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# Metronidazole
## Overview
Metronidazole is an antibiotic and antiprotozoal agent effective against anaerobic bacteria and certain protozoa.
## Primary Indications
* Treatment of *Clostridium difficile* infection (CDI).
* Treatment of various anaerobic bacterial infections, including intra-abdominal infections, gynecological infections, skin and soft tissue infections, bone and joint infections, central nervous system infections, and bacterial vaginosis.
* Treatment of protozoal infections such as trichomoniasis, giardiasis, and amebiasis.
* Surgical prophylaxis in specific situations (e.g., colorectal surgery).
## Adult Dosing
Dosing varies significantly by indication.
* **Bacterial Vaginosis:** 500 mg orally twice daily for 7 days, or a single 2 g dose orally.
* ***Clostridium difficile* Infection:** 500 mg orally every 8 hours for 10-14 days. (Note: Oral vancomycin is often preferred for initial episodes and severe CDI).
* **Anaerobic Infections (non-CDI):** Typically 500 mg to 1 g intravenously or orally every 8 hours. Duration depends on severity and site of infection, commonly 7-14 days.
* **Trichomoniasis:** Single 2 g dose orally, or 250 mg orally three times daily for 7 days.
* **Giardiasis:** 250 mg orally three times daily for 5-7 days, or 2 g orally once daily for 3 days.
* **Amebiasis:** 500-750 mg orally every 8 hours for 5-10 days.
Maximum dose generally not to exceed 4 g per day.
## Pediatric Dosing
Dosing varies by indication and weight.
* ***Clostridium difficile* Infection:** 15 mg/kg/day orally divided into 3 doses, not to exceed 500 mg per dose (or 4 g/day). Duration typically 10-14 days.
* **Anaerobic Infections (non-CDI):** 7.5 mg/kg/dose intravenously or orally every 8 hours. Usual duration 7-14 days.
* **Trichomoniasis:** Not established.
* **Giardiasis:** 5 mg/kg/dose orally three times daily for 5-7 days, maximum 250 mg/dose.
* **Amebiasis:** 10-15 mg/kg/day orally divided into 3 doses for 5-10 days, maximum 750 mg/dose.
## Dose Adjustments
* **Renal Impairment:** No dose adjustment generally needed for mild to moderate impairment. For severe impairment (CrCl < 10 mL/min), consider reducing the dose by 50% and increasing the dosing interval.
* **Hepatic Impairment:** Use with caution. Reduce dose by 30-50% in severe hepatic disease.
## Contraindications
* Hypersensitivity to metronidazole or other nitroimidazole derivatives.
* First trimester of pregnancy (use cautiously in second and third trimesters if benefits outweigh risks).
* Concurrent use of disulfiram or 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, Stevens-Johnson syndrome, pancreatitis, neutropenia, opportunistic infections.
## Key Drug Interactions
* **Alcohol:** Disulfiram-like reaction (flushing, nausea, vomiting, headache). Avoid alcohol during and for at least 3 days after treatment.
* **Warfarin:** Metronidazole can potentiate the anticoagulant effect. Monitor INR closely and adjust warfarin dose as needed.
* **Lithium:** Metronidazole may increase serum lithium levels. Monitor lithium levels.
* **Disulfiram:** Concurrent use is contraindicated.
* **Phenytoin/Phenobarbital:** May decrease metronidazole levels.
* **Fluorouracil (5-FU):** Metronidazole may increase toxicity of 5-FU.
## Monitoring
* Monitor for signs of peripheral neuropathy (numbness, tingling, pain).
* Monitor for signs of central nervous system effects (dizziness, seizures).
* Monitor for gastrointestinal side effects.
* In patients with severe hepatic impairment, monitor hepatic function.
* Monitor INR if co-administered with warfarin.
## Clinical Pearls
* Administer oral metronidazole with food to minimize gastrointestinal upset.
* Advise patients to avoid alcohol during and for at least 72 hours after completion of therapy.
* Metronidazole can cause a dark or reddish-brown urine, which is harmless.
* Consider susceptibility testing for *C. difficile* when available, as resistance can occur.
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*This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and relevant clinical guidelines for definitive patient management.*
