Ornivag 500

I N S T R U C T I O N for medical use of the medicinal product ORNIVAG 500 (ORNIVAG 500)

Composition:

Active substance: ornidazole;

1 film-coated tablet contains ornidazole 500 mg;

Excipients:

Tablet core: hypromellose (HPMC E-15), maize starch, microcrystalline cellulose, magnesium stearate;

Film coating: hypromellose (HPMC E-15), macrogol 4000, talc, Opaspray White M-1-7120 (purified water, titanium dioxide (E 171), industrial methylated spirit 74 OP, hypromellose 5 cP, sodium benzoate (E 211)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white or yellowish-white, round, biconvex film-coated tablets with a break 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. 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-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 penetrating the microbial cell, the drug's mechanism of 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, causing its 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 achieved within 3 hours.

Distribution.

Plasma protein binding of ornidazole 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 is considered optimal for various indications. After 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 single administration, 85% of the dose is excreted within the first 5 days, mainly as metabolites. Approximately 4% of the administered dose is excreted unchanged by the kidneys.

Pharmacokinetic characteristics in specific organ or system dysfunction.

Hepatic impairment.

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

Renal impairment.

The pharmacokinetics of ornidazole are not altered in renal dysfunction; therefore, dosage adjustment is not required.

Ornidazole is removed during hemodialysis. An additional dose of 500 mg ornidazole should be administered before initiating hemodialysis if the daily dose is 2 g/day, or an additional 250 mg ornidazole 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.

1. Trichomoniasis.

Urogenital infections in women and men caused by Trichomonas vaginalis.

2. Amebiasis.

All infections caused by Entamoeba histolytica (including amoebic dysentery), as well as cases of extraintestinal amoebiasis, particularly amoebic liver abscess.

3. Giardiasis.

Contraindications.

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

Blood disorders or other hematological abnormalities.

Interaction with other medicinal products and other forms of interaction.

Unlike other nitroimidazole derivatives, ornidazole does not inhibit aldehyde dehydrogenase, therefore the risk of alcohol intolerance is absent. However, ornidazole enhances the effect of oral coumarin anticoagulants, requiring appropriate dose adjustment.

Ornidazole prolongs the duration of myorelaxant action of vecuronium bromide.

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

In patients receiving lithium and imidazole derivatives, monitoring of lithium concentration, creatinine, and plasma electrolytes is required.

Special precautions.

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

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

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

Exacerbation of candidiasis may occur, requiring appropriate treatment.

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

In patients receiving lithium and imidazole derivatives, plasma concentrations of lithium, creatinine, and electrolytes should be monitored.

The effects of other medicinal products may be enhanced or diminished during treatment with this drug.

Use during pregnancy or breastfeeding.

Although studies have shown no evidence of teratogenic or fetotoxic effects of this drug, it should be used during the first trimester of pregnancy and during breastfeeding only if absolutely necessary. Administration during the second and third trimesters is possible only when the benefit to the mother outweighs the potential risk to the fetus/child.

Ability to affect reaction speed when driving or operating machinery.

When using this drug, adverse effects such as drowsiness, rigidity, dizziness, tremor, seizures, coordination disturbances, and transient loss of consciousness may occur. The possibility of such effects should be considered in patients driving vehicles or operating machinery.

Method of administration and dosage.

Tablets should be taken orally after meals, swallowing with a small amount of water.

The following dosage regimens are recommended.

Treatment of trichomoniasis

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, administered as a single dose.

b) 5-day treatment course:

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

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

Not recommended for children with body weight less than 35 kg.

Treatment of 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 dosage regimen of the drug

Table 1

Treatment of giardiasis

For adults and children with body weight over 35 kg, administer 3 tablets as a single dose in the evening; for children with body weight under 35 kg, administer a single dose calculated at 40 mg/kg body weight per day. Treatment duration is 1–2 days.

Children.

The drug should be administered to children according to the dosage recommendations specified in the section "Method of administration and dosage".

Overdose.

In case of overdose, symptoms described in detail in the section "Adverse reactions" become aggravated.

Treatment is symptomatic; no specific antidote is known.

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

In case of seizures, intravenous administration of diazepam is recommended.

Adverse reactions.

Adverse effects of the drug are dose-dependent.

Blood and lymphatic system disorders

Uncommon: manifestations of bone marrow suppression, neutropenia, leukopenia.

Immune system disorders

Uncommon: skin reactions and hypersensitivity reactions.

Nervous system disorders

Rare: tremor, rigidity, coordination disturbances, stupor, seizures, transient loss of consciousness or confusion, signs of sensory or mixed peripheral neuropathy, dizziness, somnolence, headache, ataxia, increased fatigue, spatial disorientation, excitement.

Gastrointestinal disorders

Nausea, vomiting, diarrhea, metallic taste in the mouth, taste disturbances, coated tongue, epigastric pain, dry mouth, loss of appetite.

General disorders: fever, chills, general weakness, dyspnea.

Hepatobiliary disorders: hepatotoxicity; frequency unknown: jaundice, disturbances in liver function biochemical parameters, elevated levels of liver enzymes.

Infections and infestations: exacerbation of candidiasis.

Other: darkening of urine color, cardiovascular disorders, including decreased arterial pressure.

Shelf life. 3 years.

Storage conditions.

Keep out of reach of children at a temperature not exceeding 30°C.

Packaging.

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

Prescription status.

Prescription only.

Manufacturer.

ABDI IBRAHIM Ilac Sanayi ve Ticaret A.S. /
ABDI IBRAHIM Ilac Sanayi ve Ticaret A.S.

Manufacturer's address.

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

Marketing Authorization Holder.

Delta Medical Promotions AG /
Delta Medical Promotions AG.

Address of the Marketing Authorization Holder.

26 Oetenbachgasse, Zurich CH – 8001, Switzerland /
26 Oetenbachgasse, Zurich CH – 8001, Switzerland.