Instructions for Ornidazole-Darnitsa solution for injection 0.5% bottle 100 ml No. 1
Composition
active ingredient: ornidazole;
1 ml of solution contains 5 mg of ornidazole;
Excipients: sodium chloride, hydrochloric acid, water for injections.
Dosage form
Solution for infusion.
Main physicochemical properties: clear colorless or slightly yellowish liquid.
Pharmacotherapeutic group
Antibacterials for systemic use. Imidazole derivatives. Ornidazole. ATX code J01X D03.
Pharmacological properties
Pharmacodynamics.
Ornidazole is an antiprotozoal and antibacterial agent, a derivative of 5-nitroimidazole. It easily penetrates the microbial cell and, by binding to DNA, disrupts the replication process.
Ornidazole is active against Trichomonas vaginalis, Entamoeba histolytica, Giardia lamblia (Giardia intestinalis), as well as some anaerobic bacteria, such as Bacteroides (B. fragilis, Prevotella melaninogenica, Porphyromonas spp.), Fusobacterium spp., anaerobic bacteria: Clostridium spp., sensitive strains of Eubacterium spp.; anaerobic cocci: Peptococcus spp., Peptostreptococcus spp.
The mechanism of action of ornidazole is associated with disruption of the DNA structure with selective activity against microorganisms that have enzyme systems capable of reducing the nitro group and catalyzing the interaction of ferridoxine proteins with nitro compounds. After ornidazole penetrates the microbial cell, its mechanism of action is due to the reduction of the nitro group under the influence of nitroreductases of the microorganism and the activity of the already reduced nitroimidazole. The reduction products form complexes with DNA, causing its degradation, disrupting the processes of DNA replication and transcription. In addition, the products of ornidazole metabolism have cytotoxic properties and disrupt the processes of cellular respiration.
Pharmacokinetics.
Distribution: 1 and 24 hours after an intravenous bolus injection of 1 g, the plasma concentration of ornidazole is 17.7 and 4.9 μg/ml, respectively. After a slow intravenous injection of a single dose of 20 mg/kg, the plasma concentration (Cmax) is 18.7 μg/ml, and after 24 hours it is 7.32 μg/ml.
The area under the pharmacokinetic curve (AUC) is approximately 185 mg/L/h for a single intravenous dose of 500 mg and 375 mg/L/h for a 1 g dose.
Volume of distribution after intravenous administration: 0.7–0.9 l/kg. The binding of ornidazole to plasma proteins is less than 15%. The active substance of the drug penetrates into the cerebrospinal fluid, other body fluids and tissues.
The optimal concentration of ornidazole in blood plasma is in the range of 6–36 mg/l, i.e. at a level considered optimal for the indications for use of the drug.
Metabolism: More than 90% of ornidazole is metabolized. The two main metabolites have approximately the same activity against anaerobic bacteria as ornidazole.
Elimination. The elimination half-life is 13 hours. After a single dose, 85% of the dose is excreted within the first 5 days, most of it in the urine (63% in the form of metabolites) and feces (22%). Approximately 4% of the administered dose is excreted unchanged by the kidneys. The accumulation coefficient after multiple doses of 500 mg or 1000 mg every 12 hours by healthy volunteers was 1.5-2.5.
Special patient groups.
Patients with liver disease. The half-life of ornidazole in patients with liver cirrhosis is increased to 22 hours, and clearance is reduced (35 versus 51 mL/min) compared to healthy subjects.
Patients with renal impairment. In patients with renal impairment, pharmacokinetics are not altered. Ornidazole is removed by hemodialysis.
Children: The pharmacokinetics of ornidazole in children (including neonates) are similar to those in adults.
Indication
Parenteral administration of the drug 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 ornidazole-sensitive microflora: septicemia, meningitis, peritonitis, postoperative wound infections, postpartum sepsis, septic abortion and endometritis;
prevention of infections caused by anaerobic bacteria during surgical interventions (especially during operations on the colon and rectum), during gynecological operations;
amoebic dysentery with severe course, all extraintestinal forms of amebiasis, giardiasis, liver abscess.
Contraindication
Hypersensitivity to the components of the drug or to other nitroimidazole derivatives.
Central nervous system damage.
Epilepsy.
Multiple sclerosis.
Chronic alcoholism.
Circulatory disorders, pathological blood lesions or other hematological abnormalities.
The first trimester of pregnancy.
Children weighing less than 6 kg.
Interaction with other medicinal products and other types of interactions
Effect of ornidazole on the pharmacodynamics and/or pharmacokinetics of other drugs
Concomitant use is not recommended.
Alcohol: alcohol should not be consumed during the course of treatment and for at least 3 days after stopping the drug, as the possibility of developing a disulfiram-like reaction (feeling of heat, flushing, vomiting, tachycardia) cannot be ruled out.
Oral anticoagulants: ornidazole enhances the effect of oral coumarin anticoagulants (warfarin), which requires appropriate correction of their dosage.
Cyclosporine: Concomitant use of ornidazole with cyclosporines may increase serum cyclosporine levels, therefore cyclosporine and serum creatinine should be monitored in patients receiving this combination.
International normalized ratio (INR) imbalance: Increased activity of oral anticoagulants (e.g., warfarin) may occur in patients receiving concomitant antibiotic therapy. Risk factors include infectious and inflammatory diseases, advanced age, and poor general health. It is difficult to determine whether the imbalance is caused by the infectious disease itself or by its treatment.
Vecuronium bromide: Ornidazole prolongs the muscle relaxant effect of vecuronium bromide.
5-fluorouracil: Ornidazole reduces the clearance of 5-fluorouracil when used simultaneously with nitroimidazoles, which is accompanied by an increase in the toxicity of 5-fluorouracil.
Effect of other drugs on the pharmacokinetics of ornidazole
Enzyme inducers: Concomitant use of enzyme-inducing anticonvulsants (e.g. phenobarbital) with other enzyme inducers reduces the circulation period of ornidazole in the blood serum.
Enzyme inhibitors: Enzyme inhibitors (e.g. cimetidine) increase the serum half-life of ornidazole.
Lithium: During lithium therapy, it is necessary to monitor the concentration of lithium salts, creatinine and electrolytes.
Application features
When exceeding the recommended doses, there is a certain risk of side effects in children, patients with liver damage, patients who abuse alcohol. When using high doses of ornidazole and in the case of treatment for more than 10 days, clinical and laboratory monitoring is recommended.
In individuals with a history of blood disorders, monitoring of leukocytes is recommended, especially during repeated courses of treatment.
Aggravation of central or peripheral nervous system disorders is possible during treatment with ornidazole. In the event of peripheral neuropathy, impaired coordination of movements (ataxia), dizziness or clouding of consciousness, treatment should be discontinued.
Exacerbation of candidiasis may occur, requiring appropriate treatment.
In case of hemodialysis, it is necessary to take into account the reduction in the half-life and prescribe additional doses of the drug before or after hemodialysis.
The effect of other medicines may be increased or decreased during treatment with ornidazole.
This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
Pregnancy.
Ornidazole is contraindicated in the first trimester of pregnancy. In the second and third trimesters of pregnancy, the drug should be prescribed only if absolutely necessary.
Breastfeeding period.
Ornidazole passes into breast milk, therefore, if necessary, the use of ornidazole should be discontinued.
Ability to influence reaction speed when driving vehicles or other mechanisms
When using ornidazole, such manifestations as drowsiness, muscle rigidity, dizziness, tremor, convulsions, impaired coordination, temporary loss of consciousness are possible. The possibility of such manifestations should be taken into account by patients who drive vehicles or work with other mechanisms. If any of these side effects occur, patients should refrain from driving vehicles or working with other mechanisms.
Method of administration and doses
The dosage and duration of treatment are determined by the doctor depending on the nature of the disease and treatment regimens.
The drug should be administered intravenously over 15–30 minutes.
For anaerobic systemic infections: Adults and children over 12 years of age should be given an intravenous dose of 500–1000 mg as an initial dose, followed by 500 mg every 12 hours or 1000 mg every 24 hours for 5–10 days (stepwise dose). After the patient's condition has stabilized, oral ornidazole should be switched to (e.g. 500 mg tablets, 1 tablet every 12 hours).
Children under 12 years of age with a body weight of more than 6 kg should be prescribed a daily dose of 20 mg/kg of body weight, divided into 2 administrations, for 5–10 days.
For the prevention of anaerobic infections during surgical interventions, ornidazole should be administered to adults and children aged 12 years and older at a dose of 500–1000 mg 30 minutes before surgery.
For the prevention of mixed infections, ornidazole should be used together with aminoglycosides, penicillin or cephalosporins. The drugs should be administered separately.
Severe amoebic dysentery, all extraintestinal forms of amebiasis, giardiasis, liver abscess: for adults and children over 12 years of age, the first dose is 500–1000 mg, then 500 mg every 12 hours for 3–6 days.
For children under 12 years of age with a body weight of more than 6 kg, the daily dose should be prescribed at the rate of 20–30 mg/kg of body weight, divided into 2 administrations.
Patients with impaired liver function.
In case of liver cirrhosis, the interval between administrations should be doubled.
In patients with impaired renal function, pharmacokinetics are not altered. Ornidazole is removed by hemodialysis.
Hemodialysis.
Ornidazole is excreted during hemodialysis, therefore, before starting hemodialysis, an additional 500 mg of ornidazole should be administered if the daily dose is 2 g per day, or an additional 250 mg of ornidazole if the daily dose is 1 g per day.
Children
Use in children weighing more than 6 kg.
Overdose
Symptoms: In case of overdose, the symptoms mentioned in the "Adverse reactions" section may occur, but in a more pronounced form.
Treatment: symptomatic, specific antidote unknown. In case of convulsions, intravenous diazepam is recommended.
Side effects
All adverse reactions are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 - < 1/10), uncommon (≥ 1/1,000 - < 1/100), rare (≥ 1/10,000 - < 1/1,000), rare (< 1/10,000), frequency unknown (cannot be estimated from the available data).
Respiratory, thoracic and mediastinal disorders: rare – bronchospasm.
Gastrointestinal: often - nausea, vomiting, metallic taste in the mouth, rare - abdominal pain.
Hepatobiliary system: unknown - hepatitis, changes in liver function tests.
On the part of the kidneys and urinary system: darkening of the color of urine.
Psychiatric disorders: not known – mood changes.
Nervous system: rarely - tremor, muscle rigidity, impaired coordination, convulsions, impaired consciousness, signs of sensory or mixed peripheral neuropathy; unknown - ataxia, dizziness, drowsiness, headache, loss and confusion of consciousness, asthenia, dysgeusia.
Blood and lymphatic system disorders: uncommon - bone marrow depression, neutropenia; rare - transient hematological changes (leukopenia, agranulocytosis, aplastic anemia, thrombocytopenia).
On the part of the immune system: rare - hypersensitivity reactions, including anaphylactic shock.
Skin and subcutaneous tissue disorders: uncommon – skin rash, urticaria, pruritus; rare – angioedema; unknown – fixed drug-induced rashes.
Musculoskeletal and connective tissue disorders: rare – joint pain; unknown – musculoskeletal stiffness.
Infections and infestations: frequency unknown – vaginal superinfection with Candida albicans.
General disorders and administration site conditions: fever; chills; general weakness; fatigue; shortness of breath; changes at the injection site, including pain, redness, burning sensation at the injection site.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and/or lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ° C. Do not freeze.
Keep out of reach of children.
Incompatibility
Do not mix the solution with other medicines.
Packaging
100 ml in a bottle, 1 bottle in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and address of its place of business.
Ukraine, 02093, Kyiv, Boryspilska St., 13.
