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# Metronidazole
## Overview
Metronidazole is a synthetic nitroimidazole antibiotic and antiprotozoal agent effective against anaerobic bacteria and certain protozoa.
## Primary Indications
* **Bacterial Vaginosis:** Treatment of bacterial vaginosis.
* **Trichomoniasis:** Treatment of trichomoniasis.
* **Amebiasis:** Treatment of intestinal amebiasis.
* **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, CNS infections, bone and joint infections, lower respiratory tract infections, endocarditis, bacteremia). Often used in combination with other agents.
* **Pseudomembranous Colitis:** Treatment of *Clostridium difficile*-associated diarrhea (CDAD).
* **Prophylaxis:** Prophylaxis against anaerobic infection in specific surgical procedures (e.g., colorectal surgery).
* **H. pylori Eradication:** Part of multi-drug regimens for *Helicobacter pylori* eradication.
## Adult Dosing
* **Bacterial Vaginosis:** 500 mg orally twice daily for 7 days, OR 2 g orally as a single dose, OR 0.75% vaginal gel applied intravaginally once daily for 5 days.
* **Trichomoniasis:** 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.
* **Amebiasis:**
* Intestinal: 500-750 mg orally three times daily for 5-10 days.
* Hepatic abscess: 500-750 mg orally three times daily for 5-10 days.
* **Giardiasis:** 250 mg orally three times daily for 5 days, OR 375 mg orally twice daily for 7 days.
* **Anaerobic Bacterial Infections:** 500 mg intravenously or orally every 8 hours. Duration varies by infection severity and site. Intravenous therapy may be followed by oral therapy.
* **Pseudomembranous Colitis:** 250-500 mg orally every 6-8 hours.
* **Surgical Prophylaxis:** 1 g orally or intravenously as a single dose 1 hour before surgery, or 500 mg orally or intravenously every 8 hours starting before surgery and continuing for up to 24 hours postoperatively.
## Pediatric Dosing
Dosing in pediatrics is highly dependent on indication, age, and weight, and may vary based on local protocols. Consult pediatric-specific guidelines or drug formularies.
* **Bacterial Infections:** 7.5 mg/kg orally or intravenously every 8 hours (maximum 400 mg per dose).
* **Amebiasis:**
* Intestinal: 35-50 mg/kg/day orally divided into three doses for 5-10 days (maximum 750 mg/dose).
* Hepatic abscess: 35-50 mg/kg/day orally or intravenously divided into three doses for 5-10 days (maximum 750 mg/dose).
* **Giardiasis:** 5 mg/kg orally every 8 hours for 5 days (maximum 250 mg per dose).
## Dose Adjustments
No dose adjustment is typically needed for renal impairment. In severe hepatic impairment, reduce the maintenance dose by one-third to one-half and administer every 12 hours.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazole derivatives.
* Use during the first trimester of pregnancy, except in specific situations where other treatments are not suitable for trichomoniasis.
* Concurrent use with disulfiram.
* Concurrent use with alcohol due to disulfiram-like reaction.
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, abdominal discomfort, metallic taste, headache, dizziness.
* **Less Common:** Peripheral neuropathy (especially with prolonged use), seizures, encephalopathy, aseptic meningitis, pancreatitis, rash, pruritus, urticaria, darkening of urine.
* **Rare:** Stevens-Johnson syndrome, toxic epidermal necrolysis.
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction (flushing, nausea, vomiting, tachycardia, headache). 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 of warfarin. Monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** Metronidazole may increase lithium levels, potentially leading to toxicity. Monitor lithium levels.
* **Phenytoin, Phenobarbital:** These drugs may decrease metronidazole levels.
* **5-Fluorouracil (5-FU) and Capecitabine:** Metronidazole may increase the toxicity of 5-FU and capecitabine.
## Monitoring
* **Clinical response:** Assess for improvement in signs and symptoms of infection.
* **Neurological symptoms:** Monitor for peripheral neuropathy or central nervous system effects, especially with prolonged therapy.
* **Renal and Hepatic function:** Monitor in patients with severe impairment.
* **INR:** If used concurrently with warfarin.
* **Lithium levels:** If used concurrently with lithium.
## Clinical Pearls
* Metronidazole has a metallic taste, which can be a deterrent to oral administration. Taking with food may improve GI tolerance.
* Disulfiram-like reaction with alcohol is a significant concern; patients must be strongly advised to avoid alcohol.
* Prolonged therapy increases the risk of peripheral neuropathy.
* For anaerobic infections, metronidazole is often used in combination with other antibiotics that have gram-positive and aerobic coverage.
* Can cause darkening of urine (reddish-brown), which is harmless.
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*Please verify current prescribing information and consult with a pharmacist or physician for any specific patient care decisions.*
