Ornidazole is an antibiotic primarily used to treat protozoan infections and anaerobic bacterial infections. A synthetic nitroimidazole compound, it is commercially obtained from an acid-catalyzed reaction between 2-methyl-5-nitroimidazole and epichlorohydrin. Often described as chloro-secnidazole, ornidazole shares a similar antimicrobial spectrum with metronidazole but is generally better tolerated by patients.
However, some studies have raised concerns about its relatively lower efficacy compared to metronidazole. Initially introduced for treating trichomoniasis, ornidazole was later recognized for its broader anti-protozoan and anti-anaerobic bacterial properties, leading to expanded clinical applications. Research has also investigated its potential use in managing Crohn’s disease following bowel resection.
Chemical Structure
Ornidazole, with the molecular formula C₇H₁₀ClN₃O₃ and a molar mass of 219.63 g·mol⁻¹, belongs to the class of 5-nitroimidazole derivatives. Its IUPAC name is 1-chloro-3-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ol. Structurally, it features a nitroimidazole ring with attached functional groups including a chloromethyl group, a hydroxyl group, and a methyl group.
This specific arrangement confers its antimicrobial properties while influencing its pharmacokinetic profile. The compound exists as a white to slightly yellowish crystalline solid with a melting point between 85-90°C. Its three-dimensional structure is crucial for its binding to target sites within microorganisms, allowing it to exert its therapeutic effects.
Ornidazole-Based Medicines List
Here are eight prominent medicinal products containing ornidazole:
- Tiberal – Manufactured by Deva and Roche in Turkey
- Ornidal – A standalone ornidazole formulation
- Albitrol 500 mg – Produced by Pharmactive in Turkey
- Arrow Ornidazole – Distributed by Teva in New Zealand
- Xynor – Trade name used in various global markets
- Orcipol – Combination product containing ornidazole 500 mg and ciprofloxacin 500 mg
- Madelen – One of the established brand names for ornidazole
- Ornitop – Available in 250 mg and 500 mg film-coated tablet formulations
Mechanism of Action
Ornidazole is a 5-nitroimidazole derivative that exhibits activity against anaerobic bacteria and parasites. The drug functions through a complex mechanism involving reduction of its nitro group to form cytotoxic products that interact with microbial DNA. This interaction disrupts the helical structure of DNA, inhibits protein synthesis, and ultimately leads to cell death in susceptible microorganisms.
In a noteworthy deviation from other nitroimidazoles like metronidazole, ornidazole also inhibits photosynthesis through a distinct mechanism. While having minimal effects on photosynthetic electron transport, it specifically hinders the activity of two Calvin cycle enzymes: triose-phosphate isomerase (TPI) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). This unique property makes ornidazole valuable as an efficient inhibitor of photosynthesis in research settings, particularly because inhibitors capable of penetrating cell membranes are scarce.
Ornidazole has demonstrated significant activity against important pathogens including Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis, and various anaerobic bacteria.
Pharmacokinetics
Ornidazole exhibits favorable pharmacokinetic properties that contribute to its clinical efficacy:
Absorption: Ornidazole is rapidly absorbed from the gastrointestinal tract, with approximately 90% bioavailability. Peak plasma concentrations are typically reached within 3 hours after oral administration. With repeated 500mg doses every 12 hours, peak and trough plasma concentrations are approximately 14 mcg/mL and 6 mcg/mL, respectively.
Distribution: Less than 15% of ornidazole binds to plasma proteins, allowing for extensive distribution throughout body tissues and fluids, including cerebrospinal fluid. This broad distribution profile enables the drug to reach various infection sites effectively.
Metabolism: Ornidazole undergoes metabolism in the liver, primarily forming α-hydroxymethyl and 2-hydroxymethyl metabolites. These metabolites have less activity against Trichomonas vaginalis and anaerobic bacteria compared to the unchanged compound.
Elimination: The elimination half-life of ornidazole is approximately 12-13 hours, which is longer than many similar antimicrobials. Approximately 85% of a single dose is eliminated within the first five days, mainly as metabolites. Excretion occurs primarily via urine (63%) and to a lesser extent through feces (22%). Some excretion also occurs through bile.
Therapeutic Uses
| Condition | Dosage | Duration | Notes |
|---|---|---|---|
| Amoebiasis (Intestinal) | Adults: 500 mg twice daily Children: 10-25 mg/kg in two divided doses | 5 days | Effective against Entamoeba histolytica |
| Amoebiasis (Hepatic) | Adults: 1.5 g once daily Children: 40 mg/kg once daily | 3 days | For amoebic liver abscess |
| Giardiasis | Adults: 1.5 g once daily Children: 40 mg/kg once daily | 1-2 days | For infections with Giardia lamblia |
| Trichomoniasis | 1.5 g as single dose OR 500 mg twice daily | Single dose OR 5 days | Sexual partner should also be treated simultaneously |
| Bacterial Vaginosis | 1.5 g single dose OR 500 mg once daily | Single dose OR 5-7 days | Effective against anaerobic bacteria |
| Anaerobic Infections | Varies based on infection site and severity | Typically 7-10 days | Used for various systemic infections with anaerobic involvement |
| Surgical Prophylaxis | 1 g preoperatively | Single dose | Particularly for colorectal and gynecological procedures |
Side Effects
Ornidazole treatment may result in various adverse effects, most of which are mild to moderate in severity. Gastrointestinal disturbances are the most commonly reported side effects, including nausea, digestive disorders, loss of appetite, unpleasant metallic taste, vomiting, constipation, and diarrhea. These symptoms are typically transient and resolve once treatment is discontinued.
Dermatological reactions can occur, with uncommon manifestations including itching, skin rash, and urticaria. More serious but rare cutaneous reactions include erythema multiforme and angioedema. Hepatobiliary effects have been documented as uncommon side effects, including cholestatic hepatitis, elevated liver enzyme values, jaundice, and in rare instances, pancreatitis.
Neurological adverse effects may occur, including dizziness, headache, lassitude, somnolence, fatigue, and weakness. These central nervous system effects appear to be less severe than those associated with metronidazole. Notably, seizures have not been reported with ornidazole in available studies. Other rare adverse effects include diplopia, myalgia, arthralgia, glossitis, thrush, and dark urine.
Hematological abnormalities such as leukopenia have been occasionally reported during therapy. Rarer blood disorders include agranulocytosis, thrombocytopenia, and pancytopenia. Anaphylaxis, though extremely rare, has been documented as a potential life-threatening allergic reaction to ornidazole.
Drug Interactions
Ornidazole can interact with several medications, potentially affecting treatment outcomes or increasing the risk of adverse effects. Concurrent use of ornidazole and disulfiram may lead to acute confusion or psychosis, representing a significant interaction to avoid. When administered with coumarin anticoagulants, ornidazole may enhance the anticoagulant effect, necessitating closer monitoring of coagulation parameters and possible dose adjustments of the anticoagulant.
The combination of ornidazole with vecuronium bromide has been associated with prolonged muscle relaxation time, which could be clinically relevant during surgical procedures requiring neuromuscular blockade. Unlike other nitroimidazoles, ornidazole may have less interaction with alcohol, though disulfiram-like reactions have been reported in some patients when alcohol is consumed during treatment. This requires further study before definitive recommendations can be made.
Ornidazole has been reported to decrease the clearance of 5-fluorouracil, potentially increasing the exposure and toxicity of this antineoplastic agent. Like other imidazoles, ornidazole has a mild potential to cause disulfiram-like reactions, characterized by nausea, vomiting, headache, and flushing when alcohol is ingested during treatment.
Safety Considerations
Ornidazole should be used with caution in several clinical scenarios. It is contraindicated in patients with hypersensitivity to ornidazole or other nitroimidazole derivatives. Treatment should be discontinued immediately if patients experience confusion, dizziness, or loss of coordination, as these may indicate central nervous system toxicity.
For patients on prolonged therapy, regular blood tests are recommended, particularly for those with a history of blood disorders. This monitoring helps detect potential hematological abnormalities early. Ornidazole should be avoided during pregnancy unless absolutely necessary and should be used only under strict medical supervision when required. Similarly, breastfeeding is not recommended during ornidazole treatment unless deemed essential, as the drug is excreted in breast milk.
Patients with severe hepatic impairment require dosage adjustments, typically doubling the dosing interval due to prolonged elimination half-life and reduced clearance in this population. While no dose adjustment is necessary for patients with renal impairment, those undergoing hemodialysis require an additional dose before the procedure, as ornidazole is removed during dialysis.
Due to its potential to cause dizziness and confusion, patients should be advised against driving or operating machinery after taking ornidazole. The drug is also contraindicated in patients with central nervous system disorders, particularly epilepsy or peripheral neuropathy.
Regulatory Status
Ornidazole is not approved for marketing in the United States by the U.S. Food and Drug Administration but is widely available in numerous other countries worldwide. It is included in the WHO’s classification system for antimicrobials and is categorized in the “Watch” group of the AWaRe (Access, Watch, Reserve) classification, similar to other imidazoles like metronidazole.
The drug is approved in various countries including Turkey, India, New Zealand, and many European nations for treating infections caused by susceptible anaerobic bacteria and protozoa. In the European Union, ornidazole has been investigated for specific applications, although related compounds like metronidazole have received orphan designation for conditions such as pouchitis.
Ornidazole is manufactured by several pharmaceutical companies globally, with various formulations available including oral tablets (typically 250mg and 500mg), vaginal inserts, and intravenous solutions. While not as widely prescribed as metronidazole in some regions, ornidazole remains an important antimicrobial option, particularly in settings where its pharmacokinetic profile or tolerability offers advantages over alternative treatments.
As antimicrobial resistance continues to be a global health concern, the appropriate use of ornidazole, like all antimicrobials, should follow principles of antimicrobial stewardship to preserve its efficacy for future generations.
