Ornivag 250

I N S T R U C T I O N for medical use of the medicinal product ORNIVAG 250 (ORNIVAG 250)

Composition:

Active substance: ornidazole;

One tablet contains 250 mg of ornidazole;

Excipients: hypromellose, maize starch, microcrystalline cellulose, magnesium stearate, macrogol 4000, talc, Opaspray White M-1-7120 (titanium dioxide (E 171), hypromellose, sodium benzoate (E 211)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: film-coated tablets of white or yellowish-white color, round, smooth, with a score line on one side.

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.

Ornidazole is effective against Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia (Giardia intestinalis), as well as certain anaerobic bacteria such as Bacteroides and Clostridium spp., Fusobacterium spp., and anaerobic cocci.

In terms of its mechanism of action, ornidazole is a DNA-directed 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.

Pharmacokinetics

Absorption: Ornidazole is rapidly absorbed after oral administration. The mean absorption rate is approximately 90%. Peak plasma concentration is achieved within 3 hours.

Distribution: Plasma protein binding of ornidazole is approximately 13%. The active substance penetrates very well into cerebrospinal fluid, tissues, and body fluids. Plasma concentrations remain within the range considered optimal for various therapeutic indications (6–36 mg/mL). After repeated administration of 500 mg or 1000 mg every 12 hours to healthy volunteers, the accumulation coefficient was calculated to be 1.5–2.5.

Metabolism: Ornidazole is primarily metabolized in the liver to 2-hydroxymethyl and α-hydroxymethyl metabolites. Both major metabolites exhibit lower activity against Trichomonas vaginalis and anaerobic bacteria compared to unchanged ornidazole.

Elimination: The elimination half-life is approximately 13 hours. 85% of a single dose is excreted from the body within the first 5 days, primarily in the form of metabolites. 4% of the dose is excreted unchanged in urine.

Linearity/Non-linearity: Ornidazole exhibits linear pharmacokinetics.

Characteristics of drug properties in certain patient populations

Liver function impairment: In patients with liver cirrhosis, the elimination half-life of the drug is prolonged (22 vs. 14 hours) and clearance is reduced (35 vs. 51 mL/min) compared to healthy volunteers. Patients with impaired liver function should have the dosing interval doubled.

Renal function impairment: The pharmacokinetics of ornidazole are not altered in renal impairment. Patients with impaired renal function do not require dose adjustment. Ornidazole is eliminated from the body via hemodialysis. If the daily dose is 2 g/day, an additional dose of 500 mg ornidazole should be administered before the start of hemodialysis; if the daily dose is 1 g/day, the additional dose is 250 mg.

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

Clinical characteristics.

Indications.

1. Trichomoniasis (genitourinary infections in women and men caused by Trichomonas vaginalis).
2. Amebiasis (all intestinal infections caused by Entamoeba histolytica, including amebic dysentery, and all extraintestinal forms of amebiasis, particularly amebic liver abscess).
3. Giardiasis.

Contraindications.

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

Interaction with other medicinal products and other forms of interactions.

Alcohol should not be consumed during ornidazole therapy and for 3 days after completion of treatment.

Ornidazole enhances the effect of oral anticoagulants of the coumarin type. Therefore, dosage adjustment of the anticoagulant should be performed.

Ornidazole should be used with caution in combination with cimetidine (an antihistamine agent), antiepileptic drugs such as phenytoin and phenobarbital, and lithium.

Ornidazole prolongs the muscle relaxant effect of vecuronium bromide.

Special precautions for use.

When using high doses of the drug and during treatment lasting more than 10 days, clinical and laboratory monitoring is recommended.

Pathological blood disorders or other hematological abnormalities.

Ornidazole should be used with caution in patients with CNS disorders, such as epilepsy or multiple sclerosis, or with hepatic pathology. The drug may enhance or suppress the effects of other medicinal agents.

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

Exacerbation of central or peripheral nervous system disturbances may occur during treatment. In case of peripheral neuropathy, movement coordination disorders (ataxia), dizziness, or impaired consciousness, treatment should be discontinued.

Exacerbation of candidiasis may occur, which will require 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.

Concentrations of lithium salts, creatinine, and electrolytes should be monitored during lithium therapy.

The effect of other medicinal agents may be increased or decreased 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 should be prescribed during early pregnancy or breastfeeding only if absolutely necessary, when the potential benefits to the mother outweigh the potential risks to the fetus/child.

Ability to affect reaction rate when driving or operating machinery.

Patients receiving ornidazole may experience drowsiness, dizziness, tremor, rigidity, coordination disturbances, seizures, vertigo, or transient loss of consciousness. The occurrence of such effects may impair the ability to perform tasks requiring heightened attention, including driving vehicles or operating machinery.

Method of administration and dosage.

Administer the drug orally after meals, swallowing with a small amount of water.

Standard dosages

1. Trichomoniasis

250 mg oral tablets should be taken according to the following dosage regimens: administration of a single dose or therapy for five days.

Alcohol consumption should be avoided during ornidazole treatment and for 3 days after completion of therapy, as it may cause reactions such as hyperemia, sedative effect, nausea, vomiting, decreased arterial pressure, and acute pain.

In all cases, the patient's sexual partner should also be treated using the same oral dosage regimen of the drug (first-line therapy) to prevent re-infection. Children should be given 1 dose of the drug at 25 mg/kg.

1. Amoebiasis

a) A three-day course of treatment in cases of amoebic dysentery;

b) for any forms of amoebiasis, treatment lasts 5–10 days.

1. 3. Giardiasis:

Additional information for special patient groups

Renal impairment: patients with impaired renal function do not require dose adjustment.

Hepatic impairment: in patients with impaired liver function, the dosing interval should be doubled.

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

Children.

The drug should be administered to children according to the dosage recommendations provided in the section "Directions for use and dosage".

Overdose.

In case of overdose, symptoms listed in the section "Adverse reactions" may be intensified. Treatment is symptomatic; no specific antidote is known.

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

In the event of seizures, intravenous administration of diazepam is recommended.

Adverse Reactions

Disorders of the blood and lymphatic system

Leukopenia, neutropenia, signs of bone marrow suppression.

Nervous system disorders

Somnolence, headache, dizziness, tremor, rigidity, coordination disturbances, ataxia, seizures, increased fatigue, spatial disorientation, transient loss of consciousness, confusion, excitement, and peripheral neuropathy.

General disorders

Increased body temperature, chills, general weakness, dyspnea.

Gastrointestinal disorders

Taste disturbances, metallic taste in the mouth, coated tongue, nausea, vomiting, diarrhea, epigastric discomfort, dry mouth, loss of appetite.

Hepatobiliary disorders

Jaundice, disturbances in liver function biochemical parameters, elevated levels of liver enzymes, hepatotoxicity.

Immune system disorders

Hypersensitivity reactions, including anaphylactic shock and angioneurotic edema.

Skin and subcutaneous tissue disorders

Itching, skin rashes, urticaria, skin hyperemia.

Infections and infestations

Exacerbation of candidomycosis.

Other

Darkening of urine color, cardiovascular disorders, including decreased blood pressure.

Shelf life. 3 years.

Storage conditions.

Store in a place inaccessible to children, at a temperature not exceeding 25°C.

Packaging.

10 tablets in a blister; 1, 2, or 3 blisters per cardboard box.

Prescription category. Prescription only.

Manufacturer.

Abdi Ibrahim Ilac Sanayi ve Ticaret A.S.

Manufacturer's address.

Orhan Gazi Mahallesi, Tunc Caddesi No 3, Esenyurt, Istanbul, Turkey / Orhan Gazi Mahallesi, Tunc Caddesi No 3, Esenyurt, Istanbul, Turkey.

Marketing authorization holder.

Delta Medical Promotions AG.

Address of the marketing authorization holder.

Ottenbachstrasse 26, Zurich CH–8001, Switzerland.