Flagyl
Metronidazole
Generic Name
Metronidazole
Mechanism
Metronidazole is a nitroimidazole that exerts its antibacterial and antiprotozoal effects by:
• Intracellular reduction of the nitro group in anaerobic bacteria and protozoa.
• Formation of nitro‑radical intermediates that crosslink DNA strands, inhibit nucleic‑acid synthesis, and disrupt cell membranes.
• Induction of protein biosynthesis inhibition and generation of reactive oxygen species that kill organisms with low or no oxygen levels.
Pharmacokinetics
| Parameter | Details | Clinical Implication |
| Absorption | 95 % oral bioavailability; peak plasma concentration in 1–2 h. | Fast onset; food does not significantly alter absorption. |
| Distribution | Vd 0.5–1.5 L/kg; penetrates CSF, bile, placenta, and adipose tissue. | Useful for CNS and intra‑abdominal infections. |
| Protein Binding | 10‑15 % | Minimal displacement interactions. |
| Metabolism | Hepatic microsomal (CYP2A6, CYP3A4). | Potential drug interactions with phenobarbital, phenytoin, carbamazepine, and rifampin. |
| Excretion | Renal: 50‑70 % unchanged; biliary excretion also important. | Renal dosing adjustment needed for CrCl < 50 mL/min. |
| Half‑life | 8–10 h (shorter in infants). | Determines dosing interval; can be shortened by probenecid, phenobarbital, or phenytoin. |
Indications
- Anaerobic bacterial infections: odontogenic, intra‑abdominal, pelvic abscesses, peritonitis.
- Protozoal infections: *Clostridioides difficile* colitis (often in combination), trichomoniasis, amoebiasis.
- Bacterial vaginosis and *Trichomonas* vaginitis.
- Mixed flora infections with *Escherichia coli*, *Streptococcus spp.*, *Bacteroides fragilis*, *Clostridium spp.*
Contraindications
- Severe hepatic or cholestatic jaundice (especially in infants).
- Dissulfiram‑like reaction with alcohol: patients must avoid any alcohol (even once per month) during therapy and for at least 48 h after completion.
- Pregnancy: Category B; avoid use beyond 10 weeks unless treatment benefits outweigh risk.
- Breastfeeding: excreted into milk; avoid or discontinue if mother is taking it.
- CNS disorders: Anticipate potential neurotoxicity; use caution in patients with pre‑existing neuropathy or seizures.
Dosing
| Indication | Oral | Intravenous (IV) |
| Anaerobic abscess, peritonitis | 5 – 10 mg/kg q6 h (max 500 mg q6 h) | 5 – 10 mg/kg q6 h (max 500 mg q6 h) |
| Bacterial vaginosis | 500 mg PO BID for 7 days | – |
| Trichomoniasis | 2 g PO single dose (or 500 mg BID x 7 days) | 10 mg/kg q6 h for 2 days |
| *C. difficile* colitis | 500 mg PO BID for 10–14 days | 10 mg/kg q6 h for 4–6 days |
| Amoebiasis | 500 mg PO BID for 10 days | 10 mg/kg q6 h for 4–6 days |
• Infants (≤12 mo): 7.5 mg/kg PO BID; 5 mg/kg IV q8 h.
• Renal impairment (CrCl < 30 mL/min): extend dosing interval to q12 h (oral) or switch to 8 h interval IV.
Adverse Effects
| Category | Examples |
| Common | Nausea, metallic taste, headache, dizziness, abdominal cramps, diarrhea, mouth candidiasis |
| Serious / Rare | Neurotoxicity (ataxia, peripheral neuropathy, seizures), hepatotoxicity (↑AST/ALT), hypersensitivity (rash, eosinophilia), interstitial nephritis, lactic acidosis |
Important warning: Disulfiram‑like reactions—vomiting, flushing, chest pain—occur with alcohol ingestion at any dose.
Monitoring
- Liver Function Tests (AST, ALT) if prolonged therapy (>2 weeks).
- Renal Function (Creatinine, BUN) for dose adjustment in renal impairment.
- Neurologic assessment (balance, peripheral sensation) if signs of neurotoxicity arise.
- Blood glucose for diabetic patients on high‑dose regimens.
Clinical Pearls
1. Never give IV metronidazole with concurrent iron tablets; iron can increase neurotoxic risk.
2. Probenecid, phenobarbital, or phenytoin shorten the half‑life by enhancing renal excretion—use only when rapid clearance is required.
3. “Metronidazole‑days”: In patients who cannot tolerate full regimens, a shortened course (3 days) of 500 mg BID can still be effective for many vaginal/trichomonas infections.
4. Bowel injury: High cumulative doses (>6 g) increase risk of transaminitis; maintain a cumulative dose record.
5. Kids and alcohol: Even a single spirit drink during therapy may precipitate a severe reaction—educate patients thoroughly.
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• *This concise drug card is designed for quick reference by medical students and clinicians. Always confirm dosing and indications with institutional protocols and current literature.*