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# Metronidazole
## Overview
Metronidazole is an antibiotic and antiprotozoal agent effective against anaerobic bacteria and certain protozoa.
## Primary Indications
* **Bacterial Vaginosis:** Often used in combination with other agents.
* **Trichomoniasis:** Treatment of *Trichomonas vaginalis*.
* **Giardiasis:** Treatment of *Giardia lamblia*.
* **Amebiasis:** Treatment of invasive amebiasis due to *Entamoeba histolytica*.
* **Anaerobic Bacterial Infections:** Including intra-abdominal infections, gynecologic infections, skin and soft tissue infections, bone and joint infections, CNS infections, and bacteremia.
* ***Clostridioides difficile* Infection (CDI):** Historically used, but vancomycin or fidaxomicin are preferred for initial episodes.
* **Surgical Prophylaxis:** Particularly in colorectal surgery.
* **Helicobacter pylori Eradication:** As part of a multi-drug regimen.
## Adult Dosing
Dosing varies significantly by indication.
* **Bacterial Vaginosis:**
* Oral: 500 mg orally twice daily for 7 days, or 2 g orally as a single dose.
* Vaginal gel (0.75%): Insert one applicatorful (5g) intravaginally once daily for 5 days.
* **Trichomoniasis:** 2 g orally as a single dose, or 250 mg orally three times daily for 7 days.
* **Giardiasis:** 250 mg orally three times daily for 5 days, or 2 g orally once daily for 3 days.
* **Amebiasis:**
* Intestinal amebiasis: 500-750 mg orally three times daily for 5-10 days.
* Hepatic abscess: 500-750 mg orally three times daily for 5-10 days.
* **Anaerobic Bacterial Infections:**
* Typical dose: 500 mg intravenously or orally every 8 hours.
* Maximum dose: Generally not to exceed 4 g per day.
* **CDI:** 500 mg orally three times daily for 10-14 days (consider in specific situations where other agents are contraindicated or unavailable; oral vancomycin or fidaxomicin are preferred).
* **Surgical Prophylaxis:** 1 g orally or intravenously every 8 hours, with the first dose given preoperatively. Doses may be repeated postoperatively as needed.
* ***H. pylori* Eradication:** Commonly 500 mg orally twice daily as part of a regimen (e.g., with omeprazole and clarithromycin/amoxicillin) for 10-14 days.
## Pediatric Dosing
Dosing is weight-based and depends on the indication and severity. Consult specific pediatric guidelines.
* **General Anaerobic Infections:** 15-30 mg/kg/day orally or IV divided into 3 doses. Maximum: 4 g/day.
* **Trichomoniasis:** Not recommended in children.
* **Giardiasis:** 5 mg/kg/dose orally every 8 hours for 5 days. Maximum: 250 mg/dose.
* **Amebiasis:** 35-50 mg/kg/day orally or IV divided into 3 doses for 5-10 days. Maximum: 750 mg/dose.
## Dose Adjustments
* **Hepatic Impairment:** Reduce dose by 30-50% in severe hepatic impairment.
* **Renal Impairment:** No dose adjustment typically needed for hemodialysis or peritoneal dialysis. In severe renal impairment (CrCl < 10 mL/min), consider reducing the maintenance dose by 50% and administering it every 12 hours.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazole derivatives.
* Use in the first trimester of pregnancy for trichomoniasis (alternative treatments are preferred).
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, abdominal pain, metallic taste, headache, dizziness, dark urine.
* **Serious:** Peripheral neuropathy (especially with prolonged use), seizures, encephalopathy, aseptic meningitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pancreatitis, hepatotoxicity, optic neuropathy.
* **Disulfiram-like reaction:** With alcohol.
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction (flushing, nausea, vomiting, tachycardia, headache). Advise patients to avoid alcohol during and for at least 3 days after metronidazole therapy.
* **Warfarin:** Potentiates anticoagulant effect. Monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** Metronidazole may increase lithium levels, leading to toxicity. Monitor lithium levels.
* **Phenytoin, Phenobarbital:** May decrease metronidazole efficacy.
* **Disulfiram:** Concomitant use is contraindicated due to risk of psychotic reactions.
## Monitoring
* **Clinical response:** Monitor for improvement in signs and symptoms of infection.
* **Adverse effects:** Assess for neurological symptoms (numbness, tingling, seizures), gastrointestinal upset, and signs of hypersensitivity.
* **INR:** If used concurrently with warfarin.
* **Lithium levels:** If used concurrently with lithium.
## Clinical Pearls
* Metronidazole has a metallic taste that can be bothersome. Taking with food may help alleviate gastrointestinal upset.
* Alcohol must be strictly avoided during treatment and for at least 72 hours after the last dose due to the disulfiram-like reaction.
* Peripheral neuropathy is a serious potential adverse effect, particularly with long-term or high-dose therapy. Patients should be instructed to report any neurological symptoms.
* For vaginal gel, patients should be advised that it can weaken latex condoms and diaphragms.
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*This information is intended for healthcare professionals and does not substitute for a thorough review of the complete prescribing information or consultation with a qualified prescriber. Always verify current prescribing information with the manufacturer or reliable drug compendia.*
