

CAS number.

CAS No: 1404-93-9.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

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