Metronidazole Oral Suspension is indicated in the prophylaxis and treatment of infections in
which anaerobic bacteria have been identified or are suspected as the pathogen
Metronidazole Oral Suspension is active against a wide range of pathogenic micro-organisms
notably Trichomonas vaginalis, Entamoeba histolytica, Giardia lamblia, Balantidium coli and
other species of bacteroides, fusobacteria, eubacteria, clostridia and anaerobic cocci

:It is indicated in

:Adults, Children and Newborns with a gestation age of over 40 weeks for

The treatment of septicaemia, bacteraemia, brain abscess, necrotising pneumonia- 
osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis, peritonitis and postoperative wound infections from which one or more pathogenic anaerobes have been isolated
The prevention of post-operative infections caused by anaerobic bacteria particularly species of bacteroides and anaerobic streptococci-

:Adults and Children over 10 years only for

(Bacterial vaginosis (also known as non-specific vaginitis, anaerobic vaginitis or Gardnerella vaginitis-

(Acute dental infections (e.g. acute pericoronitis and acute apical infections- 

 Anaerobically infected leg ulcers and pressure sores-

:Adults and Children for

The treatment of urogenital trichomoniasis in the female (trichomonal vaginitis) and in the male-
(All forms of amoebiasis (intestinal and extra-intestinal disease and that of symptomless cyst passers-
Giardiasis-
Acute ulcerative gingivitis-

:Children for

Eradication of Helicobacter pylori-

Consideration should be given to official guidance on the appropriate use of antibacterial agents
 

For oral administration only
:Prophylaxis

Against anaerobic infection - chiefly in the context of abdominal (especially colorectal) and gynecological surger-

 Dosage: 400mg at 8 hourly intervals during the 24 hours preceding the operation followed by postoperative intravenous or rectal administration until the patient is able to take Metronidazole Oral Suspension by mouth
.Children < 12 years: 20 – 30mg/kg as a single dose given 1 – 2 hours before surgery-
Newborns with a gestation age <40 weeks: 10mg/kg body weight as a single dose before operation
 Elderly: Caution is advised in the elderly, particularly at high doses, although there is limited information available on modification of drug-
 :Treatment of established anaerobic infection

800mg followed by 400 mg at 8 hourly intervals
 

Children > 8 weeks to 12 years of age: The usual daily dose is 20 – 30mg/kg/day as a single dose or divided into 7.5 mg/kg every 8 hours. The daily dose may be increased to 40 mg/kg, depending on the severity of the infection. Duration of treatment is usually 7 days

Children < 8 weeks of age: 15 mg/kg as a single dose daily or divided into 7.5 mg/kg every 12 hours

In newborns with a gestation age <40 weeks, accumulation of metronidazole can occur during the first week of life, which is why the concentrations of metronidazole in serum sh

:Treatment of Protozoal and Other Infections

Dosage is given in terms of metronidazole or metronidazole equivalent
 

Regular clinical and laboratory monitoring (especially leucocyte count) are advised if administration of Metronidazole for more than 10 days is considered to be necessary and patients (should be monitored for adverse reactions such as peripheral or central neuropathy (such as paraesthesia, ataxia, dizziness, convulsive seizures

There is the possibility that after Trichomonas vaginalis has been eliminated a gonococcal infection might persist

The elimination half-life of metronidazole remains unchanged in the presence of renal failure.

The dosage of metronidazole therefore needs no reduction. Such patients however, retain the metabolites of metronidazole. The clinical significance of this is not known at present.

In patients undergoing haemodialysis, metronidazole and metabolites are efficiently removed during an eight-hour period of dialysis. Metronidazole should therefore, be re-administered immediately after haemodialysis.

No routine adjustment in the dosage of Metronidazole need be made in patients with renal failure undergoing intermittent peritoneal dialysis (IPD) or continuous ambulatory peritoneal dialysis (CAPD

Metronidazole is mainly metabolised by hepatic oxidation. Substantial impairment of metronidazole clearance may occur in the presence of advanced hepatic insufficiency.

Significant cumulation may occur in patients with hepatic encephalopathy and the resulting high plasma concentrations of metronidazole may contribute to the symptoms of encephalopathy. Metronidazole should be administered with caution to patients with hepatic encephalopathy. The daily dosage may be reduced to one third and may be administered once daily.
Metronidazole should be used with caution in patients with active or chronic severe peripheral and central nervous system disease due to the risk of neurological aggravation. The sucrose content should be taken into account in patients with diabetes mellitus. Methyl and propyl hydroxybenzoates are contained in this product which may cause allergic reactions (possibly delayed)

Patients should be warned that metronidazole may darken urine

Due to inadequate evidence on the mutagenicity risk in humans, the use of Metronidazole for longer treatment than usually required should be carefully considered

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
 

:Interaction with other Medicinal Products and Other Forms of Interactions

Patients should be advised not to take alcohol during metronidazole therapy and for at least 48 hours afterwards because of the possibility of a disulfiram-like (antabuse effect) reaction-

Psychotic reactions have been reported in patients who were using metronidazole and disulfiram concurrently-
Some potentiation of anticoagulant therapy has been reported when metronidazole has been used with the warfarin type oral anti-coagulants. Dosage of the anticoagulant may require reducing Prothrombin time should be monitored

Lithium retention accompanied by evidence of possible renal damage has been reported in patients treated simultaneously with lithium and metronidazole. Lithium treatment should be tapered or withdrawn before administering metronidazole. Plasma concentration of lithium, creatinine and electrolytes should be monitored in patients under treatment with lithium while
they receive metronidazole

Patients receiving phenobarbital metabolise metronidazole at a much greater rate than normally, reducing the half-life to approximately three hours-

Increased serum carbamazepine levels and toxicity have been seen in patients given concomitant metronidazole-

Aspartate amino transferase assays may give spuriously low values in patients taking metronidazole, depending on the method used-

Clinicians who contemplate continuous therapy for the relief of chronic conditions, for periods no longer than those recommended, are advised to consider the possible therapeutic benefit against the risk of peripheral neuropathy
 

Metronidazole reduces the clearance of 5-fluorouracil and can therefore result in increased toxicity of 5-fluorouracil-

Patients receiving ciclosporin or tacrolimus with metronidazole are at risk of elevated ciclosporin / tacrolimus serum levels. Serum ciclosporin / tacrolimus and serum creatinine should be closely monitored when coadministration is necessary

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

There is inadequate evidence of the safety of metronidazole in pregnancy. Metronidazole should not therefore be given during pregnancy or during lactation unless the physician considers it essential, in these circumstances short, high dosage regimes are not recommended

A significant amount of metronidazole is found in breast milk and breast feeding should be avoided after a large dose

This could give a bitter taste to the milk

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

:The frequency of adverse events listed below is defined using the following convention

Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data)
Frequency, type and severity of adverse reactions in children are the same as in adults Serious adverse reactions occur very rarely with standard recommended regimens. However, clinicians who contemplate continuous therapy for the relief of chronic conditions, for periods longer than those recommended are advised to consider the possible therapeutic benefit against the risk of peripheral neuropathy

:Blood and lymphatic system disorder

Very rare :          granulocytosis , neutropenia , thrombocytopenia , and pancytopenia , often reversible on drug withdrawal , although fatalitis have occured . 

 Not Known     A moderat leucopenia has been reported in some patients but the white cellcount has always returned to normal befor or after treatment has been completed 

:Immune system disorders

Rare : Anaphylaxis 

Not Known :  Urticaria , Angioedema and fever

Single oral doses of Metronidazole, up to 12 g, have been reported in suicide attempts and
accidental overdoses. Symptoms reported include nausea, vomiting, and ataxia and slight
disorientation.
There is no specific antidote for metronidazole over dosages. In case of suspected massive over
dosages, symptomatic and supportive treatment should be instituted
 

The selective action of this compound against anaerobes and anoxic and hypoxic cells is due to
the mode of action.
The nitro group of metronidazole acts as electron acceptor and is thus reduced to a chemically
reactive drug form. This produces biochemical lesions in the cells, thus causing death. The major
site of action is believed to be DNA, where it causes loss of the helical structure and inhibits
synthesi
 

It is readily absorbed from the gastro-intestinal tract and widely distributed in body tissues. Half
life in plasma is about 8-10 hours. About 10% is bound to plasma proteins.
It penetrates well into body tissues and fluids, including vaginal secretions, seminal fluid, saliva
and breast milk.
Therapeutic concentrations are also achieved in cerebrospinal fluid.

Unchanged metronidazole and several metabolites are excreted in the urine, the liver is the main site of metabolism and the major metabolites are as a result of side chain oxidation, forming glucuronides

Metronidazole has been shown to be carcinogenic in the mouse and in the rat following chronic oral administration however similar studies in the hamster have given negative results

Epidemiological studies have provided no clear evidence of an increased carcinogenic risk in humans

Metronidazole has been shown to be mutagenic in bacteria in vitro. In studies conducted in mammalian cells in vitro as well as in rodent or humans in vivo, there was inadequate evidence of a mutagenic effect of metronidazole, with some studies reporting mutagenic effects, while other studies were negative

Sodium phosphate monobasic
Methyl parahydroxy benzoate (Methyl paraben)
Propyl parahydroxy benzoate (Propyl paraben)
Aluminium magnesium silicate (Veegum)
Sucrose
Saccharin sodium
Soluble banana flavor
Glycerol
Polysorbate 80 (Tween)
Ethanol 96%
Carboxymethylcellulose sodium
Purified water
 

None stated.

 

An amber PET plastic bottle is enclosed in a printed carton box along with a patient leaflet

Store below 25ºC.
 

Keep out of the reach of children.
Shake the bottle well before use
.