Flazol is indicated in adults and children for the following indications:

1. The prevention of post-operative infections due to anaerobic bacteria, particularly species

of Bacteroides, and anaerobic streptococci.

2. Treatment of urogenital trichomonas in the female (trichomonal vaginitis) and in the

male.

3. Treatment of all forms of amoebiasis (intestinal and extra-intestinal disease and that of

symptomless cyst passers).

4. Treatment of giardiasis.

5. Treatment of acute ulcerative gingivitis (Vincent’s).

6. Treatment of anaerobically-infected leg ulcers and pressure sores.

7. Treatment of acute dental infections (e.g. acute pericoronitis and acute apical infections).

8. Treatment of septicaemia, bacteraemia, brain abscess, necrotising pneumonia,

osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis, peritonitis, and postoperative

wound infections from which pathogenic anaerobes have been isolated.

9. Non specific vaginitis.

For oral administration.

Suspension can be diluted with syrup BP.

Dosage is given in terms of metronidazole or metronidazole equivalent.

Treatment of anaerobic infections:

Treatment for seven days should be satisfactory for most patients but, depending on the

clinical and bacteriological assessments, the physician might decide to prolong treatment.

The tablets or suspension may be given alone or concurrently with other appropriate

antibacterial agents.

Adults and children over 10 years - 400 mg orally three times daily.

Children and infants - Children > 8 weeks to 12 years of age: The usual daily dose is 20-

30mg/kg/day as a single dose or divided into 7.5mg/kg every 8 hours. The daily dose may

be increased to 40mg/kg, depending on the severity of the infection. Duration of treatment is

usually 7 days.

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

12 hours.

In newborns with a gestation age < 40 weeks, accumulation of metronidazole can occur

during the first week of life, therefore the concentrations of metronidazole in serum should

preferable be monitored after a few days therapy.

Prophylaxis against postoperative infections caused by anaerobic bacteria:

Children < 12 years of age: 20-30 mg/kg as a single dose given 2-3 hours before surgery

Newborns with a gestation age <40 weeks: 10mg/kg body weight as a single dose 2-3 hours

before surgery

Protozoal and other infections:

Eradication of Helicobacter pylori in paediatric patients:

As a part of a combination therapy, 20mg/kg/day not to exceed 500mg twice daily for 7-14

days. Official guidelines should be consulted before initiating therapy.

Metronidazole has no direct activity against aerobic or facultative anaerobic bacteria.

Regular clinical and laboratory monitoring (especially leucocyte count) are advised if

administration of Flazol 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).

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.

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.

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. If symptoms or signs of SJS, TEN or AGEP are present,

Metronidazole treatment must be immediately discontinued.

There is a 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 Flazol need be made in patients with renal failure

undergoing intermittent peritoneal dialysis (IDP) 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 the

encephalopathy. Flazol should therefore, be administered with caution to patients with

hepatic encephalopathy. The daily dosage should be reduced to one third and may be

administered once daily.

Patients should be warned that metronidazole may darken urine.

Due to inadequate evidence on the mutagenicity risk in humans (see section 5.3), the use of

Metronidazole for longer treatment than usually required should be carefully considered.

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 anticoagulants. Dosage of the latter may require reducing.

Prothrombin times should be monitored. There is no interaction with heparin.

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 concentrations of lithium, creatinine and electrolytes should be monitored in patients

under treatment with lithium while they receive metronidazole.

Patients receiving phenobarbital or phenytoin metabolise metronidazole at a much greater

rate than normally, reducing the half-life to approximately 3 hours.

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

toxicity of 5 fluorouracil.

Patients receiving ciclosporin are at risk of elevated ciclosporin serum levels. Serum

ciclosporin 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 be given during pregnancy or during lactation unless the physician considers it

essential; in these circumstances the short, high-dosage regimens are not recommended.

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).

Serious adverse reactions occur rarely with standard recommended regimens. 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 disorders:

Very rare: agranulocytosis, neutropenia, thrombocytopenia, pancytopenia

Not known: leucopenia.

Immune system disorders:

Rare: anaphylaxis

Not known: angioedema, urticaria, fever.

Metabolism and nutrition disorders:

Not known: anorexia.

Psychiatric disorders:

Very rare: psychotic disorders, including confusion and hallucinations.

Not known: depressed mood

Nervous system disorders:

Very rare:

• encephalopathy (e.g. confusion, fever, headache, hallucinations, paralysis, light sensitivity,

disturbances in sight and movement, stiff neck) and subacute cerebellar syndrome (e.g.

ataxia, dysarthria, gait impairment, nystagmus and tremor) which may resolve on

discontinuation of the drug.

• drowsiness, dizziness, convulsions, headaches

Not known:

• during intensive and/or prolonged metronidazole therapy, peripheral sensory neuropathy or

transient epileptiform seizures have been reported. In most cases neuropathy disappeared

after treatment was stopped or when dosage was reduced.

• aseptic meningitis

Eye disorders:

Very rare: vision disorders such as diplopia and myopia, which, in most cases, is transient.

Not Known: optic neuropathy/neuritis

Ear and labyrinth disorders:

Not known: hearing impaired/hearing loss (including sensorineural), tinnitus

Gastrointestinal disorders:

Not known: taste disorders, oral mucositis, furred tongue, nausea, vomiting, gastro-intestinal

disturbances such as epigastric pain and diarrhoea. Hepatobiliary disorders:

Very rare:

 increase in liver enzymes (AST, ALT, alkaline phosphatase), cholestatic or mixed

hepatitis and hepatocellular liver injury, jaundice and pancreatitis which is reversible on 

drug withdrawal.

 cases of liver failure requiring liver transplant have been reported in patients treated

with metronidazole in combination with other antibiotic drugs.

Skin and subcutaneous tissue disorders:

Very rare: skin rashes, pustular eruptions, acute generalised exanthematous pustulosis,

pruritis, flushing

Not known: erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis,

fixed drug eruption

Musculoskeletal, connective tissue and bone disorders:

Very rare: myalgia, arthralgia.

Renal and urinary disorders:

Very rare: darkening of urine (due to metronidazole metabolite).

To report any side effect(s)

• Saudi Arabia:

The National Pharmacovigilance Center (NPC):

Fax: +966-11-205-7662

SFDA Call Center: 19999

E-mail: npc.drug@sfda.gov.sa

Website: https://ade.sfda.gov.sa

• Other GCC States:

Please contact the relevant competent authority.

Single oral doses of metronidazole, up to 12g have been reported in suicide attempts and

accidental overdoses. Symptoms were limited to vomiting, ataxia and slight disorientation. There

is no specific antidote for metronidazole overdosage. In cases of suspected massive overdose,

symptomatic and supportive treatment should be instituted.

Pharmacotherapeutic code: Antibacterials for systemic us, ATC code: J01X D01

Metronidazole is active against a wide range of pathogenic micro-organisms notably species

of Bacteroides, Fusobacteria, Clostridia, Eubacteria, anaerobic cocci and Gardnerella

vaginalis. It is also active against Trichomonas, Entamoeba histolytica, Giardia lamblia and

Balantidium coli.

After a 400mg metronidazole (or equivalent) single oral dose, given either as metronidazole

benzoate 6.4% suspension or metronidazole tablet, tmax is delayed by approximately 2

hours (3h versus 50 minutes), Cmax decreased by 45% and AUC by 20% corresponding to a

decrease in relative bioavailability of 20% of the oral suspension compared to the tablet. No

change in elimination half-life is reported. These slight differences in the rate and extent of

metronidazole absorption are due to the transformation of metronidazole benzoate to the

active compound metronidazole by hydrolysation in the gastrointestinal tract.

Metronidazole is excreted in milk but the intake of a suckling infant of a mother receiving

normal dose would be considerably less than the therapeutic dosage for infants.

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 Benzoate

Sodium Chloride

Saccharin Sodium

Povidone K30

Carboxymethylcellulose Sodium

Colloidal Silicone Dioxide

Simethicone Emulsion

Cremophor RH40

Propylparaben

Mehtylparaben

Sorbitol Solution

Sucrose

Liqiud Flavour Banana

This medicinal product must not be mixed with other medicinal products except syrup BP for dilution.

Store below 30 °C.

125 ml amber glass bottle with white plastic temper evident child resistant cap

containing 120 ml suspension, each bottle labeled and packed in a printed carton with

plastic measuring cup and folded leaflet.

No special requirements