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# Metronidazole
## Overview
Metronidazole is a nitroimidazole antibiotic and antiprotozoal agent effective against anaerobic bacteria and certain protozoa. It is available in oral, intravenous, and topical formulations.
## Primary Indications
* **Bacterial Vaginosis:** Treatment of bacterial vaginosis.
* **Trichomoniasis:** Treatment of symptomatic trichomoniasis.
* **Amebiasis:** Treatment of amebiasis (intestinal and extraintestinal).
* **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, CNS infections, lower respiratory tract infections, endocarditis). Often used in combination therapy.
* **_Clostridioides difficile_ Infection (CDI):** Treatment of _C. difficile_ associated diarrhea. (Note: Oral vancomycin is generally preferred for initial episodes of non-severe CDI).
* **Prophylaxis:** Prophylaxis against anaerobic infections in specific surgical procedures (e.g., colorectal surgery).
* **Rosacea:** Topical treatment for inflammatory lesions of rosacea.
## 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% gel, one applicatorful (5g) intravaginally once daily for 5 days.
* **Trichomoniasis:**
* Oral: 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:**
* Invasive Amebiasis: 500-750 mg orally or IV three times daily for 5-10 days.
* Asymptomatic Cyst Passers: 250 mg orally three times daily for 7-10 days.
* **Giardiasis:**
* Oral: 250 mg orally three times daily for 5 days.
* **Anaerobic Bacterial Infections:**
* Oral/IV: 500 mg every 8 hours. Dosing duration depends on severity and site of infection, typically 7-14 days.
* Severe infections may require higher doses (e.g., 1 g IV every 8 hours).
* **_Clostridioides difficile_ Infection:**
* Oral: 500 mg orally three times daily for 10-14 days. (Use is declining due to increased resistance and availability of vancomycin).
* **Surgical Prophylaxis:**
* IV: 1 g as a single dose within 12 hours before surgery, OR 500 mg every 8 hours starting before surgery and continuing for up to 24 hours postoperatively.
* **Rosacea (Topical):**
* 0.75% Gel/Cream: Apply thin layer to affected areas twice daily.
* 1% Gel/Cream: Apply thin layer to affected areas once daily.
## Pediatric Dosing
Dosing is weight-based and depends on the indication.
* **Amebiasis:**
* Oral: 35-50 mg/kg/day divided into 3 doses for 5-10 days (maximum 750 mg/dose).
* **Giardiasis:**
* Oral: 15 mg/kg/day divided into 3 doses for 5 days (maximum 250 mg/dose).
* **Anaerobic Bacterial Infections:**
* Oral/IV: 7.5 mg/kg/dose every 8 hours, OR 15 mg/kg/dose every 12 hours (maximum 1 g/dose). Duration varies (7-14 days).
* **_C. difficile_ Infection:**
* Oral: 10 mg/kg/dose every 8 hours for 10-14 days (maximum 500 mg/dose).
## Dose Adjustments
* **Hepatic Impairment:** Use with caution. Reduced doses may be necessary in severe hepatic impairment. Monitor for toxicity.
* **Renal Impairment:** No dose adjustment needed for hemodialysis or peritoneal dialysis. However, caution is advised in severe renal impairment, though specific dose adjustments are not usually recommended.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazoles.
* Active central nervous system (CNS) disease.
* First trimester of pregnancy (especially for systemic use, though risk is generally considered low).
* Use with disulfiram (within 14 days) due to potential for psychotic reactions.
* Concomitant use of alcohol due to disulfiram-like reaction.
## Adverse Effects
Common: Nausea, vomiting, diarrhea, abdominal pain, metallic taste, headache, dizziness.
Serious: Peripheral neuropathy (especially with prolonged use), seizures, encephalopathy, leukopenia, Stevens-Johnson syndrome, anaphylaxis, pancreatitis, dark urine.
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction (flushing, nausea, vomiting, headache, palpitations). Advise patient to avoid alcohol during treatment and for at least 3 days after completion.
* **Warfarin:** Metronidazole can potentiate the anticoagulant effect of warfarin. Monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** Metronidazole can 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.
* **Disulfiram:** Concurrent use can lead to confusion, psychosis, and ataxia. Avoid use within 14 days of each other.
## Monitoring
* Monitor for signs and symptoms of peripheral neuropathy (numbness, tingling, pain).
* Monitor for signs and symptoms of CNS toxicity (seizures, encephalopathy).
* Monitor complete blood counts (CBC) with differential if treatment is prolonged or in patients with a history of blood dyscrasias.
* Monitor INR if patient is on warfarin.
* Monitor lithium levels if patient is on lithium.
## Clinical Pearls
* Instruct patients to avoid alcohol during therapy and for at least 72 hours after the last dose.
* A metallic taste is common and can be reduced by taking with food.
* For _C. difficile_, oral vancomycin is generally preferred for initial episodes, particularly non-severe.
* Topical formulations are generally associated with fewer systemic side effects.
* IV metronidazole is a common component of treatment for intra-abdominal infections and other serious anaerobic infections.
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*Disclaimer: This information is intended for clinical use and does not substitute for professional medical judgment. Always consult the most current prescribing information and relevant clinical guidelines before making treatment decisions.*
