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Metronidazole

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Metronidazole, Flagyl

  • See Also
  1. Clindamycin
  • Indications
  1. Conditions
    1. Anaerobic Infections
    2. Intraabdominal Infections (e.g. Diverticulitis)
    3. Pelvic Inflammatory Disease
    4. Bacterial Vaginosis
    5. Helicobacter Pylori
    6. Trichomoniasis
    7. Amebiasis
    8. Giardiasis
    9. Pseudomembranous colitis (Clostridioides difficile)
  2. Organisms
    1. Protozoal Infection
      1. Trichomonas
      2. Entamoeba histolytica
      3. Giardia
    2. Anaerobic Bacteria infection
      1. Bacteroides fragilis
      2. Clostridioides difficile
      3. Peptococcus
  • Contraindications
  1. Cockayne Syndrome
    1. Risk of lethal hepatotoxicity with Metronidazole
  • Mechanism
  1. Nitroimidazole Antibiotic (includes tindazole, secnidazole)
  2. Inhibits Protein synthesis in susceptible organisms by disrupting DNA helix, resulting in DNA breakage
  • Medications
  1. Metronidazole Systemic
    1. Intravenous Solution
    2. Tablets: 250, 375 and 500 mg
    3. Extended Release: 750 mg
  2. Metronidazole Topical (e.g. Metrogel): 1% and 0.75% gels, creams and lotions
    1. See Roseacea
  3. Metronidazole Vaginal (e.g. Metrogel Vaginal): 0.75% gel
    1. A 1.3% gel is also available (Nuvessa)
    2. See Bacterial Vaginosis
  • Dosing
  • Adult
  1. See Helicobacter Pylori
  2. See Bacterial Vaginosis
  3. See Diverticulitis
  4. See Pelvic Inflammatory Disease
  5. See Amoeba Histolytica Dysentery and Amebic Liver Abscess
  6. See Pseudomembranous colitis (Clostridioides difficile)
  7. Taking with food decreases gastric irritation
  8. Anaerobic Bacterial Infection
    1. Intravenous (administer each IV dose over 1 hour)
      1. Loading dose: 15 mg/kg up to 1000 mg IV
      2. Maintenance dose: 7.5 mg/kg up to 500 mg IV every 6 to 8 hours
    2. Oral
      1. Take 250 to 750 mg orally three to four times daily
  • Dosing
  • Child
  1. See Amoeba Histolytica Dysentery and Amebic Liver Abscess
  2. Taking with food decreases gastric irritation
  3. Anaerobic Bacterial Infection
    1. Intravenous (administer each IV dose over 1 hour)
      1. Load: Metronidazole 15 mg/kg IV (up to 1000 mg) over 1 hour
      2. Maintenance: Metronidazole 7.5 mg/kg/dose (up to 500 mg/dose) IV every 8 hours
        1. Decrease dosing interval to every 12 hours in age <1 week old
    2. Oral
      1. Give 7.5 to 12.5 mg/kg/dose (up to 500 to 750 mg/dose) three times daily
  • Pharmacokinetics
  1. Half-Life: 8 hours
  2. Some of drug is metabolized via Glucuronidation
  3. Renal excretion (mostly unchanged in the urine)
  • Adverse Effects
  1. Carcinogenic in mice and rats (FDA Black box warning)
  2. Disulfiram Reaction (Antabuse Effect)
    1. Alcohol induced Flushing, Vomiting and Headache
    2. Since the 1960s, Alcohol has been strictly cautioned against when taking Metronidazole
    3. More recent data suggests no inhibition of aldehyde dehydrogenase as is seen with Disulfiram
    4. Safest to avoid Alcohol with Metronidazole, but interactions appear to be very uncommon
    5. (2021) Presc Lett 28(10): 58
  3. Gastrointestinal intolerance
    1. Nausea
    2. Anorexia
    3. Bloating
    4. Abdominal cramping
  4. Neurotoxicity (stop immediately if these occur)
    1. Seizures
    2. Encephalopathy
    3. Aseptic Meningitis
    4. Optic Neuropathy
    5. Cerebellar dysfunction (e.g. Ataxia, Dizziness)
    6. Peripheral Neuropathy (e.g. distal Paresthesias)
  5. Other effects
    1. Urine Color change
      1. Darker Urine
  • Drug Interactions
  1. Alcohol or Disulfiram
    1. See Disulfiram reaction under adverse effects above
    2. Avoid Alcohol for 3 days after last dose
    3. Avoid Disulfiram for 2 weeks after last dose
  2. Warfarin
    1. Increases INR
  3. Other interactions
    1. Barbiturates
    2. Lithium
    3. Phenytoin
  • Safety
  1. Pregnancy Class B Medication
    1. Avoid in first trimester pregnancy
  2. Unknown safety in Lactation
    1. However, generally avoided in Lactation
    2. May resume Breast Feeding at 12 to 24 hours after a single Metronidazole dose
  • Resources
  1. Metronidazole Tablet (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c90da73c-e48e-411a-bd75-0b107f1141cc
  2. Metronidazole Intravenous Solution (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d2112f37-5080-4a19-bcc3-6386b49abe1d
  • References
  1. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 110-1
  2. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  3. Burtin (1995) Am J Obstet Gynecol 172:525-9 [PubMed]