Usage
Levofloxacin + Ornidazole is a fixed-dose combination antibiotic used to treat various bacterial and parasitic infections, particularly those affecting the gastrointestinal tract. This combination is effective against a broad spectrum of bacteria, including some anaerobic species, and specific protozoa. It is commonly prescribed for conditions like:
- Infectious diarrhea and dysentery (amoebic and bacterial)
- Gynecological infections
- Intra-abdominal infections
- Skin and soft tissue infections
Pharmacological Classification:
- Levofloxacin: Fluoroquinolone antibiotic
- Ornidazole: Nitroimidazole antibacterial and antiprotozoal
Mechanism of Action:
Levofloxacin inhibits bacterial DNA gyrase and topoisomerase IV, enzymes essential for bacterial DNA replication and repair. Ornidazole damages bacterial and parasitic DNA by forming reactive reduction products, disrupting nucleic acid synthesis. The combined action provides a broader spectrum of antimicrobial coverage.
Alternate Names
There isn’t a universally recognized international nonproprietary name (INN) for this fixed-dose combination. The individual components have the following INNs: Levofloxacin and Ornidazole.
Brand Names: This combination is marketed under various brand names, including Levoxn OR, Lenoflox OZ, Levodoc Oz, and others depending upon the location and local pharmaceutical companies. You can refer to source [17] for an extensive, albeit not exhaustive, list of brands.
How It Works
Pharmacodynamics:
- Levofloxacin: Bactericidal action by inhibiting DNA gyrase and topoisomerase IV, preventing bacterial DNA replication and transcription.
- Ornidazole: Bactericidal and antiprotozoal action by damaging DNA and inhibiting nucleic acid synthesis.
Pharmacokinetics:
- Levofloxacin: Well-absorbed orally, achieving peak plasma concentrations within 1-2 hours. It is widely distributed in tissues and is primarily eliminated renally.
- Ornidazole: Also well-absorbed orally, metabolized in the liver, and excreted primarily in urine.
Mode of Action:
- Levofloxacin: Targets bacterial DNA gyrase and topoisomerase IV.
- Ornidazole: Forms reactive metabolites that interact with DNA.
Elimination Pathways:
- Levofloxacin: Predominantly renal excretion.
- Ornidazole: Primarily urinary excretion of metabolites after hepatic metabolism.
Dosage
Dosage is determined by the patient’s age, weight, renal function, and the infection’s severity.
Standard Dosage
Adults:
The usual dose is 250-750 mg of Levofloxacin and 500-1000 mg of Ornidazole, given once or twice daily for durations usually ranging from 5 to 14 days depending on the infection.
Children:
This combination is generally not recommended for children under 18 due to potential adverse effects on developing cartilage. Safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary based on renal function.
- Patients with Renal Impairment: Dose reduction is necessary based on creatinine clearance. Source [11] and [20] have some reference to adjustments based on creatinine clearance.
- Patients with Hepatic Dysfunction: Caution is advised, and dosage adjustments may be necessary.
- Patients with Comorbid Conditions: Careful assessment is required, particularly for those with epilepsy, diabetes, or a history of tendon disorders.
Clinical Use Cases
Dosage in specific clinical scenarios should be guided by local guidelines and expert consultation, as clinical studies specifically addressing these cases with this combination are generally not available. Always consider infection severity and patient-specific factors.
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use/Emergency Situations: No specific dosage recommendations for this combination are universally established for these scenarios. Treatment is guided by the infection type and severity, patient factors, and local/institutional guidelines.
Dosage Adjustments
Adjustments based on creatinine clearance are needed for renal impairment. Refer to source [11] and [20] for example values. Liver function should be assessed, and dosage adjustments may be necessary. No specific information for metabolic disorders or genetic polymorphisms is available regarding this drug combination specifically.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, headache, dizziness, constipation, insomnia, abdominal pain, metallic taste.
Rare but Serious Side Effects:
Tendinitis, tendon rupture, peripheral neuropathy, seizures, Clostridium difficile-associated diarrhea, hypersensitivity reactions (including anaphylaxis), QT prolongation, hypoglycemia, hepatotoxicity.
Long-Term Effects:
Peripheral neuropathy and tendon damage may persist even after discontinuation.
Adverse Drug Reactions (ADR):
Any signs of hypersensitivity, seizures, severe gastrointestinal issues, or cardiac arrhythmias require immediate medical attention.
Contraindications
- Hypersensitivity to levofloxacin, ornidazole, or other quinolones/nitroimidazoles.
- Epilepsy or conditions that lower seizure threshold.
- History of tendon disorders related to quinolone use.
- Pregnancy and breastfeeding (except in extenuating circumstances).
- Children and adolescents under 18 years of age.
- Myasthenia gravis.
Drug Interactions
- CYP450 Interactions: No significant CYP450 interactions are typically associated with this combination.
- Other Drug Interactions: Antacids, multivitamins containing metals (iron, zinc, magnesium), warfarin, theophylline, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids. Source [12] and [16] mention interactions with commonly prescribed drugs.
- Food and Lifestyle Interactions: Alcohol should be avoided due to increased risk of adverse effects (dizziness, disulfiram-like reaction with ornidazole). Dairy products can reduce the absorption of Levofloxacin. However, source [18] indicates that the evidence for this reduction might be scant.
Pregnancy and Breastfeeding
Pregnancy Safety Category: Contraindicated. Levofloxacin and ornidazole can cross the placenta and pose potential risks to the developing fetus (cartilage damage, developmental issues).
Breastfeeding: Contraindicated. Both drugs are excreted in breast milk and may cause adverse effects in infants.
Drug Profile Summary
- Mechanism of Action: Levofloxacin inhibits bacterial DNA gyrase and topoisomerase IV; ornidazole damages DNA.
- Side Effects: Nausea, vomiting, diarrhea, headache, dizziness, seizures, tendinitis, peripheral neuropathy.
- Contraindications: Hypersensitivity, epilepsy, tendon disorders, pregnancy, breastfeeding, children <18 years.
- Drug Interactions: Antacids, multivitamins, warfarin, theophylline, NSAIDs, corticosteroids, alcohol, dairy products.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Varies by infection and patient; generally 250-750 mg Levofloxacin + 500-1000mg of Ornidazole once/twice daily.
- Monitoring Parameters: Renal function, liver function, ECG (for QT interval), signs of hypersensitivity, tendon pain.
Popular Combinations
This combination itself is a popular pairing for treating mixed infections.
Precautions
- General Precautions: Evaluate renal and hepatic function, history of seizures/tendon disorders, allergies.
- Specific Populations: See contraindications for pregnancy, breastfeeding, and children.
- Lifestyle Considerations: Avoid alcohol. It might be advisable to avoid dairy products.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Levofloxacin + Ornidazole?
A: The dosage depends on the infection and patient factors. The usual adult dose is 250-750 mg of Levofloxacin + 500-1000 mg of Ornidazole, given once or twice daily, for 5-14 days. Dose adjustments are needed for renal impairment. It is not recommended for children under 18.
Q2: What are the common side effects?
A: Nausea, vomiting, diarrhea, headache, dizziness, constipation are commonly reported.
Q3: What are the serious side effects?
A: Tendinitis, tendon rupture, seizures, peripheral neuropathy, C. difficile infection, QT prolongation are rare but serious side effects.
Q4: Can this combination be used during pregnancy?
A: No, it is contraindicated in pregnancy due to potential harm to the fetus.
Q5: Can this combination be used while breastfeeding?
A: No, it is contraindicated while breastfeeding as both drugs are excreted in breast milk.
Q6: What are the major drug interactions?
A: Antacids, metal-containing multivitamins, some antibiotics, warfarin, theophylline, NSAIDs, corticosteroids and alcohol.
Q7: What precautions should be taken in patients with renal disease?
A: Dose adjustment is essential based on creatinine clearance.
Q8: What conditions does Levofloxacin + Ornidazole treat?
A: It is primarily used for bacterial and parasitic infections of the gastrointestinal tract, such as infectious diarrhea and dysentery, and is effective against a broad range of bacterial and protozoal pathogens.
Q9: Can this medication be crushed or chewed?
A: No, tablets should be swallowed whole with water.
Q10: What should a patient do if they miss a dose?
A: Take the missed dose as soon as you remember, unless it is almost time for your next dose. Do not double the dose.
