Indications are based on the anti-parastic and anti-bacterial activity of metronidazole and
on its pharmacokinetic characteristics.
It is intended for the treatment of infections due to the pathogens susceptible to
metronidazole:
- Ameobiasis.
- Giardiasis.
- Lambliasis.
- Urogenital trichomoniasis.
- Non-specific vaginitis.
- Anaerobic bacterial infections:
- Curative treatment of medico-surgical infectious due to susceptible anaerobic
pathogens.
- Prophylaxis against infections caused by susceptible anaerobic pathogens in high risk
Module 1 Administrative Information AMRIZOLE 250 mg Film-Coated Tablets
1.3.1 Summary of Product Characteristics (SPC)
surgical contexts.
- Following prophylactic or curative treatment by infection, of infections due to
susceptible anaerobes.
- Intra-abdominal infections including peritonitis, intra-abdominal abscess and liver
abscess.
- Skin and skin structure infections.
- Gynecologic infections including endometritis, endomyometritis, tubo-ovarian
abscess and postsurgical vaginal cuff infection.
- Bacterial septicemia.
- Bone and joint infections as adjunctive therapy.
- Central nervous system infections including meningitis and brain abscess.
- Lower respiratory tract infections including pneumonia, empyema and lung abscess.
- Endocarditis.

Amboebiasis:
- Adult: 1.50 g daily, in 3 divided doses.
- Children: 30 to 40 mg/kg/day in 3 divided doses.
In hepatic ameobiasis, at the abscess stage, the abscess must be evacuated concomitantly
with metronidazole treatment. The duration of the treatment is 7 consecutive days.
Giardiasis:
- Adult: 0.750 to 1g daily for 5 consecutive days.
- Children: from 2 to 5 days: 250 mg/day, from 5 to 10 years: 375 mg/day, from 10 to
15 years: 500 mg/day.
Lambliasis: For 5 consecutive days.
- Adult: 750 mg to 1g per day.
- Children: from 2 to 5 years: 250 mg daily, from 5 to 10 years: 375 mg daily, from 10
to 15 years: 500 mg daily.
Trichomiasis:
- In female (urethritis and vaginitis due to Trichomonas): single dose of 2g to 500
mg/day by oral route in two divided doses for 10 days. Whether or not the partner
presents clinical signs of infection with Trichomonas vaginitis, he must be treated
concurrently, even in the absence of positive laboratory test.
Module 1 Administrative Information AMRIZOLE 250 mg Film-Coated Tablets
1.3.1 Summary of Product Characteristics (SPC)
- In males (urethritis due to Trichomoniasis): 2g in a single dose, or 500 mg by oral
route in 2 divided doses for 10 days.
Non-specific vaginitis: 500 mg, twice daily for 7 days. The partner must be treated
simultaneously.
Anaerobic infections (as first line or substitute treatment):
- Adults: 1 to 1.5 g/day.
- Children: 20 to 30 mg/kg/day.
Surgical chemoprophylaxis:
Metronidazole must be combined with a product active against Enterobacteria.
- Adult: one 500 mg dose every 8 hours, beginning the treatment approximately 48
hours before surgery, appears to be effective. The last dose must be administered at
the least 12 hours before surgery. The goal of chemoprophylaxis is to reduce the
bacterial inoculum in the gastrointestinal tract at the time of surgery, it is therefore
useless to continue the antibiotic in the postoperative period, at least by the oral
route.
- Children: some protocol at a dosage of 20 to 30 mg/kg/day.

Warning:
Treatment should be discontinued in case of ataxia, vertigo, hallucinations or mental
confusion.
Risk aggravation of the neurological condition must be taken into account in patients
with active or chronic severe central or peripheral neurological disorders.
Alcohol should be avoided during metronidazole administration and one day after
because of the possibility of disulfiram-like reaction (Antabuse effect).
Precautions:
- There is no suspicion of carcinogenity in man although the product has proved
carcinogenic in a certain strain of mice.
- Differential blood count especially leucocytes should be monitored, if there is a
history of blood dyscrasia or in high dose and/or prolonged treatment than the
Module 1 Administrative Information AMRIZOLE 250 mg Film-Coated Tablets
1.3.1 Summary of Product Characteristics (SPC)
recommended dosages. Should leucopenia occur, treatment continuation will depend
on the severity of the infection.
- Patients should be monitored for adverse reactions as peripheral and central
neuropathy (i.e. parathesia, dizziness, ataxia and convulsion seizures)
- Metronidazole should be administered with caution in patients with hepatic
encephalopathy.
- Known or previously unrecognized candidiasis may present more prominent
symptoms during therapy with metronidazole and requires treatment with
candidacidal agent.
- Prescribing AMRIZOLE in the absence of a proven or strongly suspended bacterial
infection or a prophylactic indication is unlikely to provide benefit to the patient and
increases the risk of the development of drug-resistant bacteria.
- Patients should be counseled that antibacterial drugs including AMRIZOLE should
only be used to treat bacterial infections. They do not treat viral infections (e.g.
common cold). When AMRIZOLE is prescribed to treat a bacterial infection, patients
should be told that although it is common to feel better early of therapy, the
medication should be taken exactly as directed. Skipping doses or not completing the
full courses of therapy may decrease the effectiveness of the immediate treatment and
increase the likelihood that bacterial will develop resistance and will not be treatable
by AMRIZOLE or other antibacterial drugs in the future.

Disulfiram: Disulfiram may lead to delirium or mental confusion (psychotic reactions).
Alcohol: Alcoholic beverages and drugs containing alcohol should be avoided during
treatment with metronidazole and at least one day after discontinuing treatment because
of the possibility of disulfiram-like (antabuse effect) reaction (flushing, vomiting and
tachycardia).
Warfarin: because of the potentiation of oral anticoagulants effect and hemorrhagic risk
(decrease in the oral anticoagulants hepatic catabolism), prothrombin level should be
monitored more frequently. Oral anticoagulant dosage must be adjusted during
metronidazole treatment and 8 days after discontinuation.
Vecuronium (non-depolarizing neuromuscular blocking agent): Metronidazole
potentiates the action of vecuronium.
Module 1 Administrative Information AMRIZOLE 250 mg Film-Coated Tablets
1.3.1 Summary of Product Characteristics (SPC)
5-flouro-uracil: Metronidazole increases the toxic effect of 5-florouracil due to 5-
florouracil reduce clearance.
Lithium: plasma level of lithium may be increased by metronidazole. Plasma lithium
concentration, creatinine and electrolytes should be monitored in patients who are coadministered
lithium metronidazole.
Cyclosporin: risk of cyclosporin serum level elevation, serum cyclosporin and serum
creatinine should be closely monitored when coadministration is necessary.
Phenytoin or phenobarbital: increased elimination of metronidazole results in reduced
plasma levels.
Busulfan: plasma levels of busulfan may be increased by metronidazole, which may lead
to severe busulfan toxicity.
Interactions with laboratory investigations:
Metronidazole may immobilise Treponema and hence result in a false positive
Treponema pallidum immobilisation test.

Pregnancy category B:
Metronidazole has shown evidence of tetratogenicity or fetotoxicity in animal studies.
Case studies of several hundred pregnancies in which metronidazole was administered
during the first trimester did not show evidence of any particular malformation.
Studies of identical number of patients treated with metronidazole after the first trimester
have not shown evidence of fetal toxicity.
Therefore, pregnancy is not a contraindication for the use of metronidazole, however it
should be used very cautiously in case of necessity.
Lactation:
Metronidazole should be avoided due to the fact that it passes into breast milk.
Carcinogenesis:
Metronidazole has shown evidence of carcinogenic activity in a number of studies
involving chronic, oral administration in mice and rats.

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.

Two serious adverse reactions reported in patients treated with metronidazole have been
convulsive seizures and peripheral neuropathy, the latter characterized mainly by
numbness or parasthesia of an extremity. Since persistent peripheral neuropathy has been
reported in some patients receiving prolonged administration of metronidazole, patients
should be specifically warned about these reactions and should be told to stop the drug
and report immediately to their physicians if any neurologic symptoms occur.
The most common adverse reactions reported have been referable to the gastrointestinal
tract, particularly nausea reported by about 12% of patients, sometimes accompanied by
headache, anorexia and occasionally vomiting, diarrhea, epigastric distress and
abdominal cramping.
Constipation has also been reported.
The following reactions have been reported during treatment with metronidazole:
- Mouth: a sharp, unpleasant metallic taste is not unusual, furry tongue, glossitis and
stomatitis have occurred, these may be associated with a sudden overgrowth of
candida which may occur during therapy.
- Hematopoietic: reversible neutropenia (leucopenia), rarely, reversible
thrombocytopenia.
- Cardiovascular: flattening of the T-wave may be seen in electrocardiographic tracings.
- Central nervous system: convulsive seizures, peripheral neuropathy, dizziness,
vertigo, incoordination, ataxia, confusion, irritability, depression, weakness and
insomnia.
- Hypersensitivity: urticaria, erythematous rash, flushing, nasal congestion, dryness of
the mouth (or vagina or vulva), and fever.
- Renal: dysuria, cyctitis, polyuria, incontinence, and a sense of pelvic pressure.
Instances of darkened urine have been reported by approximately one patient in
100,000. Although the pigment which is probably responsible for this phenomenon
has not been positively identified, it is almost certainly a metabolite of metronidazole
and seems to have no clinical significance.
- Other: proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis
Module 1 Administrative Information AMRIZOLE 250 mg Film-Coated Tablets
1.3.1 Summary of Product Characteristics (SPC)
and fleeting joint pains, sometimes resembling "serum sickness". 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.
Rare cases of pancreatitis, which generally abated on withdrawal of the drug, have been
reported.

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.

Metronidazole is an anti-infective agent belonging to 5-nitroimidazole group.
Antibacterial spectrum of metronidazole concerns exclusively anaerobic pathogens:
Susceptible species:
- More than 90% of the species are susceptible(s).
- Peptostreptococcus, C.perfringes, C.difficile, Bacteroides fragilis, Bacteroides sp.,
Fusobacterium, Clostridium sp., Prevotella, Veillonella.
Species with inconstant susceptibility:
- The susceptibility of the pathogens should be tested by an antibiogram.
- Bifidobacterium, Eubacterium.
Normally resistant species:
- More than 50% of the species are resistance(R).
- Propionibacterium, Actinomyces, Mobiluncus.
Anti-parastic activity:
- Trichomonas vaginitis, Giardiasis intestinalis, Entamoeba hystolytica.

Bioavailability:
- Metronidazole is rapidly absorbed following oral administration, at least 80% is
absorbed in less than one hour.
- The serum peak concentrations achieved following oral administration are similar to
those obtained following intravenous of equivalent doses.
- The oral bioavailability is 100% and not modified by ingestion of food.
Distribution:
- After a single dose administration of 500 mg of metronidazole the average peak serum
level is of 10 mg/ml. one hour after the ingestion.
- The plasma half-life is 8 to 10 hours.
- The plasma protein binding is low <20%.
- The volume of distribution is high, on average 40L (i.e. 0.65 L/KG).
- Diffusion is rapid and tissue concentrations are similar to serum concentrations in
lungs, kidneys, live, skin, bile, CSF, saliva, seminal fluid and vaginal secretions.
- Metronidazole crosses the placental barrier and is excreted in breast milk.
Metabolism:
- Metronidazole is metabolized by oxidation in the liver into two metabolites:
The alcoholic metabolite which has a bactericidal activity on the anaerobic pathogens on
overage 30% in comparison with the metronidazole and an elimination half-life of 11
hours
The acid metabolite is low with a bactericidal activity of 5%.
Elimination:
- Hepatic and biliary concentrations are high. Colon and fecal concentrations are low.
- Excretion is mainly urinary, metronidazole and its metabolites represent 35 to 65% of
the ingested dose.

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.
Module 1 Administrative Information AMRIZOLE 250 mg Film-Coated Tablets
1.3.1 Summary of Product Characteristics (SPC)
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.

Dibasic Calcium Phosphate
Maize starch
Povidone
Colloidal Silicon Dioxide
Magnesium Stearate
Hydroxypropyl Methyl Cellulose.
Titanium Dioxide
Ethanol (95 %)
 

Not applicable.

Store at below 30ºC. in dry place.
Carton box containing a pamphlet and 2 (AL/PVC) strips, each of 10 tablets.

Not applicable.

No special requirements.