Ornidazole-kv

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

Composition:

Active substance: 1 tablet contains ornidazole 500 mg;

Excipients: maize starch, microcrystalline cellulose, magnesium stearate, hydroxypropylmethylcellulose;

Coating: film-coating mixture Opadry II White (hydroxypropylmethylcellulose, lactose monohydrate, polyethylene glycol, titanium dioxide (E 171), triacetin).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white or almost white, round-shaped, biconvex 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 (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-group proteins with nitro compounds. After entering the microbial cell, the drug's mechanism of action involves 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 DNA degradation and disruption of 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 achieved 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 corresponds to levels considered optimal for various indications. After 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.

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 specific organ or system impairments.

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

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).
• Amebiasis (all intestinal infections caused by Entamoeba histolytica, including amoebic dysentery, and all extraintestinal forms of amebiasis, particularly amoebic liver abscess).
• Giardiasis.
• Prophylaxis of infections caused by anaerobic bacteria following surgical interventions on the large intestine and gynecological procedures.

Contraindications.

Hypersensitivity to the components of the medicinal product or to other nitroimidazole derivatives. Patients with central nervous system disorders (epilepsy, brain lesions, multiple sclerosis); pathological blood disorders or other hematological abnormalities.

Interaction with other medicinal products and other types of interactions.

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

Ornidazole potentiates 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 period 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, monitoring of leukocytes is recommended, especially during repeated courses of treatment.

Exacerbation of central or peripheral nervous system disorders 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, which will require appropriate treatment.

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.

Lithium salt, creatinine, and electrolyte concentrations 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.

The drug contains lactose and therefore should not be used in patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

It is known that 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 is contraindicated during the first trimester of pregnancy. During the second and third trimesters of pregnancy, the drug should be used only if absolutely necessary, when the potential benefits to the mother outweigh the potential risks to the fetus/child.

If use of the drug is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

When using 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 taken into account for patients who drive or operate machinery.

Method of administration and dosage.

Ornidazole-KV should be taken orally after meals, swallowing with a small amount of water.

Trichomoniasis

Recommended dosing regimens of the drug:

a) 1-day treatment course:

• adults and children with body weight over 35 kg – 3 tablets as a single evening dose;
• daily dose for children with body weight over 20 kg is 25 mg of ornidazole per 1 kg of body weight as a single dose.

b) 5-day treatment course:

• adults and children with body weight over 35 kg – 2 tablets daily (1 tablet in the morning and 1 tablet in the evening).

The drug is not recommended for children with body weight less than 35 kg.

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

Amoebiasis

Possible treatment regimens:

a) 3-day treatment course for patients with amoebic dysentery;

b) 5–10-day treatment course for all forms of amoebiasis.

Recommended dosing regimen of the drug:

Table 1

Giardiasis

For adults and children with body weight over 35 kg: administer 3 tablets once daily in the evening. For children with body weight below 35 kg: single dose at 40 mg/kg body weight per day. Treatment duration is 1–2 days.

Prophylaxis of infections caused by anaerobic bacteria

Postoperative therapy usually lasts 5–10 days; however, duration should be determined based on clinical condition of the patient. Ornidazole-KV tablets should be administered after stabilization of the patient's condition and ability to take oral medication independently. Administer 1 tablet every 12 hours.

For children, the daily dose is 20 mg per 1 kg body weight given in 2 divided doses over 5–10 days.

To prevent mixed infections, Ornidazole-KV should be used in combination with aminoglycosides, penicillin-group antibiotics, and cephalosporin antibiotics.

Medications should be administered separately.

Children

Contraindicated in children under 3 years of age.

Ornidazole-KV should be administered to children according to dosage recommendations specified in the section "Method of administration and dosage***"***.

Overdose

Symptoms: in case of overdose, possible symptoms include loss of consciousness, headache, dizziness, tremor, seizures, dyspeptic disorders, or increased severity of other adverse reactions.

Treatment: symptomatic; specific antidote is unknown.

To remove ornidazole from the body, gastric lavage or hemodialysis is recommended.

In case of seizures, intravenous diazepam is recommended.

Adverse reactions.

Adverse effects of ornidazole are dose-dependent.

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

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

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

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

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

Hepatobiliary disorders: jaundice, hepatotoxicity, changes in liver function tests.

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. 5 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister; 1 blister per pack.

Prescription category. Prescription only.

Manufacturer.

JSC "KYIV VITAMIN PLANT".

Manufacturer's address and location of its business activity.

38, Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua.