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# Metronidazole
## Overview
Metronidazole is an antibiotic and antiprotozoal agent effective against anaerobic bacteria and certain parasites.
## Primary Indications
* **Bacterial Vaginosis:** Treatment of bacterial vaginosis.
* **Trichomoniasis:** Treatment of trichomoniasis.
* **Giardiasis:** Treatment of giardiasis.
* **Amebiasis:** Treatment of amebiasis.
* **Anaerobic Infections:** Treatment of serious anaerobic bacterial infections (e.g., intra-abdominal infections, skin and soft tissue infections, gynecologic infections, bacterial vaginosis, pelvic inflammatory disease, endocarditis, bone and joint infections, central nervous system infections, lower respiratory tract infections, and *Clostridioides difficile*-associated diarrhea). Often used in combination therapy.
* **H. pylori Eradication:** Component of multi-drug regimens for *Helicobacter pylori* eradication.
* **Surgical Prophylaxis:** Surgical prophylaxis in specific procedures (e.g., colorectal surgery).
## Adult Dosing
Dosing varies significantly by indication and formulation (oral, IV, vaginal, topical).
* **Bacterial Vaginosis:**
* Oral: 500 mg orally twice daily for 7 days, OR 2 g orally as a single dose.
* Vaginal Gel 0.75%: One applicatorful (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 375 mg orally twice daily for 7 days.
* **Giardiasis:**
* Oral: 250 mg orally three times daily for 5 days.
* **Amebiasis:**
* Oral: 500-750 mg orally three times daily for 5-10 days.
* IV: 500 mg every 8 hours for 5-10 days.
* **Anaerobic Infections (Serious):**
* Oral: 500 mg every 8 hours.
* IV: 15 mg/kg loading dose, then 7.5 mg/kg every 6-8 hours (maximum 4 g/day).
* **H. pylori Eradication (part of triple/quadruple therapy):**
* Oral: Typically 250-500 mg orally twice or three times daily in combination with other agents for 10-14 days.
* **Surgical Prophylaxis (Colorectal):**
* Oral/IV: 1 g orally or IV 1-2 hours before surgery, or 500 mg every 8 hours starting before surgery and continuing for up to 24 hours postoperatively.
## Pediatric Dosing
Dosing is typically weight-based and depends on the indication and severity.
* **Amebiasis:**
* Oral: 35-50 mg/kg/day divided into 3 doses for 5-10 days (maximum 750 mg/dose or 2 g/day).
* **Giardiasis:**
* Oral: 15-30 mg/kg/day divided into 3 doses for 5 days (maximum 250 mg/dose or 2 g/day).
* **Anaerobic Infections (Serious):**
* IV: 7.5 mg/kg every 8 hours. Loading dose of 15 mg/kg may be used for severe infections.
## Dose Adjustments
* **Hepatic Impairment:** Use with caution. Reduce total daily dose by 50% in patients with severe hepatic disease.
* **Renal Impairment:** No dose adjustment generally needed for oral or IV formulations for mild to moderate renal impairment. For severe renal impairment (CrCl < 30 mL/min), consider reducing the dose by 50% if administered every 8 hours. For IV administration, consider extending the interval or reducing the dose. Hemodialysis may remove metronidazole; consider redosing after dialysis.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazole derivatives.
* Concomitant use of disulfiram or alcohol during therapy and for at least 3 days after discontinuation.
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, abdominal pain, metallic taste, anorexia, glossitis, stomatitis.
* **Serious:** Peripheral neuropathy (can be irreversible), central nervous system effects (seizures, encephalopathy, cerebellar dysfunction), Stevens-Johnson syndrome, toxic epidermal necrolysis, leukopenia, thrombopenia, pancreatitis, opportunistic fungal infections.
* **Alcohol Interaction:** Disulfiram-like reaction (flushing, headache, nausea, vomiting, sweating, palpitations, dyspnea).
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction. Avoid alcohol during and for at least 3 days after treatment.
* **Warfarin:** Potentiates anticoagulant effect; monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** May increase serum lithium levels, potentially leading to toxicity. Monitor lithium levels.
* **Phenytoin/Phenobarbital:** May decrease metronidazole efficacy.
* **Disulfiram:** Concurrent use is contraindicated due to potential for psychotic reactions.
* **Cyclosporine:** May increase cyclosporine levels. Monitor cyclosporine levels.
* **5-Fluorouracil (5-FU):** May increase the toxicity of 5-FU.
## Monitoring
* Monitor for signs and symptoms of neuropathy (numbness, tingling, pain).
* Monitor for signs of CNS toxicity.
* Monitor blood counts if prolonged therapy or high doses are used.
* Monitor INR if used concurrently with warfarin.
* Monitor lithium levels if used concurrently with lithium.
## Clinical Pearls
* A metallic taste is a common side effect and can be managed by good oral hygiene or chewing sugar-free gum.
* The disulfiram-like reaction with alcohol is severe; emphasize strict avoidance.
* For *C. difficile*-associated diarrhea, oral metronidazole is generally reserved for mild-to-moderate disease or as an alternative to oral vancomycin.
* IV metronidazole should be infused slowly.
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*This information is intended for healthcare professionals and does not replace current prescribing information. Always consult the most recent product labeling and clinical guidelines.*
