Metronidazole

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications: 

• Treatment of infections in which anaerobic bacteria have been identified or are suspected as pathogens, particularly Bacteroides fragilis and other species of Bacteroides, and including other species for which metronidazole is bactericidal, such as fusobacteria, eubacteria, clostridia and anaerobic streptococci (metronidazole has been used successfully for anaerobic infections in the following conditions: pelvic inflammatory disease and postoperative wound infection. Combined therapy is often indicated as there are usually mixed infections)
• Prevention of postoperative abdominal and pelvic infections due to anaerobic bacteria
  - Given before and after colonic surgery
  - Given before and after gynaecological surgery
  - Given before and after appendicectomy

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other imidazoles
• Coadministration with busulfan

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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South African recommendations

Caution in the following patient groups

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Hepatic encephalopathy

Alcohol

• Patients should be advised not to take alcohol during metronidazole therapy and for at least one day afterwards because of the possibility of a disulfiram-like reaction

Pseudomembranous colitis

• Pseudomembranous colitis has been reported with the use of metronidazole

Condoms containing fatty/oily excipients

• The simultaneous use of metronidazole suppositories with condoms containing fatty/oily excipients may increase the risk of rupture of the latex

Busulfan coadministration

• Coadministration with busulfan: As plasma levels of busulfan may be increased significantly, it may lead to severe busulfan toxicity and death

Mutagenic and carcinogenic properties

• Studies have shown metronidazole to be mutagenic in bacteria and carcinogenic in some animals

Blood dyscrasias and nervous system disease

• Metronidazole should be used with great care in patients with blood dyscrasias or with active or chronic disease of the central and peripheral nervous system

Peripheral neuropathy and CNS toxicity

• All patients receiving metronidazole for more than 10 days should be monitored and treatment discontinued if signs of peripheral neuropathy or central nervous system toxicity develop. Doses should be reduced in patients with severe liver disease

Anti-treponemal activity

• Metronidazole has anti-treponemal activity and may mask the immunological response seen in untreated early syphilis; contacts of syphilis receiving metronidazole should probably be screened for an additional 4 to 8 weeks

Urine discolouration

• Patients should be warned that metronidazole may darken urine (due to metronidazole metabolite)

Driving a vehicle or performing hazardous tasks

• 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

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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Forms avail. in SA and covered in this monograph: sup

Infections caused by: Trichomonas vaginalis, other protozoa, including Entamoeba histolytica and Giardia lamblia, obligate anaerobic bacteria, whether they are Gram-positive or -negative and bacilli or cocci, Bacteroides fragilis, Bacteroides fragilis, fusobacteria, eubacteria, clostridia and anaerobic streptococci

South African registered indications and dosages

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

Treatment of infections in which anaerobic bacteria have been identified or are suspected as pathogens, particularly Bacteroides fragilis and other species of Bacteroides, and including other species for which metronidazole is bactericidal, such as fusobacteria, eubacteria, clostridia and anaerobic streptococci

• Rectal (sup): 1g, inserted into the rectum 8hrly; Treatment duration: 7 days or longer, until oral medication becomes feasible

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Suppository to be used in patients for whom oral medication is not possible or is contraindicated

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Metronidazole has been used successfully for anaerobic infections in the following conditions:
Pelvic inflammatory disease and postoperative wound infection. Combined therapy is often indicated as there are usually mixed infections

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Prevention of postoperative abdominal and pelvic infections due to anaerobic bacteria
- Given before and after gynaecological surgery
- Given before and after appendicectomy
- Given before and after colonic surgery

• Rectal (sup): 1g, 2-4hrs before surgery; Repeat 8hrly until feeding becomes possible; Then: substitute with Oral (tab): 200mg, 8hrly

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Suppository to be used in patients for whom oral medication is not possible or is contraindicated

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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Paed. forms avail. in SA and covered in this monograph: sup

Infections caused by: Trichomonas vaginalis, other protozoa, including Entamoeba histolytica and Giardia lamblia, obligate anaerobic bacteria, whether they are Gram-positive or -negative and bacilli or cocci, Bacteroides fragilis, Bacteroides fragilis, fusobacteria, eubacteria, clostridia and anaerobic streptococci

South African registered indications and dosages

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

Treatment of infections in which anaerobic bacteria have been identified or are suspected as pathogens, particularly Bacteroides fragilis and other species of Bacteroides, and including other species for which metronidazole is bactericidal, such as fusobacteria, eubacteria, clostridia and anaerobic streptococci

Rectal (sup)

• 1-5 years: 250mg, 8hrly; Treatment duration: 3 days; Then: 250mg, 12hrly
• 5-10 years: 500mg, 8hrly; Treatment duration: 3 days; Then: 500mg, 12hrly

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Based on weight: Rectal (sup): 7.5 mg/kg body mass per rectum every 8 hours

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Prevention of postoperative abdominal and pelvic infections due to anaerobic bacteria
- Given before and after colonic surgery
- Given before and after gynaecological surgery
- Given before and after appendicectomy

Rectal (sup)

• 1-5 years: 250mg, 2-4hrs before surgery, 8hrly until feeding becomes possible; Then substitute with oral medication 7.5mg/kg, 8hrly
• 5-10 years: 500mg, 2-4hrs before surgery, 8hrly until feeding becomes possible; Then substitute with oral medication 7.5mg/kg, 8hrly

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Suppository to be used in patients for whom oral medication is not possible or is contraindicated

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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Pregnancy

South African recommendations

• Caution
• Safety in pregnancy has not been established. Metronidazole crosses the placental barrier. Use in pregnancy should be carefully evaluated

Breastfeeding

South African recommendations

• Caution
• Safety in lactation has not been established. Metronidazole is excreted in breast milk. Use in lactation should be carefully evaluated

Fertility

South African recommendations

• No information available

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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South African recommendations

• Caution; no information available

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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South African recommendations

• Caution; no dose adjustment recommended
  Metronidazole should be administered with caution to patients with hepatic encephalopathy

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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South African recommendations

• Caution; no information available

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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Blood and Lymphatic System Disorders

Frequency unknown

• Leucopenia

Less frequent

• Agranulocytosis
• Neutropenia
• Thrombocytopenia

Immune System Disorders

Less frequent

• Anaphylaxis

Frequency unknown

• Angioedema
• Urticaria

Metabolism and Nutrition Disorders

Frequency unknown

• Anorexia

Psychiatric Disorders

Less frequent

• Psychotic disorders including confusion, irritability and hallucinations
• Changes in mood or mental state such as depression or confusion

Nervous System Disorders

Frequency unknown

• Peripheral neuropathy, usually presenting as numbness or tingling in the extremities
• Epileptiform seizures

Less frequent

• Weakness
• Dizziness
• Drowsiness
• Insomnia
• Encephalopathy (e.g. confusion)
• Subacute cerebellar syndrome (e.g. ataxia, dysarthria, gait impairment, nystagmus, tremor)

Eye Disorders

Less frequent

• Transient vision disorders such as diplopia and myopia

Respiratory, Thoracic and Mediastinal Disorders

Frequency unknown

• Nasal congestion

Gastrointestinal Disorders

Frequent

• Gastrointestinal disturbances, especially nausea and taste disorders
• Nausea is sometimes accompanied by headache and vomiting
• Diarrhoea
• Dry mouth
• Furred tongue
• Oral mucositis
• Stomatitis

Less frequent

• Antibiotic-associated colitis

Frequency unknown

• Pseudomembranous colitis

Hepato-biliary Disorders

Frequency unknown

• Pancreatitis
• Raised liver enzyme values

Less frequent

• Reversible abnormal liver function
• Cholestatic hepatitis sometimes with jaundice

Skin and Subcutaneous Tissue Disorders

Frequency unknown

• Skin rashes
• Fever
• Flushing
• Pruritus

Less frequent

• Pustular eruptions
• Mild erythematous eruptions with fleeting joint pains resembling serum sickness

Musculoskeletal, Connective Tissue and Bone Disorders

Frequency unknown

• Myalgia
• Arthralgia

Renal and Urinary Disorders

Less frequent

• Urethral discomfort
• Darkening of the urine

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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• Disulfiram
• Warfarin (oral anticoagulant therapy)
• Lithium
• Ciclosporin
• Phenytoin
• Phenobarbital
• 5-Fluorouracil
• Busulfan
• Cimetidine

Other interactions

• Alcohol

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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None routine. Specific cases may require

• Prothrombin time/INR (when in combination with anticoagulant therapy)
• Plasma concentrations of lithium, creatinine and electrolytes (in patients under treatment with lithium)
• Serum ciclosporin

Additional observations

• Signs of peripheral neuropathy or central nervous system toxicity

Please note that the products associated with this active ingredient monograph have all been discontinued in the South African market (Effective: March 2023). The information in this monograph has not been updated and remains on the EMGuidance platform for reference purposes only.

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The parent compound penetrates the cell membrane unchanged, but once inside the cell the nitro group is reduced in the redox conditions prevalent in the anaerobic cell. The reduced product is known to damage DNA causing eventual death of the organism.

Metronidazole has antiprotozoal activity against Trichomonas vaginalis and other protozoa, including Entamoeba histolytica and Giardia lamblia. It does not affect the acidophilic flora of the vagina and it has no effect on Candida species. Metronidazole has bactericidal activity against obligate anaerobic bacteria, whether they are Gram-positive or -negative and bacilli or cocci. It has no antibacterial activity against aerobic and facultative anaerobic bacteria. Metronidazole does not interfere with the activity of antibacterial agents which are active against a variety of aerobes and facultative anaerobes.

Spectrum of activity: Trichomonas vaginalis, other protozoa, including Entamoeba histolytica and Giardia lamblia, obligate anaerobic bacteria, whether they are Gram-positive or -negative and bacilli or cocci, Bacteroides fragilis, Bacteroides fragilis, fusobacteria, eubacteria, clostridia and anaerobic streptococci.

Capsule 200mg

• Narobic (Alliance)

Tablet 200mg

• Acuzole (Pharmascript)
• Adco-Metronidazole (Adcock Ingram)
• Ambral (Thebe)
• Anaerobyl (Medicine Dev)
• Bemetrazole (Ranbaxcy)
• Flagyl (Sanofi) originator
• Medamet (Caps Pharma)
• Metagyl (Oethmaan Biosims)
• Metazol (Akacia)
• Merck metronidazole (Xixia)
• Metronidazole Dezzo (Dezzo)
• Sandoz metronidazole (Sandoz)
• Trichazole (Pharmacare)

Tablet 400mg

• Acuzole (Pharmascript)
• Adco-metronidazole (Adcock Ingram)
• Amzole (Innovata)
• Anaerobyl (Medicine Dev)
• Bemetrazole (Ranbaxy Pharmaceuticals)
• Bio-metronidazole (Biotech)
• Dynametron (Akacia)
• Flagyl (Sanofi) originator
• Metagyl Forte (Oethmaan Biosims)
• Metazol (Alliance Pharma)
• Metrostat (Adcock Ingram)
• Metrazole (Pharmacorp)
• Metronidazole Dezzo (Dezzo)
• Nidasall 400 (Innovata Pharmaceuticals)
• Sandoz metronidazole (Sandoz)
• Trichazole (Pharmacare)

Suspension (per 5ml) 200mg

• Flagyl (Sanofi) originator

Injection (per 100ml) 500mg

• Bio-Metronidazole (Biotech)
• Flagyl (Sanofi) originator
• Metronidazole B braun (B Braun)
• Metris (Dezzo Trading)
• Sabax metronidazole (Adcock Ingram) 
• Trichazole ( Fresenius Kabi)

Suppository 500mg

• Flagyl (Sanofi) originator

Suppository 1g

• Flagyl (Sanofi) originator

Also available in the following form: Gel.