Ornizol®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ORNIZOL® (ORNIZOL®)

Composition:

Active substance: ornidazole;

1 tablet contains ornidazole equivalent to 100% substance 500 mg;

Excipients: microcrystalline cellulose; povidone; talc; sodium starch glycolate (type A); lactose monohydrate; calcium stearate; coating mixture "Opadry II White" (containing hypromellose; lactose monohydrate; titanium dioxide (E 171); triacetin; polyethylene glycol/macrogol).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: film-coated tablets of white color, oval-shaped, with a biconvex surface, with a score line on one side of the tablet and the marking "KMP" on the other side. In cross-section, the core is white or almost white.

Pharmacotherapeutic group. Agents used in amoebiasis and other protozoal infections. Nitroimidazole derivatives. Ornidazole.

ATC code P01AB03.

Pharmacological Properties

Pharmacodynamics

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

Ornidazole acts via a DNA-targeting mechanism 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 reduction of the nitro group under the influence of microbial nitroreductases, leading to activation of the reduced nitroimidazole. The reduction products form complexes with DNA, causing DNA degradation and disrupting DNA replication and transcription processes. Furthermore, 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 after administration.

Distribution. Plasma protein binding 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 indications. Following 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 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. After a single dose, 85% of the administered dose is excreted within the first 5 days, mainly as metabolites. About 4% of the administered dose is excreted unchanged by the kidneys.

Pharmacokinetic characteristics 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 (35 mL/min compared to 51 mL/min in healthy individuals).

Kidney. 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 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 (including neonates). The pharmacokinetics of ornidazole in children, including neonates, are similar to those in adults.

Clinical characteristics.

Indications.

Trichomoniasis (urogenital 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 hepatic amebic abscess).

Giardiasis.

Contraindications.

Hypersensitivity to the drug or to other nitroimidazole derivatives. Patients with CNS disorders (epilepsy, brain lesions, multiple sclerosis).

Pathological blood disorders or other hematological abnormalities.

Interaction with other medicinal products and other forms of interaction.

Alcohol should not be consumed during the course of treatment and for at least 3 days following discontinuation of the drug. Ornidazole enhances the effect of oral anticoagulants of the coumarin group, requiring appropriate adjustment of their dosage.

Ornidazole prolongs the muscle relaxant effect of vecuronium bromide.

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

Special precautions for use

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

In patients with a history of blood disorders, leukocyte monitoring 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, movement coordination disorders (ataxia), dizziness, or impaired consciousness, treatment should be discontinued.

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

The risk of adverse effects increases in children, patients with liver impairment, and patients who abuse alcohol, if the recommended doses are exceeded.

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

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

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

Use with caution in patients with impaired liver function.

The drug contains lactose as an excipient and therefore should not be used in patients with galactose intolerance, lactase deficiency, or glucose/galactose malabsorption.

Use during pregnancy or breastfeeding

Ornidazole has not shown teratogenic or fetal toxic effects. However, since controlled studies in pregnant women have not been conducted, the drug should be prescribed during early pregnancy or breastfeeding only if absolutely indicated and if the potential benefit to the mother outweighs the potential risk to the fetus/infant.

Ability to affect reaction rate while driving or operating machinery

When using Ornidazole®, manifestations 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 who drive vehicles or operate machinery.

Dosage and Administration

Ornizol® should always be taken orally after food intake.

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

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

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

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

Since administration of ornidazole may cause reactions such as flushing, numbness, warmth, nausea, and vomiting, as well as possible hypotension and tinnitus, alcohol consumption should be avoided for at least 3 days after taking 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 drug dosing regimen

Children.

Specifics of using the drug in children are specified in the section "Administration and dosage."

Overdose.

Manifests as an intensification of adverse reaction symptoms.

Treatment: no specific antidote is known; in the event of seizures, diazepam should be administered. Symptomatic therapy.

Side effects.

From the lymphatic system and blood-forming system: signs of bone marrow suppression, leukopenia, neutropenia.

From the nervous system: drowsiness, headache, dizziness, tremor, rigidity, coordination disorders, ataxia, seizures, fatigue, spatial disorientation, temporary loss of consciousness, confusion, excitement, and peripheral neuropathy.

General disorders: increased body temperature, chills, general weakness, shortness of breath.

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

From the hepatobiliary system: unknown – jaundice, disturbances in liver function biochemical parameters, elevated liver enzyme levels; hepatotoxicity.

From the immune system: hypersensitivity reactions, including anaphylactic shock, angioedema.

From the skin and subcutaneous tissue: skin rashes, urticaria, skin hyperemia, itching.

Infections and infestations: exacerbation of candidiasis.

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

Shelf life. 4 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 tablets per blister, 1 blister per carton.

Prescription category. Prescription only.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and location of business activity.
139 Saksaganskoho Street, Kyiv, 01032, Ukraine.