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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 symptomatic trichomoniasis.
* **Amebiasis:** Treatment of intestinal amebiasis (amebic dysentery) and extraintestinal amebiasis (e.g., amebic liver abscess).
* **Giardiasis:** Treatment of giardiasis.
* **Anaerobic Bacterial Infections:** Treatment of serious anaerobic bacterial infections (e.g., intra-abdominal infections, skin and soft tissue infections, gynecologic infections, bone and joint infections, central nervous system infections, lower respiratory tract infections, endocarditis). Often used in combination with other agents.
* **Pseudomembranous Colitis:** Alternative agent for *Clostridioides difficile* infection (CDI) in specific circumstances, though vancomycin is preferred for initial episodes.
* **H. pylori Eradication:** Component of multi-drug regimens for *Helicobacter pylori* eradication.
## Adult Dosing
* **Bacterial Vaginosis:**
* Oral: 500 mg twice daily for 7 days OR 2 g as a single dose.
* Vaginal gel 0.75%: 5 g (one applicatorful) inserted intravaginally once daily for 5 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: 500-675 mg three times daily for 5-10 days.
* Extra-intestinal: Oral: 500-675 mg three times daily for 5-10 days, followed by a luminal agent.
* **Giardiasis:**
* Oral: 250 mg three times daily for 5-7 days OR 2 g once daily for 3 days.
* **Anaerobic Bacterial Infections:**
* Oral: 500 mg every 8 hours.
* IV: 500 mg every 8 hours.
* Duration varies based on infection severity and site, typically 7-10 days.
* **Pseudomembranous Colitis (CDI):**
* Oral: 250-500 mg every 6-8 hours. (Vancomycin is generally preferred).
* **H. pylori Eradication (part of triple/quadruple therapy):**
* Oral: Typically 500 mg twice daily in combination regimens.
## Pediatric Dosing
Dosing is highly dependent on indication, weight, and severity. Always consult specific pediatric guidelines.
* **Intestinal Amebiasis:**
* Oral: 35-50 mg/kg/day divided into three doses for 5-10 days (maximum 750 mg/day).
* **Giardiasis:**
* Oral: 15 mg/kg/day divided into three doses for 5-7 days (maximum 250 mg/dose).
* **Anaerobic Bacterial Infections:**
* Oral/IV: 7.5 mg/kg/dose every 8 hours (maximum 400 mg/dose) OR 15 mg/kg/day divided into three doses (maximum 2000 mg/day). Duration varies.
## Dose Adjustments
* **Hepatic Impairment:** Use with caution. Reduce dose by 50% in severe hepatic disease.
* **Renal Impairment:** No dose adjustment is generally recommended for intermittent hemodialysis or peritoneal dialysis. For CrCl < 10 mL/min, consider reducing the maintenance dose by 50% and administering it at the usual intervals.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazoles.
* Use within 14 days of disulfiram administration (due to potential for disulfiram-like reaction).
* Active central nervous system disease.
* First trimester of pregnancy (relative contraindication, particularly for systemic use; risk-benefit assessment needed).
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, metallic taste, abdominal pain, headache, dizziness, anorexia.
* **Serious:** Peripheral neuropathy (especially with prolonged use), seizures, encephalopathy, leukopenia, thrombocytopenia, Stevens-Johnson syndrome, toxic epidermal necrolysis, pancreatitis, severe allergic reactions.
* **Disulfiram-like reaction:** With concurrent alcohol intake (flushing, nausea, vomiting, tachycardia, palpitations).
* **Darkened urine:** Harmless but can be alarming.
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction. Avoid alcohol during treatment and for at least 3 days after.
* **Warfarin:** Metronidazole can potentiate the anticoagulant effect. 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:** May decrease metronidazole efficacy by increasing its metabolism.
* **Disulfiram:** Avoid concurrent use due to potential for acute psychotic reactions.
## Monitoring
* **Clinical response:** Assess for improvement in signs and symptoms of infection.
* **Neurological status:** Monitor for signs of peripheral neuropathy or central nervous system effects, especially with prolonged therapy.
* **Complete blood count (CBC):** Consider monitoring CBC, especially in patients receiving prolonged or high-dose therapy, for potential leukopenia.
* **Liver function tests (LFTs):** Monitor in patients with hepatic impairment.
* **INR:** Monitor closely if co-administered with warfarin.
## Clinical Pearls
* Metronidazole has activity against anaerobic bacteria and protozoa.
* A metallic taste is common and can affect medication adherence.
* Advise patients to avoid alcohol during therapy and for at least 72 hours after completion due to the risk of a disulfiram-like reaction.
* Peripheral neuropathy can be irreversible; discontinue therapy if symptoms develop.
* Consider prescribing a luminal agent (e.g., diloxanide furoate) after treatment for invasive amebiasis to eradicate residual intestinal parasites.
* For IV use, metronidazole is often compatible with normal saline and dextrose 5% in water. Check specific compatibility information.
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**Educational Disclaimer:** This information is intended for healthcare professionals and is not a substitute for current prescribing information. Always verify the most up-to-date drug information with the product manufacturer's package insert or other reliable clinical resources.
