Tiberal®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TIBERAL® (TIBERAL®)

Composition:

Active substance: ornidazole;

One film-coated tablet contains ornidazole 500 mg;

Excipients:

Tablet core: maize starch, microcrystalline cellulose, hydroxypropylmethylcellulose, magnesium stearate;

Coating: hydroxypropylmethylcellulose, talc, titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

Tablets are cylindrical, biconvex, white or white with a yellowish tint, almost odorless, with an embossing "DEVA" on one side.

Diameter 11.6 – 12.8 mm, thickness 5.7 – 6.8 mm.

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, leading to activation of the reduced nitroimidazole. The reduction products form complexes with DNA, causing DNA degradation and disrupting DNA replication and transcription processes. Additionally, the drug's metabolites possess cytotoxic properties and interfere with microbial cellular respiration.

Pharmacokinetics

Absorption: After oral administration, ornidazole is rapidly absorbed from the gastrointestinal tract. On average, bioavailability is approximately 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.

Plasma concentrations of ornidazole range between 6–36 mg/L, which corresponds to levels considered optimal for various indications. Following repeated administration at doses of 500 mg and 1000 mg 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 exhibit lower activity against Trichomonas vaginalis and anaerobic bacteria compared to 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, primarily as metabolites. Approximately 4% of the administered dose is excreted unchanged by the kidneys.

Pharmacokinetic characteristics in organ or system dysfunction

Liver: In patients with hepatic cirrhosis, the elimination half-life of the active substance increases to 22 hours, and clearance decreases (from 35 to 51 mL/min) compared to healthy volunteers.

Kidney: The pharmacokinetics of ornidazole are not significantly 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 ornidazole if the daily dose is 1 g/day.

Pediatric population (including neonates): The pharmacokinetics of ornidazole in children, including neonates, is similar to that observed in adults.

Clinical characteristics.

Indications.

Trichomoniasis (urogenital 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.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients or to other nitroimidazole derivatives. 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.

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

Ornidazole enhances the effect of oral anticoagulants of the coumarin group, requiring appropriate adjustment of their dosage.

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

Ornidazole prolongs the muscle relaxant effect of vecuronium bromide.

Special precautions for use.

When high doses of the drug are used or treatment is continued for more than 10 days, clinical and laboratory monitoring is recommended.

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

Exacerbation of disorders affecting the central or peripheral nervous system may occur during treatment. If peripheral neuropathy, disturbances in motor coordination (ataxia), dizziness, or confusion occur, drug administration should be discontinued.

Exacerbation of candidiasis is possible and may require appropriate treatment.

Exceeding the recommended doses increases the risk of adverse effects in children, patients with liver impairment, and patients who abuse alcohol.

When hemodialysis is performed, a reduced elimination half-life should be taken into account, and additional doses of the drug should be administered either before or after hemodialysis.

Concentrations of lithium salts and electrolytes, as well as creatinine levels, 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.

Use during pregnancy or breastfeeding.

In experimental studies, Tiaberal® did not show 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 indicated, when the potential benefits to the mother outweigh the potential risks to the fetus/child.

Ability to influence reaction speed when driving or operating machinery.

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

Dosage and Administration.

Tiberal® should always be taken orally after meals.

Patients with renal impairment: dose adjustment is not required for patients with impaired kidney function.

Patients with hepatic impairment: the dosing interval should be doubled in patients with severe hepatic impairment.

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

Trichomoniasis: 500 mg tablets are used according to single-dose or five-day treatment regimens.

Since administration of ornidazole may cause reactions such as flushing, numbness, hot sensations, nausea and vomiting, as well as possible hypotension and tinnitus, alcohol consumption should be avoided for at least 3 days after taking the medicinal product.

Table 1

To prevent possible re-infection, the sexual partner should undergo the same course of treatment.

The single daily dose for children is 25 mg/kg.

Amebiasis

Possible treatment regimens:

• 3-day treatment course for patients with amoebic dysentery;
• 5-10 day treatment course for all forms of amebiasis.

Table 2

Recommended dosing regimen of the drug

Giardiasis

Table 3

Recommended dosage regimen of the drug

Children.

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

Overdose.

In case of overdose, symptoms mentioned in the section "Adverse reactions" may occur, but in a more pronounced form. Treatment is symptomatic; there is no known specific antidote. In case of seizures, intravenous administration of diazepam is recommended.

Adverse reactions.

From the lymphatic and hematopoietic systems: bone marrow suppression manifestations, leukopenia, neutropenia.

From the nervous system: drowsiness, headache, dizziness, tremor, rigidity, coordination disorders, ataxia, seizures, fatigue, spatial disorientation, transient loss of consciousness, confusion, excitement, and peripheral neuropathy.

General disorders: increased body temperature; chills; general weakness; dyspnea.

From the gastrointestinal tract: taste disturbances, metallic taste in the mouth, coated tongue, nausea, vomiting, diarrhea, epigastric pain, dry mouth, loss of appetite.

From the hepatobiliary system: unknown – jaundice, abnormalities in liver function biochemical parameters, elevated liver enzymes; hepatotoxicity.

From the immune system: hypersensitivity reactions, including anaphylactic shock, angioneurotic edema.

From the skin and subcutaneous tissue: skin rashes, urticaria, skin hyperemia, pruritus.

Infections and infestations: exacerbation of candidiasis.

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

Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of this medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 5 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

Store at a temperature not exceeding 30°C, in a light-protected place. Keep out of the reach of children.

Packaging.

No. 10 (10x1): 10 tablets in a blister; 1 blister per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Deva Holding A.Ş.

Manufacturer's location and business address.

Çerkezköy Organize Sanayi Bölgesi, Karaağaç Mah. Atatürk Cad. No. 32, Kapaklı / Tekirdağ / Turkey.

Marketing Authorization Holder.

Deva Holding A.Ş.

Marketing Authorization Holder's location and business address.

Halkalı Merkez Mah. Basin Ekspres Cad. No. 1, 34303 Küçükçekmece, Istanbul, Turkey.