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# Metronidazole
## Overview
Metronidazole is a nitroimidazole antibiotic effective against anaerobic bacteria and certain protozoa.
## Primary Indications
* **Bacterial Vaginosis:** Treatment of bacterial vaginosis.
* **Trichomoniasis:** Treatment of *Trichomonas vaginalis* infections.
* **Amebiasis:** Treatment of intestinal and extraintestinal amebiasis.
* **Giardiasis:** Treatment of *Giardia lamblia* infections.
* **Anaerobic Bacterial Infections:** Treatment of serious anaerobic bacterial infections, often in combination with other agents. Examples include intra-abdominal infections, gynecologic infections, skin and soft tissue infections, and bone and joint infections.
* **Pseudomembranous Colitis:** Treatment of *Clostridioides difficile*-associated diarrhea.
* **Surgical Prophylaxis:** Preoperative prophylaxis for colorectal surgery.
* **H. pylori Eradication:** Part of combination therapy for *Helicobacter pylori* eradication.
## Adult Dosing
Dosing varies significantly by indication.
* **Bacterial Vaginosis:**
* Oral: 500 mg twice daily for 7 days, OR 2 g as a single dose.
* Vaginal gel 0.75%: One applicatorful (5 g) inserted vaginally once daily for 5 days.
* **Trichomoniasis:**
* Oral: 2 g as a single dose, OR 250 mg three times daily for 7 days, OR 375 mg twice daily for 7 days.
* **Amebiasis:**
* Intestinal: 500-650 mg three times daily for 5-10 days.
* Extra-intestinal: 500-650 mg three times daily for 5-10 days, followed by a luminal amebicide.
* **Giardiasis:**
* Oral: 250 mg three times daily for 5 days, OR 2 g once daily for 3 days.
* **Anaerobic Bacterial Infections (Non-CNS):**
* IV: 500 mg every 8 hours.
* Oral: 500 mg every 8 hours.
* Dosage may be increased to 750 mg to 1 g every 8 hours for severe infections, but this is less common.
* **Pseudomembranous Colitis:**
* Oral: 500 mg three times daily for 10-14 days. (Vancomycin is generally preferred for initial episodes and often for severe cases).
* **Surgical Prophylaxis:**
* IV: 1 g as a single dose given within 1 hour before surgery.
* **H. pylori Eradication:**
* Oral: Typically 500 mg twice daily in combination with other agents for 10-14 days.
## Pediatric Dosing
Dosing in children is weight-based and depends on the indication.
* **General Anaerobic Infections:**
* IV/Oral: 15 mg/kg/day divided into 3 doses, not to exceed 40 mg/kg/day or the adult dose of 4 g/day.
* **Amebiasis:**
* IV/Oral: 35-50 mg/kg/day divided into 3 doses for 5-10 days. Maximum 750 mg/dose or 4 g/day.
* **Giardiasis:**
* IV/Oral: 15 mg/kg/day divided into 3 doses for 5 days. Maximum 250 mg/dose or 750 mg/day.
* **Trichomoniasis:**
* Oral: 15 mg/kg/day divided into 2 doses for 7 days. Maximum 250 mg/dose or 2 g total.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment generally recommended for hemodialysis or peritoneal dialysis. However, monitor for adverse effects.
* **Hepatic Impairment:** Use with caution. Dose reduction may be necessary in severe hepatic insufficiency.
## Contraindications
* Known hypersensitivity to metronidazole or other nitroimidazole derivatives.
* First trimester of pregnancy (though debated, generally avoided unless essential).
* Concurrent use of disulfiram (within 2 weeks).
## Adverse Effects
* **Common:** Nausea, vomiting, metallic taste, anorexia, abdominal distress, diarrhea, headache, dizziness.
* **Serious:**
* **Neurologic:** Peripheral neuropathy (especially with prolonged use), seizures, encephalopathy, aseptic meningitis, cerebellar dysfunction.
* **Hypersensitivity:** Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis.
* **Hematologic:** Neutropenia, thrombocytopenia.
* **Hepatotoxicity:** Liver damage.
* **Gastrointestinal:** Pancreatitis.
* **Other:** Darkened urine (harmless), dyspareunia (vaginal gel).
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction (flushing, nausea, vomiting, tachycardia, shortness of breath). Advise patients to avoid alcohol during and for at least 3 days after therapy.
* **Disulfiram:** Avoid concurrent use due to risk of psychosis and confusion.
* **Warfarin:** Potentiates anticoagulant effect; increased INR and bleeding risk. Monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** May increase serum lithium levels, leading to toxicity. Monitor lithium levels.
* **Phenytoin/Phenobarbital:** May decrease metronidazole efficacy.
* **Cyclosporine:** May increase cyclosporine levels. Monitor cyclosporine levels.
* **5-Fluorouracil (5-FU):** Increased toxicity of 5-FU.
## Monitoring
* Monitor for signs and symptoms of neurotoxicity (numbness, tingling, dizziness, seizures) especially with prolonged therapy.
* Monitor for hypersensitivity reactions.
* Monitor INR if used with warfarin.
* Monitor lithium levels if co-administered.
* Monitor for effectiveness, especially for anaerobic infections and protozoal infestations.
## Clinical Pearls
* The metallic taste is common and may lead to decreased oral intake.
* Advise patients to avoid alcohol during and for 3 days after treatment to prevent a disulfiram-like reaction.
* Oral metronidazole has an unpleasant taste; consider refrigeration or flavoring if palatability is an issue.
* For parenteral administration, dilute reconstituted solutions before IV infusion.
* Considered a "B" pregnancy category drug, generally avoided in the first trimester. Use in the second and third trimesters only if clearly needed.
* Discontinue therapy if peripheral neuropathy or other signs of neurotoxicity develop.
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**Disclaimer:** This information is intended for healthcare professionals and does not replace comprehensive drug information resources. Always verify current prescribing information, guidelines, and local protocols before making clinical decisions.
