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Metronidazole

1. Generic & Brand Names

  • Generic: Metronidazole

  • Brands: Flagyl® (global), Metrogel® (topical), Nidagel® (vaginal)

  • Formulations:

    • Tablets (250mg, 500mg)

    • Oral suspension (200mg/5mL)

    • IV infusion (500mg/100mL)

    • Topical gel (0.75-1%)

2. Drug Class & Mechanism

  • Class: Nitroimidazole antibiotic/antiparasitic

  • Mechanism:

    • Forms toxic radicals → disrupts DNA/RNA synthesis

    • Bactericidal against anaerobes, antiprotozoal

  • Spectrum:

    • Anaerobic bacteria: Bacteroides, Clostridioides difficile

    • Parasites: Giardia, Entamoeba, Trichomonas

    • NOT for: Aerobic bacteria or viruses

3. FDA-Approved Uses

ConditionKey Indications
Diarrhea/ColitisC. difficile infection (CDI)
Dental InfectionsAcute necrotizing ulcerative gingivitis, periodontitis
Parasitic InfectionsGiardiasis, amebiasis
Surgical ProphylaxisColorectal surgery (anaerobic cover)

4. Dosing Regimens

IndicationAdult DoseDuration
C. difficile Colitis500 mg PO q8h10-14 days
Acute Gingivitis500 mg PO q8h3-7 days
Giardiasis250 mg PO q8h5-7 days
Surgical Prophylaxis500 mg IV pre-op + q8h × 24h1 day
Renal Adjustment:

  • Severe hepatic impairment: ↓ dose by 50%

  • Dialysis: Give post-dialysis

5. Side Effects

Common (≥10%)Serious (<1%)
Metallic tastePeripheral neuropathy (irreversible)
Nausea/vomitingSeizures/encephalopathy
Dark urinePancreatitis
HeadacheLeukopenia
Disulfiram-like reaction (with alcohol)Stevens-Johnson Syndrome

6. Black Box Warnings & Contraindications

  • 🚫 Absolute Contraindications:

    • First-trimester pregnancy (Category X for trichomoniasis)

    • Hypersensitivity to nitroimidazoles

    • Alcohol consumption (risk of violent nausea/vomiting)

  • Critical Warnings:

    • Carcinogenicity: Positive in rodent studies → avoid unnecessary long-term use

    • CNS toxicity: Risk ↑ with high doses or history of seizures

7. Drug Interactions

MedicationRiskManagement
AlcoholDisulfiram reaction (flushing, tachycardia)Avoid during + 72h post-treatment
Warfarin↑ INR → bleedingMonitor INR closely
Lithium↑ Toxicity (tremor, confusion)Avoid combo
Phenytoin↑ Phenytoin levels → toxicityMonitor serum levels

8. Key Clinical Applications

▶️ For Diarrhea:

  • First-line for:

    • Moderate-severe C. difficile infection

    • Giardia-induced traveler's diarrhea

  • Avoid for:

    • Viral diarrhea (norovirus)

    • Campylobacter (rising resistance)

▶️ For Dental Infections:

  • Used for:

    • Acute necrotizing ulcerative gingivitis ("trench mouth")

    • Aggressive periodontitis (with scaling/root planing)

  • Typical regimen: 500 mg q8h × 3-5 days

9. Pediatric Use

AgeDose for Giardiasis/CDI
>3 years7.5 mg/kg q8h (max 500 mg)
Avoid <3 yrs unless life-threatening infection

10. Storage & Administration

  • Tablets: 15-30°C; protect from light

  • Oral suspension:

    • Refrigerate after reconstitution

    • Discard after 7 days

  • IV: Administer over 30-60 min; avoid PVC containers

Clinical Practice Warnings

⚠️ Alcohol Interaction:

  • Avoid all alcohol (including mouthwash/cough syrups) during and ≥72h after treatment

  • Reactions include vomiting, flushing, tachycardia

⚠️ Neurotoxicity Signs:

  • Stop immediately for numbness, ataxia, or seizures

⚠️ Dental-Specific Notes:

  • Combine with amoxicillin for odontogenic abscesses

  • Not for routine prophylaxis - reserve for severe anaerobic infections

✅ Alternatives for CDI:

  • Mild cases: Vancomycin 125 mg PO q6h

  • Recurrent cases: Fidaxomicin

Metronidazole vs. Vancomycin for CDI

ParameterMetronidazoleVancomycin (PO)
Cost$$$$$
Efficacy (mild CDI)78%81%
Systemic AbsorptionMinimal (gut-targeted)Minimal
Side EffectsMetallic taste, nauseaRare
Recurrence Rate25-30%15-20%

Patient Counseling Essentials

  1. "Avoid ALL alcohol - including sauces, perfumes, and hand sanitizers."

  2. "Take with food to reduce nausea."

  3. "Dark urine is normal (drug metabolite)."

  4. "Stop for neurological symptoms (dizziness, numbness)."

💡 Pro Tip: For dental infections, use topical metronidazole gel (0.75%) in periodontal pockets to reduce systemic exposure.

Prescribing Status: Widely available; monitor for resistance in Bacteroides (>10% in some regions). Report adverse events to FDA MedWatch.


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