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# Metronidazole
## Overview
Metronidazole is an antibiotic and antiprotozoal agent effective against anaerobic bacteria and certain protozoa.
## Primary Indications
* **Bacterial Vaginosis:** Treatment of bacterial vaginosis.
* **Trichomoniasis:** Treatment of *Trichomonas vaginalis* infection.
* **Amebiasis:** Treatment of intestinal and extraintestinal amebiasis.
* **Giardiasis:** Treatment of *Giardia lamblia* infection.
* **Anaerobic Bacterial Infections:** Treatment of serious infections caused by susceptible anaerobic bacteria (e.g., intra-abdominal infections, gynecologic infections, skin and soft tissue infections, bone and joint infections, CNS infections, lower respiratory tract infections, endocarditis). Often used in combination therapy.
* **Pseudomembranous Colitis:** Treatment of *Clostridioides difficile*-associated diarrhea.
* **Surgical Prophylaxis:** Prophylaxis against anaerobic infection in specific surgical procedures (e.g., colorectal surgery).
* **H. pylori Eradication:** Part of multi-drug regimens for *Helicobacter pylori* eradication.
## Adult Dosing
Dosing varies significantly by indication.
* **Bacterial Vaginosis:**
* Vaginal gel: 0.75% gel, one applicatorful (5g) intravaginally once daily for 5 days.
* Oral: 500 mg twice daily for 7 days.
* **Trichomoniasis:**
* Oral: A single 2-gram dose, or 250 mg twice daily for 7 days, or 375 mg twice daily for 7 days.
* **Amebiasis:**
* Intestinal: 500-750 mg orally 3 times daily for 7-10 days.
* Extra-intestinal (e.g., liver abscess): 500-750 mg orally 3 times daily for 7-10 days, or 375-750 mg IV every 8 hours. Consider initial IV therapy followed by oral.
* **Giardiasis:**
* Oral: 250 mg 3 times daily for 5-7 days.
* **Anaerobic Bacterial Infections:**
* Oral: 500 mg every 8 hours.
* IV: 500 mg every 8 hours, or 15 mg/kg initial dose followed by 7.5 mg/kg every 8 hours.
* Maximum dose: Generally 4 grams per day.
* **Pseudomembranous Colitis:**
* Oral: 500 mg every 8 hours.
* **Surgical Prophylaxis:**
* Oral: 1 gram orally 1-2 hours before surgery, then 500 mg every 8 hours for up to 24 hours post-operatively.
* IV: 500 mg IV every 8 hours.
* **H. pylori Eradication:**
* Oral: Typically 500 mg twice daily as part of a multi-drug regimen (e.g., with bismuth and tetracycline).
## Pediatric Dosing
Dosing is weight-based and depends on the indication.
* **Serious Anaerobic Infections:**
* Oral/IV: 7.5 mg/kg/dose every 8 hours.
* Maximum dose: 4 grams per day.
* **Amebiasis:**
* Oral: 35-50 mg/kg/day divided into 3 doses for 7-10 days. Maximum 750 mg/dose.
* **Giardiasis:**
* Oral: 5 mg/kg/dose every 8 hours for 5-7 days. Maximum 250 mg/dose.
* **Bacterial Vaginosis:** Not typically used in children.
* **Trichomoniasis:** Not typically used in children.
## Dose Adjustments
* **Hepatic Impairment:** Use with caution. In severe hepatic impairment, consider reducing the dose by 30-50% and monitoring for toxicity.
* **Renal Impairment:** No dose adjustment typically needed for moderate renal impairment. In severe renal impairment (CrCl < 10 mL/min), consider reducing the maintenance dose by 50% if the duration of therapy is prolonged. Hemodialysis effectively removes metronidazole; administer dose after dialysis.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazole derivatives.
* Concurrent use of disulfiram.
* First trimester of pregnancy (relative contraindication, weigh risks and benefits).
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, abdominal pain, metallic taste, headache, dizziness.
* **Serious:**
* **Neurologic:** Peripheral neuropathy (paresthesia, numbness), seizures, encephalopathy, cerebellar toxicity (ataxia, dysarthria, nystagmus).
* **Hypersensitivity:** Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis.
* **Hematologic:** Neutropenia, thrombocytopenia.
* **Hepatic:** Liver injury.
* **Gastrointestinal:** Pancreatitis.
* **Other:** Darkening of urine (harmless), candidiasis (oral or vaginal).
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction (flushing, nausea, vomiting, tachycardia, shortness of breath). Advise patients to avoid alcohol during therapy and for at least 72 hours after completion.
* **Disulfiram:** Risk of psychotic reactions. Avoid concurrent use.
* **Warfarin:** Potentiates anticoagulant effect. Monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** May increase lithium levels, leading to toxicity. Monitor lithium levels.
* **Phenytoin, Phenobarbital:** May decrease metronidazole levels.
* **5-Fluorouracil (5-FU):** May increase the toxicity of 5-FU.
* **Cyclosporine:** Metronidazole may increase cyclosporine levels.
## Monitoring
* **Clinical response:** Monitor for improvement in signs and symptoms of infection.
* **Adverse effects:** Assess for neurological symptoms, gastrointestinal upset, and signs of hypersensitivity.
* **Hepatic function:** Monitor liver function tests in patients with severe hepatic impairment or those on long-term therapy.
* **Renal function:** Monitor if indicated by patient's condition.
* **INR:** Monitor closely if co-administered with warfarin.
* **Lithium levels:** Monitor if co-administered with lithium.
## Clinical Pearls
* Metronidazole has a metallic taste which can decrease compliance.
* Advise patients to avoid alcohol during treatment and for 72 hours after.
* Peripheral neuropathy is a serious adverse effect, especially with prolonged use. Discontinue if symptoms occur.
* Metronidazole can be used IV or orally for many anaerobic infections.
* For *H. pylori* eradication, compliance with multi-drug regimens is crucial.
This information is intended for healthcare professionals and does not replace consultation with current prescribing information or clinical guidelines. Always verify current dosing and safety information with official drug references.
