Ornidazole-novopharm

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

Composition:

Active substance: ornidazole;

1 ml of solution contains 5 mg of ornidazole;

Excipients: sodium chloride, sodium hydroxide, concentrated hydrochloric acid, water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical characteristics: clear, colorless or slightly yellow liquid.

Pharmacotherapeutic group. Antibacterial agents for systemic use. Imidazole derivatives. ATC code J01X D03.

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-directed medicinal 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 penetrating the microbial cell, the mechanism of ornidazole’s action involves 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 DNA degradation and disruption of DNA replication and transcription processes. Additionally, ornidazole metabolites possess cytotoxic properties and interfere with cellular respiration.

Pharmacokinetics

Distribution. One and 24 hours after intravenous bolus administration of 1 g, plasma concentrations of ornidazole are 17.7 and 4.9 µg/mL, respectively. After slow intravenous infusion of a single 20 mg/kg dose, the maximum plasma concentration (Cmax) is 18.7 µg/mL, decreasing to 7.32 µg/mL after 24 hours.

The area under the pharmacokinetic curve (AUC) is approximately 185 mg·h/L following a single 500 mg intravenous dose and 375 mg·h/L for a 1 g dose.

The volume of distribution after intravenous administration is 0.7–0.9 L/kg. Protein binding of ornidazole to plasma proteins is less than 15%. The active substance penetrates into cerebrospinal fluid, other body fluids, and tissues.

The optimal plasma concentration of ornidazole ranges between 6–36 mg/L, which corresponds to the level considered optimal for the drug's indications.

Metabolism. Over 90% of ornidazole is metabolized. Two major metabolites exhibit approximately the same activity against anaerobic bacteria as ornidazole itself.

Elimination. The elimination half-life is 13 hours. After single-dose administration, 85% of the dose is excreted within the first 5 days, primarily via urine (63% as metabolites) and feces (22%). Approximately 4% of the administered dose is excreted unchanged by the kidneys. The accumulation ratio after multiple doses of 500 mg or 1000 mg administered every 12 hours in healthy volunteers ranged from 1.5 to 2.5.

Special Patient Groups

Patients with hepatic impairment. The elimination half-life of ornidazole is prolonged to 22 hours in patients with liver cirrhosis, and clearance is reduced (35 mL/min compared to 51 mL/min) compared to healthy individuals.

Patients with renal impairment. The pharmacokinetics of ornidazole are not altered in patients with impaired renal function. Ornidazole is removed by hemodialysis.

Children. The pharmacokinetics of ornidazole in children (including newborns) are similar to those in adults.

Clinical characteristics.

Indications.

Parenteral administration of the medicinal product is indicated in cases of acute and severe infection or when oral administration is not possible, in the following diseases and conditions:

• anaerobic systemic infections caused by microorganisms sensitive to ornidazole: septicemia, meningitis, peritonitis, postoperative wound infections, sepsis, septic abortion and endometritis;
• prophylaxis of infections caused by anaerobic bacteria during surgical interventions (especially surgeries on the colon and rectum), and gynecological operations;
• severe course of amebic dysentery, all extraintestinal forms of amebiasis, giardiasis, hepatic abscess.

Contraindications.

Hypersensitivity to the components of the medicinal product or to other nitroimidazole derivatives. Central nervous system disorders, epilepsy, multiple sclerosis, chronic alcoholism. Circulatory disorders, pathological blood disorders or other hematological abnormalities.

Interaction with other medicinal products and other types of interactions.

Alcohol should not be consumed during the treatment course and for at least 3 days after discontinuation of the medicinal product, as a disulfiram-like reaction (flushing, sensation of warmth, vomiting, tachycardia) cannot be excluded.

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

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

Ornidazole prolongs the muscle relaxant effect of vecuronium bromide.

Possible increase in toxicity of 5-fluorouracil when administered concurrently with nitroimidazoles.

When ornidazole is used concomitantly with cyclosporine, there is a risk of increased cyclosporine serum levels.

Special precautions for use.

When recommended doses are exceeded, there is a certain risk of adverse effects in children, patients with liver disease, and patients who abuse alcohol. When high doses of ornidazole are used or treatment lasts longer 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 central or peripheral nervous system disorders may occur during ornidazole therapy. If peripheral neuropathy, motor coordination disturbances (ataxia), dizziness, or impaired consciousness occur, treatment should be discontinued.

Exacerbation of candidiasis may occur, requiring appropriate treatment.

In patients undergoing hemodialysis, 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 effects of other medicinal products may be increased or decreased during ornidazole treatment.

The medicinal product contains 15.4 mmol (354 mg) of sodium per 100 ml of solution, which should be considered in patients on a controlled-sodium diet.

Use during pregnancy or breastfeeding.

Ornidazole is contraindicated during the first trimester of pregnancy. In the second and third trimesters, the drug may be used only under strict medical indications. If ornidazole use is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

During ornidazole use, symptoms such as drowsiness, muscle rigidity, dizziness, tremor, seizures, coordination disturbances, and transient loss of consciousness may occur. Patients should take into account the possibility of such effects when driving or operating machinery.

Administration and Dosage

The dosage and duration of treatment are determined by a physician depending on the nature of the disease and treatment regimen.

The medicinal product should be administered intravenously over 15–30 minutes.

For anaerobic systemic infections: in adults and children aged 12 years and older, the initial dose is 500–1000 mg, followed by 500 mg every 12 hours or 1000 mg every 24 hours for 5–10 days (step-down dosing). Once the patient's condition has stabilized, oral administration of ornidazole should be initiated (e.g., 500 mg tablets, 1 tablet every 12 hours).

For children under 12 years of age with body weight exceeding 6 kg, the daily dose should be calculated at 20 mg/kg body weight, divided into two doses, administered over 5–10 days.

For prophylaxis of anaerobic infections during surgical procedures: in adults and children aged 12 years and older, ornidazole should be administered at a dose of 500–1000 mg 30 minutes before surgery.

To prevent mixed infections, ornidazole should be used in combination with aminoglycosides, penicillin, or cephalosporins. The medicinal products should be administered separately.

Severe amebic dysentery, all extraintestinal forms of amebiasis, giardiasis, liver abscess: for adults and children aged 12 years and older, the first dose is 500–1000 mg, followed by 500 mg every 12 hours for 3–6 days.

For children under 12 years of age with body weight exceeding 6 kg, the daily dose should be calculated at 20–30 mg/kg body weight, divided into two doses.

Patients with hepatic impairment.

In patients with liver cirrhosis, the dosing interval should be doubled.

Patients with renal impairment.

Renal insufficiency does not affect the pharmacokinetics of ornidazole; therefore, dose adjustment is not required.

Hemodialysis.

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

Children.

Ornidazole is contraindicated in children with body weight less than 6 kg.

Overdose.

In case of overdose, symptoms described 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

The frequency of adverse reactions is defined as follows: very common (≥ 1/10); common (≥ 1/100 to <1/10); uncommon (≥ 1/1000 to <1/100); rare (≥ 1/10,000 to <1/1000); very rare (<1/10,000); frequency not known (cannot be estimated from available data).

Infections and infestations: frequency not known – vaginal superinfection with Candida albicans.

Blood and lymphatic system disorders: uncommon – bone marrow suppression, neutropenia; very rare – transient hematological changes (leukopenia, agranulocytosis, aplastic anemia, thrombocytopenia).

Immune system disorders: very rare – hypersensitivity reactions, including anaphylactic shock.

Psychiatric disorders: not known – mood changes.

Nervous system disorders: rare – tremor, muscle rigidity, coordination disturbances, seizures, disturbances of consciousness, signs of sensory or mixed peripheral neuropathy; not known – ataxia, dizziness, somnolence, headache, loss and confusion of consciousness, dysgeusia.

Respiratory, thoracic and mediastinal disorders: very rare – bronchospasm.

Gastrointestinal disorders: common – nausea, vomiting, metallic taste in the mouth; very rare – abdominal pain.

Hepatobiliary disorders: not known – hepatitis, changes in liver function tests.

Skin and subcutaneous tissue disorders: uncommon – skin rashes, urticaria, pruritus; very rare – angioneurotic edema; not known – fixed drug eruptions.

Musculoskeletal and connective tissue disorders: very rare – joint pain; not known – stiffness of the musculoskeletal system.

General disorders and administration site conditions: increased body temperature, chills, general weakness; fatigue; reactions at the injection site, including pain, redness, burning sensation at the injection site.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children. Do not use any remaining medicinal product.

Incompatibilities.

The medicinal product must not be mixed with other injectable solutions.

Packaging.

100 ml in a bottle; 1 bottle in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Limited liability company "Novofarm-Biosyntez".

Manufacturer's address and place of business.

38, Zhytomyrska Street, city of Zvyagel, Zvyagelskyi district, Zhytomyr region, 11700, Ukraine.