Orgil®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ORGYL®

Composition:

Active substance: ornidazole;

One tablet contains 500 mg of ornidazole;

Excipients: microcrystalline cellulose, maize starch, magnesium stearate, sodium croscarmellose, Oparidry 03B53217 orange coating: hypromellose, titanium dioxide (E 171), FCF yellow (E 110), polyethylene glycol.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: round, orange film-coated tablets.

Pharmacotherapeutic group.

Agents used in amoebiasis and other protozoal infections. Nitroimidazole derivatives. Ornidazole. ATC code P01AB03.

Pharmacological properties.

Pharmacodynamics.

Ornidazole is an antiprotozoal and antibacterial agent, a derivative of 5-nitroimidazole. It is active against Trichomonas vaginalis, Entamoeba histolytica, Giardia lamblia (also known as Giardia intestinalis), as well as certain anaerobic bacteria such as Bacteroides, Clostridium spp., Fusobacterium spp., and anaerobic cocci.

Mechanistically, ornidazole is a DNA-directed agent with selective activity against microorganisms possessing enzymatic systems capable of reducing the nitro group and catalyzing the interaction of ferredoxin-like proteins with nitro compounds. After entering the microbial cell, the drug's mechanism of action involves reduction of the nitro group by microbial nitroreductases, leading to the formation of active reduced metabolites of nitroimidazole. The reduction products form complexes with DNA, causing DNA degradation and disrupting DNA replication and transcription processes. Additionally, the drug's metabolites exhibit cytotoxic properties and interfere with cellular respiration.

Pharmacokinetics.

Absorption.

Following oral administration, ornidazole is rapidly absorbed from the gastrointestinal tract. On average, bioavailability is approximately 90%. Maximum plasma concentration is achieved within 3 hours.

Distribution.

Plasma protein binding of ornidazole is approximately 13%. The active substance penetrates into cerebrospinal fluid, other body fluids, and tissues.

The plasma concentration of ornidazole ranges between 6–36 mg/L, which corresponds to levels considered optimal for various clinical indications. After repeated administration of 500 mg and 1000 mg doses every 12 hours in healthy volunteers, the accumulation coefficient ranges from 1.5 to 2.5.

Metabolism.

Ornidazole is metabolized in the liver primarily into 2-hydroxymethyl- and α-hydroxymethyl metabolites. Both metabolites are less active against Trichomonas vaginalis and anaerobic bacteria compared to the unchanged ornidazole.

Excretion.

The elimination half-life is approximately 13 hours. After a single dose, about 85% of the administered dose is excreted within the first 5 days, primarily as metabolites. Approximately 4% of the administered dose is excreted unchanged in the urine.

Pharmacokinetic characteristics in specific organ or system dysfunction.

Hepatic impairment.

The elimination half-life of the active substance is prolonged to approximately 22 hours in patients with liver cirrhosis, and clearance is reduced (35 mL/min compared to 51 mL/min in healthy volunteers).

Renal impairment.

The pharmacokinetics of ornidazole are not significantly altered in renal impairment; therefore, dosage adjustment is not required.

Ornidazole is removed during hemodialysis. An additional dose of 500 mg should be administered prior to hemodialysis if the daily dose is 2 g/day, or an additional 250 mg if the daily dose is 1 g/day.

Children.

The pharmacokinetics of ornidazole in children (including neonates) is similar to that in adults.

Clinical characteristics.

Indications.

Trichomoniasis (genitourinary infections in women and men caused by Trichomonas vaginalis).

Amebiasis (all intestinal infections caused by Entamoeba histolytica, including amoebic dysentery, and all extraintestinal forms of amebiasis, particularly amoebic liver abscess).

Giardiasis.

Contraindications.

Hypersensitivity to the active substance, to other components of the drug, or to other nitroimidazole derivatives. Patients with central nervous system disorders (epilepsy, brain lesions, multiple sclerosis); blood dyscrasias or other hematological disorders.

Interaction with other medicinal products and other forms of interaction.

Although ornidazole (unlike other nitroimidazole derivatives) does not inhibit aldehyde dehydrogenase, alcohol should not be consumed during treatment with Orgil® and for at least 3 days after discontinuation of the drug.

Ornidazole enhances the effect of oral anticoagulants of the coumarin group, requiring appropriate dose adjustment.

Ornidazole prolongs the muscle relaxant effect of vecuronium bromide.

Concomitant use of phenobarbital and other enzyme inducers reduces the circulation period of ornidazole in blood serum, whereas enzyme inhibitors (e.g., cimetidine) increase it.

Lithium.

Concomitant use of ornidazole with lithium preparations should be accompanied by monitoring of lithium salt and electrolyte concentrations, as well as serum creatinine levels (see section "Special precautions").

Special precautions.

When using high doses of the drug and in cases of treatment lasting more than 10 days, clinical and laboratory monitoring is recommended.

In patients with a history of blood disorders, monitoring of leukocytes is recommended, especially when repeated courses of treatment are administered.

Exacerbation of disorders of the central or peripheral nervous system may occur during treatment with the drug. In case of peripheral neuropathy, disturbances in motor coordination (ataxia), dizziness, or impaired consciousness, treatment should be discontinued.

Exacerbation of candidiasis may occur, requiring appropriate therapy.

When hemodialysis is performed, a reduced elimination half-life should be taken into account, and additional doses of the drug should be administered either before or after hemodialysis.

Concentrations of lithium salts, creatinine, and electrolytes should be monitored during lithium therapy.

The effect of other medicinal products may be increased or decreased during treatment with this drug.

Use with caution in patients with impaired liver function.

Excipients.

The drug contains the azo dye tartrazine (Yellow FCF), which may cause allergic reactions.

Use during pregnancy or breastfeeding.

Animal studies have not shown teratogenic or toxic effects of ornidazole on the fetus. Since controlled studies in pregnant women have not been conducted, the drug is contraindicated during the first trimester of pregnancy. The drug should be prescribed during the second and third trimesters only if absolutely indicated, when potential benefits to the mother outweigh the potential risk to the fetus/child. If ornidazole use is necessary, breastfeeding should be discontinued.

Ability to influence reaction rate when driving or operating machinery.

Ornidazole may cause symptoms such as drowsiness, muscle rigidity, dizziness, tremor, seizures, impaired coordination, and transient loss of consciousness. The possibility of such effects should be taken into account for patients driving vehicles or operating machinery.

Method of administration and dosage.

Orgil® should be taken orally after meals, swallowing with a small amount of water.

Since administration of ornidazole may lead to such reactions as flushing, numbness, hot sensations, nausea and vomiting, arterial hypotension and tinnitus are also possible. Alcohol consumption should be avoided for at least 3 days after taking the medicinal product.

Trichomoniasis

500 mg tablets are used according to either a single-dose or five-day treatment regimen.

Since administration of ornidazole may lead to such reactions as flushing, numbness, hot sensations, nausea and vomiting, arterial hypotension and tinnitus are also possible. Alcohol consumption should be avoided for at least 3 days after taking the medicinal product.

Table 1

To prevent possible reinfection, the sexual partner should undergo the same course of treatment.

The single daily dose for children is 25 mg/kg.

Amebiasis

Possible treatment regimens:

• 3-day treatment course for patients with amoebic dysentery;
• 5–10-day treatment course for all forms of amebiasis.

Table 2

Recommended dosing regimen of the drug

Giardiasis

Table 3

Recommended dosage regimen of the drug

Patients with renal impairment: dose adjustment is not required for patients with renal function disorders.

Patients with hepatic impairment: the dosing interval should be doubled for patients with severe hepatic impairment.

Elderly patients: clinical data regarding use in elderly patients are lacking.

Children.

The medicinal product should be administered to children according to the dosage recommendations provided in the section "Administration and dosage".

Overdose.

In case of overdose, symptoms mentioned in the section "Adverse reactions" may occur, but in a more pronounced form. Treatment is symptomatic; no specific antidote is known. In case of seizures, intravenous administration of diazepam is recommended.

Adverse reactions.

Blood and lymphatic system disorders: manifestations of bone marrow suppression, including bone marrow depression, leukopenia, neutropenia.

Immune system disorders: hypersensitivity reactions, including skin allergic reactions, anaphylactic shock, angioedema.

Skin and subcutaneous tissue disorders: skin rashes, pruritus, urticaria, skin hyperemia.

Nervous system disorders: headache, fatigue, excitement, confusion, tremor, rigidity, coordination disorders, ataxia, seizures, transient loss of consciousness, signs of sensory or mixed peripheral neuropathy, dizziness, somnolence, spatial disorientation.

Gastrointestinal disorders: nausea, vomiting, metallic taste in the mouth, coated tongue, dry mouth, taste disturbances, diarrhea, epigastric pain, dyspepsia, loss of appetite.

Hepatobiliary disorders: jaundice, hepatotoxicity, abnormalities in liver function biochemical parameters, increased levels of liver enzymes.

General disorders: increased body temperature; chills; general weakness; dyspnea.

Infections and infestations: exacerbation of candidiasis.

Other: darkening of urine color, cardiovascular disorders, including decreased blood pressure.

Shelf life. 3 years.

Storage conditions.

Store at temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister; 1 blister in a cardboard pack.

Prescription status. Prescription only.

Manufacturer.

KUSUM HEALTHCARE PVT LTD.

Manufacturer's address and location of business activity.

SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.

INSTRUCTIONS

for medical use of the medicinal product

ORGIL®

(ORGYL®)

Composition:

Active substance: ornidazole (ornidazole);

1 tablet contains 500 mg of ornidazole;

Excipients: microcrystalline cellulose, maize starch, magnesium stearate, sodium croscarmellose, Opadry 03B53217 orange coating: hypromellose, titanium dioxide (E 171), yellow FCF (E 110), polyethylene glycol.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: round film-coated tablets of orange color.

Pharmacotherapeutic group.

Agents used in amoebiasis and other protozoal infections. Nitroimidazole derivatives. Ornidazole. ATC code P01AB03.

Pharmacological Properties

Pharmacodynamics

Ornidazole is an antiprotozoal and antibacterial agent, a derivative of 5-nitroimidazole. It is active against Trichomonas vaginalis, Entamoeba histolytica, Giardia lamblia (Giardia intestinalis), as well as certain anaerobic bacteria such as Bacteroides, Clostridium spp., Fusobacterium spp., and anaerobic cocci.

In terms of its mechanism of action, ornidazole is a DNA-targeting agent with selective activity against microorganisms possessing enzymatic systems capable of reducing the nitro group and catalyzing the interaction of ferredoxin-like proteins with nitro compounds. After penetrating the microbial cell, the drug's action is mediated by the reduction of the nitro group under the influence of microbial nitroreductases and the activity of the already reduced nitroimidazole. The reduction products form complexes with DNA, leading to its degradation and disrupting DNA replication and transcription processes. Additionally, the drug's metabolites exhibit cytotoxic properties and interfere with cellular respiration.

Pharmacokinetics

Absorption

After oral administration, ornidazole is rapidly absorbed from the gastrointestinal tract. On average, absorption is about 90%. Maximum plasma concentration is reached within 3 hours.

Distribution

Protein binding of ornidazole to plasma proteins is approximately 13%. The active substance penetrates into cerebrospinal fluid, other body fluids, and tissues.

The concentration of ornidazole in blood plasma ranges between 6–36 mg/L, which is considered optimal for various indications. Following repeated administration of 500 mg and 1000 mg doses every 12 hours to healthy volunteers, the accumulation coefficient ranges from 1.5 to 2.5.

Metabolism

Ornidazole is metabolized in the liver, primarily forming 2-hydroxymethyl and α-hydroxymethyl metabolites. Both metabolites are less active against Trichomonas vaginalis and anaerobic bacteria than unchanged ornidazole.

Excretion

The elimination half-life is approximately 13 hours. Within the first 5 days after a single dose, 85% of the administered dose is excreted, mainly as metabolites. Approximately 4% of the ingested dose is excreted unchanged by the kidneys.

Pharmacokinetic characteristics in specific organ or system dysfunction

Hepatic impairment

The elimination half-life of the active substance increases to 22 hours in patients with liver cirrhosis, and clearance decreases (35 compared to 51 mL/min) relative to healthy volunteers.

Renal impairment

The pharmacokinetics of ornidazole are not altered in renal impairment; therefore, dosage adjustment is not required.

Ornidazole is removed during hemodialysis. An additional dose of 500 mg ornidazole should be administered before the start of hemodialysis if the daily dose is 2 g/day, or an additional 250 mg if the daily dose is 1 g/day.

Children

The pharmacokinetics of ornidazole in children (including newborns) is similar to that in adults.

Clinical characteristics.

Indications.

Trichomoniasis (genitourinary infections in women and men caused by Trichomonas vaginalis).

Amoebiasis (all intestinal infections caused by Entamoeba histolytica, including amoebic dysentery, and all extraintestinal forms of amoebiasis, particularly amoebic liver abscess).

Giardiasis.

Contraindications.

Hypersensitivity to the active substance, to other components of the drug, or to other nitroimidazole derivatives. Patients with central nervous system disorders (epilepsy, brain lesions, multiple sclerosis); blood dyscrasias or other hematological disorders.

Interaction with other medicinal products and other forms of interaction.

Although ornidazole (unlike other nitroimidazole derivatives) does not inhibit aldehyde dehydrogenase, alcohol consumption should be avoided during treatment with Orgil® and for at least 3 days after discontinuation of the drug.

Ornidazole potentiates the effect of oral anticoagulants of the coumarin group, requiring appropriate dose adjustment.

Ornidazole prolongs the muscle-relaxant effect of vecuronium bromide.

Concomitant use of phenobarbital and other enzyme inducers reduces the serum circulation half-life of ornidazole, whereas enzyme inhibitors (e.g., cimetidine) increase it.

Lithium.

Concomitant use of ornidazole with lithium preparations should be accompanied by monitoring of lithium and electrolyte concentrations, as well as serum creatinine levels (see section "Special precautions for use").

Special precautions.

When using high doses of the drug and in cases of treatment exceeding 10 days, clinical and laboratory monitoring is recommended.

In patients with a history of blood disorders, monitoring of leukocytes is recommended, especially when repeated courses of treatment are administered.

Exacerbation of central or peripheral nervous system disorders may occur during treatment with the drug. In case of peripheral neuropathy, impaired motor coordination (ataxia), dizziness, or clouding of consciousness, treatment should be discontinued.

Exacerbation of candidiasis may occur, which will require appropriate treatment.

When hemodialysis is performed, the reduced elimination half-life should be taken into account, and additional doses of the drug should be administered before or after hemodialysis.

Serum concentrations of lithium salts, creatinine, and electrolytes should be monitored during lithium therapy.

The effect of other medicinal products may be enhanced or diminished during treatment with this drug.

Use with caution in patients with impaired liver function.

Excipients.

The drug contains the azo dye tartrazine (Yellow FCF), which may cause allergic reactions.

Use during pregnancy or breastfeeding.

Animal studies have not revealed teratogenic or toxic effects of ornidazole on the fetus. Since controlled studies in pregnant women have not been conducted, the drug is contraindicated during the first trimester of pregnancy. Ornidazole should be prescribed during the second and third trimesters only if absolutely necessary, when potential benefits to the mother outweigh the potential risk to the fetus/child. If ornidazole must be used, breastfeeding should be discontinued.

Ability to affect reaction rate when driving or operating machinery.

During treatment with ornidazole, symptoms such as drowsiness, muscle rigidity, dizziness, tremor, seizures, impaired coordination, and transient loss of consciousness may occur. The possibility of such effects should be considered in patients who drive or operate machinery.

Method of Administration and Dosage.

Orgil® should be taken orally after meals, swallowing with a small amount of water.

Since administration of ornidazole may lead to such reactions as flushing, numbness, hot sensations, nausea, and vomiting, arterial hypotension and tinnitus are also possible. Alcohol consumption should be avoided for at least 3 days following administration of the medicinal product.

Trichomoniasis

500 mg tablets are used according to single-dose or five-day treatment regimens.

Since administration of ornidazole may lead to such reactions as flushing, numbness, hot sensations, nausea, and vomiting, arterial hypotension and tinnitus are also possible. Alcohol consumption should be avoided for at least 3 days following administration of the medicinal product.

Table 1

To prevent possible re-infection, the sexual partner should undergo the same course of treatment.

The single daily dose for children is 25 mg/kg.

Amoebiasis

Possible treatment regimens:

• 3-day treatment course for patients with amoebic dysentery;
• 5-10 day treatment course for all forms of amoebiasis.

Table 2

Recommended dosage regimen of the drug

Giardiasis

Table 3

Recommended dosing regimen of the drug

Patients with renal impairment: dose adjustment is not required for patients with renal function impairment.

Patients with hepatic impairment: the dosing interval should be doubled for patients with severe hepatic impairment.

Elderly patients: clinical data on use in elderly patients are lacking.

Children.

The medicinal product should be administered to children according to the dosage recommendations provided in the section "Directions for use and dosage".

Overdose.

In case of overdose, symptoms mentioned in the section "Adverse reactions" may occur, but in a more pronounced form. Treatment is symptomatic; there is no known specific antidote. In case of seizures, intravenous administration of diazepam is recommended.

Adverse reactions.

Blood and lymphatic system disorders: bone marrow suppression, including myelosuppression, leukopenia, neutropenia.

Immune system disorders: hypersensitivity reactions, including skin allergic reactions, anaphylactic shock, angioneurotic edema.

Skin and subcutaneous tissue disorders: skin rashes, pruritus, urticaria, skin hyperemia.

Nervous system disorders: headache, fatigue, excitement, confusion, tremor, rigidity, coordination disturbances, ataxia, seizures, transient loss of consciousness, signs of sensory or mixed peripheral neuropathy, dizziness, somnolence, spatial disorientation.

Gastrointestinal disorders: nausea, vomiting, metallic taste in the mouth, coated tongue, dry mouth, taste disturbances, diarrhea, epigastric pain, dyspepsia, loss of appetite.

Hepatobiliary disorders: jaundice, hepatotoxicity, abnormalities in liver function biochemical parameters, increased levels of liver enzymes.

General disorders: increased body temperature; chills; general weakness; dyspnea.

Infections and infestations: exacerbation of candidiasis.

Other: darkening of urine color, cardiovascular disorders, including decreased arterial pressure.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets per blister; 1 blister per cardboard pack.

Prescription category. By prescription only.

Manufacturer.

KUSUM HEALTHCARE PVT LTD.

Manufacturer's address and place of business.

Plot No. M-3, Indore Special Economic Zone, Phase-II, Pithampur, Distt. Dhar, Madhya Pradesh, Pin 454774, India