From the Guidelines
Metronidazole is associated with significant side effects, including a disulfiram-like reaction with alcohol consumption, neurological effects, and gastrointestinal disturbances, as reported in a 2019 study 1. The most notable side effect is a disulfiram-like reaction that occurs when alcohol is consumed during treatment or within 48-72 hours after completing therapy, causing severe nausea, vomiting, flushing, headache, and abdominal cramps.
- Patients must strictly avoid alcohol while taking metronidazole, as emphasized in the 2002 CDC guidelines for treating bacterial vaginosis 1.
- Other common side effects include:
- Metallic taste in the mouth
- Nausea
- Vomiting
- Diarrhea
- Abdominal discomfort
- Neurological side effects can occur, particularly with prolonged use or higher doses, including:
- Dizziness
- Headache
- Confusion
- In rare cases, seizures or peripheral neuropathy (numbness or tingling in extremities), as noted in the 2019 update of the WSES guidelines for managing Clostridioides difficile infection 1. Metronidazole may darken urine to a brownish color, which is harmless but can be concerning if unexpected.
- Rarely, serious adverse effects include:
- Stevens-Johnson syndrome
- Pseudomembranous colitis The drug works by disrupting bacterial DNA, which explains its effectiveness against anaerobic bacteria and certain parasites, but also contributes to its side effect profile. Patients should report persistent or severe side effects to their healthcare provider immediately, as recommended in the 2019 guidelines 1.
From the FDA Drug Label
ADVERSE REACTIONS Two serious adverse reactions reported in patients treated with metronidazole have been convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity Central Nervous System:Convulsive seizures, peripheral neuropathy, dizziness, vertigo, incoordination, ataxia, confusion, irritability, depression, weakness, and insomnia.
Significant side effects of metronidazole include:
- Convulsive seizures
- Peripheral neuropathy, characterized by numbness or paresthesia of an extremity These side effects are considered serious and patients should be warned about them and instructed to stop the drug and report immediately to their physicians if any neurologic symptoms occur 2.
From the Research
Significant Side Effects of Metronidazole
- Peripheral neuropathy: Metronidazole has been associated with peripheral neuropathy, a condition characterized by damage to the peripheral nerves, which can cause symptoms such as numbness, tingling, and weakness in the hands and feet 3, 4, 5.
- Neurotoxicity: Metronidazole can cause neurotoxicity, which can manifest as symptoms such as ataxic gait, dysarthria, seizures, and encephalopathy 6, 7.
- Gastrointestinal side effects: Metronidazole can cause gastrointestinal side effects such as nausea, abdominal pain, and diarrhea 5.
- Disulfiram-like reaction: Metronidazole can cause a disulfiram-like reaction when taken with alcohol, which can lead to symptoms such as flushing, nausea, and vomiting 4.
- Genotoxicity: Metronidazole has been shown to have genotoxic effects in animal models, although the risk in humans is still controversial 5.
Risk Factors for Significant Side Effects
- Prolonged therapy: Prolonged therapy with metronidazole (>4 weeks of treatment and/or 42 g cumulative dose) may increase the risk of developing neurological complications, such as peripheral polyneuropathy 3.
- High cumulative dose: A high cumulative dose of metronidazole (e.g. 168 g) may increase the risk of developing peripheral neuropathy 3.