Consumer medicine information

Metronidazole Juno

Metronidazole

BRAND INFORMATION

Brand name

Metronidazole Juno

Active ingredient

Metronidazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Metronidazole Juno.

SUMMARY CMI

Metronidazole Juno

Consumer Medicine Information (CMI) summary

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

1. Why am I given Metronidazole Juno?

Metronidazole Juno contains the active ingredient metronidazole. Metronidazole Juno is used to treat serious infections caused by bacteria and other organisms and to prevent certain infections that may occur during surgery.

For more information, see Section 1. Why am I being given Metronidazole Juno? in the full CMI.

2. What should I know before I am given Metronidazole Juno?

Do not use if you have ever had an allergic reaction to Metronidazole or any of the ingredients listed at the end of the CMI. Tell your doctor if you drink alcohol or ingest products containing propylene glycol or if you are on a low sodium diet.

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

For more information, see Section 2. What should I know before I am given Metronidazole Juno? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Metronidazole Juno 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 will I be given Metronidazole Juno?

Metronidazole Juno is given by injection into a vein. The usual adult dose of Metronidazole Juno is 500 mg every eight hours for the course of treatment, or as decided by your doctor.

More instructions can be found in Section 4. How will I be given Metronidazole Juno? in the full CMI.

5. What should I know while using Metronidazole Juno?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Metronidazole Juno.
  • If you get a sore, white mouth or tongue while receiving or soon after stopping Metronidazole Juno, tell your doctor. Also tell your doctor if you get vaginal itching or discharge.
  • If you get severe diarrhoea tell your doctor, pharmacist or nurse immediately. Do not take any diarrhoea medicine without first checking with your doctor.
Things you should not do
  • Do not drink any alcohol or ingest products containing propylene glycol while being treated with (and for at least three days after stopping) Metronidazole Juno
Driving or using machines
  • Be careful driving or operating machinery until you know how Metronidazole Juno affects you.
  • This medicine may cause dizziness, confusion, hallucination (hearing or seeing strange or unusual things), convulsions (“fits”) or affect how you see things. Some adverse reactions may impair the ability to drive or operate machines.
Drinking alcohol
  • Tell your doctor if you drink alcohol or ingest products containing propylene glycol.
  • The use of alcohol or alcohol-containing products before, during and up to 72 hours after receiving metronidazole may make you feel sick, vomit or have stomach cramps, headaches, tachycardia or flushing.
Looking after your medicine
  • This medicine will be stored in the pharmacy or on the ward.
  • It will be kept in a cool, dry place, protected from light, where the temperature stays below 25°C.

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

6. Are there any side effects?

Side effects may occur, such as vaginal or oral thrush, vomiting, diarrhoea, metallic taste, dryness of the mouth, confusion, irritability, hypersensitivity reactions (such as swelling of the face, lips, mouth, throat or neck which may cause difficulty swallowing or breathing, skin reactions).

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

Metronidazole Juno

Active ingredient: Metronidazole

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

1. Why am I being given Metronidazole Juno?
2. What should I know before I am given Metronidazole Juno?
3. What if I am taking other medicines?
4. How will I be given Metronidazole Juno?
5. What should I know while using Metronidazole Juno?
6. Are there any side effects?
7. Product details

1. Why am I being given Metronidazole Juno?

Metronidazole Juno contains the active ingredient Metronidazole.

Metronidazole is antibiotic which aims to kill or stop the growth of bacteria that cause infection.

Metronidazole Juno is used to:

  • Treat serious bacterial infections when antibiotics cannot be given orally
  • Prevent certain infections that may occur after surgery.

Ask your doctor if you have any questions about why Metronidazole Juno has been prescribed for you.

Your doctor may have prescribed Metronidazole Juno for another reason.

This medicine is not addictive. This medicine is only available with a doctor's prescription.

2. What should I know before I am given Metronidazole Juno?

Warnings

Do not use Metronidazole Juno if:

  • You are allergic to Metronidazole, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine. Symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.
  • You have/have had a blood disorder.
  • You have a disease or disorder involving the brain, spinal cord or nerves.
  • You have taken disulfiram (a medicine used to treat chronic alcohol dependence) within the last two weeks.
  • You have drunk any alcohol or products containing propylene glycol.
  • You have Cockayne syndrome.

If you are unsure whether you should be given this medicine, talk to your doctor.

Check with your doctor if you:

  • Have or have had any of the following medical conditions:
    - blood disease or history of blood disease
    - disease or disorder involving the brain, spinal cord or nerves
    - liver disease or any liver problems
    - heart disease or any heart problems
    - any kidney problems
    - Crohn's disease, an inflammatory disease of the intestines
  • Drink alcohol. Do not drink alcohol during (and for 3 days after stopping) treatment with metronidazole.
  • Are on a low sodium diet.

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.

Metronidazole Juno may affect your developing baby if you use it during pregnancy.

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

Metronidazole passes into breast milk and may affect your baby.

If you have not told your doctor about any of the above, tell your doctor before you are given Metronidazole.

Contraceptives

Talk to your doctor about the need for additional method of contraception while receiving Metronidazole Juno.

Some antibiotics may decrease the effectiveness of some birth control pills, although this has not been shown with metronidazole.

3. What if I am taking other medicines?

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

Some medicines may interfere with metronidazole. These include:

  • warfarin, or other medicines used to prevent blood clots
  • disulfiram, a medicine used to treat chronic alcohol dependence
  • some anticancer medicines such as carmustine, cyclophosphamide, fluorouracil and 5-fluorouracil and busulfan
  • azathioprine, a medicine used to suppress the immune system
  • lithium, a medicine used to treat some types of depression
  • corticosteroids such as prednisone or cortisone
  • cimetidine, a medicine used to treat ulcers
  • phenytoin, a medicine used to treat convulsions
  • phenobarbitone, a medicine to treat convulsions or for sedation
  • ciclosporin, a medicine used to help prevent organ transplant rejection or to treat certain problems with the immune system
  • medicines that affect the heart rate or heart rhythm.

These medicines may be affected by metronidazole 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 will advise you.

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

4. How will I be given Metronidazole Juno?

How Metronidazole Juno is given

Metronidazole Juno is given by injection into a vein.

It must only be given by a doctor or nurse.

Your doctor will decide what dose of metronidazole to give you and how long you will need to be given this medicine for.

The dose will vary from patient to patient. This will depend on your age, weight, type of infection and how well your kidneys and liver are working. However, the usual adult dose of Metronidazole Intravenous Infusion is 500mg every eight hours for the course of treatment, as decided by your doctor.

Your doctor will decide the right dose for you. However, depending on your condition and how you react to the medicine, your doctor may give you a different dose.

If you are given too much Metronidazole Juno

As Metronidazole Juno is most likely to be given to you in hospital under the supervision of your doctor, it is very unlikely that you will be given too much. However if you experience severe side effects tell your doctor immediately.

Symptoms of an overdose may include the side effects listed below in the 'Side Effects' section but are usually of a more severe nature.

You should immediately: phone the Poisons Information Centre (by calling 13 11 26), contact your doctor, or go to the Emergency Department at your nearest hospital.

5. What should I know while using Metronidazole Juno?

Things you should do

Call your doctor straight away if:

  • You become pregnant while you are being treated with Metronidazole Juno.
  • You get severe diarrhoea. Do this even if it occurs several weeks after Metronidazole Juno has been stopped. Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care. Do not take an diarrhoea medicine without first checking with your doctor.
  • You get any type of skin rash. Metronidazole can increase your risk of serious and sometimes fatal reactions. These skin reactions may appear as a skin rash that can be widespread with blisters, swelling, pain, burning, itching or peeling, often with fever.

Tell your doctor if:

  • The symptoms of your infection do not improve, or if they become worse.
  • You get a sore, white mouth or tongue while receiving or soon after stopping Metronidazole Juno. Also tell your doctor if you get vaginal itching or discharge. This may mean you have a fungal / yeast infection called thrush. Sometimes the use of metronidazole allows fungi / yeast to grow and the above symptoms to occur. Metronidazole does not work against fungi / yeast.

If you are using Metronidazole Juno for 10 days or longer, make sure you have any tests of your blood and nervous system that your doctor may request.

If you are about to start using any new medicine, tell your doctor and pharmacist that you are being treated with Metronidazole Juno.

If you need to have any other blood tests, tell your doctor you are receiving Metronidazole Juno. Metronidazole may affect the results of some laboratory tests.

Remind any doctor, dentist or pharmacist you visit that you are using Metronidazole Juno.

Things you should not do

Do not drink alcohol or any alcoholic drinks while being treated with (and for at least three day after stopping) Metronidazole Juno. The use of alcohol or products containing propylene glycol with metronidazole may make you feel sick, vomit or have stomach cramps, headaches or flushing.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Metronidazole Juno affects you.

Metronidazole Juno may cause dizziness, confusion, hallucination (hearing or seeing strange or unusual things), convulsions (“fits”) or affect how you see things. Some adverse reactions to metronidazole may impair the ability to drive or operate machines.

Drinking alcohol

Tell your doctor if you drink alcohol or ingest products containing propylene glycol.

Do not drink alcohol or ingest products containing propylene glycol before, during and at least three days after stopping treatment with Metronidazole Juno. Metronidazole and alcohol or products containing propylene glycol together can cause abdominal cramps, nausea, vomiting, headaches, tachycardia (fast heart rate) and flushing.

Looking after your medicine

Metronidazole Juno will be stored appropriately in the pharmacy or on the ward.

The infusion should be kept in a cool dry place, protected from light, where the temperature stays below 25°C.

6. Are there any side effects?

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

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

Less serious side effects

Less serious side effectsWhat to do
  • nausea, vomiting, loss of appetite
  • abdominal pain, indigestion or discomfort
  • constipation/diarrhoea
  • metallic or unpleasant taste in the mouth
  • swollen red or sore tongue
  • sore red mouth
  • ulcers or cold sores
  • oral thrush - white, furry, sore tongue and/or mouth
  • swollen red or sore tongue
  • vaginal thrush - sore and itchy vagina and/or discharge
  • dryness of the mouth, vagina or genitals
  • loss of sex drive or painful sex
  • joint pains
  • nasal congestion
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • confusion, irritability, depression, disorientation
  • clumsiness, lack of co-ordination, problems with moving or balancing
  • difficulty in speaking
  • headache, stiff neck and extreme sensitivity to bright light
  • dizziness or spinning sensation
  • problems with sleeping
  • fits or seizures
  • ringing/ persistent noise in the ears (tinnitus) or other hearing problems
  • blurred vision/double vision or other eye problems
  • yellowing of the eyes/skin or flushing
  • swelling or redness along the vein which is extremely tender when touched.
  • frequent or painful urination
  • blood or pus in the urine
  • more or darker urine than normal
  • loss of control of your bladder or bowels
  • feeling of pressure around the pelvis
  • sore back passage, sometimes with bleeding or discharge
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.

Very Serious side effects

Very serious side effectsWhat to do
  • sudden signs of allergy such as rash, itchiness, hives, swelling of the face, lips, mouth, throat or neck which may cause difficulty swallowing or breathing
  • skin rash that can be widespread with blisters, swelling, pain, burning, itching or peeling, often with fever
  • tingling or numbness of the hands or feet, pins and needles or muscle weakness
  • severe blisters and bleeding in the lips, eyes, mouth, nose and genitals
  • signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • severe abdominal cramps or stomach cramps
  • watery and severe diarrhoea, which may also be bloody
  • fast, erratic heartbeats and/or fainting.
Call your doctor straight away, go to the Emergency department at you nearest hospital if you notice any of these serious side effects.

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

Other side effects not listed here may occur in some people

Some of these side effects (change in liver, levels of blood cells or changes in heart rhythm) can only be found when your doctor does tests from time to time to check your progress.

Reporting side effects

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

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

7. Product details

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

What Metronidazole Juno contains

Active ingredient
(main ingredient)		Metronidazole
Other ingredients
(inactive ingredients)
  • Citric acid
  • Dibasic sodium phosphate
  • Sodium chloride
  • Water for Injections

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

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes

What Metronidazole Juno looks like

Metronidazole Juno is a colourless to pale yellow solution supplied in a plastic minibag of 100 mL volume for infusion.

It is available in the folllowing strength:

  • 500 mg/100 mL

AUST R 129476

Who distributes Metronidazole Juno

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

This leaflet was prepared in November 2024

Published by MIMS February 2025

BRAND INFORMATION

Brand name

Metronidazole Juno

Active ingredient

Metronidazole

Schedule

S4

 

1 Name of Medicine

Metronidazole.

2 Qualitative and Quantitative Composition

Metronidazole Juno contains Metronidazole EP 5 mg/mL, citric acid 0.36 mg/mL, dibasic sodium phosphate 0.6 mg/mL equivalent to dibasic sodium phosphate dodecahydrate 1.5 mg/mL, and sodium chloride 7.4 mg/mL in water for injections. Each mL contains 0.135 mmol sodium.
Metronidazole is a white or yellowish, crystalline powder, slightly soluble in water, in acetone, in alcohol and in methylene chloride.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Metronidazole Juno is an almost colourless to pale yellow, sterile, isotonic, preservative-free, ready to use solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Metronidazole Juno is indicated for:
treatment of severe anaerobic infection when oral medication is not possible or is contraindicated, when immediate anti-anaerobic therapy is required.
metronidazole may be used prophylactically to prevent infection of the surgical site which may have been contaminated or potentially contaminated with anaerobic organisms. Procedures in which this may be assumed to have happened include appendectomy, colonic surgery, vaginal hysterectomy, abdominal surgery in the presence of anaerobes in the peritoneal cavity and surgery performed in the presence of anaerobic septicaemia.

4.2 Dose and Method of Administration

Metronidazole Juno contains no microbial agent. It should be used in one patient on one occasion only and any residue discarded.
A maximum of 4 g should not be exceeded during a 24 hour period.

Dosage.

Adult.

The adult dose is 500 mg metronidazole (i.e. 100 mL) by infusion eight hourly.

Children over 12 years.

Same dosage as adults.

Children under 12 years.

Eight hourly as for adults but the single intravenous dose is based on 7.5 mg (1.5 mL) metronidazole/kg bodyweight.

Geriatric.

Use adult dosage with care as some degree of impaired hepatic or renal function may be present in elderly patients. In elderly patients, the pharmacokinetics of metronidazole may be altered; therefore, monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly.

Method of administration.

Adult.

Metronidazole should be infused intravenously at the rate of 5 mL (25 mg) per minute. Metronidazole infusion may be administered alone or concurrently (but separately) with other appropriate antibacterial agents in parenteral dosage forms (see Compatibility with intravenous infusions and other medicines). Other intravenous drugs or infusions should, if possible, be discontinued during its administration.
For prophylactic use the appropriate dose should be infused shortly before surgery and repeated 8 hourly for the next 24 hours.
Dosages should be decreased in patients with severe hepatic disease; plasma metronidazole levels should be monitored. In elderly patients, the pharmacokinetics of metronidazole may be altered; therefore, monitoring of serum levels may be necessary to adjust metronidazole dosage accordingly.
Parenteral drugs should be inspected visually for particulate matter and discolouration prior to administration, wherever solution or container permit. Do not use if the solution is cloudy or precipitated or if the seal is not intact. While the solution should be protected from direct sunlight during administration, exposure to fluorescent light for short periods will not result in its degradation.
Do not use plastic infusion bags in series connections. This practice could result in air embolism due to air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Duration of therapy.

Treatment for seven days should be satisfactory for most patients but, depending on clinical and bacteriological assessment, the clinician might decide to prolong treatment, e.g. for the eradication of infection from sites which cannot be drained or are liable to endogenous recontamination by anaerobic pathogens from the gut, oropharynx or female genital tract. Oral medication should be substituted as soon as possible.

Instructions to be given to the patient.

1. Patients, especially pregnant women, should be warned to refrain from alcohol whilst taking metronidazole.
2. Patients should be advised to report any signs of toxicity, especially neurological disturbances, to their doctor.
3. Patients should be warned about the possibility of their urine darkening in colour.

Note.

Prevention of infection at the surgical site requires that adequate tissue concentrations of the drug should have been achieved at the time of surgery. The dose and route of administration should be selected in each case to achieve this objective.
Although metronidazole has been used for some years in children, recent evidence concerning mutagenicity and tumorigenicity suggests that caution should be exercised when using metronidazole in this age group.
In infants and other patients maintained on intravenous infusions, metronidazole may be diluted 1 in 5 or greater with isotonic intravenous infusions (Sodium Chloride 0.9%, Glucose-Saline combinations, Glucose 5%) but not Sodium Lactate Compound (Hartman's) Infusion or Sodium Chloride Compound (Ringer's) Infusion (see Compatibility with intravenous infusions and other medicines).

Dosage adjustments.

Renal impairment.

In patients on twice weekly haemodialysis, metronidazole and its major active metabolite are rapidly removed during an 8 hour period of dialysis, so the plasma concentration quickly falls below the therapeutic range. Hence, a further dose of metronidazole would be needed after dialysis to restore an adequate plasma concentration. In patients with renal failure the half life of metronidazole is unchanged but those of its major metabolites are prolonged 4-fold or greater. The accumulation of the hydroxy metabolite could be associated with side effects and measurement of its plasma concentrations by high pressure liquid chromatography (HPLC) has been recommended.
In the absence of haemodialysis, the plasma clearance and elimination half-life of metronidazole are equivalent to those in patients with normal renal clearance, so dosage adjustment is not necessary.
While the pharmacokinetics of metronidazole are little changed in the presence of anuria, there is retention of the metabolites, the clinical significance of which is unknown.

Hepatic impairment.

As metronidazole is partly metabolised in the liver, caution should be exercised in patients with impaired liver function. Empirical dosage reduction and serum level monitoring may be necessary.

Compatibility with intravenous infusions and other medicines.

Metronidazole Juno may be diluted to 1 in 5 or greater with appropriate volumes of Sodium Chloride 0.9%, Glucose-Saline combinations, Glucose 5% or potassium chloride injections 20 mmol/L and 40 mmol/L. While physically compatible with Compound Sodium Lactate infusion (Hartman's Solution) and Compound Sodium Chloride Infusion (Ringer's Solution), metronidazole is not chemically compatible with them over extended periods of time. Therefore, addition of Metronidazole Juno to these solutions is not recommended. However, it may be delivered through the administration set Y-site of fast-running infusions of Hartman's or Ringer's Solutions. While Glucose 10% is compatible, its use as a diluent and vehicle is not recommended because of the high osmolarity of the resulting solution.

4.3 Contraindications

Patients with evidence of or a history of blood dyscrasias. Occasionally a moderate leucopenia has been observed during administration. However, no persistent haematological abnormalities have been observed in animals or clinical studies (see Section 4.4 Special Warnings and Precautions for Use).
Active organic disease of the central nervous system.
Hypersensitivity to metronidazole, other nitro-imidazoles or any of the excipients.
Patients who have taken disulfiram within the last two weeks should not be administered metronidazole. Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who were using disulfiram concurrently (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Consumption of alcohol or products containing propylene glycol. Use of oral metronidazole is associated with a disulfiram-like reaction to alcohol, including abdominal cramps, nausea, vomiting, headaches, and flushing. Discontinue consumption of alcohol or products containing propylene glycol during and for at least three days after therapy with metronidazole (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Patients with Cockayne syndrome. Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes have been reported after initiation of metronidazole in patients with Cockayne syndrome (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.4 Special Warnings and Precautions for Use

Hypersensitivity reactions.

Hypersensitivity reactions including severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Stevens-Johnson Syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported with the use of metronidazole. Symptoms can be serious and potentially life threatening (see Section 4.8 Adverse Effects (Undesirable Effects)). If symptoms or signs of SCARs develop, discontinue metronidazole immediately and institute appropriate therapy.
Advise patients that metronidazole may increase the risk of serious and sometimes fatal dermatological reactions, including TEN, SJS and DRESS. Instruct the patient to be alert for skin rash, blisters, fever or other signs and symptoms of these hypersensitivity reactions. Advise patients to stop treatment with metronidazole immediately if they develop any type of rash and seek medical attention.

Alcohol.

Alcoholic beverages, drugs containing alcohol or products containing propylene glycol should not be consumed by patients being treated with metronidazole and for at least three days after treatment as nausea, vomiting, abdominal cramps, headaches, tachycardia and flushing may occur. There is the possibility of a disulfiram-like (Antabuse) effect reaction. (See Section 4.3 Contraindications.)

Treatment of bacterial infections.

Patients should be counselled that antibacterial drugs, including metronidazole, should only be used to treat bacterial infections. They do not treat viral infections (e.g. the common cold). When metronidazole is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be completed for the full course of therapy. Otherwise, this may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by metronidazole or other antibacterial drugs in the future.

Use in patients with blood dyscrasias.

Metronidazole is a nitroimidazole and should be used with care in patients with evidence of or history of blood dyscrasia. A moderate leucopenia has been observed during its administration; however, no persistent hematologic abnormalities attributable to metronidazole have been observed in clinical studies. (See Section 4.3 Contraindications.) Total and differential leukocytes counts are recommended before and after therapy.

Long term therapy.

If metronidazole is to be administered for more than 10 days, it is recommended that haematological tests, especially total and differential leukocyte counts, be carried out regularly and that patients be monitored for adverse reactions such as peripheral or central neuropathy (such as paresthesia, ataxia, dizziness, convulsive seizures). If leucopenia or abnormal neurological signs occur, the drug should be discontinued immediately.

Cardiac function impairment.

Care should be taken because of the sodium content (0.135 mmol/mL) in this dosage form.

Sodium retention.

Administration of solutions containing sodium ions may result in sodium retention. Care should be taken when administering Metronidazole Juno to patients receiving corticosteroids or patients predisposed to oedema. (See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.)

Central and peripheral nervous system.

Metronidazole should be used with caution in patients with active or chronic severe peripheral or central nervous system diseases due to the risk of neurological damage. Patients should be warned about the potential for confusion, dizziness, hallucinations, convulsions or transient visual disorders and advised not to drive or use machinery if these symptoms occur.
Cases of encephalopathy and peripheral neuropathy (including optic neuropathy) have been reported with metronidazole. Encephalopathy has been reported in association with cerebellar toxicity characterised by ataxia, dizziness and dysarthria. CNS lesions seen on MRI have been described in reports of encephalopathy. CNS symptoms are generally reversible within days to weeks upon discontinuation of metronidazole. CNS lesions seen on MRI have also been described as reversible.
Peripheral neuropathy, mainly of sensory type has been reported and is characterised by numbness or paraesthesia of the extremities.
Convulsive seizures have been reported in patients treated with metronidazole.
Cases of aseptic meningitis have been reported with metronidazole. Symptoms can occur within hours of dose administration and generally resolve after metronidazole therapy is discontinued.
The appearance of abnormal neurological signs demands the prompt discontinuation of metronidazole therapy and, when severe, immediate medical attention. See Section 4.8 Adverse Effects (Undesirable Effects).

Candidiasis.

Candida overgrowth in the gastrointestinal or genital tract may occur during metronidazole therapy and may require treatment with a candicidal drug.

Surgical drainage.

Use of metronidazole does not obviate the need for aspiration of pus whenever indicated, such as in amoebic hepatic abscess or abscesses in other inaccessible positions.

Pseudomembranous colitis.

Pseudomembranous colitis associated with the administration of metronidazole has been reported.

Ototoxicity.

A number of cases of deafness associated with the use of metronidazole have been reported.

Drug resistant bacteria.

Prescribing metronidazole in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Use in hepatic impairment.

Since metronidazole is mainly metabolised by hepatic oxidation, accumulation of metronidazole and its metabolites in plasma is likely in patients with severely impaired hepatic function. Metronidazole should therefore be administered with caution and at reduced doses to patients with severe hepatic impairment.
For patients with mild to moderate hepatic impairment, no dosage adjustment is needed but these patients should be monitored for metronidazole associated adverse events (see Section 4.2 Dose and Method of Administration).
Metronidazole may interfere with certain chemical analysis of serum aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), triglycerides and hexokinase glucose to give abnormally low values.

Use in renal impairment.

In patients on twice weekly haemodialysis, metronidazole and its major active metabolite are rapidly removed during an 8 hour period of dialysis, so that the plasma concentration quickly falls below the therapeutic range. Hence, a further dose of metronidazole would be needed after dialysis to restore an adequate plasma concentration.
In patients with renal failure the half-life of metronidazole is unchanged, but those of its major metabolites are prolonged 4-fold or greater. The accumulation of the hydroxy metabolite could be associated with side effects and measurement of its plasma concentration by high pressure liquid chromatography (HPLC) has been recommended. See Section 4.2 Dose and Method of Administration.

Use in the elderly.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

Metronidazole may show negative interference with continuous flow spectrophotometry of aspartate aminotransferase (previously GOT), so that hepatocellular damage which is detectable by raised serum AST may be missed. Metronidazole may interfere with AST (SGOT), ALT (SGPT), LDH, triglycerides or glucose determinations when these are based on the decrease in ultraviolet absorbance which occurs when NADH is oxidised to NAD. Metronidazole interferes with these assays because the drug has an absorbance peak of 322 nanometres at pH 7, which is close to the 340 nanometre absorbance peak of NADH; this causes an increase in absorbance at 340 nanometre resulting in falsely decreased values.
Instructions to be given to patients:
patients should be warned to refrain from consumption of alcohol whilst taking metronidazole;
patients should be advised to report any signs of toxicity, especially neurological disturbances, to the doctor;
patients should be warned about the possibility of their urine darkening in colour.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Alcohol.

Metronidazole appears to inhibit alcohol dehydrogenase and other alcohol oxidising enzymes. Mild disulfiram-like reactions including flushing, headache, nausea, vomiting, abdominal cramps and sweating have occurred in patients ingesting alcohol while being treated with metronidazole. Patients should be advised that alcoholic beverages, drugs containing alcohol or products containing propylene glycol should not be consumed during metronidazole therapy and for at least three days afterwards because of the possibility of a disulfiram-like (Antabuse effect) reaction (flushing, vomiting, tachycardia). See Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use.

Disulfiram.

Administration of disulfiram with metronidazole has been associated with acute psychoses and confusion in some patients; therefore, the two drugs should not be administered concurrently. Metronidazole should not be given to patients who have taken disulfiram within the last two weeks (see Section 4.3 Contraindications).

Anticoagulants.

Metronidazole enhances the activity of warfarin, and if metronidazole is to be given to patients receiving this or other anticoagulants, the dosages of the latter should be recalibrated.
There is an increased haemorrhagic risk caused by decreased hepatic metabolism. Prothrombin times should be monitored as should anticoagulant activity.

Ciclosporin.

There is a risk of ciclosporin serum levels increasing when it is used in combination with metronidazole. Serum ciclosporin and serum creatinine should be closely monitored when coadministration is necessary.

Phenobarbitone and phenytoin.

The simultaneous administration of drugs that induce microsomal hepatic enzyme activity, such as phenobarbitone, pentobarbitone or phenytoin, may accelerate the elimination of metronidazole, resulting in reduced plasma concentrations and increased concentrations of its 2-hydroxymethyl metabolite. Impaired clearance of phenytoin has also been reported.

Lithium.

Initiation of short-term metronidazole therapy in patients stabilised on relatively high dosages of lithium has been reported to increase serum lithium concentrations, resulting in signs of lithium toxicity in several patients. Serum lithium and serum creatinine levels should be obtained several days after beginning metronidazole therapy to detect any increase that may precede clinical symptoms of lithium intoxication.

Cimetidine.

The simultaneous administration of drugs that decrease microsomal hepatic enzyme activity, such as cimetidine, may prolong the half-life and decrease the plasma clearance of metronidazole. It is not clear if ranitidine exerts a similar effect.

Corticosteroids.

Care should be taken when administering metronidazole infusion to patients receiving corticosteroid therapy or to patients predisposed to oedema since administration of solutions containing sodium ions may result in sodium retention.

Drugs that prolong the QT interval.

QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.

Cyclophosphamide and BiCNU (carmustine).

Metronidazole should be used with caution in patients who are receiving BiCNU or cyclophosphamide as a drug interaction shown in mice leads to increased toxicity.

Busulfan.

Plasma levels of busulfan may be increased by metronidazole, which may lead to severe busulfan toxicity. Metronidazole should not be administered concomitantly with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole are available, and concomitant administration with busulfan is medically needed, frequent monitoring of busulfan plasma concentration should be performed and the busulfan dose should be adjusted accordingly.

Fluorouracil and azathioprine.

Transient neutropenia has been reported in twelve patients who received oral and intravenous metronidazole in conjunction with intravenous fluorouracil and in at least one patient who received oral metronidazole in conjunction with azathioprine.

5-Fluorouracil.

Metronidazole used in combination with 5-fluorouracil may lead to reduced clearance resulting in increased toxicity.
Also see Section 4.2, Compatibility with intravenous infusions and other medicines.
Also see Section 6.2 Incompatibilities.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B2)
Metronidazole should not be given in the first trimester of pregnancy as it crosses the placenta and rapidly enters fetal circulation. As its effects on human fetal organogenesis are not known, its use in pregnancy should be carefully evaluated. Although it has not been shown to be teratogenic in either human or animal studies, such a possibility cannot be excluded.
Use of metronidazole for trichomoniasis in the second and third trimesters of pregnancy be restricted to those in whom local palliative treatment has been inadequate to control symptoms.
 Metronidazole is secreted in breast milk (see Section 5.2 Pharmacokinetic Properties). There are reports of diarrhoea and Candida infection in breastfed infants of mothers receiving treatment with metronidazole.
There are no data on the effects of metronidazole on milk production.
Animal studies have shown the potential for tumorigenicity after oral metronidazole was administered chronically to rats and mice (see Section 5.3 Preclinical Safety Data, Genotoxicity, Carcinogenicity). In view of the tumorigenic and mutagenic potential of metronidazole (see Section 5.3 Preclinical Safety Data, Genotoxicity, Carcinogenicity), breastfeeding is not recommended.

4.7 Effects on Ability to Drive and Use Machines

Patients should be warned about the potential for confusion, dizziness, hallucinations, convulsions or transient visual disorders and advised not to drive or use machinery if these symptoms occur.

4.8 Adverse Effects (Undesirable Effects)

When administered intravenously, metronidazole is well tolerated.

Gastrointestinal.

The most common adverse reactions have involved the gastrointestinal tract and include vomiting, diarrhoea, epigastric distress, abdominal cramping; constipation and oral mucositis.
A metallic, sharp unpleasant taste is not unusual. Furry tongue, glossitis and stomatitis have occurred; these may be associated with Candida overgrowth.
Patients with Crohn's disease are known to have an increased incidence of gastrointestinal and certain extraintestinal cancers. There have been some reports in the medical literature of breast and colon cancer in Crohn's disease patients who have been treated with metronidazole at high doses for extended periods of time. A cause and effect relationship has not been established.
Rare cases of pancreatitis, abating on withdrawal of the drug, have been reported.
There have been a number of reports both in Australia and in overseas literature of cases of pseudomembranous colitis whilst on metronidazole therapy.

Haematological.

A moderate leukopenia may occasionally be observed. If this occurs, the total leukocyte count may be expected to return to normal after the course of medication is completed. One case of bone marrow depression has been reported. If profound bone marrow suppression occurs, use of metronidazole should be ceased and appropriate supportive therapy instituted. Cases of agranulocytosis, neutropenia or thrombocytopenia have been reported.
Thrombophlebitis has been reported after intravenous infusion. Thrombophlebitis can be minimised or avoided by limiting the duration of infusion and frequent resting of the indwelling IV cannula.

Neurological.

The most serious adverse reactions in patients treated with metronidazole injection have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy. There have been reports of encephalopathy (e.g. confusion) and subacute cerebellar syndrome (e.g. ataxia, dysarthria, gait impairment, nystagmus and tremor), which may resolve with the discontinuation of the drug. Confusion, irritability, depression, weakness, and insomnia have been experienced as has peripheral neuropathy, characterised mainly by numbness or paresthesia of an extremity. Since persistent peripheral neuropathy has been reported in some patients receiving prolonged metronidazole therapy, such subjects should be specifically warned about these reports and told to stop the drug and report immediately if any neurological symptoms occur. Headache, dizziness, vertigo, incoordination, syncope and dysarthria have also been reported. Transient vision disorders such as diplopia and myopia have been reported.

Psychiatric disorders.

Psychotic disorders such as confusion and hallucinations have been reported. Depression and depressed mood have been experienced.
Psychotic reactions have been reported in alcoholic patients receiving metronidazole and disulfiram concurrently. Metronidazole should not be given to patients who have taken disulfiram in the previous two weeks.

Hepatic disorders.

Increase in liver enzymes (AST, ALT, alkaline phosphatase), cholestatic or mixed hepatitis and hepatocellular liver injury, sometimes with jaundice, have been reported.
Cases of liver failure requiring liver transplant have been reported in patients treated with metronidazole in combination with other antibiotic drugs; all spiramycin except one case of tetracycline.
Cases of severe irreversible hepatotoxicity/acute liver failure, including cases with fatal outcomes with very rapid onset after initiation of systemic use of metronidazole, have been reported in patients with Cockayne Syndrome (latency from drug start to signs of liver failure as short as 2 days) (see Section 4.3 Contraindications).

Auditory and vestibular.

Impaired hearing/hearing loss (including sensorineural) and tinnitus have been reported.

Eye disorders.

Optic neuropathy/neuritis and transient vision disorders such as diplopia, myopia, blurred vision, decreased visual acuity and changes in colour vision have been reported.

Dermatological, body as a whole.

Hypersensitivity reactions include erythematous rash, pruritus, flushing, urticaria, fever, angioedema and anaphylactic shock. Nasal congestion and dryness of the mouth have been reported. Mild erythematous eruptions have been experienced, as have fleeting joint pains sometimes resembling serum sickness. Pustular eruptions and acute generalised exanthematous pustulosis have been reported. Dermatitis bullous and fixed drug eruption has been reported. Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP) have also been reported.

Genito-urinary tract.

Proliferation of Candida also may occur in the vagina. Dryness of the vagina or vulva, pruritus, dysuria, cystitis and a sense of pelvic pressure have been reported. Very rarely, dyspareunia, fever, polyuria, incontinence, decrease in libido, proctitis and pyuria have occurred in patients receiving the drug.
Instances of darkened urine have been reported and this manifestation has been the subject of investigation. Although the pigment which is probably responsible for this phenomenon has not been positively identified, it almost certainly is a metabolite of metronidazole. It seems certain that it is of no clinical significance and may be encountered only when metronidazole is administered in higher than recommended doses.

Cardiac.

QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval. Flattening of the T-wave may be seen in ECG tracings.

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

Overdosage with metronidazole appears to be associated with very few abnormal signs or symptoms. Disorientation and vomiting may occur, especially after ingestion of large amounts. In the event of accidental overdosage, treatment consists of supportive and symptomatic measures.
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.

Metronidazole is active in vitro against anaerobic bacteria and as an antiprotozoal agent. It does not appear to possess any clinically relevant activity against facultative anaerobes or obligate aerobes. Against susceptible organisms, metronidazole is generally bactericidal at concentrations equal to or slightly higher than the minimal inhibitory concentrations (MIC).
Metronidazole has been shown to have in vitro activity against many anaerobic Gram-negative bacilli including Bacteroides fragilis and other Bacteroides sp., Fusobacterium, Eubacterium, Clostridium and anaerobic Streptococci. Metronidazole is also active against a wide range of pathogenic protozoa including Trichomonas vaginalis and other trichomonads, Entamoeba histolytica, Giardia lamblia, Balantidium coli and the causative organisms of active ulcerative gingivitis.

Susceptibility tests.

Dilution or diffusion techniques.

Either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. National Committee for Clinical Laboratory Standards). 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

Note.

Polarographic estimation of metronidazole in serum or urine tends to give higher values than microbiological assay because the former measures both unchanged drug and metabolites. Erroneously high serum values may be obtained in the presence of severe renal failure because of the retention of metabolites in the blood.

Absorption.

Following intravenous infusion, peak plasma levels of metronidazole occur at the end of the infusion.

Distribution.

Metronidazole is distributed widely throughout body tissues both intracellularly and extracellularly. It is found in saliva and breast milk in concentrations equivalent to those in plasma. It also crosses the placenta and is found in the CSF. Therapeutic levels have been found in abscesses, bile, CSF, seminal fluid and in synovial fluid.

Protein binding.

There is no significant plasma protein binding of metronidazole.

Metabolism.

Metronidazole is partly metabolised in the liver by both acid oxidation and glucuronide conjugation. The principal metabolites are the hydroxy metabolite (1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole) and the acid metabolite (1-acetic acid-2-methyl-5-nitroimidazole). The hydroxy metabolite has approximately 30% of the bioactivity of metronidazole against anaerobic bacteria whereas the acid metabolite has only 5% of the activity of unchanged metronidazole.

Excretion.

About 15 to 20% of an administered dose is excreted in the urine as unchanged metronidazole. Overall, about 50-80% of an administered dose is excreted as nitro-containing compounds, of which unchanged metronidazole and the hydroxymethyl homologue each account for about one third. The fate of the remainder of an administered dose is unknown. Metronidazole is also excreted into saliva and breast milk reaching concentrations equivalent to those in plasma.

Half life.

The half life of metronidazole after single, intravenous infusion has been reported as 7.3 ± 1.0 hours.

5.3 Preclinical Safety Data

Genotoxicity.

Metronidazole has been found to be mutagenic in bacteria and some animal species. In studies on the mutagenic potential of metronidazole, the Ames mutagenicity test was positive while several nonbacterial tests in animals were negative. In patients suffering from Crohn's disease, metronidazole increased chromosome abnormalities. In addition, the drug has been shown to be tumorigenic in rodents. The benefit/risk ratio should therefore be carefully assessed in each case, particularly in relation to the severity of the disease and the age of the patient.

Carcinogenicity.

Metronidazole has shown evidence of tumorigenic activity in a number of studies involving chronic oral administration in mice and rats. Most prominent among the effects in the mouse was the promotion of pulmonary tumorigenesis. This has been observed in multiple studies in that species, including one study in which the animals were dosed on an intermittent schedule (administration during every fourth week only). The published results of one of the mouse studies indicated an increase in the incidence of malignant lymphomas as well as pulmonary neoplasms associated with lifetime feeding of the drug. All these effects were statistically significant.
In the rat, there was a statistically significant increase in the incidence of various neoplasms, particularly mammary tumours, among female rats administered metronidazole over that noted in the concurrent female control groups. Two lifetime tumorigenicity studies in hamsters have been performed and reported to be negative.
Results of a retrospective epidemiological study of 771 women treated with metronidazole for T. vaginalis have not revealed any statistically significant increase in cancer incidence over that expected in the normal population. The apparent increase in cervical carcinoma in situ in the metronidazole treated group was no different from the incidence in women documented to have had trichomoniasis not treated by metronidazole. Because of the limitations of a relatively small retrospective study, these results do not provide definite answers and the risk of carcinogenicity emphasises the need to avoid indiscriminate use of the drug.

6 Pharmaceutical Particulars

6.1 List of Excipients

Citric acid, dibasic sodium phosphate, sodium chloride, water for injections.

6.2 Incompatibilities

Metronidazole Juno is incompatible with aluminium; do not use equipment containing aluminium components (e.g. needle or cannula hubs). Other drugs should not be added directly to Metronidazole Juno. If used with a primary intravenous fluid system, the primary solution should be discontinued during metronidazole infusion.

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. Protect from light.

6.5 Nature and Contents of Container

Metronidazole Juno 500 mg in 100 mL (sterile) is available in 10 and 20* infusion bags (PE) per pack.
*20 pack size not marketed.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.


Chemical name: 2-(5-nitro-2-methylimidazol-1-yl)ethanol.
Molecular formula: C6H9N3O3.
Molecular weight: 171.2.

CAS number.

443-48-1.

7 Medicine Schedule (Poisons Standard)

Schedule 4.

Summary Table of Changes