Ornidazole-astrafarm

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ORNIDAZOLE-ASTRAPHARM (ORNIDAZOLE-ASTRAPHARM)

Composition:

Active substance: ornidazole;

1 capsule contains ornidazole equivalent to 100% substance – 500 mg;

Excipients: potato starch, magnesium stearate;

Capsule shell composition: gelatin, titanium dioxide (E 171), indigo carmine-blue 2 (E 132), azorubine (E 122).

Pharmaceutical form. Capsules.

Main physicochemical properties: hard gelatin capsules size № 0, cylindrical in shape with hemispherical ends; body – white, cap – blue. The capsule contents are a pale yellow crystalline powder.

Pharmacotherapeutic group.

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

Pharmacological Properties.

Pharmacodynamics.

Ornidazole is a protozoacidal 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.

Ornidazole acts as 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, its mechanism of action involves the reduction of the nitro group under the influence of microbial nitroreductases, resulting in the activation of the nitroimidazole. The reduced metabolites form complexes with DNA, leading to DNA degradation and disruption of DNA replication and transcription processes. Additionally, ornidazole metabolites exhibit cytotoxic properties and interfere with microbial cellular respiration.

Pharmacokinetics.

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

Distribution: plasma protein binding of ornidazole is about 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 is considered optimal for various indications. After repeated administration of 500 mg and 1000 mg every 12 hours in healthy volunteers, the accumulation ratio 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 compared to unchanged ornidazole.

Elimination: 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 administered dose is excreted unchanged by the kidneys.

Special pharmacokinetic considerations in organ dysfunction.

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

Kidney: the pharmacokinetics of ornidazole are not altered in renal impairment; therefore, dose adjustment is not required.

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

Children (including newborns): the pharmacokinetics of ornidazole in children (including newborns) are similar to those 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 amebic dysentery, and all extraintestinal forms of amebiasis, particularly amoebic liver abscess).

Giardiasis.

Contraindications.

Hypersensitivity to ornidazole or any other component of the drug, or to other derivatives of nitromidazoles. Central nervous system disorders (epilepsy, brain lesions, multiple sclerosis); blood disorders or other hematological abnormalities.

Interaction with other medicinal products and other forms of interaction.

Alcohol should not be consumed during treatment and for at least 3 days after discontinuation of the drug.

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

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

Ornidazole prolongs the muscle relaxant effect of vecuronium bromide.

Special precautions for use.

When high doses of the drug are used or treatment is continued for more than 10 days, clinical and laboratory monitoring is recommended.

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

Worsening of central or peripheral nervous system disorders may occur during treatment. If peripheral neuropathy, movement coordination disorders (ataxia), dizziness, or impaired consciousness occur, the drug should be discontinued.

Exacerbation of candidiasis is possible and may 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 lithium and electrolyte concentrations, as well as creatinine levels, 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.

Use during pregnancy or breastfeeding.

In experimental studies, ornidazole showed no teratogenic or toxic effects on the fetus. Since controlled studies in pregnant women have not been conducted, the drug may be prescribed during early pregnancy or breastfeeding only if absolutely indicated, when the potential benefits of the drug for the mother clearly outweigh the potential risks to the fetus/child.

Ability to affect reaction speed when driving or operating machinery.

When ornidazole is used, adverse effects such as drowsiness, rigidity, dizziness, tremor, seizures, impaired coordination, and transient loss of consciousness may occur. The possibility of such effects should be considered in patients driving vehicles or operating machinery.

Dosage and Administration.

Ornidazole should always be taken orally after food intake.

Patients with renal impairment: dose adjustment is not required in patients with impaired kidney function.

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

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

Trichomoniasis: 500 mg capsules are administered according to single-dose or 5-day treatment regimens.

Ornidazole may cause reactions such as flushing, numbness, hot flashes, nausea, and vomiting, as well as possible arterial hypotension and tinnitus. Alcohol consumption should be avoided for at least 3 days after taking the drug.

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.

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 dosing regimen of the drug

Giardiasis

Table 3

Recommended dosage regimen of the drug

Children.

The drug is 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. There is no specific antidote. In case of seizures, intravenous diazepam is recommended.

Adverse reactions.

Infections and infestations: exacerbation of candidomycosis.

Blood system disorders: signs of bone marrow suppression, leukopenia, neutropenia.

Nervous system disorders: drowsiness, headache, dizziness, tremor, rigidity, coordination disturbances, ataxia, seizures, fatigue, spatial disorientation, transient loss of consciousness, confusion, excitement, and peripheral neuropathy.

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

Hepatobiliary disorders: unknown – jaundice, abnormalities in liver function biochemical parameters, elevated liver enzymes; hepatotoxicity.

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

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

General disorders: increased body temperature; chills; general weakness; dyspnea; darkening of urine color; cardiovascular disorders, including decreased blood pressure.

Shelf life. 3 years.

Storage conditions.

Store in a dry, light-protected place at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 capsules per blister; 1 blister per carton.

Prescription category. Prescription only.

Manufacturer.

LLC "ASTRAFARM".

Manufacturer's address and location of business activity.

Ukraine, 08132, Kyiv-Sviatoshyn district, city of Vyshneve, Kyivska St., 6.

INSTRUCTIONS

for medical use of the medicinal product

ORNIDAZOLE-ASTRAFARM

(ORNIDAZOLE-ASTRAPHARM)

Composition:

Active ingredient: ornidazole;

1 capsule contains ornidazole equivalent to 100% substance – 500 mg;

Excipients: potato starch, magnesium stearate;

Capsule shell composition: gelatin, titanium dioxide (E 171), indigocarmine-blue 2 (E 132), azorubine (E 122).

Medicinal form. Capsules.

Main physicochemical properties: hard gelatin capsules №0, cylindrical in shape with hemispherical ends; body – white, cap – blue. Capsule contents – pale yellow crystalline powder.

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 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 group proteins with nitro compounds. After penetration into the microbial cell, its mechanism of action involves reduction of the nitro group under the influence of microbial nitroreductases and activity of the already reduced nitroimidazole. The reduction products form complexes with DNA, causing its degradation and disrupting DNA replication and transcription processes. In addition, the drug's metabolites possess cytotoxic properties and disrupt microbial 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: plasma protein binding of ornidazole is approximately 13%. The active substance penetrates into cerebrospinal fluid, other body fluids, and tissues.

Ornidazole plasma concentration ranges between 6–36 mg/L, which is considered optimal for various indications related to the drug's use. After repeated administration at doses of 500 mg and 1000 mg every 12 hours in healthy volunteers, the accumulation ratio is 1.5–2.5.

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: elimination half-life is approximately 13 hours. After single administration, 85% of the dose is excreted within the first 5 days, mainly as metabolites. About 4% of the administered dose is excreted unchanged by the kidneys.

Special features of pharmacokinetics in organ or system dysfunction.

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

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

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

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

Clinical characteristics.

Indications.

Trichomoniasis (urogenital 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 ornidazole or any other component of the drug, or to other nitroimidazole derivatives. Central nervous system disorders (epilepsy, brain lesions, multiple sclerosis); blood disorders or other hematological abnormalities.

Interaction with other medicinal products and other types of interactions.

Alcohol consumption should be avoided throughout the treatment course 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.

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

Ornidazole prolongs the muscle-relaxant effect of vecuronium bromide.

Special precautions.

When high doses are used or treatment continues for more than 10 days, clinical and laboratory monitoring is recommended.

In patients with a history of blood disorders, leukocyte count monitoring is recommended, especially during repeated treatment courses.

Worsening of central or peripheral nervous system disorders may occur during treatment. If peripheral neuropathy, movement coordination disturbances (ataxia), dizziness, or confusion occur, drug administration should be discontinued.

Exacerbation of candidomycosis may occur, which may require appropriate treatment.

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

Serum lithium salts, electrolyte concentrations, and creatinine levels should be monitored during lithium therapy.

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

Use with caution in patients with impaired liver function.

Use during pregnancy or breastfeeding.

In experimental studies, ornidazole did not show teratogenic or toxic effects on the fetus. Since controlled studies in pregnant women have not been conducted, the drug should be prescribed during early pregnancy or breastfeeding only when absolutely necessary, when potential benefits to the mother outweigh the potential risks to the fetus/child.

Ability to affect reaction speed when driving or operating machinery.

When using ornidazole, adverse effects such as drowsiness, rigidity, dizziness, tremor, seizures, impaired coordination, and transient loss of consciousness may occur. The possibility of such effects should be taken into account for patients driving vehicles or operating machinery.

Administration and dosage.

Ornidazole should always be taken orally after meals.

Patients with renal insufficiency: dose adjustment is not required in patients with impaired kidney function.

Patients with hepatic insufficiency: the dosing interval should be doubled in patients with severe hepatic insufficiency.

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

Trichomoniasis: capsules 500 mg are used in single-dose or 5-day treatment regimens.

Ornidazole intake may cause reactions such as flushing, numbness, warmth, nausea, and vomiting, as well as possible arterial hypotension and tinnitus. Alcohol should not be consumed for at least 3 days after taking the drug.

Table 1

To avoid the possibility of reinfection, 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 drug dosing regimen

Giardiasis

Table 3

Recommended dosing regimen of the drug

Children.

The drug is administered to children according to the dosage recommendations specified 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. Specific antidote is unknown. In case of seizures, intravenous diazepam is recommended.

Adverse Reactions.

Infections and infestations: exacerbation of candidiasis.

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

Nervous system disorders: drowsiness, headache, dizziness, tremor, rigidity, coordination disturbances, ataxia, seizures, increased fatigue, spatial disorientation, transient loss of consciousness, confusion, excitement, and peripheral neuropathy.

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

Hepatobiliary disorders: unknown – jaundice, abnormalities in liver function biochemical parameters, increased liver enzyme levels; hepatotoxicity.

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

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

General disorders: increased body temperature; chills; general weakness; dyspnea; darkening of urine color; cardiovascular disorders, including decreased arterial pressure.

Shelf life. 3 years.

Storage conditions.

Store in a dry, protected from light place at temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 capsules in a blister; 1 blister per box.

Prescription status. Prescription only.

Manufacturer.

LLC "ASTRAFARM".

Manufacturer's address and location of operations.

6 Kyivska Street, Vyshneve, Kyiv-Sviatoshyn district, 08132, Ukraine.