ORGYL 500 mg Tablets Antiprotozoal Agent<br> COMPOSITION:
Each film coated tablet contains;
Ornidazole 500 mg
DESCRIPTION :
Orange coloured, film coated, round shaped tablets.

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

RECOMMENDED DOSE:
Trichomoniasis:
There are two possible therapeutic regimens: Single-dose therapy ; five-days therapy. The tablets should be taken after meals.
(a) Single dose therapy:
3 tablets in the evening
(b) Five days therapy:
2 tablets (1 tablet morning and evening)
The dosage for children is 25 mg per kg body weight per day, given in a single dose.
Amoebiasis:
Three days:
3 tablets in one evening dose. Five to ten days: 2 tablets (1 tablet morning and evening)
Giardiasis (lambliasis): One to two days: 3 tablets in the evening in one dose
Anaerobic Infections: Prophylaxis: 1500 mg orally, 12 hours before surgery the 500 mg 12-hourly for 3 to 5 days postoperatively
MODE OF ADMINISTRATION:
The tablet 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:
Mild side effects such as somnolence, headache and gastrointestinal disturbances like nausea and vomiting may occur.
Disturbances of the CNS such as dizziness, tremor, rigidity, poor coordination, seizures, tiredness, vertigo, temporary loss of consciousness and signs of sensory or mixed peripheral neuropathy have been observed in isolated cases. Taste disturbances, abnormal liver function tests and skin reactions have been observed.
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.

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.
Somnolence, dizziness, tremor, rigidity, poor coordination, seizures, vertigo or temporary loss of consciousness may occur in patients receiving Orgyl. If they occur, such effects may affect tasks requiring alertness including the patient’s ability to drive and operate machinery.
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.

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.
CONTRAINDICATIONS:
Orgyl is contraindicated in patients with known hypersensitivity to the medicine or to other nitroimidazole derivatives.

PHARMACODYNAMIC PROPERTIES:
After passive absorption into bacterium cell, the nitro group of ornidazole is reduced to amine group by ferredoxin 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, Porphyromonas, 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 PROPERTIES:
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 are 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 of ornidazole in neonates and young children are similar to those in adults.
STORAGE CONDITIONS:
Store below 30°C. Store in cool and dry place.
DOSAGE FORMS AND PACKAGING AVAILABLE:
10 tablets are packed in a Amber PVC blister; 10 blisters are in a carton box.
NAME AND ADDRESS OF MANUFACTURER:
Kusum Healthcare Pvt. Ltd. SP 289(A), RIICO Indl. Area,
Chopanki, Bhiwadi (Rajasthan), India
DATE OF REVISION OF PACKAGE INSERT:
Not Applicable
MM Reg. No.:
1709AA 4706