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# Metronidazole
## Overview
Metronidazole is a synthetic nitroimidazole antibiotic with activity against anaerobic bacteria and certain protozoa.
## Primary Indications
* **Bacterial Vaginosis:** Treatment of bacterial vaginosis.
* **Trichomoniasis:** Treatment of symptomatic 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 with other antibiotics.
* **_Clostridioides difficile_ Infection (CDI):** Treatment of mild-to-moderate CDI.
* **Surgical Prophylaxis:** Prophylaxis against anaerobic infection in specific surgical procedures (e.g., colorectal surgery).
* **Helicobacter pylori Eradication:** Part of multi-drug regimens for _H. pylori_ eradication.
## Adult Dosing
* **Bacterial Vaginosis:**
* Vaginal gel 0.75%: Insert 5 g vaginally once daily for 5 days.
* Oral: 500 mg twice daily for 7 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: Oral 500-750 mg every 8 hours for 5-10 days.
* Extra-intestinal (e.g., liver abscess): Oral 500-750 mg every 8 hours for 5-10 days, or IV 500 mg every 8 hours.
* **Giardiasis:**
* Oral: 250 mg three times daily for 5-7 days.
* **Anaerobic Bacterial Infections:**
* Oral: 500 mg every 8 hours.
* IV: 500 mg every 8 hours.
* Duration varies depending on severity and site of infection, typically 7-14 days.
* **_Clostridioides difficile_ Infection (CDI):**
* Oral: 500 mg every 8 hours for 10-14 days.
* **Surgical Prophylaxis:**
* Oral: 1 g as a single dose 1 hour before surgery.
* IV: 1 g as a single dose 1 hour before surgery, or 500 mg every 8 hours beginning preoperatively and continuing for up to 12 hours postoperatively.
* **_H. pylori_ Eradication:**
* Oral: Typically 500 mg twice daily in combination with other agents (e.g., proton pump inhibitor and amoxicillin or clarithromycin) for 10-14 days.
## Pediatric Dosing
Dosing is often weight-based and depends on the indication and severity of infection. Consult specific pediatric guidelines or drug compendia.
* **Amebiasis:**
* Oral: 35-50 mg/kg/day divided into 3 doses for 5-10 days (maximum 750 mg/dose).
* **Giardiasis:**
* Oral: 15 mg/kg/day divided into 3 doses for 5-7 days (maximum 250 mg/dose).
* **Anaerobic Bacterial Infections:**
* Oral: 7.5-15 mg/kg/day divided into 3 doses.
* IV: 7.5-15 mg/kg/dose every 8 hours (maximum 15 mg/kg/dose or 4 g/day, whichever is less).
## Dose Adjustments
* **Hepatic Impairment:** Reduce dose by 50% in severe hepatic impairment. Avoid use in hepatic encephalopathy.
* **Renal Impairment:** No dose adjustment generally needed for routine hemodialysis. For moderate to severe renal impairment (CrCl < 30 mL/min), consider reducing the dose frequency to every 12 hours.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazole derivatives.
* Concurrent use with disulfiram or alcohol (within 3 days).
## Adverse Effects
Common: Nausea, vomiting, diarrhea, metallic taste, headache, dizziness, rash, dark urine.
Serious: Peripheral neuropathy (especially with prolonged use), seizures, Stevens-Johnson syndrome, pancreatitis, encephalopathy, leukopenia, thrombophlebitis (with IV administration).
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction (flushing, nausea, vomiting, tachycardia, dyspnea). Avoid alcohol during and for at least 3 days after treatment.
* **Disulfiram:** Concurrent use can lead to psychotic reactions. Avoid concurrent use.
* **Warfarin:** Metronidazole can potentiate the anticoagulant effect. Monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** Metronidazole can increase serum lithium levels, leading to toxicity. Monitor lithium levels.
* **Phenytoin/Phenobarbital:** May decrease metronidazole levels.
* **5-Fluorouracil (5-FU):** Metronidazole may increase the toxicity of 5-FU.
## Monitoring
* **Clinical response:** Assess for improvement in signs and symptoms of infection.
* **Peripheral neuropathy:** Monitor for numbness, tingling, or pain in extremities, especially with prolonged therapy.
* **Renal and hepatic function:** Especially in patients with pre-existing impairment or those receiving high doses.
* **Lithium levels:** If used concurrently.
* **INR:** If used concurrently with warfarin.
## Clinical Pearls
* The metallic taste is common and can be reduced by taking with food.
* Alcohol consumption must be strictly avoided during treatment and for 72 hours after the last dose due to a disulfiram-like reaction.
* For IV administration, dilute and infuse over 30-60 minutes.
* Metronidazole can cause dark or reddish-brown urine.
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*Disclaimer: This information is intended for healthcare professionals. Please consult the most current prescribing information and relevant guidelines for complete details. Always verify drug information with a trusted resource before making clinical decisions.*
