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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 trichomoniasis.
* **Amoebiasis:** Treatment of amoebic infections (intestinal and extraintestinal).
* **Giardiasis:** Treatment of giardiasis.
* **Anaerobic Bacterial Infections:** Treatment of susceptible anaerobic bacterial infections, including intra-abdominal infections, skin and skin structure infections, gynecologic infections, CNS infections, and bone and joint infections. Often used in combination with other agents for polymicrobial infections.
* ***Clostridioides difficile* Infection (CDI):** Historically used for mild to moderate CDI, though vancomycin or fidaxomicin are preferred for initial episodes.
* **Helicobacter pylori Eradication:** Part of multidrug regimens for *H. pylori* eradication.
* **Surgical Prophylaxis:** Prophylaxis against anaerobic infection in specific surgical procedures.
## Adult Dosing
* **Bacterial Vaginosis:**
* Oral: 500 mg orally twice daily for 7 days, or 2 grams as a single oral dose.
* Vaginal Gel 0.75%: 5 grams (one applicatorful) vaginally once daily for 5 days.
* **Trichomoniasis:**
* Oral: 2 grams as a single oral dose, or 250 mg orally three times daily for 7 days, or 500 mg orally twice daily for 7 days.
* **Amoebiasis:**
* Acute Intestinal Amoebiasis (Amoebic Dysentery): 500-750 mg orally three times daily for 5-10 days.
* Extra-intestinal Amoebiasis (e.g., Liver Abscess): 500-750 mg orally three times daily for 5-10 days, followed by a luminal agent (e.g., paromomycin).
* **Giardiasis:** 250 mg orally three times daily for 5-7 days.
* **Anaerobic Bacterial Infections:**
* Oral/IV: 500 mg every 8 hours. Usual duration 7-10 days.
* Maximum dose: Generally, 4 grams per day.
* ***Clostridioides difficile* Infection (CDI):**
* Oral: 500 mg orally three times daily for 10-14 days (consider for mild-to-moderate disease only if other agents are unavailable or contraindicated).
* ***Helicobacter pylori* Eradication:** 500 mg orally twice daily in combination with other agents (e.g., PPI and amoxicillin/clarithromycin) for 10-14 days.
* **Surgical Prophylaxis:**
* Oral/IV: 1 gram orally or IV 1-2 hours before surgery, or 500 mg orally or IV every 8 hours starting 4 hours before surgery and continuing for up to 24 hours postoperatively.
## Pediatric Dosing
Dosing varies significantly by indication and age. Consult specific pediatric guidelines.
* **Bacterial Infections (Non-CNS):** 15-30 mg/kg/day orally or IV divided into 3 doses. Maximum: 4 grams/day.
* **Amoebiasis:**
* Intestinal: 35-50 mg/kg/day orally divided into 3 doses for 5-10 days.
* Extra-intestinal: 50 mg/kg/day orally or IV divided into 3 doses for 5-10 days, followed by a luminal agent.
* **Giardiasis:** 15 mg/kg/day orally divided into 3 doses for 5-7 days. Maximum: 250 mg/dose.
* **Trichomoniasis:** Consult specific pediatric guidelines; generally not recommended for children unless no other options are suitable due to potential for resistance and lack of robust data.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment recommended. Metronidazole and its metabolites are hemodialyzed. If patient is on hemodialysis, consider giving dose after dialysis.
* **Hepatic Impairment:** Use with caution in severe hepatic impairment. Reduce dose by 50% if Child-Pugh score is 10-15 and by 75% if score is >15. Monitor for toxicity.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazoles.
* History of hypersensitivity to related compounds.
* Use in the first trimester of pregnancy for trichomoniasis (risk/benefit assessment required).
* Concomitant use with disulfiram or alcohol.
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, abdominal pain, metallic taste, headache, dizziness, anorexia.
* **Less Common:** Rash, urticaria, pruritus, peripheral neuropathy (especially with prolonged use), seizures, encephalopathy, leukopenia, thrombophlebitis (IV formulation).
* **Rare:** Pancreatitis, optic neuropathy.
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction (flushing, nausea, vomiting, tachycardia, severe headache). Advise patients to avoid alcohol during treatment and for at least 72 hours after completion.
* **Disulfiram:** Avoid concurrent use; may cause psychotic reactions.
* **Warfarin:** Metronidazole can potentiate the anticoagulant effect of warfarin. 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 increase metronidazole metabolism, decreasing efficacy.
* **Cyclosporine:** Metronidazole may increase cyclosporine levels. Monitor cyclosporine levels.
* **5-Fluorouracil (5-FU):** Metronidazole may increase the toxicity of 5-FU.
## Monitoring
* Monitor for signs and symptoms of peripheral neuropathy (numbness, tingling, pain). Discontinue if neuropathy occurs.
* Monitor for central nervous system effects (dizziness, headache, seizures).
* Monitor for hematologic effects (leukopenia) with prolonged or high-dose therapy.
* Monitor INR in patients receiving warfarin.
* Monitor lithium and cyclosporine levels if used concurrently.
## Clinical Pearls
* The metallic taste is a common and often bothersome side effect.
* Advise patients to avoid alcohol during therapy and for at least 72 hours after the last dose.
* IV metronidazole can cause thrombophlebitis; dilute appropriately and infuse slowly.
* For anaerobic infections, metronidazole is often used in combination with other antibiotics that cover aerobic organisms.
* Ensure adequate treatment duration for all indications to prevent recurrence and resistance.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant guidelines for complete and up-to-date details before making clinical decisions.*
