Consumer medicine information

Flagyl S

Metronidazole

BRAND INFORMATION

Brand name

Flagyl S

Active ingredient

Metronidazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Flagyl S.

SUMMARY CMI

Flagyl® S

Consumer Medicine Information (CMI) summary

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

1. Why am I using Flagyl S?

Flagyl S contains the active ingredient metronidazole benzoate (liquid). Flagyl S is used to treat certain infections caused by bacteria and other organisms in different parts of the body. It is also used to prevent or treat certain infections that may occur during surgery.

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

2. What should I know before I use Flagyl S?

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

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

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

3. What if I am taking other medicines?

Some medicines may interfere with Flagyl S and affect how it works.

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

4. How do I use Flagyl S?

Follow the instructions provided and use Flagyl S until your doctor tells you to stop.

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

5. What should I know while using Flagyl S?

Things you should do
  • Tell your doctor straight away if the symptoms of your infection do not improve or become worse, if you become pregnant or if you are about to start taking any new medicines.
  • Stop taking this medicine and tell your doctor straight away if you have irrational thoughts, hallucinations, feeling confused or feeling depressed, including thoughts of self-harm or suicide.
Things you should not do
  • Do not stop taking Flagyl S if you feel better. If you do not complete the full course prescribed by your doctor, all of the bacteria/organisms causing your infection may not be killed.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how Flagyl S affects you.
Drinking alcohol
  • Do not drink alcohol or consume any medication containing alcohol while using Flagyl S and for at least 24 hours after stopping treatment.
Looking after your medicine
  • Keep Flagyl S suspension in a cool dry place where the temperature stays below 25°C.

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

6. Are there any side effects?

Serious side effects: Allergic reaction: Some symptoms of an allergic reaction include skin rash, itching, shortness of breath or swelling of the face, lips or tongue, which may cause difficulty in swallowing or breathing. If you have been on prolonged Flagyl S therapy, you may experience unusual numbness of the feet or hands. Posterior reversible encephalopathy syndrome (PRES) - A brain condition with symptoms such as headache, confusion, visual disturbance and seizures.

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

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

Flagyl® S (flaj-ill)

Active ingredients: Metronidazole benzoate (met-ro(h)-nide-ah-zole benz-o(h)-ate) 200 mg/5 mL oral suspension

Consumer Medicine Information (CMI)

This leaflet provides important information about using Flagyl S. 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 Flagyl S.

Where to find information in this leaflet:

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

1. Why am I using Flagyl S?

Flagyl S contains the active ingredient metronidazole benzoate (liquid). Flagyl S is an antibiotic that belongs to a group of medicines called nitroimidazoles.

Flagyl S is used to treat certain infections caused by bacteria and other organisms in different parts of the body.

It is also used to prevent or treat certain infections that may occur during surgery.

This medicine works by killing or stopping the growth of bacteria and other organisms causing these infections.

Your doctor may have prescribed Flagyl S for another reason.

Ask your doctor if you have any questions about why Flagyl S has been prescribed for you.

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

There is no evidence that this medicine is addictive.

2. What should I know before I use Flagyl S?

Warnings

Do not use Flagyl S if:

  • you are allergic to metronidazole or any other nitroimidazoles, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.
  • you have evidence of, or have a history of, a blood disorder.
  • you have, or have ever had, a disease of the brain, spinal cord or nerves.
  • the expiry date on the pack has passed. If you use this medicine after the expiry date has passed it may have no effect at all, or worse, an entirely different effect.
  • the packaging is torn or shows signs of tampering.

Check with your doctor if you:

  • have any allergies to any other medicines or any other substances such as foods, preservatives or dyes.
  • have or have ever had any health problems/ medical conditions including:
    - a blood disorder
    - disease of the brain, spinal cord or nerves
    - liver or kidney disease
    - an inflammatory disease of the small intestine (e.g., Crohn's disease)
    - Cockayne syndrome
  • drink alcohol. Do not drink alcohol during (and for 24 hours after stopping) treatment with Flagyl S.

If you have not told your doctor or pharmacist about any of the above, tell them before you start using Flagyl S.

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.

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 Flagyl S and affect how well it works. These include:

  • any medication that may cause ECG disturbances (certain anti-arrhythmics (medicines for heart rhythm disorders), certain antibiotics, psychotropic medicines)
  • warfarin or other medicines used to prevent blood clots
  • Antabuse® (disulfiram), a medicine used to treat chronic alcohol dependence
  • Medications containing alcohol (ethanol), e.g., some cough syrups
  • some anticancer drugs, such as carmustine, cyclophosphamide monohydrate, 5-fluorouracil or busulfan
  • phenytoin, a drug used to treat convulsions
  • phenobarbital (phenobarbitone), a medicine for convulsions or sedation
  • cimetidine, a medicine used to treat gastric reflux and ulcers
  • lithium, a medicine used to treat manic depressive illness and some other types of depression
  • cyclosporin, a medicine used to prevent organ transplant rejection or to treat immune responses

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

You may need different amounts of your medicine or you may need to take different medicines. Your doctor will advise you.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while taking Flagyl S.

4. How do I use Flagyl S?

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information contained in this CMI.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to use

  • The dose will vary from patient to patient. Your doctor will decide the right dose for you.
  • Follow the instructions provided when Flagyl S was prescribed, including the number of days it should be taken.

How long to use

  • For treating infection, Flagyl S suspension is usually taken for 7 days, however, your doctor may decide to reduce or extend your treatment. Your doctor will tell you how much Flagyl S to take.

How to take Flagyl S suspension

Flagyl S suspension should be taken at least one hour before a meal or food.

This medicine works better if taken on an empty stomach.

If you forget to use Flagyl S

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, take it as soon as you remember, then go back to taking it as you would normally.

Do not take a double dose to make up for the dose you missed.

If you have trouble remembering to take/use Flagyl S, ask your pharmacist for some hints.

If you use too much Flagyl S

If you think that you have used too much Flagyl S, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling Australia 13 11 26)
  • 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.

If you take too much suspension you may experience vomiting and a feeling of disorientation.

5. What should I know while using Flagyl S?

Things you should do

Call your doctor straight away if:

  • the symptoms of your infection do not improve or become worse
  • you become pregnant
  • you are about to start taking any new medicines

Some people being treated with metronidazole can experience mental health problems such as irrational thoughts, hallucinations, feeling confused or feeling depressed, including thoughts of self-harm or suicide.

These symptoms can occur even in people who have never had similar problems before. If you or others around you notice any of these side effects stop taking this medicine and seek medical advice straight away.

If you experience abdominal pain, cramps, diarrhoea with possible bloody stools (which may be signs of inflammatory bowel disease).

If you experience symptoms such as headache, confusion, visual disturbance and seizures (which may be signs of a brain condition namely Posterior Reversible Encephalopathy Syndrome or PRES).

If you get a sore, white mouth or tongue while taking or soon after stopping Flagyl S treatment, tell your doctor. 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 Flagyl S allows fungi/yeast to grow and the above symptoms to occur. Flagyl S does not work against fungi/yeast.

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

If you need to have a blood test while using Flagyl S, tell your doctor as Flagyl S may affect the results of some laboratory tests.

Remind any doctor, dentist or pharmacist you visit that you are using Flagyl S.

Things you should not do

  • Do not give Flagyl S to anyone else, even if they have the same condition as you.
  • Do not use Flagyl S to treat any other medical complaints unless your doctor tells you to.
  • Do not stop taking your suspension if you feel better.
  • If you do not complete the full course prescribed by your doctor, all of the bacteria/organisms causing your infection may not be killed. These bacteria/organisms may continue to grow and multiply so that your infection may not clear completely or may return.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Flagyl S affects you.

While using Flagyl S you may feel dizzy or experience vertigo (spinning sensation), confused, hallucinations (see or hear things that are not there), convulsions (have fits) or temporary eyesight problems (such as blurred or double vision). If this happens, do not drive or use any machinery or tools.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may make you feel very sick, vomit, have stomach cramps, headaches and flushing.

Do not drink alcohol during (and for 24 hours after stopping) treatment with Flagyl S.

Looking after your medicine

  • Keep Flagyl S suspension in a cool dry place where the temperature stays below 25°C.

Follow the instructions in the carton on how to take care of your medicine properly.

Store in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

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
General
  • joint pain
Mouth-related
  • oral thrush - white, furry, sore or inflamed tongue and mouth
  • dry mouth
Ear-related
  • hearing problems
Urinary disorders
  • unusual urination patterns (e.g., difficulty in passing urine, large amounts of urine, incontinence, or pus in urine)
Respiratory related
  • stuffy nose, nasal congestion
Gastrointestinal
  • nausea, which may be accompanied by headache, loss of appetite, and vomiting
  • diarrhoea, stomach discomfort, abdominal cramping or constipation, strange taste in mouth
Central nervous system-related
  • confusion, irritability, depression, or sleeplessness
  • convulsions, dizziness, weakness, feeling of incoordination or uncoordinated movements
  • vertigo (spinning sensation)
Heart-related
  • Changes in electrical activity of the heart seen on an Electrocardiogram (QT prolongation) has been observed particularly when metronidazole was administered with drugs with potential to prolong QT interval.
Skin-related
  • skin rashes, flushing, itching
Eye-related
  • eye problems, including blurred or double vision
Liver-related
  • yellowing of the skin or eyes, which may be jaundice
Gynecological
  • vaginal thrush - sore and itchy vagina and/or discharge
  • dryness of the vagina or vulva
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
  • Allergic reaction. Some symptoms of an allergic reaction include skin rash, itching, shortness of breath or swelling of the face, lips or tongue, which may cause difficulty in swallowing or breathing.
  • If you have been on prolonged Flagyl S therapy you may experience unusual numbness of the feet or hands.
  • Posterior reversible encephalopathy syndrome (PRES) - A brain condition with symptoms such as headache, confusion, visual disturbance and seizures.
Stop using Flagyl S, and tell your doctor immediately

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.

Reporting side effects

After you have received medical advice for any side effect you experience, you can report side effects as follows:

Australia: 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 Flagyl S contains

Active ingredient
(main ingredient)		Flagyl S - 200 mg metronidazole benzoate/5 mL of liquid
Other ingredients
(inactive ingredients)		Flagyl S suspension also contains monobasic sodium phosphate, aluminium magnesium silicate, sucrose, methyl and propyl hydroxybenzoate, ethanol, natural soluble lemon flavour 50 06-0404, orange oil terpeneless.

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

What Flagyl S looks like

There are three forms of Flagyl: Flagyl tablets, Flagyl S suspension and Flagyl suppositories. Flagyl tablets and suppositories are covered by a separate CMI.

Flagyl S suspension (Aust R 27501) is a creamy white to yellow liquid with an orange/lemon odour in a 100 mL bottle.

Who distributes Flagyl S

Flagyl S is supplied in Australia by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Australia
Freecall No: 1800 818 806

This leaflet was prepared in January 2025

Flagyl-s-ccdsv18-cmiv13--30jan25

Published by MIMS March 2025

BRAND INFORMATION

Brand name

Flagyl S

Active ingredient

Metronidazole

Schedule

S4

 

1 Name of Medicine

Metronidazole benzoate.

2 Qualitative and Quantitative Composition

Flagyl S suspension 6.4% w/v (metronidazole 200 mg/5 mL) contains 320 mg of metronidazole benzoate, equivalent to 200 mg of metronidazole, per 5 mL.
Metronidazole benzoate is 1-(2-benzoyloxyethyl)-2-methyl-5-nitroimidazole.

List of excipients with known effect.

Hydroxybenzoates, sugars.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

A white or cream suspension with a slight yellow tinge, and with an odour of orange and lemon.

4 Clinical Particulars

4.1 Therapeutic Indications

Anaerobic infections.

Treatment of infections in which anaerobic bacteria have been identified or are suspected as pathogens, particularly Bacteroides fragilis and other species of bacteroides and other species such as Fusobacteria, Eubacteria, Clostridia and anaerobic Streptococci. Flagyl has been used successfully in septicaemia; bacteraemia; brain abscess; necrotising pneumonia; osteomyelitis; puerperal sepsis; pelvic abscess; pelvic cellulitis; postoperative wound infections.

Notes.

a) Because of the slow absorption and delayed peak plasma level, Flagyl S suspension is not recommended for use in the acute situation.
b) Metronidazole is inactive against aerobic and facultative anaerobic bacteria.

Other indications.

Oral treatment of urogenital trichomoniasis in the female (trichomonal vaginitis) and in the male, and for the treatment of bacterial vaginosis. The male consort of females suffering from urogenital trichomoniasis should be treated concurrently; all forms of amoebiasis (intestinal and extraintestinal disease and that of symptomless cyst passers); giardiasis; acute ulcerative gingivitis.

4.2 Dose and Method of Administration

Flagyl S suspension is administered orally.
It is recommended that the dose should be taken at least one hour before a meal.
Rinse out the measuring glass to ensure that the correct dose is taken.
A maximum of 2.4 g should not be exceeded during a 24 hour period. 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 and, therefore, monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly.

Oral.

Summarised in Table 1.
Surgical prophylaxis.

Note.

Prevention of infections at the surgical site requires that adequate tissue concentration 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.
As oral ingestion is often prohibited 12 hours or longer before surgery, and may not be practical for a variable period following surgery, the suspension is not considered to be an appropriate formulation for prophylactic use. In addition, due to the lower and delayed peak serum levels with this formulation, each dose should be the equivalent of 800 mg of metronidazole. The first dose should be administered three to four hours before surgery, then repeated every eight hours for 24 hours.

4.3 Contraindications

Patients with evidence of or a history of blood dyscrasias should not receive the drug since upon occasion a mild leucopenia has been observed during its administration. However, no persistent haematological abnormalities have been observed in animals or clinical studies.
Active organic disease of the central nervous system.
Hypersensitivity to metronidazole and other imidazoles.

4.4 Special Warnings and Precautions for Use

Alcohol.

Alcoholic beverages and drugs containing alcohol, should not be consumed by patients being treated with metronidazole as nausea, vomiting, abdominal cramps, headaches, tachycardia and flushing may occur.

Candidiasis.

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

Cockayne syndrome.

Cases of severe hepatotoxicity/ acute hepatic failure, including cases with a fatal outcome with very rapid onset after treatment initiation in patients with Cockayne syndrome have been reported with products containing metronidazole for systemic use. In this population, metronidazole should therefore be used after careful benefit risk assessment and only if no alternative treatment is available. Liver function tests must be performed just prior to the start of therapy, throughout and after end of treatment until liver function is within normal ranges, or until the baseline values are reached. If the liver function tests become markedly elevated during treatment, the drug should be discontinued.
Patients with Cockayne syndrome should be advised to immediately report any symptoms of potential liver injury to their physician and stop taking metronidazole.

Severe bullous skin reactions.

Cases of severe bullous skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or acute generalised exanthematous pustulosis (AGEP) have been reported with metronidazole (see Section 4.8 Adverse Effects (Undesirable Effects)). If symptoms or signs of SJS, TEN or AGEP are present, metronidazole treatment must be immediately discontinued.

Long-term therapy.

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

Surgical drainage.

Use of metronidazole does not obviate the need for aspirations of pus whenever indicated.

Nervous system.

Metronidazole should be used with caution in patients with active or chronic severe peripheral and 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 operate machinery if these symptoms occur.

Suicidal ideation.

Cases of suicidal ideation with or without depression have been reported during treatment with metronidazole. Patients should be advised to discontinue treatment and contact their healthcare provider immediately if they experience psychiatric symptoms during treatment.

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.

Use in hepatic impairment.

No information available. As metronidazole is partly metabolised in the liver, caution should be exercised in patients with impaired liver function or hepatic encephalopathy.
Flagyl may interfere with certain chemical analysis of serum aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), triglycerides and glucose hexokinase to give abnormally low values.

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 interfere with certain types of blood test determinations in blood (aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], triglycerides, glucose), which may lead to false negative or an abnormally low result. These analytical determinations are based on a decrease in ultraviolet absorbance, a fact that occurs when nicotinamide adenine dinucleotide hydrogen (NADH) is oxidized to nicotinamide adenine dinucleotide (NAD). The interference is due to the similarity in the absorption peaks of NADH (340 nanometer) and metronidazole (322 nanometer) at pH 7.

4.5 Interactions with Other Medicines and Other Forms of Interactions

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 metabolism. Prothrombin times should be monitored as should anticoagulant activity.
The simultaneous administration of drugs that induce microsomal liver enzymes, such as phenytoin or phenobarbital (phenobarbitone), may accelerate the elimination of metronidazole, resulting in reduced plasma levels; impaired clearance of phenytoin has also been reported.
The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may prolong the half-life and decrease plasma clearance of metronidazole.
In patients stabilised on relatively high doses of lithium, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Serum lithium and serum creatinine levels and electrolytes should be obtained several days after beginning metronidazole to detect any increase that may precede clinical symptoms of lithium intoxication.
Psychotic reactions have been reported in patients who were using metronidazole and disulfiram concurrently. Metronidazole should not be given to patients who have taken disulfiram within the last two weeks.
Carmustine, cyclophosphamide monohydrate: metronidazole should be used with caution in patients receiving these drugs.
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.
Metronidazole used in combination with 5-fluorouracil may lead to reduced clearance of 5-fluorouracil, resulting in increased toxicity.
Patients should be advised not to take alcohol during therapy or for at least one day afterwards because of the possibility of a disulfiram-like (Antabuse) effect reaction.
Plasma levels of busulfan may be increased by metronidazole, which may lead to severe busulfan toxicity.
QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.

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 enters foetal circulation rapidly. As its effects on foetal 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 should 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). In view of its tumorigenic and mutagenic potential (see Section 5.3 Preclinical Safety Data), breastfeeding is not recommended.

4.7 Effects on Ability to Drive and Use Machines

Patients should be warned about the potential for confusion, dizziness, vertigo, hallucinations, convulsions or transient visual disorders and advised not to drive or operate machinery if these symptoms occur. See Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects).

4.8 Adverse Effects (Undesirable Effects)

Gastrointestinal effects.

When given orally, metronidazole is well tolerated. The most common adverse reactions refer to the gastrointestinal tract, particularly nausea, sometimes accompanied by headache, anorexia and occasionally vomiting, diarrhoea, epigastric pain or distress and abdominal cramping; constipation, oral mucositis and taste disorders have also been reported. A metallic, sharp, unpleasant taste is not unusual. Cases of pancreatitis, which abated on withdrawal of the drug, have been reported. Crohn's disease patients are known to have an increased incidence of gastrointestinal and certain extraintestinal cancers. If patients receiving metronidazole drink alcoholic beverages, they may experience abdominal distress, nausea, vomiting, flushing or headache. A modification of the taste of alcoholic beverages has also been reported.
Furry tongue, tongue discolouration, glossitis and stomatitis have occurred; these may be associated with a sudden overgrowth of Candida which may occur during effective therapy.

Body as a whole.

Hypersensitivity reactions include 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. Fixed drug eruption has been reported. Stevens-Johnson syndrome and toxic epidermal necrolysis have also been reported.

Liver.

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.

Haematology.

A moderate leucopenia may be observed occasionally. If this occurs, the total leucocyte 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 Flagyl should be ceased and appropriate supportive therapy instituted. Cases of agranulocytosis, neutropenia or thrombocytopenia have been reported.

Psychiatric/CNS disorders.

Dizziness, vertigo, incoordination, headache and convulsive seizures have been reported. Psychotic disorders such as confusion and hallucinations have been reported. Depression, depressed mood, insomnia, irritability, weakness have been experienced, as has peripheral neuropathy, characterised mainly by numbness or paraesthesia of an extremity. There have been reports of encephalopathy (e.g. confusion, vertigo) and subacute cerebellar syndrome (e.g. ataxia, dysarthria, gait impairment, nystagmus and tremor), which may resolve with discontinuation of the drug. Since persistent peripheral neuropathy has been reported in some patients receiving prolonged administration of metronidazole, such subjects should be specifically warned about these reports and should be told to stop the drug and report immediately if any neurological symptoms occur. Aseptic meningitis has been reported.
Frequency not known: vertigo.

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.

Ear and labyrinth disorders.

Impaired hearing/ hearing loss (including sensorineural) and tinnitus have 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 of 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 special investigation. Although the pigment which is probably responsible for this phenomenon has not been positively identified, it is almost certainly 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.

Cardiovascular.

Flattening of the T wave may be seen in ECG tracings.
Frequency not known: QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.

Reporting suspected adverse reactions.

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 (Australia) or nzphvc.otago.ac.nz/reporting/ (New Zealand).

4.9 Overdose

Symptoms.

Overdosage with metronidazole appears to be associated with very few abnormal signs or symptoms. Disorientation, ataxia and vomiting may occur, especially after ingestion of large amounts. In case of suspected massive overdosages, a symptomatic and supportive treatment should be instituted.
Single oral doses of metronidazole, up to 12 g, have been reported in suicide attempts and accidental overdoses.

Treatment.

There is no specific antidote for metronidazole overdosage. In cases of suspected overdosage, a symptomatic and supportive treatment should be instituted.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia) or the National Poisons Centre, 0800 POISON or 0800 764 766 (New Zealand).

5 Pharmacological Properties

Metronidazole benzoate itself is not systemically available following oral administration. It is hydrolysed before or during absorption through the gut wall so that only metronidazole can be detected in the circulation.

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antibacterials for systemic use, ATC code J01X D01.

Mechanism of action.

Metronidazole is effective in vitro against several species of anaerobic bacteria, particularly Bacteroides fragilis and other species of bacteroides, and other species such as fusobacteria, eubacteria, clostridia, and anaerobic streptococci. The MIC for most susceptible anaerobes is < 6.2 microgram/mL.

Note.

Metronidazole is inactive against aerobic and facultative anaerobic bacteria.
Metronidazole is active against a wide range of pathogenic microorganisms notably Trichomonas vaginalis and other trichomonads, Entamoeba histolytica, Giardia lamblia, Balantidium coli and the causative organisms of acute ulcerative gingivitis.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Maximum mean plasma metronidazole concentration are 16.6 microgram/mL at 5.1 hours after administration of a single oral dose of metronidazole benzoate equivalent to 2 g metronidazole and 4.6 microgram/mL at 3.2 hours after administration of a single oral dose of metronidazole benzoate, equivalent to 400 mg metronidazole. An oral dose of two 200 mg tablets of metronidazole in the same trial gave mean peak serum levels of 8.5 microgram/mL at 0.8 hours after administration. Total absorption from metronidazole benzoate suspension was somewhat lower than from the tablets. In children, the time to reach peak serum level is quite variable (3.6 to 5.1 hours).
Mean elimination half-lives are 9.7 hours following metronidazole benzoate suspension (2 g metronidazole) and 8.6 hours following metronidazole benzoate suspension (400 mg metronidazole).

Distribution.

Metronidazole is widely distributed in body tissues and fluids and is not protein bound to any significant degree.
Metronidazole diffuses across the blood brain barrier and placenta and is found in the breast milk of nursing mothers in concentrations equivalent to those in serum.

Metabolism.

No data available.

Excretion.

Most of the dose is excreted in the urine as metronidazole and its metabolites including oxidation products and glucuronides.

5.3 Preclinical Safety Data

Genotoxicity.

In studies on the mutagenic potential of metronidazole, the Ames test was positive while several nonbacterial tests in animals were negative. In the patients with Crohn's disease, metronidazole increased the chromosome abnormalities in circulating lymphocytes. The use of metronidazole for longer treatment than usually required should be carefully weighed (see Section 4.4 Special Warnings and Precautions for Use) and the benefit/ risks 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 been shown to be tumorigenic and carcinogenic in rodents.

6 Pharmaceutical Particulars

6.1 List of Excipients

Aluminium magnesium silicate, ethanol, methyl hydroxybenzoate, monobasic sodium phosphate, natural soluble lemon flavour 50 06-0404 (PI 225), orange oil terpeneless, propyl hydroxybenzoate, sucrose.

6.2 Incompatibilities

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

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

Glass bottle.
Pack size: 100 mL.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.


CAS number.

13182-89-3.
Slightly yellow crystalline powder with a melting point of 99 to 102°C. Solubility at 25°C (g/100 mL solvent): 12.2 x 10-3 in water, 2 in ethanol, 5 in methanol and 25.6 in acetone. The pH of metronidazole benzoate suspensions in water is 5 to 6.5.

7 Medicine Schedule (Poisons Standard)

Schedule 4. Prescription Only Medicine.

Summary Table of Changes