COMPOSITION

Each film coated tablet contains;

Ornidazole 500 mg

ADDITONAL INGREDIENTS:

Excipients:

Microcrystalline cellulose, maize starch, croscarmellose sodium, magnesium stearate, purified water, opadry 03B53217 orange.

INDICATIONS

1. Bacterial vaginosis (non-specific vaginitis).

2. Trichomoniasis. Genitourinary infections in women and men due to Trichomonas vaginalis.

3.Amoebiasis. All intestinal infections due to Entamoeba histolytica, including amoebic dysentery. All extraintestinal forms of amoebiasis, especially amoebic liver abscess.

4. Giardiasis (lambliasis).

5. Infections due to anaerobic bacteria. Treatment of infections such as septicaemia, meningitis,

peritonitis, postoperative wound infections, puerperal sepsis, septic abortion, and endometritis, with demonstrated or suspected involvement of susceptible bacteria (see Properties and Effects).

6. Prophylaxis during surgical interventions, particularly those involving the colon, and in

gynaecological operations.

RECOMMENDED DOSE:

Oral

Amoebic Dysentery Adult:

1.5 as a single daily dose for three days. Alternatively for patients > 60 kg: 1 g bid for three days

Child:

40 mg/kg daily.

Giardiasis

Adult:

1-1.5g as a single dose for 1-2 days.

Child:

30-40 mg/kg daily.

Trichomoniasis

Adult:

1.5g as a single dose or 0.5 g bid for 5 days. Treat sexual partners concominantly.

Amoebiasis

Adult:

0.5 g bid for 5-10 days.

Child:

25 mg/kg as a single dose for 5-10 days

The tablets must always be taken after meals.

In all cases, the sexual partner should also be treated using the same oral dosage so as to avoid reinfection.

MODE OF ADMINISTRATION

The tablets must always be taken after meals.

In all cases, the sexual partner should also be treated using the same oral dosage so as to avoid

reinfection.

UNDESIRABLE EFFECTS

Ornidazole is contraindicated in patients hypersensitive to ornidazole and other nitroimidazoles. Nitroimidazoles and also ornidazole are considered safe drugs as only minor side effects have been observed. The most frequent side effects are an unpleasant taste, nausea, vomiting, abdominal discomfort and diarrhea. Serious side effects such as seizures and peripheral neuropathy are very rarely encountered in conventional doses. Side effects may occur more frequently following large, single doses but were reported to subside rapidly.

The acute oral LD50 of ornidazole in rats is 1.780 mg/kg. Reported LD50 value for mice is 1.420 mg/kg orally. Ornidazole administrated orally in mice at a dose level of 400 mg/kg/day for 13 weeks did not produce any toxicity except weight loss.

Nitroimidazoles are generally considered mutagenic chemicals. The nitrogen group present in nitroimidazole derivatives is considered responsible for the mutagenicity of these compounds. In a study, mutagenicity was observed with Klebsiella pneumoniae and Salmonella typhimurium TA.

Ornidazole was revealed to be mutagenic in Salmonella typhimurium, but negative results have been observed in other tests, such as micronucleus in mice and chromosome aberrations. Long-term carcinogenicity studies were also conducted with ornidazole (high dose 400 mg/kg/day) by administering in rats for two years. At the end of this study no carcinogenicity was recorded for Ornidazole.

Like other nitroimidazoles, ornidazole is widely distributed in the body, cross the placenta and appears in breast milk. When administered during pregnancy, no teratogenic effect was observed with ornidazole in mice, rats and rabbits.

Local and systemic tolerability of ornidazole was excellent in humans when used in pregnancy, and patients showed complete remission without premature delivery. Children born to the trial patients showed normal initial development and their growth was normal.

There was no evidence of ornidazole accumulation, and the pharmacokinetic parameters were very similar to those seen in healthy subjects. Therefore, dosage regimen requires no adjustment during pregnancy.

Ornidazole has the advantage of fewer side effects in rats in which species its antifertility action has been documented It has contraceptive properties in male, but not female, rats. It produces infertility by inhibiting epididymal sperm motility in terms of decreased sperm velocity. These effects are rapidly reversible after the cessation of treatment.

Ornidazole, the therapeutic use of which is quite distinct from the treatment of chronic alcoholism, may produce a disulfiram-like reaction with alcohol (flushing of the face and neck, palpitations, dizzi ness, nausea, etc.) in some cases. The mechanism of this reaction is thought to be related with an inhibition of acetaldehyde dehydrogenase. Patients should be warned against the possibility of interactions with alcohol.

Besides interaction with alcohol, ornidazole potentiates the effect of coumarin-type oral anticoagulants. The dosage of the anticoagulant has to be adjusted accordingly. Ornidazole also prolongs the musclerelaxant effect of vecuronium bromide.

ADVERSE DRUG REACTIONS:

*”Inform doctors about unexpected reactions after using drugs.”

INTERACTIONS WITH OTHER MEDICAMENTS

In contrast to other nitroimidazole derivatives, ordinazole does not inhibit aldehyde dehydrogenase and is therefore not incompatible with alcohol. However, ornidazole potentiates the effect of coumarin type oral anticoagulants. The dosage of the anticoagulant has to be adjusted accordingly. Ornidazole prolongs the muscle-relaxant effect of vecuronium bromide.

PREGNANCY AND LACTATION:

Extensive studies in various species have revealed no sign of any teratogenic or foetotoxic action of Orgyl. However, no controlled studies have been carried out in pregnant women. As a matter of principle, Orgyl should not be prescribed in early pregnancy or to nursing mothers except when absolutely necessary.

WARNING AND PRECAUTIONS:

Caution should be exercised in patients with diseases of the CNS, e.g., epilepsy or multiple sclerosis. The effect of other medicines can be intensified or impaired.

Children:

There are no data relatively medication administration in children under 1 year old.

Special indications:

During the treatment of Trichomoniasis it is necessary to treat both of the partners.

OVERDOSE AND TREATMENT

In cases of overdosage the symptoms mentioned under Undesirable Effects occur in more severe form. No specific antidote is known. The administration of diazepam is recommended if cramps occur.

CONTRAINDICATION

Hypersensitivity for medication components.

Orgyl is contraindicated for patients with CNS affection, epilepsy, during the periods of pregnancy and lactation and for children under 1 year old.

PHARMACEUTICAL FORM: Film-coated Tablets

PHARMACOTHERAPEUTIC GROUP: Antimicrobial

PHARMACOLOGICAL PROPERTIES:

PHARMACODYNAMIC PROPERTIES:

After passive absorption into bacterium cell, the nitro group of ornidazole is reduced to amine group by ferrodoxin type redox system. The formation of redox intermediate intracellular metabolites is believed to be the key component of microorganism killing for Ornidazole.

The drug is active against anaerobic bacteria viz. Peptostreptococcus, Clostridium, B. fragilis, Prevotella, Porphyronomas, Fusobacterium and protozoa viz. E. histolytica, T. vaginalis, G. intestinalis etc. Rationale for combination of ciprofloxacin and ornidazole.

Ornidazole which is a new derivative of nitroimidazole series has a longer half-life. It is recommended to be given twice a day. Therefore, it appears appropriate to combine ornidazole and ciprofloxacin as fixed dose combinations. Moreover, FDC will provide broad spectrum of activity as individual drugs are active against different pathogens.

PHARMACOKINETIC

Absorption

Following oral administration ornidazole is rapidly absorbed. Mean absorption is 90%. Peak plasma concentrations are reached within three hours.

Distribution

The mean volume of distribution after i.v. administration is 1 litre per kg. Plasma protein binding of ornidazole is about 13%. The active ingredient of Orgyl penetrates the cerebrospinal fluid, the body fluids and the tissues very effectively. Plasma concentrations are within the range considered to be optimal for the various indications (6 to 36 mg/l). After repeated administration of 500 mg or 1000 mg every twelve hours to healthy volunteers, an accumulation factor of 1.5-2.5 calculated.

Biotransformation

Ornidazole is mainly metabolised to 2-hydroxymethyl and a-hydroxymethyl metabolites in the liver. Both main metabolites are less active against Trichomonas vaginalis and anaerobic bacteria than the unchanged ornidazole.

Elimination

The half-life is about thirteen hours. 85% of a single dose is eliminated within the first five days, most of this being metabolised. 4% of the dose is excreted as unaltered substance in the urine.

Pharmacokinetics in Special Populations:

Patients with hepatic impairment:

In patients with liver cirrhosis the elimination half-life is longer (22 versus 14 hours) and clearance lower (35 versus 51 ml/min) than in healthy subjects. The dosing interval should be doubled in patients with severe hepatic impairment.

Patients with renal impairment:

The pharmacokinetics of ornidazole is unaltered in renal impairment. Dose adjustment is therefore unnecessary in patients with impaired renal function. Ornidazole is removed by haemodialysis. An additional dose of 500 mg of ornidazole should be administered if the daily dose is 2 g/d, or an additional dose of 250 mg ornidazole if the daily dose is 1 g/d, should therefore be administered before the start of hemodialysis.

Neonates and children:

The pharmacokinetics or ornidazole in neonates and young children are similar to those in adults.