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# Metronidazole
## Overview
Metronidazole is an antimicrobial agent effective against anaerobic bacteria and certain protozoa.
## Primary Indications
* Treatment of trichomoniasis
* Bacterial vaginosis
* Treatment of amebiasis (intestinal and extraintestinal)
* Treatment of giardiasis
* Treatment of anaerobic bacterial infections (e.g., intra-abdominal infections, skin and soft tissue infections, gynecologic infections, bone and joint infections, CNS infections, lower respiratory tract infections, endocarditis)
* Part of combination therapy for *Clostridium difficile* infection (CDI)
* Surgical prophylaxis
## Adult Dosing
* **Trichomoniasis:** 2 grams as a single dose, OR 250 mg orally twice daily for 7 days, OR 375 mg orally twice daily for 7 days.
* **Bacterial Vaginosis:** 500 mg orally twice daily for 7 days, OR 2 grams orally as a single dose.
* **Amebiasis:**
* Intestinal: 500-675 mg orally 3 times daily for 5-10 days.
* Extra-intestinal: 500-675 mg orally 3 times daily for 5-10 days. Follow with a luminal amebicide (e.g., paromomycin or diiodohydroxyquin) for asymptomatic cyst passers.
* **Giardiasis:** 250 mg orally 3 times daily for 5 days, OR 2 grams orally once daily for 3 days.
* **Anaerobic Bacterial Infections:** 500 mg IV or orally every 8 hours. Duration varies by infection site and severity, typically 7-14 days. Maximum dose generally 4 grams daily.
* **Clostridium difficile infection (CDI):** 500 mg orally every 8 hours for 10-14 days (for initial episode, non-severe). IV formulation may be used if oral route is not feasible.
* **Surgical Prophylaxis:** 1 gram IV 1-2 hours before surgery, or 500 mg orally every 8 hours for a total of 3 doses starting before surgery.
## Pediatric Dosing
Dosing varies significantly by indication and age/weight. Consult specific pediatric guidelines.
* **Trichomoniasis/Giardiasis:** Generally 15-50 mg/kg/day divided into 2-3 doses. Maximum 2 grams per day.
* **Bacterial Infections:** 7.5-15 mg/kg/dose IV or orally every 8 hours. Maximum 4 grams daily.
* Specific dosing for amebiasis in children requires careful calculation based on weight and indication.
## Dose Adjustments
* **Renal Impairment:** No dose adjustment generally needed. However, the active metabolite of metronidazole can accumulate in severe renal impairment. Consider reducing dose or extending interval if creatinine clearance is <10 mL/min.
* **Hepatic Impairment:** Reduce dose by 33-50% in severe hepatic insufficiency.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazole derivatives.
* Concurrent use of disulfiram or alcohol within 3 days of last dose (due to disulfiram-like reaction).
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, abdominal discomfort, metallic taste, headache, dizziness.
* **Serious:** Peripheral neuropathy (especially with prolonged use or high doses), seizures, Stevens-Johnson syndrome, erythema multiforme, encephalopathy, leukopenia, thrombophlebitis (with IV administration).
* **Disulfiram-like reaction:** Flushing, nausea, vomiting, tachycardia, palpitations, shortness of breath if alcohol is consumed during or shortly after treatment.
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction. Avoid alcohol during treatment and for at least 3 days after.
* **Disulfiram:** Potential for acute psychotic reactions. Avoid concurrent use.
* **Warfarin:** Increased anticoagulant effect. Monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** Can increase lithium levels, leading to toxicity. Monitor lithium levels.
* **Phenytoin/Phenobarbital:** May decrease metronidazole effectiveness.
* **Fluorouracil (5-FU):** May increase toxicity of 5-FU.
## Monitoring
* Monitor for signs and symptoms of peripheral neuropathy (numbness, tingling, pain).
* Monitor for signs of hypersensitivity reactions.
* Monitor for gastrointestinal side effects.
* Monitor for neurological side effects (dizziness, seizures).
* Monitor white blood cell count, especially in patients receiving prolonged therapy.
* Monitor INR if patient is on warfarin.
## Clinical Pearls
* Metronidazole has a metallic taste which can affect compliance. Taking with food may reduce nausea.
* Avoid alcohol during therapy and for 72 hours after the last dose.
* IV administration can cause thrombophlebitis; use in a dilute solution and rotate infusion sites.
* For *C. difficile* infection, oral therapy is preferred over IV if feasible.
* Prolonged or high-dose use increases the risk of peripheral neuropathy.
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***Disclaimer:** This information is intended for clinical decision support and does not replace professional medical judgment. Always consult the most current prescribing information and relevant clinical guidelines before making treatment decisions.*
