Usage
Metronidazole is prescribed for a range of bacterial and parasitic infections. It’s effective against anaerobic bacteria (those that thrive without oxygen) and certain protozoa. Specifically, it’s used to treat:
- Bacterial vaginosis: An overgrowth of bacteria in the vagina.
- Trichomoniasis: A sexually transmitted infection caused by a parasite.
- Amebiasis: An infection caused by the Entamoeba histolytica parasite.
- Giardiasis: An infection of the small intestine caused by the Giardia lamblia parasite.
- Anaerobic bacterial infections: Such as those affecting the abdomen, skin, bone, joints, and respiratory tract.
Pharmacological Classification: Antibiotic and antiprotozoal.
Mechanism of Action: Metronidazole enters the bacterial/protozoal cell and disrupts DNA synthesis and structure, ultimately leading to cell death.
Alternate Names
Metronidazole is sometimes known internationally as just “metronidazole.”
Brand Names: Flagyl, Flagyl ER, Metrogel, MetroCream, Noritate
How It Works
Pharmacodynamics: Metronidazole’s action disrupts DNA structure and function in susceptible anaerobic bacteria and protozoa. This damage inhibits nucleic acid synthesis, resulting in microbial cell death.
Pharmacokinetics:
- Absorption: Well-absorbed orally. Peak serum concentrations reached in 1-2 hours.
- Distribution: Widely distributed throughout the body, including cerebrospinal fluid, abscesses, and other tissues.
- Metabolism: Metabolized in the liver, primarily by oxidation.
- Elimination: Primarily excreted in the urine, with a small amount in feces. Elimination half-life is approximately 8 hours.
Mode of Action (Cellular/Molecular): Metronidazole undergoes intracellular reductive activation by anaerobic organisms. The reduced metabolites interact with DNA, forming unstable molecules and causing strand breakage, ultimately leading to cell death.
Receptor Binding, Enzyme Inhibition or Neurotransmitter Modulation: Not specifically applicable. Its primary mechanism is direct DNA damage.
Elimination Pathways: Primarily renal excretion; some hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Bacterial infections: 500 mg every 8 hours or 7.5 mg/kg every 6 hours for 7-10 days (not exceeding 4 g/day).
- Amebiasis: 500-750 mg three times daily for 5-10 days.
- Trichomoniasis: Single 2 g oral dose, or 250 mg three times daily for 7 days, or 375 mg twice daily for 7 days.
- Bacterial Vaginosis: 750 mg once daily for 7 days or 500 mg twice daily for 7 days, or 2 g single dose.
Children:
- Amebiasis: 35-50 mg/kg/day divided into three doses for 10 days.
- Other Infections: 7.5 mg/kg every 6 hours for 7-10 days (not exceeding 4 g/day).
- Neonates (< 8 weeks): 15 mg/kg once daily or 7.5 mg/kg every 12 hours.
Special Cases:
- Elderly Patients: Dosage adjustment may be necessary due to decreased hepatic function. Monitor closely.
- Patients with Renal Impairment: Caution advised; adjust dose in severe renal impairment.
- Patients with Hepatic Dysfunction: Dose reduction required in moderate to severe hepatic impairment.
- Patients with Comorbid Conditions: Individualized dosing may be needed based on specific conditions.
Clinical Use Cases
Dosage recommendations for specific medical settings are the same as the standard dosage guidelines and should be adjusted based on the patient’s condition and other factors like age, weight, and organ function.
Dosage Adjustments
Dose modifications may be necessary in cases of renal or hepatic dysfunction. Close monitoring of drug levels and patient response is essential.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, metallic taste, headache, dizziness.
Rare but Serious Side Effects:
Seizures, peripheral neuropathy (numbness or tingling in extremities), encephalopathy (brain dysfunction), Stevens-Johnson syndrome (severe skin reaction).
Long-Term Effects:
Peripheral neuropathy can persist even after discontinuation.
Adverse Drug Reactions (ADR):
Severe skin reactions, anaphylaxis, blood dyscrasias (abnormal blood cell counts).
Contraindications
- Hypersensitivity to metronidazole or other nitroimidazoles.
- First trimester of pregnancy (generally avoided, though may be used if benefit outweighs risk).
- Active central nervous system disease (use with caution).
- Blood dyscrasias (use with caution).
Drug Interactions
- Alcohol: Disulfiram-like reaction (flushing, headache, nausea, vomiting).
- Disulfiram: May cause psychotic reactions.
- Warfarin and other coumarin anticoagulants: Enhanced anticoagulant effect.
- Lithium: Increased lithium levels.
- Busulfan: Increased busulfan levels.
- CYP450 interactions: May inhibit metabolism of certain drugs metabolized by this enzyme system.
Pregnancy and Breastfeeding
- Pregnancy: Generally considered safe after the first trimester, but used only when clearly needed.
- Breastfeeding: Small amounts are present in breast milk. May temporarily interrupt breastfeeding or monitor infant for side effects (e.g., diarrhea, thrush).
Drug Profile Summary
- Mechanism of Action: Disrupts DNA synthesis in anaerobic bacteria and protozoa.
- Side Effects: Nausea, vomiting, metallic taste, headache, dizziness; rarely: seizures, peripheral neuropathy.
- Contraindications: Hypersensitivity, first trimester pregnancy.
- Drug Interactions: Alcohol, disulfiram, warfarin, lithium.
- Pregnancy & Breastfeeding: Generally safe after first trimester; small amounts in breast milk.
- Dosage: Varies depending on infection; see detailed dosage section.
- Monitoring Parameters: CBC, liver function tests, neurological status (with prolonged use).
Popular Combinations
Metronidazole is often used in combination with other antibiotics for polymicrobial infections, particularly those involving anaerobic bacteria. One example is its use with amoxicillin and a proton pump inhibitor for the treatment of Helicobacter pylori infections.
Precautions
- General Precautions: Assess for allergies, hepatic and renal function. Monitor for neurologic symptoms.
- Specific Populations: See “Special Cases” under Dosage.
- Lifestyle Considerations: Avoid alcohol during treatment and for at least 3 days after completion. Avoid products containing propylene glycol.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Metronidazole?
A: Dosage varies depending on the infection and patient characteristics. See the detailed Dosage section above.
Q2: Can Metronidazole be used during pregnancy?
A: Generally avoided in the first trimester. Can be used after the first trimester if the benefit outweighs the risk.
Q3: What are the common side effects of Metronidazole?
A: Nausea, vomiting, diarrhea, metallic taste, headache, and dizziness.
Q4: Can I drink alcohol while taking Metronidazole?
A: No. Alcohol should be avoided during treatment and for at least 3 days after the last dose due to the risk of a disulfiram-like reaction.
Q5: What should I do if I experience side effects?
A: Contact your doctor or healthcare provider to discuss management strategies or alternative treatments.
Q6: How long does it take for Metronidazole to work?
A: Improvement is typically seen within a few days, but the full course of treatment should be completed.
Q7: Can Metronidazole be used to treat bacterial vaginosis?
A: Yes, Metronidazole is a common and effective treatment for bacterial vaginosis.
Q8: Does Metronidazole interact with other medications?
A: Yes, Metronidazole can interact with certain medications, such as warfarin, lithium, and disulfiram. Be sure to inform your doctor about all other medications you are taking.
Q9: 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 your regular dosing schedule. Do not take a double dose to make up for a missed one.
