Metronidazole

# Metronidazole ## Overview - **Classification**: Nitroimidazole antibiotic, antiprotozoal. - **Mechanism**: Diffuses into microorganisms, inhibits DNA synthesis and causes DNA damage. Bactericidal against anaerobes and protozoa. ## Primary Indications 1. **Anaerobic Bacterial Infections** - Intra-abdominal, skin/soft tissue, gynecologic, bone/joint, CNS infections. 2. **Protozoal Infections** - Amebiasis, giardiasis, trichomoniasis. 3. **_Clostridioides difficile_ Infection (CDI)** - Mild to moderate cases. ## Adult Dosing ### Standard Dosing **Anaerobic Infections (e.g., Intra-abdominal, Gynecologic)** - **Dose**: **500 mg** - **Frequency**: Every **8 hours** - **Route**: IV or PO - **Duration**: 7-14 days, or as clinically indicated. **_Clostridioides difficile_ Infection (Mild to Moderate)** - **Dose**: **500 mg** - **Frequency**: Every **8 hours** - **Route**: PO - **Duration**: 10-14 days. **Trichomoniasis** - **Dose**: **2 grams** (single dose) or **500 mg** - **Frequency**: Single dose or twice daily - **Route**: PO - **Duration**: Single dose or 7 days (for 500 mg BID). **Amebiasis (Intestinal/Hepatic Abscess)** - **Dose**: **500-750 mg** - **Frequency**: Every **8 hours** - **Route**: PO - **Duration**: 5-10 days. ### Dose Adjustments - **Renal Impairment**: No routine dose adjustment for CrCl >10 mL/min. - For CrCl <10 mL/min: Reduce dose by **50%** or extend interval to **Q12-24H**. - Hemodialysis: Administer dose after dialysis session. - **Hepatic Impairment**: Reduce dose by **30-50%** in severe hepatic dysfunction (Child-Pugh C). - Monitor closely for adverse effects, especially CNS toxicity. - **Elderly Patients**: No specific dose adjustment; monitor for adverse effects due to potential altered pharmacokinetics. ## Pediatric Dosing ### Neonates (0-28 days) - **Indication**: Anaerobic infections, empiric sepsis. - **Dose**: **7.5-15 mg/kg** (IV/PO) - **Frequency**: Every **12-48 hours**, dependent on gestational age (GA) and postnatal age (PNA). - GA <28 weeks & PNA 0-7 days: **7.5 mg/kg Q48H**. - GA <28 weeks & PNA >7 days: **7.5 mg/kg Q24H**. - GA 28-34 weeks & PNA 0-7 days: **7.5 mg/kg Q24H**. - GA 28-34 weeks & PNA >7 days: **15 mg/kg Q24H**. - GA >34 weeks & PNA 0-7 days: **15 mg/kg Q12H**. - GA >34 weeks & PNA >7 days: **15 mg/kg Q12H**. - **Maximum**: **500 mg/dose**. - **Special Notes**: Longer dosing intervals due to immature hepatic metabolism. Monitor for neurotoxicity. ### Infants (1-12 months) - **Indication**: Anaerobic infections, protozoal. - **Dose**: **15-30 mg/kg/day** (IV/PO) - **Frequency**: Divided every **8 hours**. - **Maximum**: **1 gram/day**. ### Children (1-12 years) - **Indication**: Anaerobic infections, amebiasis, giardiasis. - **Dose**: **30 mg/kg/day** (IV/PO) - **Frequency**: Divided every **8 hours**. - **Maximum**: **1 gram/day** for general use; up to **2 grams/day** for severe infections. - Amebiasis: **35-50 mg/kg/day** divided Q8H (max 2250 mg/day) for 5-10 days. ### Adolescents (13-18 years) - **Dose**: Use **adult dosing** guidelines. - **Maximum**: **Adult maximum doses**. ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to metronidazole or other nitroimidazole derivatives. - **Absolute**: Concomitant use of disulfiram (within 14 days). - **Absolute**: Concomitant use of alcohol or propylene glycol-containing products. - **Absolute**: First trimester of pregnancy (relative for Trichomoniasis with specific indications). ### Common Adverse Effects - **Very Common (>10%)**: Nausea, metallic taste, headache. - **Common (1-10%)**: Vomiting, diarrhea, abdominal cramps, dizziness, dark urine, candidiasis. - **Serious but Rare**: Seizures, peripheral neuropathy (especially with prolonged use), aseptic meningitis, SJS/TEN. ### Key Drug Interactions - **Alcohol**: Disulfiram-like reaction (flushing, palpitations, nausea, vomiting, headache). **AVOID** alcohol during and for **3 days** after therapy. - **Warfarin**: Potentiates anticoagulant effect, increasing bleeding risk. **Monitor INR closely**, adjust warfarin dose. - **Lithium**: May increase lithium levels, leading to toxicity. **Monitor lithium levels**. - **Busulfan**: Increased busulfan exposure, risk of toxicity. **Avoid concurrent use**. - **Phenytoin/Phenobarbital**: May decrease metronidazole efficacy. Monitor clinical response. ## Monitoring & Follow-up - **Before Treatment**: Assess hepatic and renal function if baseline impairment is suspected. - **During Treatment**: Monitor for CNS toxicity (seizures, peripheral neuropathy), especially with high doses or prolonged use. - Monitor INR frequently if on warfarin. - **Clinical Signs**: Resolution of infection symptoms; observe for severe adverse reactions. ## Clinical Pearls - 💡 **Tip 1**: Administer oral metronidazole with food to minimize GI upset (nausea, metallic taste). - 💡 **Tip 2**: Emphasize complete alcohol avoidance (including OTC products, mouthwash) during and for **at least 3 days** after treatment due to disulfiram-like reaction. - 💡 **Tip 3**: IV infusions should be administered over **30-60 minutes**. - 💡 **Tip 4**: Darkening of urine is a harmless, expected side effect and not cause for concern. - 💡 **Tip 5**: Educate patients on symptoms of peripheral neuropathy (numbness, tingling) with prolonged or high-dose therapy. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.