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# Metronidazole
## Overview
Metronidazole is a synthetic nitroimidazole antibiotic and antiprotozoal agent effective against anaerobic bacteria and certain protozoa.
## Primary Indications
* **Bacterial Vaginosis:** Treatment of bacterial vaginosis.
* **Trichomoniasis:** Treatment of trichomoniasis.
* **Amebiasis:** Treatment of amebiasis (intestinal and extraintestinal).
* **Giardiasis:** Treatment of giardiasis.
* **Anaerobic Bacterial Infections:** Treatment of serious anaerobic bacterial infections (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 *Clostridium difficile*-associated diarrhea.
* **Surgical Prophylaxis:** Prophylaxis against anaerobic infection in specific surgical procedures.
* **Helicobacter pylori Eradication:** Part of multi-drug regimens for *H. pylori* eradication.
## Adult Dosing
* **Bacterial Vaginosis:**
* Oral: 500 mg orally twice daily for 7 days, OR 2 g orally as a single dose.
* Vaginal Gel (0.75%): 5 g intravaginally once daily for 5 days.
* **Trichomoniasis:**
* Oral: 2 g orally as a single dose, OR 250 mg orally three times daily for 7 days, OR 500 mg orally twice daily for 7 days.
* **Amebiasis:**
* Intestinal: 500-750 mg orally every 8 hours for 5-10 days.
* Extra-intestinal (e.g., liver abscess): 500-750 mg orally every 8 hours for 5-10 days, or 1.5 g orally once daily or in 3 divided doses for 5-10 days.
* **Giardiasis:**
* Oral: 250 mg orally three times daily for 5 days.
* **Anaerobic Bacterial Infections:**
* Oral/IV: 500 mg every 8 hours. Doses may be increased to 750-1000 mg every 8 hours depending on severity and susceptibility. Usual duration 7-10 days.
* IV: Dosing for severe infections is often higher, but consult specific institutional protocols.
* **Pseudomembranous Colitis:**
* Oral: 500 mg orally every 8 hours. Vancomycin is often preferred for initial episodes.
* **Surgical Prophylaxis:**
* Oral/IV: 1 g orally or IV 1-2 hours before surgery, followed by 500 mg orally or IV every 8 hours for up to 24 hours postoperatively.
* **H. pylori Eradication:**
* Oral: Commonly 500 mg orally twice daily in combination with other agents (e.g., PPI, amoxicillin or clarithromycin) for 10-14 days.
## Pediatric Dosing
Dosing is highly variable depending on the indication and patient weight.
* **General Anaerobic Infections:**
* Oral/IV: 15-30 mg/kg/day in 3 divided doses. Maximum daily dose is typically 2.2 g (or 400 mg per dose for oral suspensions).
* **Amebiasis:**
* Oral: 35-50 mg/kg/day in 3 divided doses for 5-10 days. Maximum 750 mg/dose.
* **Giardiasis:**
* Oral: 15 mg/kg/day in 3 divided doses for 5 days. Maximum 250 mg/dose.
* **Trichomoniasis:**
* Oral: 15 mg/kg/day in 3 divided doses for 7 days. Maximum 250 mg/dose.
*Note: Dosing for neonates requires careful consideration of gestational age and weight, and often involves specialized protocols.*
## Dose Adjustments
* **Renal Impairment:** No dose adjustment is typically needed in renal impairment. However, metronidazole is removed by hemodialysis and peritoneal dialysis; if given during dialysis, supplemental doses may be required.
* **Hepatic Impairment:** Dose reduction may be necessary in severe hepatic impairment. Consider reducing the dose by one-third to one-half and monitoring for toxicity.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazole derivatives.
* Active CNS disease.
* First trimester of pregnancy (risk vs. benefit assessment, especially for non-emergency indications).
## 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, neutropenia, pancreatitis, dark or reddish-brown urine.
* **Disulfiram-like reaction:** A severe reaction (flushing, nausea, vomiting, tachycardia, shortness of breath) can occur if alcohol is consumed during and for at least 3 days after treatment.
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction (see Adverse Effects). Advise patients to avoid alcohol.
* **Warfarin:** Metronidazole can potentiate the anticoagulant effect of warfarin. Monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** Metronidazole may increase serum lithium levels, potentially leading to toxicity. Monitor lithium levels.
* **Phenytoin, Phenobarbital:** These drugs can decrease the serum concentration of metronidazole.
* **Cyclosporine:** Metronidazole may increase serum cyclosporine levels. Monitor cyclosporine levels.
* **5-Fluorouracil (5-FU):** Metronidazole may increase the toxicity of 5-FU. Avoid concurrent use or monitor closely.
## Monitoring
* Monitor for signs and symptoms of neuropathy (numbness, tingling, pain, weakness).
* Monitor complete blood counts if prolonged therapy or high doses are used.
* Monitor for signs of CNS toxicity (seizures, encephalopathy).
* Assess therapeutic response based on clinical signs and symptoms.
* Monitor INR if the patient is on warfarin.
## Clinical Pearls
* Advise patients to avoid alcohol during and for at least 3 days after therapy to prevent a disulfiram-like reaction.
* The metallic taste is a common, though often transient, side effect.
* Neuropathy can be irreversible; discontinue if symptoms arise and consider alternative agents for prolonged therapy.
* Metronidazole can cause dark or reddish-brown urine, which is harmless.
* For *H. pylori* eradication, adherence to the multi-drug regimen is crucial for success.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant literature for complete details and to ensure patient safety. Dosing may vary based on specific patient factors and local protocols.*
