COMPOSITION:

Active substance:

оrnidazole;

1 tablet contains 500 mg of ornidazole.

Excipients:

microcrystalline cellulose, corn starch, croscarmellose sodium, magnesium stearate, Opadry O3B53217 orange coating.

INDICATIONS:

Trichomoniasis (urinogenital infections in male and female caused by Trіchomonas vagіnalіs);

amebiasis (all of intestinal infections caused by Entamoeba hіstolytіca, including amebic dysentery, all of abenteric forms of amebiasis, especially hepatic amoebiasis);

lambliasis.

Prophylaxis of infections caused by anaerobic bacteria after colon operations and in gynecology.

DOSAGE:

Orgyl® is used per oral after meal only and with some water.

Trichomoniasis:

Recommended schemes of the preparation dosage:

a) treatment course – 1 day:

– adults and children over 35 kg – 3 tablets as a single dose in the evening;

– daily dose for children over 20 kg is 25 mg of ornidazole per 1 kg of body weight and is used in the evening;

b) treatment course – 5 days:

– adults and children over 35 kg – 2 tablets (1 tablet in the morning and 1 tablet in the evening).

It is not recommended to use this scheme in children below 35 kg.

Sexual partner should undergo the same treatment course to avoid re-infection.

Amebiasis:

Possible schemes of the treatment:

a) 3 days for the treatment of patients with amebic dysentery;

b) 5 – 10 days for the treatment of all other amebiasis forms.

Recommended schemes of the preparation dosage:

ADVERSE REACTIONS:

Skin and general reactions of hypersensitivity:

in rare cases – itch, skin redness; rare – general reactions of hypersensitivity (anaphylactic and anaphylactoid) with such symptoms as urticaria, bronchus spasms and possible severe asphyxia, very rare – skin and mucous membrane oedema (for example, oedema of face skin and pharynx tunica mucosa); sudden blood pressure decrease and shock; QT-interval lengthening, hypersensitivity to sunlight and UV-light; in single cases – acute skin and mucous membrane rash with wheals formation such as Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome) and erythema multiforme. More easy skin reactions can precede general reactions of hypersensitivity. These reactions may occur after the first dose and within several minutes or hours after usage.

Gastro-intestinal tract:

often – nausea, diarrhoea; in single cases – loss of appetite, vomiting, abdominal pain, indigestion; rare – blood diarrhoea, which sometimes can be with signs of intestine inflammation, including pseudomembranous colitis; very rare – decreasing of blood sugar content (hypoglycemia), which probably has a special importance for insular diabetes patients. Symptoms of hypoglycemia may be limosis, nervousness, perspiration, limb tremor.

As for other quinolones it is known that they can cause porphyria attack in patients with porphyria. It may concern Tigeron too.

Central nervous system:

in single cases – headache, dizziness/stupor, somnolence, sleep disturbance; rare – disagreeable feeling, for example, hand paraesthesia, tremor, anxiety, apprehensiveness, fits and mental confusion; very rare – disturbance of vision and hearing, disturbance of taste and nose, decreased sense of touch, and psychotic reactions such as hallucination and depressive shifts of mood, psychotic reactions with dangerous behavior for one’s own self, including suicidal idea and action. Movement processes disturbance, also during walking.

Cardiovascular system:

rare – tachycardia, blood pressure reduction; very rare – collapse similar to shock.

Muscular-skeletal system:

rare – tendon lesion, including its inflammation, pain in joint and muscle; very rare – tendon tear (for example, Achilles tendon rupture). This side effect can appear within 48 hours from the treatment start and can affect Achilles tendons of both legs. It is possible muscle weakness, which may have a special importance for patients with severe miastenia; in single cases – musculature affection (rabdomyolisis).

Liver:

often – increased liver enzymes indexes (ALT, AST); in some cases – increased indexes of bilirubin and creatinine of blood serum; very rare – liver reactions such as liver inflammation.

Kidney:

kidney function impairment up to acute kidney insufficiency, for example, due to allergic reactions (interstitial nephritis).

Blood system:

in some cases – increase of definite blood cells quantity (eosinophilia), decrease of leukocyte quantity (leukocytopenia); rare – decrease of quantity of definite leukocyte (neutropenia), decrease of thrombocyte quantity (thrombocytopenia), which can cause high inclination toward haemorrhage and bleeding; very rare – rather significant decreasing of quantity of definite leukocyte (agranulocytosis), which can lead to severe disease symptoms (long-term or recurrent fever, pharyngitis, expressed disease state); in single cases – decrease of erythrocyte quantity due to its destruction (hemolytic anemia), reduced quantity of all types of blood cells (pancytopenia).

Other:

in rare cases – general weakness (asthenia); very rare – fever, allergic reactions of pulmones (allergic pneumonia) or small blood vessel (vasculitis).

Usage of any antibacterial drugs can cause disorders associated with their influence on normal microflora of human organism. As a result of this secondary infection can be developed that will require additional treatment.

Drug interactions:

Levofloxacin absorption is significantly decreases in concurrent usage with antacids, which contain magnesium and aluminium, and with drugs, which contain iron salt. Recommended time period between usages of Tigeron and mentioned above drugs should be not less than 2 hours. Bioavailability of Tigeron tablets is significantly decreased

As far as during clinical trials it was not approved interaction of Levofloxacin and theophylline it was possible a significant decreasing of spastic threshold in concurrent usage of quinolones with theophylline, nonsteroidal anti-inflammatory drugs and other agents, which reduce spastic threshold. Levofloxacin concentration in presence of fenbufen was approximately 13% upper than those one during Levofloxacin usage only. Probenecid and cimetidine statistically reliably influence on Levofloxacin excretion. Kidney clearance of Levofloxacin is decreased in presence of probenecid by 34%, but in presence of cimetidine – by 24%. Due to this both drugs can block tubular excretion of Levofloxacin. Half-life period of cyclosporine is enlarged by 33% in concurrent usage with Levofloxacin.

In concurrent usage with antagonists of K vitamin, for example warfarin, coagulation tests (PT / international normalizing ratio) and/or bleeding, which may be severe, are increased. In consideration to this in patients, who concurrently take antagonists of K vitamin, coagulation indexes should be controlled.

It is not recommended Levofloxacin concomitant usage with alcohol.

Pregnancy and lactation:

Tigeron can not be used during pregnancy and lactation because of absence of studies on human and possible articular cartilage lesion by quinolones in growing organism.

If during Tigeron treatment pregnancy is determined a doctor should be informed about it.

Children:

The preparation is not used in children and adolescences less than 18 years old because of possible articular cartilage lesion.

PRECAUTIONS:

In use of high doses of the preparation and in case of the treatment course over 10 days it is recommended to carry out a clinical and laboratory monitoring.

In patients with blood disorders in anamnesis it is recommended a control of leucocytes, especially in case of re-treatment course.

Enhancement of disorders of central and peripheral nervous systems can be observed during the preparation treatment. In case of peripheral neuropathy, ataxia, dizziness or confusion it is necessary to discontinue the treatment.

Acute condition of candidosis may be observed that will require relevant treatment.

In case of hemodialysis carrying out it is necessary to take into account a half-life period decreasing and to administer additional doses of the preparation before or after hemodialysis.

Concentrations of lithium salts, creatinine and electrolytes should be controlled during the therapy by lithium.

The effect of medicines can be increased or reduced during the preparation treatment.

Symptoms:

convulsions, depression, peripheral neuritis, and symptoms mentioned in “Side effects” section, but in more severe form.

Treatment is symptomatic, specific antidote is unknown, in convulsions – intravenous introduction of diazepam. Gastric lavage or hemodialysis is recommended for ornidazole excretion from the organism.

Ability to influence reaction velocity while driving or operating any other mechanisms.

Orgyl® can influence on ability to drive cars or operate complicated machines, therefore in case of central nervous system side effects appearance (somnolence, rigidity, dizziness, tremor, convulsions, hypotaxia, temporal loss of consciousness) it is necessary to avoid such activity.

CONTRAINDICATIONS:

Hypersensitivity to the preparation components and other nitroimidazole derivates. Patients with CNS affection (epilepsy, cerebral affection, disseminated sclerosis);

pathological blood affection or other hematological anomalies. Periods of pregnancy and lactation. Children age less than 3 years old.

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamics:

Ornidazole is an antiprotozoal and antibacterial agent; it is a derivative of 5-nitroimidazole. It is effective against Trichomonas vaginalis, Entamoeba histolitica, Giardia lamblia (Giardia intestinalis) and some other anaerobic bacteria, such as Gardnerella vaginalis, Bacteroides and Clostridium spp., Fusobacterium spp., and anaerobic coccus.

By mechanism of action ornidazole is a DNA-tropic agent with selective activity against microorganisms, which have enzyme systems able to renew nitro group and catalyze an interaction of ferredoxin proteins with nitrocompounds. After preparation penetration into microbial cell the mechanism of its action is cause by renovation of nitro group under an influence of nitroreductase of microorganism and activity of renewed nitroimidazole. Products of renovation form complexes with DNA, causing its degradation, disturb processes of replication and transcription of DNA. In addition, products of preparation metabolism have cytostatic properties and disturb processes of cell respiration.

Pharmacokinetics:

After per oral intake ornidazole is quickly absorbed in GIT. In average absorption is 90%. Maximal concentration in plasma is within the limits of 3 hours.

Ornidazole binding to plasma proteins is approximately 13%. Active substance penetrates into cerebrospinal fluid and other fluids of the organism and tissues.

Ornidazole concentration in plasma is within diapason of 6 – 36 mg/l, i. e. on the level, which is considered as optimal for different indications for use. After multiuse of 500 mg and 1000 mg doses in healthy volunteers every 12 hours the cumulation factor is 1.5 – 2.5.

Ornidazole is metabolized in liver with production of 2-hydroxymethyl and α-hydroxymethyl metabolites. Both metabolites are less active against Trichomonas vaginalis and anaerobic bacteria than unchanged ornidazole.

The period of half life is about 13 hours. After single use 85% of the dose are excreted during the first 5 days, mainly as metabolites. About 4% of used dose is excreted by kidney in unchanged form.

Hepatic insufficiency:

half-life of active substance in liver cirrhosis is increased up to 22 hours, clearance is decreased (35 versus 51 ml/min) in comparison with healthy volunteers.

Kidney insufficiency:

Ornidazole pharmacokinetics is not changed in kidney dysfunction, therefore the dose of the preparation should not be adjusted.

Ornidazole is excreted in haemodialysis. Before haemodialysis procedure it is necessary to use additional 500 mg of ornidazole if daily dose is 2 g per day or additional 250 mg of ornidazole if daily dose is 1 g per day.

Children:

Ornidazole pharmacokinetics in children is similar to pharmacokinetics in adults.

PHARMACEUTICAL CHARACTERISTICS:

General physic-chemical properties:

round, orange, film coated tablets.

Shelf-life:

3 years.

Storage:

Store in dry, protected from light place, at the temperature not more than 25° C. Keep it out of reach of children. Package:

10 tablets are in a blister, 1 blister is in a carton box.

Conditions of supply:

By prescription.