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# Metronidazole
## Overview
Metronidazole is an antibiotic and antiprotozoal agent. It is effective against anaerobic bacteria and certain protozoa.
## Primary Indications
* **Bacterial Vaginosis:** Treatment of bacterial vaginosis.
* **Trichomoniasis:** Treatment of *Trichomonas vaginalis* infection.
* **Amoebiasis:** Treatment of invasive amoebiasis.
* **Giardiasis:** Treatment of *Giardia lamblia* infection.
* **Anaerobic Bacterial Infections:** Treatment of serious anaerobic bacterial infections (e.g., intra-abdominal infections, gynecologic infections, skin and soft tissue infections, bone and joint infections, CNS infections, lower respiratory tract infections, endocarditis). Often used in combination therapy.
* **Pseudomembranous Colitis:** Treatment of *Clostridioides difficile*-associated diarrhea (CDAD).
* **Surgical Prophylaxis:** Perioperative prophylaxis, particularly in colorectal surgery.
* **H. pylori Eradication:** Component 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. A second course may be necessary for persistent infections.
* **Amoebiasis:**
* **Dysentery:** 500-800 mg orally three times daily for 5-10 days.
* **Hepatic Abscess:** 500-800 mg orally three times daily for 5-10 days, followed by a tissue amoebicide (e.g., paromomycin) if intestinal lumen involvement is suspected.
* **Giardiasis:** 250 mg orally three times daily for 5 days, OR 2 g orally once daily for 3 days.
* **Anaerobic Bacterial Infections:** 500 mg IV or orally every 8 hours. Duration varies by infection site and severity, typically 7-14 days. Higher doses may be used for severe infections.
* **Pseudomembranous Colitis:** 500 mg orally three times daily for 10-14 days. Vancomycin is generally preferred for severe or initial episodes.
* **Surgical Prophylaxis:** 1 g IV or 500 mg orally 1 hour before surgery, followed by 500 mg orally every 8 hours for up to 12 hours post-operatively.
* **H. pylori Eradication:** Typically 500 mg orally twice daily in combination with other agents for 10-14 days.
## Pediatric Dosing
Dosing is highly dependent on indication and weight.
* **General Anaerobic Infections:** 15 mg/kg/day orally or IV, divided into 3 doses, not to exceed 400 mg per dose. Maximum daily dose of 2.25 g. Duration typically 7-14 days.
* **Amoebiasis:**
* **Intestinal:** 35-50 mg/kg/day orally, divided into 3 doses, for 5-10 days.
* **Extraintestinal:** 35-50 mg/kg/day orally or IV, divided into 3 doses, for 5-10 days. Maximum daily dose of 2.25 g.
* **Giardiasis:** 5 mg/kg/dose orally three times daily for 5 days. Maximum 250 mg/dose.
## Dose Adjustments
* **Renal Impairment:** No dose adjustment is generally needed in mild to moderate renal impairment. In severe impairment (CrCl < 10 mL/min), consider reducing the dose by 50% and extending the dosing interval, though data is limited. Metronidazole and its metabolites are removed by hemodialysis.
* **Hepatic Impairment:** Reduce dose by 30-50% in severe hepatic impairment.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazole derivatives.
* First trimester of pregnancy (relative contraindication, risk-benefit assessment needed).
* Concomitant use of disulfiram (within the last 2 weeks).
* Concomitant use of alcohol.
## Adverse Effects
Common: Nausea, vomiting, diarrhea, abdominal pain, metallic taste, headache, dizziness.
Serious: Peripheral neuropathy, seizures, encephalopathy, leukopenia, pancreatitis, Stevens-Johnson syndrome, anaphylaxis, disulfiram-like reaction with alcohol.
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction (flushing, throbbing headache, nausea, vomiting, sweating, chest pain, palpitations). Advise patients to avoid alcohol during treatment and for at least 3 days after.
* **Warfarin:** Potentiates anticoagulant effect. Monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** Metronidazole can increase serum lithium levels. Monitor lithium levels.
* **Phenytoin/Phenobarbital:** May decrease metronidazole levels.
* **Disulfiram:** Avoid concomitant use; risk of psychoses.
* **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).
* Monitor for central nervous system effects (dizziness, seizures, encephalopathy).
* Monitor CBC if prolonged therapy or high doses are used.
* Monitor INR if used with warfarin.
* Monitor lithium levels if used with lithium.
## Clinical Pearls
* The metallic taste is a common side effect.
* Advise patients to avoid alcohol during therapy and for at least 72 hours after the last dose to prevent a disulfiram-like reaction.
* For vaginal gel, instruct patients on proper administration.
* Oral metronidazole may be taken with or without food.
* In *H. pylori* eradication, strict adherence to the multi-drug regimen is crucial for success.
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*This information is intended for healthcare professionals. Always consult the official prescribing information and relevant clinical guidelines for complete details and to ensure patient-specific appropriateness. Dosing may vary based on institutional protocols and specific patient factors.*
