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# Metronidazole (Metrogyl)
## Overview
Metronidazole is a nitroimidazole antibiotic and antiprotozoal agent.
## Primary Indications
* **Bacterial Vaginosis:** Treatment of vaginal infections.
* **Trichomoniasis:** Treatment of urogenital protozoal infections.
* **Amebiasis:** Treatment of intestinal and extraintestinal amebiasis.
* **Giardiasis:** Treatment of intestinal protozoal infections.
* **Anaerobic Bacterial Infections:** Treatment of intra-abdominal infections, skin and skin structure infections, gynecologic infections, bacterial vaginosis, and certain respiratory tract infections.
* **Prophylaxis:** Surgical prophylaxis, particularly in colorectal surgery.
* **_Clostridioides difficile_ Infection (CDI):** Treatment of CDI (though oral vancomycin or fidaxomicin are generally preferred for initial episodes).
* **Helicobacter pylori Eradication:** Part of combination therapy.
## Adult Dosing
* **Bacterial Vaginosis:**
* Oral: 500 mg twice daily for 7 days.
* Vaginal gel 0.75%: One applicatorful (5g) inserted vaginally once daily for 5 days.
* **Trichomoniasis:**
* Oral: Single dose of 2 grams, or 250 mg three times daily for 7 days, or 500 mg twice daily for 7 days.
* **Amebiasis:**
* Intestinal: 500-750 mg orally every 8 hours for 7-10 days.
* Extra-intestinal (e.g., liver abscess): 500-750 mg orally every 8 hours for 7-10 days, or 50 mg/kg/day IV divided every 8 hours (max 4g/day) for 7-10 days.
* **Giardiasis:**
* Oral: 250 mg three times daily for 5-7 days, or 500 mg twice daily for 5 days.
* **Anaerobic Bacterial Infections:**
* Oral/IV: 500 mg every 8 hours. Usual duration 7-10 days.
* Maximum dose: 4 grams per day.
* **Surgical Prophylaxis (Colorectal):**
* Oral/IV: 1 gram given IV within 12 hours of incision, or 500 mg orally every 8 hours starting prior to surgery. Doses are often repeated intraoperatively if surgery is prolonged (>12 hours). Continue postoperatively for up to 24 hours.
* **CDI:**
* Oral: 500 mg every 8 hours for 10-14 days. (Note: Other agents are often preferred first-line).
* **_H. pylori_ Eradication:**
* Oral: 250-500 mg with meals twice or three times daily in combination with other agents (e.g., bismuth, tetracycline, proton pump inhibitor) for 10-14 days.
## Pediatric Dosing
Dosing is often weight-based and depends on the indication. Consult specific pediatric guidelines or a pediatric infectious disease specialist.
* **Intestinal Amebiasis:**
* Oral: 35-50 mg/kg/day divided into three doses for 7-10 days. Maximum 750 mg/dose.
* **Giardiasis:**
* Oral: 5 mg/kg per dose three times daily for 5 days (max 250 mg/dose).
* **Anaerobic Infections:**
* Oral/IV: 7.5 mg/kg per dose every 8 hours or 15 mg/kg per dose every 12 hours.
* Maximum dose: 4 grams per day.
## Dose Adjustments
* **Renal Impairment:** No dose adjustment typically needed for mild to moderate renal impairment. For severe impairment (CrCl < 10 mL/min), consider extending the dosing interval or reducing the dose, though data is limited. Metronidazole is partially removed by hemodialysis.
* **Hepatic Impairment:** Use with caution in severe hepatic impairment. May require dose reduction, especially with parenteral administration.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazole derivatives.
* Use during the first trimester of pregnancy for non-emergent indications due to theoretical concerns.
* Concurrent use with disulfiram.
* Concurrent use with alcohol (disulfiram-like reaction).
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, abdominal discomfort, metallic taste, headache, dizziness.
* **Serious:** Peripheral neuropathy (especially with prolonged use), seizures, encephalopathy, aseptic meningitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, leukopenia, thrombocytopenia, pancreatitis, dark urine (harmless).
* **Disulfiram-like reaction:** Flushing, headache, nausea, vomiting, chest pain, palpitations, hypotension if taken with alcohol.
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction. Avoid alcohol during treatment and for at least 3 days after discontinuation.
* **Disulfiram:** Potential for psychotic reactions. Avoid concurrent use.
* **Warfarin:** May potentiate anticoagulant effect. Monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** May increase serum lithium levels, leading to toxicity. Monitor lithium levels.
* **Phenobarbital:** May decrease metronidazole levels.
* **5-Fluorouracil (5-FU) and capecitabine:** Metronidazole may increase toxicity of 5-FU by inhibiting its clearance.
* **Busulfan:** Metronidazole may increase busulfan levels.
## Monitoring
* Monitor for signs and symptoms of peripheral neuropathy (numbness, tingling, pain) with prolonged use.
* Monitor for central nervous system effects (dizziness, confusion, seizures).
* Monitor CBC if prolonged therapy or high doses are used.
* Monitor lithium levels if co-administered.
* Monitor INR if co-administered with warfarin.
## Clinical Pearls
* A metallic taste is a common and often bothersome side effect.
* Avoid alcohol during therapy and for at least 72 hours after the last dose due to a disulfiram-like reaction.
* Urine may turn a reddish-brown color, which is harmless.
* For _C. difficile_ infection, oral vancomycin or fidaxomicin are generally preferred over metronidazole for initial episodes.
* Parenteral formulations are generally not interchangeable with oral doses on a mg-per-mg basis; consult specific product information.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant guidelines for complete details.*
