• Some Adverse Reactions to Metronidazole

  • Gastrointestinal

    • The most common adverse reactions are GI-related. Patients often report nausea, sometimes accompanied by abdominal discomfort, cramping, or diarrhea.¹

      • Metallic taste is extremely common described as a bitter, metallic taste in the mouth that can persist throughout the course.¹

      • Vomiting can occur, particularly with higher doses or if alcohol is ingested (see interactions).

        • Taking the medication with food can minimize stomach upset (though extended-release tablets should be taken on an empty stomach as per prescribing information).

  • Neurologic Effects

    • Peripheral neuropathy

      • Peripheral neuropathy is an important dose- and duration-related toxicity.³ 

        • Long-term or high-dose metronidazole (typically courses exceeding 2–4 weeks or repeated treatments) can cause a symmetric peripheral neuropathy, characterized by numbness or paresthesias in the extremities.⁴ 

        • Presentation of peripheral neuropathy associated with metronidazole administration may result from axonal degeneration and can take weeks to recover.⁵  

      • Central nervous system (CNS) effects

        • These effects are less common but more serious:

          • metronidazole can cause headache, dizziness, ataxia, or, rarely, seizures.³  

            • Encephalopathy with cerebellar dysfunction (affecting coordination and speech) has been reported, particularly in patients on very high doses; MRI lesions in the cerebellum have been observed, which were reversible after stopping the drug.^3,6

      • Aseptic meningitis

        • This is a rare idiosyncratic reaction that can occur soon after administration in some patients.³

          • Given these potential CNS effects, any new neurologic symptom under metronidazole therapy warrants evaluation of the risk/benefit of continuing.

          • Most often, neurologic adverse effects resolve upon discontinuation.³

  • Hypersensitivity and Dermatologic

    • Allergic reactions to metronidazole are uncommon but can occur.

      • Rash, pruritus, flushing, or urticaria have been reported infrequently.¹

      • More severe Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis are exceedingly rare, but there have been reports (especially when metronidazole is combined with other agents like mebendazole).¹  

        • Metronidazole is also reported to cause a syndrome called DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) in rare instances.³  

          • Patients should stop the drug at the first sign of serious skin reaction and seek medical attention.³ 

      • Fever and angioedema may occur but are uncommon.⁷ 

      • Topical metronidazole (for rosacea) can cause local irritation, redness, dryness, or stinging of the skin¹.

  • Hematologic

    • A mild, transient leukopenia (drop in white blood cell count) has been noted during metronidazole therapy in some patients.^3,8

      • It usually does not progress to a severe degree and recovers after therapy.

        • Metronidazole should be used cautiously in patients with a history of blood dyscrasias.⁹ 

• Drug-Drug Interactions

  • An extensive list of drug-drug interactions is available in FDA labeling documentation. For example:

    • FDA labeling: Metronidizole (updated: 10/2023) https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/018890s055lbl.pdf

August, 2025