Topical treatment of Trichomonas vaginitis and non specific vaginitis.
It is important to take into account official recommendations concerning the appropriate use of antibacterial.

This medicine is for adults only.
For information, the usual dosage is:
1 suppository per day by vaginal route in combination, if necessary, with an oral treatment.
Your partner must be necessarily treated as well, whether or not he has a clinical signs.
In all cases comply with your doctor’s prescription.

Frequency and time of administration of the medicine:
Once daily.
The suppository is administered preferably at bedtime.
Duration of treatment:
To be effective, this antibiotic should be used regularly at prescribed doses and for as long as your doctor has recommended.
This disappearance of fever or any other symptoms does not mean that you are completely cured. The possible feeling of tiredness is not due to the antibiotic treatment but the infection itself. Reducing or suspending your treatment would have no effect on this feeling and would delay your recovery.
The duration of this treatment ranges from 7 to 10 days as indicated, but this treatment should not be prescribed for more than 10 days and must not be repeated more than 2 to 3 times a year.
NOTE; distinguish, where appropriate, between therapeutics and prophylactic doses, and between dosages recommended for different clinical uses.

-In case of history of hematological disorder as well as during treatment at high doses and/or for long periods; it is recommended to regularly monitor white blood cell count.
-In the event of leucopenia, the opportunity to prolong the treatment depends on the seriousness of the infection.
- If for compelling reasons, metronidazole must be administered longer than the usually recommended durations, it is recommended that haematological test, especially leucocyte count should be carried out regularly and that patients should be monitored for adverse reactions such as peripheral or central neuropathy (such as paresthesia, ataxia, vertigo, convulsive seizures).
- Metronidazole should be administered with caution to patients with hepatic encephalopathy.

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

Due to Metronidazole absorption, the following interactions can be seen if used concomitantly with the drugs below:
1. Alcohol: Alcohol intolerance (disulfiram - like reaction).
2. Amiodaron: Increase in risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest).
3. Astemizole and terfenadine: Metronidazole inhibits the metabolism of these drugs and increases their plasma concentrations.
4. Disulfiram: Central nervous system related effects (e.g. psychotic reactions).
5. Phenytoin: Increase in blood levels of phenytoin, decrease in blood levels of Metronidazole.
6. Phenobarbital: Decrease in blood levels of Metronidazole.
7. Fluorouracil: Increase in blood levels and toxicity of fluorouracil.
8. Carbamazepine: Increase in blood concentration of carbamazepine.
9. Lithium: Increase in blood levels and lithium toxicity.
10. Oral anticoagulants: Increase in anticoagulant effect.
11. Cyclosporine: Increase in cyclosporine toxicity risk.
12. Cimetidine: Increase in blood levels of Metronidazole and the risk of neurologic side effects.
Interference with blood levels of liver enzymes, glucose (hexokinase method), theophylline and procainamide have been observed during the treatment with Metronidazole.

Pregnancy:
As metronidazole crosses the placental barrier and as its effects on human fetal organogenesis are not known, its use in pregnancy should be carefully evaluated.
Breast-feeding:
As metronidazole is excreted in human milk, unnecessary exposure to the drug should be avoided.

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

Gastrointestinal system:
-Innocuous digestive upsets: (epigastric cramps, nausea, vomiting, diarrhea)
-Glossitis with feelings of dry mouth, stomatitis, metallic taste in mouth, anorexia,
-Extremely rarely reversible cases of pancreatitis when the treatment is stopped.
Skin and Hypersensitivity reactions:
- Rash, congestive flushes, pruritus, urticaria
-Cutaneous sometimes febrile manifestations urticaria, Quincke’s oedema, rarely anaphylactic shock
- Very rare pustular eruptions.
Central and peripheral nervous system:
-Headache , convulsions, dizziness
-Peripheral sensory neuropathy.
-Very rare reports of encephalopathy (e.g. confusions) and subacute cerebellar syndrome (e.g. ataxia, dysathria, gait impairment, nystagmus, vertigo and tremor), which may resolve with discontinuation of the drug.
Psychiatric disorders:
- Psychotic disorders including confusion, hallucinations
Vision disorders:
- Transient vision disorders such as diplopia, myopia
Hematology:

Very rare cases of neutropenia, agranulocytosis and thrombocytopenia have been reported
Hepatic symptoms:
-Very rare cases of reversible abnormal liver function tests and cholestatic hepatitis have been
reported.
Miscellaneous:
-Reddish-brown coloration of the urine may be seen, due to the presence of water soluble pigments derived from metabolization of the medicine.

Some administrations of unique dose up to 12 g have been reported during suicide attempts and accidental overdoses. Symptoms were limited to vomiting, ataxia and slight disorientation. There is no specific antidote for overdosage of Metronidazole. In case of massive overdosage, the treatment is symptomatic.

Pharmacotherapeutic Group: Anti-bacterial and anti-protozoal.
ATC Code: G01AF01
AMRIZOLE Vaginal Suppositories contains Metronidazole for anti-bacterial and anti-trichomonal effects. Metronidazole, a 5-nitroimidazole derivative is an anti-protozoal and an antibacterial agent and is effective against several infections caused by anaerobic bacteria and protozoa, such as Trichomonas vaginalis, Gardnerella vaginalis and anaerobic bacteria including anaerobic streptococci.

1-Absorption:
Bioavailability of Metronidazole by this route is 20% compared to the oral route. Steady state levels of Metronidazole in plasma ranged from 1.1 to 5.0 μg /ml after daily intr-avaginal application.
2- Distribution:
It is widely distributed in body tissues and fluids including bile, bone, breast, milk, cerebral abscesses, cerebrospinal fluid, liver and liver abscesses, saliva, seminal fluids and vaginal secretion, and achieves concentrations similar to those in plasma. It crosses the placenta and rapidly enters to fetal circulation. No more than 20% is bound to plasma proteins. Distribution volume is 0.25-0.85 L/kg.
3- Biotransformation:
It is metabolized in the liver by oxidation, hydroxy metabolite is active. Major metabolites of Metronidazole, hydroxy and acetic acid metabolites, are excreted in urine. The hydroxy metabolite has a 30% of biological activity of Metronidazole.

4-Elimination:
Half-life is 6-11 hours. About 6%-15% of Metronidazole dose is excreted with faeces, 60%-80% is unchanged and excreted in urine as its metabolites. Approximately 20% of Metronidazole is excreted in the urine as unchanged drug.

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.

Polyethylene glycol base.

Not applicable.

Store at temperature below 25°C.

Amrizole vaginal suppositories are presented in opaque milky (PVC/LDPE) rotoplast moulds strip containing 5 suppositories.

Not special requirements.