Consumer medicine information

Metrogyl

Metronidazole

BRAND INFORMATION

Brand name

Metrogyl

Active ingredient

Metronidazole

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Metrogyl.

What is in this leaflet

This leaflet answers some common questions about Metrogyl.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking Metrogyl against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What Metrogyl is used for

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

Metrogyl may also be used to prevent or treat certain infections that may occur during surgery.

Metrogyl is an antibiotic which belongs to a group of medicines called nitroimidazoles. These medicines work by killing or stopping the growth of bacteria and other organisms causing these infections.

Your doctor may have prescribed Metrogyl for another reason.

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

Metrogyl is available only with a doctor's prescription.

There is no evidence that this medicine is addictive.

Before you take Metrogyl

When you must not take it

Do not take Metrogyl if you are allergic to medicines containing metronidazole, any other nitroimidazole medicine or any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include skin rash, itching or hives, swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing, wheezing or shortness of breath.

Do not take Metrogyl if:

  • you have ever had or are having an active disease of the central nervous system (brain, spinal cord or nerves)
  • have evidence of, or history of a blood disorder.

Do not take Metrogyl if the expiry date (Exp.) printed on the pack has passed.

Do not take Metrogyl if the packaging shows signs of tampering or the tablets do not look quite right.

Before you start to take it

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor if you are pregnant or plan to become pregnant. Your doctor will discuss the risks and benefits of taking Metrogyl during pregnancy.

Tell your doctor if you are breastfeeding or wish to breastfeed. Like many other medicines Metrogyl passes into breast milk and may harm your baby. Metrogyl is not recommended in breastfeeding.

Tell your doctor if you have any medical conditions, especially the following:

  • a blood disorder
  • disease of the brain, spinal cord or nerves
  • kidney problems
  • liver problems
  • an inflammatory disease of the small intestines (e.g. Crohn's disease)
  • Cockayne syndrome
  • you drink alcohol.
    Do not drink alcohol during (and for 24 hours after stopping) treatment with Metrogyl.

Your doctor may want to take special care if you have any of these conditions.

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

Taking other medicines

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

Some medicines may be affected by Metrogyl, or may affect how well it works. These include:

  • warfarin, or other medicines used to prevent blood clots
  • disulfiram, a medicine used to treat chronic alcohol dependence
  • Medications containing alcohol (ethanol), e.g. some cough syrups
  • some anticancer drugs such as carmustine (BCNU), cyclophospamide, 5-fluorouracil or busulfan
  • lithium, a medicine used to treat mood swings and some types of depression
  • phenytoin, a medicine used to treat convulsions
  • phenobarbital (phenobarbitone), medicines used to treat convulsions or sedation
  • cimetidine, a medicine used to treat reflux and ulcers
  • ciclosporin, a medicine used to prevent organ transplant rejection or to treat immune responses.

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

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist. Your doctor and pharmacist may have more information on medicines to be careful with or avoid while taking Metrogyl.

How to take Metrogyl

How much to take

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

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

The dose varies from patient to patient. Your doctor will tell you how many tablets you need to take each day and when to take them. This depends on your condition and whether or not you are taking any other medicines.

How to take Metrogyl

Swallow the tablets whole with a glass of water.

Do not crush or chew the tablets.

Metrogyl tablets, however, can be broken in half if your doctor has prescribed half a tablet.

When to take Metrogyl

Take Metrogyl with or immediately after food. This will lessen the chance of a stomach upset.

If you are taking more than a single dose of Metrogyl, space the doses evenly throughout the day.

If you forget to take Metrogyl

If you are taking more than a single dose of Metrogyl, and 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 the missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

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

If you are not sure what to do, ask your doctor or pharmacist.

If you have any questions about this, check with your doctor or pharmacist.

If you have trouble remembering to take Metrogyl, ask your pharmacist for some hints.

How long to take Metrogyl for

Keep taking Metrogyl until you finish the bottle, or for as long as your doctor recommends.

For treating infections, Metrogyl is usually taken for 7 days, however your doctor may prescribe Metrogyl for longer or shorter periods of time depending on the condition you are being treated for.

Your doctor will tell you how much Metrogyl to take.

Check with your doctor if you are not sure how long you should be taking it for.

If you take too much Metrogyl (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much Metrogyl. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much Metrogyl, you may feel disorientated, unsteadiness when walking and vomiting may occur.

While you are taking Metrogyl

Things you must do

Before starting any new medicine, tell your doctor or pharmacist that you are taking Metrogyl.

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

Make sure you have any blood tests that your doctor requests, especially if you are taking Metrogyl for longer than 10 days or if you are elderly.

If you have to have any other blood tests, tell your doctor that you are taking Metrogyl.

Metrogyl may affect the results of some tests.

If you notice a persistent numbness, tingling or weakness of the arms or legs, stop taking Metrogyl and tell your doctor immediately.

If you become pregnant while taking Metrogyl, stop taking it and tell your doctor immediately.

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

Things you must not do

Do not drink any alcohol while taking Metrogyl and for at least 24 hours after stopping treatment. Drinking alcohol may make you feel very sick, vomit, have stomach cramps, headaches and flushing.

Do not stop taking Metrogyl, even if you feel better after a few days, unless advised by your doctor. Your infection may not clear completely if you stop taking your medicine too soon because the bacteria/organism causing your infection may not have been killed. These bacteria/organisms may continue to grow and multiply so that your infection may not improve or it can return again.

Do not use Metrogyl to treat any other conditions unless your doctor tells you to.

Do not give Metrogyl to anyone else, even if they have the same condition as you.

Things to be careful of

Be careful driving or operating machinery until you know how Metrogyl affects you.

Metrogyl may cause confusion, dizziness or hallucinations in some people. If any of these occur, do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Metrogyl even if you do not think the problem is connected with the medicine or is not listed in this leaflet.

Like all other medicines, Metrogyl may have unwanted side effects in some people. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

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

Tell your doctor if you notice any of the following and they worry you:

  • oral thrush - white, furry sore or inflamed tongue and mouth
  • vaginal thrush - sore and itchy vagina with or without discharge
  • nausea, which may be accompanied by headache, loss of appetite, and vomiting
  • diarrhoea, stomach discomfort, abdominal cramping or constipation, strange taste in mouth
  • convulsions, dizziness, weakness, feeling of incoordination or uncoordinated movements
  • confusion, irritability, depression or sleeplessness
  • skin rashes, flushing, itching
  • stuffy nose, dry mouth, nasal congestion, dryness of the mouth (or vagina or vulva)
  • unusual urination patterns (e.g. difficulty in passing urine, large amounts of urine, incontinence, or pus in urine)
  • joint pain
  • eye problems, including blurred or double vision
  • hearing problems
  • yellowing of the skin or eyes, which may be jaundice

If any of the following happen, stop taking Metrogyl and tell your doctor immediately, or go to Accident and Emergency at the nearest hospital:

  • skin rash, itchiness, hives
  • swelling of the face, lips, mouth, throat or neck which may cause difficulty swallowing or breathing
  • tingling or numbness in the hands or feet, or muscle weakness
  • severe upper stomach pain, often with nausea and vomiting.

If you have been on prolonged Metrogyl therapy and experience any unusual numbness of the feet or hands, stop taking Metrogyl, and tell your doctor immediately.

Other side effects not listed above may also occur in some patients.

Tell your doctor if you notice anything that is making you feel unwell.

After taking Metrogyl

Storage

Keep Metrogyl where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep your tablets in a cool dry place where the temperature stays below 30°C. Protect from light.

Do not store Metrogyl or any other medicine in the bathroom or near a sink.

Do not leave Metrogyl in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking Metrogyl, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Metrogyl comes in 2 strengths of tablets:

  • Metrogyl 200 - round white tablet marked MZ/200 on one side and G on the reverse
  • Metrogyl 400 - round yellow tablet marked MZ/400 on one side and G on the reverse.

Metrogyl 200 and Metrogyl 400 available as 21 tablets.

Metrogyl 200 is also available as 250 tablets (hospital use only).

Ingredients

The active ingredient in Metrogyl is metronidazole.

Each Metrogyl tablet contains either 200 mg or 400 mg of metronidazole.

The tablets also contain:

  • lactose monohydrate
  • disodium edetate
  • ethylcellulose
  • sodium starch glycollate
  • colloidal anhydrous silica
  • guar gum
  • magnesium stearate.

Metrogyl 400 also contains quinoline yellow CI 47005 (E104).

The tablets are gluten free.

Metrogyl tablets contain sulfites and sugars (as lactose and galactose).

Sponsor

Metrogyl is supplied in Australia by:

Alphapharm Pty Limited
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

Australian registration numbers:
Metrogyl 200 - Aust R 17654
Metrogyl 400 - Aust R 17655

This leaflet was prepared in June 2019.

Metrogyl_cmi\Jun19/00

Published by MIMS September 2019

BRAND INFORMATION

Brand name

Metrogyl

Active ingredient

Metronidazole

Schedule

S4

 

1 Name of Medicine

Metronidazole.

6.7 Physicochemical Properties

Metronidazole is a 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole.

Chemical structure.


CAS number.

443-48-1.
Metronidazole has a melting point of 159-162°C. A saturated solution of aqueous metronidazole has a pH of between 6 and 7.5. Solubility (g/100 mL) of metronidazole at 20°C: 1 in water; 0.5 in ethanol; 0.4 in chloroform; slightly soluble in ether; soluble in dilute acids.

2 Qualitative and Quantitative Composition

Metrogyl 200 and Metrogyl 400 contains the active ingredient metronidazole 200 mg and metronidazole 400 mg respectively.
Metronidazole crystals are white to brownish in colour.
Metrogyl tablets also contain sulfites and sugars (as lactose and galactose).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Metrogyl 200.

200 mg tablet: white marked MZ/200 on one side, G on the reverse.

Metrogyl 400.

400 mg tablet: yellow marked MZ/400 on one side, G on the reverse.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

No data available.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Pharmacokinetic.

Metronidazole is readily absorbed, peak serum concentration is reached approximately 1 to 2 hours after an oral dose. Food does not significantly affect absorption and the bioavailability of the dose approaches 100% when compared with intravenous administration. Traces of metronidazole are detectable after 24 hours. The biological half-life of oral metronidazole has been determined as 6 to 7 and 7.3 hours respectively.
Metronidazole is widely distributed in body tissues and fluids. It crosses the blood brain barrier and the placenta. The concentration in breast milk of nursing mothers is similar to those in serum. The serum half-life of unchanged metronidazole is about 8 to 10 hours. Metronidazole is excreted in the urine as unchanged drug and its metabolites including acid oxidation products and glucuronides. Metronidazole is not protein bound to any significant degree. Most of the dose is excreted in the urine as metronidazole and its metabolites, including acid oxidation products and glucuronides.

Microbiology.

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. Metronidazole also displays antibacterial activity in vitro against several species of anaerobic bacteria including Bacteroides fragilis and other species of Bacteroi, and other species such as Fusobacteria, Eubacteria, Clostridia and anaerobic Streptococci. The minimum inhibitory concentration (MIC) for most susceptible anaerobes is < 6.2 microgram/mL.
Metronidazole is inactive against aerobic and facultative anaerobic bacteria.

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 patients with Crohn's disease, metronidazole increased the chromosome abnormalities in circulating lymphocytes.

Carcinogenicity.

In addition, the drug has been shown to be tumorigenic and carcinogenic in rodents. 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/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.

4 Clinical Particulars

4.1 Therapeutic Indications

Metronidazole is indicated in the oral treatment of:
1. Urogenital trichomoniasis in the female (trichomonal vaginitis) and in the male. The male consort of females suffering from urogenital trichomoniasis should be treated concurrently.
2. Bacterial vaginosis.
3. All forms of amoebiasis (intestinal and extraintestinal disease).
4. Giardiasis.
5. Acute ulcerative gingivitis.
6. Anaerobic infections including septicaemia, bacteraemia, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis and postoperative wound infections, in which the pathogens have been identified as Bacteroides fragilis and other species of Bacteroides, and other species such as Fusobacteria, Eubacteria, Clostridia and anaerobic Streptococci.
Metronidazole may be used prophylactically to prevent infection by anaerobic organisms of the surgical site following appendicectomy, colonic surgery, vaginal hysterectomy, abdominal surgery in the presence of anaerobes in the peritoneal cavity and surgery performed in the presence of anaerobic septicaemia.

4.3 Contraindications

1. Patients with active organic disease of the central nervous system.
2. Patients with evidence of, or 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.
3. 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, or for at least 24 hours afterwards, as nausea, vomiting, abdominal cramps, headaches, tachycardia, and flushing may occur. There is the possibility of a disulfiram-like (Antabuse) effect reaction.

Candidiasis.

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

Cockayne syndrome.

Cases of severe hepatotoxicity/ acute hepatic failure, including cases with a fatal outcome with a very rapid onset after treatment initiation, have been reported in patients with Cockayne syndrome, with products containing metronidazole for systemic use. In this population, metronidazole should therefore be used, after careful risk-benefit assessment, with caution in these patients, and only if there is no alternative treatment available.
Liver function tests must be performed just prior to the start of therapy, throughout and after end of treatment under liver function is within normal ranges, or until the baseline values are reached. If the liver function 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, (such as sustained new onset abdominal pain, anorexia, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine or itching), 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 neuropathy or central neuropathy (such as paresthesia, ataxia, dizziness, 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 aspiration 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 use machinery if these symptoms occur.

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.
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.
Dosage should be reduced or dosage intervals increased (see Section 4.2 Dose and Method of Administration).

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, resulting in plasma concentration falling 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.

Use in the elderly.

The pharmacokinetics of metronidazole may be altered and therefore monitoring of serum levels may be necessary to adjust the metronidazole dosage accordingly (see Section 4.2 Dose and Method of Administration).

Paediatric use.

No data available.

Effects on laboratory tests.

Metronidazole may interfere with certain chemical analyses of serum aspartate transaminase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglycerides and hexokinase glucose, to give abnormally low values.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Warfarin.

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

Alcohol.

Alcoholic beverages and drugs containing alcohol should not be consumed during metronidazole therapy and for at least one day afterwards because the possibility of a disulfiram-like (Antabuse effect) reaction (vomiting, tachycardia and flushing).

Carmustine (BCNU) or cyclophosphamide.

Metronidazole should be used with caution in patients receiving these drugs.

Lithium.

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.

Disulfiram.

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.

Hepatic enzyme inducers.

The simultaneous administration of drugs that induce microsomal hepatic enzymes, such as phenytoin or (phenobarbital) phenobarbitone, may accelerate the elimination of Metrogyl, resulting in reduced plasma levels; impaired clearance of phenytoin has also been reported.

Hepatic enzyme inhibitors.

The simultaneous administration of drugs that decrease microsomal hepatic enzyme activity, such as cimetidine, may prolong the half-life and decrease plasma clearance of metronidazole.

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.

5-Fluorouracil.

Metronidazole used in combination with 5-fluorouracil may lead to reduced clearance of 5-fluorouracil, resulting in increased toxicity.

Busulfan.

Plasma levels of busulfan may be increased by metronidazole, which may lead to severe busulfan toxicity.

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 fetal circulation rapidly. 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 should be restricted to those in whom local palliative treatment has been inadequate to control symptoms.
If a patient is treated during the 2nd or 3rd trimesters of pregnancy for urogenital trichomoniasis, the 2 g stat dose therapy should not be used as it results in higher serum levels which reach the fetal circulation.
Metronidazole is secreted in breast milk (see Section 5.2 Pharmacokinetic Properties). In view of its tumorigenic and mutagenic potential, breastfeeding is not recommended (see Section 5.3 Preclinical Safety Data).

4.8 Adverse Effects (Undesirable Effects)

Gastrointestinal.

Metronidazole when given orally is well tolerated. 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. Patients with Crohn's disease 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 shocks. 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 metronidazole should be ceased and appropriate supportive therapy instituted. Cases of agranulocytosis, neutropenia or thrombocytopenia have been reported.

Psychiatric/central nervous system 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) and subacute cerebellar syndrome (e.g. ataxia, dysarthria, gait impairment, nystagmus and tremor), which may resolve with the 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.

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.

Genitourinary 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 a 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.

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.

4.2 Dose and Method of Administration

Summarised in Table 1.
A maximum of 4 g should not be exceeded during 24 hour period.

Oral.

The tablets should be swallowed, without chewing, with half a glass of water. Treatment for seven days should be satisfactory for most patients but, depending on clinical and bacteriological assessment, the clinician might decide to prolong treatment.
In patients with impaired liver function, dosage should be reduced or dosage intervals increased. Plasma metronidazole levels should be monitored (see Section 4.4 Special Warnings and Precautions for Use).
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. Plasma metronidazole levels should be monitored (see Section 4.4 Special Warnings and Precautions for Use).

Urogenital trichomoniasis.

The usual oral dosage is shown in Table 1. To prevent reinfection, the partner should receive a similar course of treatment concurrently.
If treated during the second or third trimester, the one day course of therapy should not be used as it results in higher serum levels which reach the foetal circulation (see Section 4.6 Fertility, Pregnancy and Lactation).
When repeat courses of the drug are required, it is recommended that an interval of four to six weeks elapse between courses and the presence of the trichomonad be reconfirmed by appropriate laboratory measures. Total and differential leucocyte counts should be made before and after retreatment.

Surgical prophylaxis.

Note.

Prevention of infection at the surgical site requires that adequate tissue concentration of the drug should have been achieved at the time of surgery. The doses and route of administration should be selected in this case to achieve this objective.
As an oral ingestion is often prohibited 12 hours or longer before surgery, and it may not be practical for a variable period following surgery, tablets are not considered to be an appropriate formulation for prophylactic use. However, if oral intake is not contraindicated and is feasible following surgery, 400 mg may be taken one to two hours before surgery and repeated every eight hours for 24 hours.

4.7 Effects on Ability to Drive and Use Machines

Patients should be warned about the potential for confusion, dizziness, hallucinations or convulsions or transient visual disorders and advised not to drive or use machinery if these symptoms occur. See Section 4.4 Special Warnings and Precautions for Use.

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 Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Metrogyl 200 and Metrogyl 400 contain the following excipients: lactose monohydrate, disodium edetate, ethylcellulose, sodium starch glycollate, colloidal anhydrous silica, guar gum, magnesium stearate and quinoline yellow C147005 (Metrogyl 400 only).

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 30°C. Protect from light.

6.5 Nature and Contents of Container

Metrogyl 200.

Container type: HDPE bottle.
Pack sizes: 21 or 250 tablets.

Metrogyl 400.

Container type: HDPE bottle.
Pack sizes: 5 or 21 tablets.
Some pack sizes may not be marketed.

6.6 Special Precautions for Disposal

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

Summary Table of Changes