What are the side effects and warnings of metronidazole (Flagyl)?

Metronidazole Side Effects and Warnings

Metronidazole should be used with caution due to its significant side effect profile, particularly the risk of potentially irreversible neurotoxicity with prolonged or repeated courses of treatment. 1

Common Side Effects

• Gastrointestinal effects:

  • Nausea (reported in approximately 12% of patients) 2
  • Vomiting
  • Diarrhea
  • Epigastric distress
  • Abdominal cramping
  • Constipation
  • Metallic taste in mouth 2

• Oral manifestations:

  • Sharp, unpleasant metallic taste
  • Furry tongue
  • Glossitis
  • Stomatitis (may be associated with Candida overgrowth) 2

Serious Adverse Reactions

Neurological Complications

• Peripheral neuropathy - characterized by numbness or paresthesia of extremities 2

  • Can be persistent and potentially irreversible with prolonged administration 1, 2
  • Requires immediate discontinuation upon appearance of abnormal neurologic signs 2

• Central nervous system effects:

  • Convulsive seizures 2
  • Dizziness
  • Vertigo
  • Incoordination
  • Ataxia
  • Confusion
  • Irritability
  • Depression
  • Weakness
  • Insomnia 2

Other Significant Adverse Effects

• Hematologic: Reversible neutropenia (leukopenia); rarely, reversible thrombocytopenia 2

• Cardiovascular: Flattening of the T-wave on ECG 2

• Hypersensitivity reactions:

  • Urticaria
  • Erythematous rash
  • Flushing
  • Nasal congestion
  • Dryness of mouth, vagina, or vulva
  • Fever 2

• Genitourinary:

  • Dysuria
  • Cystitis
  • Polyuria
  • Incontinence
  • Sense of pelvic pressure
  • Darkened urine (rare) 2

• Other:

  • Candida proliferation in the vagina
  • Dyspareunia
  • Decreased libido
  • Proctitis
  • Joint pains 2

Special Warnings

Alcohol Interaction

• Patients consuming alcohol while taking metronidazole may experience:
  • Abdominal distress
  • Nausea
  • Vomiting
  • Flushing
  • Headache
  • Altered taste of alcoholic beverages 2
  • This is known as a disulfiram-like reaction 1

Pregnancy Considerations

• Contraindicated during the first trimester of pregnancy 1
• May be used during second and third trimesters when benefits outweigh risks 1
• Multiple studies have not demonstrated consistent association between metronidazole use during pregnancy and teratogenic or mutagenic effects in infants 1

Duration of Treatment Concerns

• Repeated or prolonged courses should be avoided due to risk of cumulative and potentially irreversible neurotoxicity 1
• Persistent peripheral neuropathy has been reported in patients receiving prolonged administration 2, 3

Clinical Use Limitations

• For Clostridioides difficile infection (CDI):

  • Should be limited to treatment of initial episodes of mild-moderate CDI 1
  • Not recommended for severe CDI (vancomycin preferred) 1
  • Not recommended for patients with multiple recurrences 4

• For trichomoniasis and bacterial vaginosis:

  • Metronidazole gel is not recommended for trichomoniasis (efficacy <50%) 1
  • Oral metronidazole is preferred for these conditions 1

Monitoring and Management

• Patients should be specifically warned about neurologic reactions and instructed to stop the drug and report immediately if any neurologic symptoms occur 2
• Prompt discontinuation is generally associated with full clinical recovery and radiological resolution of neurologic complications 3
• Monitor for signs of peripheral neuropathy during treatment
• Avoid prolonged or repeated courses when possible 1

Specific Patient Populations

• Elderly patients: May be at higher risk for adverse effects, particularly neurological complications
• Patients with CNS diseases: Administer with caution 2
• Patients with liver disease: May have reduced clearance of the drug
• Immunocompromised patients: May experience more severe side effects

By understanding these side effects and warnings, healthcare providers can better monitor patients on metronidazole therapy and intervene promptly if complications arise.