Usage
Nimorazole is prescribed for the treatment of:
- Trichomoniasis: A sexually transmitted infection caused by the parasite Trichomonas vaginalis.
- Bacterial vaginosis: An infection caused by an overgrowth of certain bacteria in the vagina.
- Amoebiasis: An infection caused by the parasite Entamoeba histolytica, affecting the intestines or other organs.
- Giardiasis: An infection of the small intestine caused by the parasite Giardia lamblia.
- Acute ulcerative gingivitis: A severe form of gum infection.
It is also used as a radiosensitizer in the treatment of head and neck cancers, enhancing the effects of radiation therapy on hypoxic tumor cells.
Pharmacological classification: Antiprotozoal, antibacterial, radiosensitizer. Nimorazole belongs to the nitroimidazole class.
Mechanism of Action (brief): Nimorazole acts by disrupting DNA synthesis and damaging DNA within microorganisms, leading to cell death. In hypoxic tumor cells, it is preferentially reduced, forming reactive metabolites that increase DNA damage, making the cells more sensitive to radiation.
Alternate Names
No widely used alternate generic names exist. A previous investigational name was K-1900.
Brand Names: Various brand names exist depending on the region. Examples include Naxogin, Nitromidazole.
How It Works
Pharmacodynamics: Nimorazole is selectively absorbed by anaerobic bacteria and protozoa. Inside these organisms, it undergoes reductive activation, generating cytotoxic metabolites. These metabolites damage microbial DNA, inhibiting DNA repair and leading to cell death. Similarly, under hypoxic conditions in tumor cells, nimorazole undergoes reduction, forming reactive intermediates that damage DNA and increase sensitivity to radiation therapy.
Pharmacokinetics:
- Absorption: Nimorazole is well-absorbed after oral administration, reaching peak plasma concentrations in approximately 1-2 hours. Food may slightly delay absorption but doesn’t significantly affect bioavailability.
- Metabolism: Metabolized primarily in the liver, with minor pathways involving reduction and glucuronidation.
- Elimination: Excreted primarily in the urine, with a small amount in feces. Elimination half-life is variable, but generally around 8-12 hours in adults.
Mode of Action (cellular/molecular level): Enters susceptible cells by passive diffusion. Under low oxygen conditions, the nitro group of nimorazole is reduced, generating a radical anion. This anion then interacts with DNA, forming adducts and causing strand breaks. This DNA damage disrupts replication and transcription, leading to cell death.
Receptor binding/enzyme inhibition: No specific receptor binding or enzyme inhibition known.
Elimination pathways: Primarily renal excretion, some hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Trichomoniasis: 2 g as a single dose OR 500 mg twice daily for 5-7 days. Sexual partners should be treated concurrently.
- Amoebiasis: 500-750 mg twice daily for 5-10 days.
- Giardiasis: 500 mg twice daily for 5-7 days.
- Acute ulcerative gingivitis: 500 mg twice daily for 2 days.
- Radiosensitizer: 1.2 g/m² orally approximately 90 minutes prior to each radiation fraction. In case of twice-daily fractions, the second dose is reduced to 1 g. Total cumulative dose should not exceed 40 g/m² or 75g.
Children:
Dosing should be weight-based and determined by a physician. Limited data exists for pediatric use outside of specific protocols. For amoebiasis, typical dosing ranges from 35-50 mg/kg/day divided into three doses for 10 days.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary in cases of renal or hepatic impairment.
- Patients with Renal Impairment: Caution and dose reduction may be needed, as it’s primarily renally eliminated.
- Patients with Hepatic Dysfunction: Caution advised. Dose adjustment may be required in moderate to severe impairment.
- Patients with Comorbid Conditions: Case-by-case evaluation is required.
Clinical Use Cases
The listed clinical use cases (Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations) are not typically indications for nimorazole. It’s primarily used as an anti-infective and a radiosensitizer as described above.
Dosage Adjustments
Adjustments based on renal/hepatic function and other comorbid conditions should be made in consultation with a physician.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Headache
- Dizziness
- Metallic taste
- Diarrhea
- Anorexia (loss of appetite)
- Epigastric pain (upper abdominal pain)
- Skin Rash
Rare but Serious Side Effects:
- Peripheral neuropathy
- Seizures
- Liver toxicity
- Leukopenia (low white blood cell count)
- Thrombocytopenia (low platelet count)
- Stevens-Johnson syndrome
Long-Term Effects:
Peripheral neuropathy can be a long-term side effect with prolonged use.
Adverse Drug Reactions (ADR): Severe skin reactions (Stevens-Johnson syndrome), hematological abnormalities (leukopenia, thrombocytopenia), hepatotoxicity, seizures.
Contraindications
- Hypersensitivity to nimorazole or other nitroimidazole derivatives.
- First trimester of pregnancy (use with caution in subsequent trimesters if benefits outweigh risks)
- Active central nervous system diseases
- Severe hepatic impairment
- Severe renal impairment
Drug Interactions
- Alcohol: Disulfiram-like reaction (nausea, vomiting, flushing, headache)
- Coumarin anticoagulants (e.g., warfarin): Increased anticoagulant effect
- Disulfiram: May increase risk of neurotoxicity
- Lithium: Potential for increased lithium levels.
- Phenytoin: Nimorazole may increase phenytoin levels
- Fluorouracil: Nimorazole can enhance fluorouracil toxicity.
Pregnancy and Breastfeeding
- Pregnancy: Avoid during the first trimester. Use with caution in later trimesters only if clearly needed.
- Breastfeeding: Excreted in breast milk. Weigh risks versus benefits. Interrupt breastfeeding or consider an alternative medication.
Drug Profile Summary
- Mechanism of Action: Disrupts DNA synthesis in anaerobic microorganisms and hypoxic tumor cells.
- Side Effects: Nausea, vomiting, headache, metallic taste, peripheral neuropathy (rare).
- Contraindications: Hypersensitivity to nitroimidazoles, first trimester pregnancy, severe hepatic/renal impairment.
- Drug Interactions: Alcohol, coumarin anticoagulants, lithium, disulfiram, phenytoin.
- Pregnancy & Breastfeeding: Avoid in first trimester; caution in later pregnancy and breastfeeding.
- Dosage: Varies depending on indication, usually 500mg - 2g. For radiosensitization: 1.2 g/m² pre-radiotherapy.
- Monitoring Parameters: Liver function tests, complete blood count (especially during prolonged therapy), neurological examination (for peripheral neuropathy).
Popular Combinations
- Nimorazole is sometimes combined with other antibiotics, particularly ofloxacin, for treating mixed infections.
- Used in conjunction with radiotherapy for head and neck cancers.
Precautions
- General Precautions: Assess for allergies, liver and renal function, and history of neurological disorders.
- Specific Populations: Use with caution in pregnancy and breastfeeding, and in patients with hepatic or renal dysfunction.
- Lifestyle Considerations: Avoid alcohol consumption during treatment. Caution with driving/operating machinery if dizziness or other CNS effects occur.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nimorazole?
A: Dosage varies depending on the infection being treated. Please refer to the detailed dosage guidelines provided above.
Q2: What are the common side effects of Nimorazole?
A: Common side effects include nausea, vomiting, headache, dizziness, and a metallic taste in the mouth.
Q3: How does Nimorazole work as a radiosensitizer?
A: It selectively targets hypoxic tumor cells, making them more sensitive to the effects of radiation therapy by enhancing DNA damage.
Q4: Can Nimorazole be used during pregnancy?
A: It should be avoided during the first trimester. Use with caution in the second and third trimesters only if the benefits outweigh the potential risks.
Q5: Are there any drug interactions I should be aware of?
A: Yes. Avoid alcohol consumption during nimorazole treatment. It can also interact with certain medications, such as warfarin and disulfiram.
Q6: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue with your regular schedule.
Q7: How long does a course of Nimorazole treatment usually last?
A: Treatment duration depends on the specific infection and can range from a single dose to several days or weeks.
Q8: Is Nimorazole safe for patients with liver or kidney problems?
A: Caution is advised in patients with hepatic or renal impairment. Dose adjustments may be necessary. Consult a physician.
Q9: Can Nimorazole be used in children?
A: Limited data exists for pediatric use. Weight-based dosing under the guidance of a physician is essential.
This information is current as of February 16, 2025, and is intended for use by qualified medical professionals. It should not be considered medical advice for patients. Always consult updated medical references and guidelines for the most current information.
