What are the side effects of Metronidazole?

Metronidazole Side Effects

Metronidazole is associated with gastrointestinal side effects (particularly nausea in ~12% of patients), a disulfiram-like reaction with alcohol, and most critically, peripheral neuropathy with prolonged therapy that can be cumulative and potentially irreversible. 1, 2

Common Side Effects

Gastrointestinal Effects

• Nausea is the most frequently reported adverse effect, occurring in approximately 12% of patients, sometimes accompanied by headache, anorexia, and vomiting 2
• Diarrhea, epigastric distress, abdominal cramping, and constipation are also commonly reported 2
• Abdominal pain is a well-documented mild to moderate side effect 3

Taste and Oral Effects

• A sharp, unpleasant metallic taste is not unusual and represents one of the most characteristic side effects 2
• Furry tongue, glossitis, and stomatitis may occur, potentially associated with sudden overgrowth of Candida during therapy 2
• Dryness of the mouth has been reported 2

Serious Neurological Side Effects

Peripheral Neuropathy

• Peripheral neuropathy is characterized mainly by numbness or paresthesia of an extremity and has been reported with prolonged administration 2
• Repeated or prolonged courses of metronidazole are associated with cumulative and potentially irreversible neurotoxicity (strong recommendation, moderate quality of evidence) 4
• Patients should be specifically warned about these reactions and told to stop the drug immediately and report to their physician if any neurologic symptoms occur 2

Central Nervous System Effects

• Convulsive seizures represent one of the two most serious adverse reactions reported 2
• Dizziness, vertigo, incoordination, ataxia, confusion, irritability, depression, weakness, and insomnia have been documented 2
• Encephalopathy has been reported in rare cases, particularly with high doses or prolonged therapy 3, 5
• Dysarthria and ataxic gait can occur, especially with cumulative doses exceeding 140 grams 5

Neurotoxicity in Overdose Settings

• Neurotoxic effects, including seizures and peripheral neuropathy, have been reported after 5 to 7 days of high doses (6 to 10.4 g every other day) when studied as a radiation sensitizer 2

Alcohol Interaction

Patients who consume alcoholic beverages while taking metronidazole may experience a disulfiram-like reaction including abdominal distress, nausea, vomiting, flushing, or headache 2

• A modification of the taste of alcoholic beverages has also been reported 2

Hematologic Effects

• Reversible neutropenia (leukopenia) can occur 2
• Reversible thrombocytopenia is rare 2

Cardiovascular Effects

• Flattening of the T-wave may be seen in electrocardiographic tracings 2

Hypersensitivity Reactions

• Urticaria, erythematous rash, flushing, nasal congestion, dryness of various mucous membranes, and fever have been reported 2

Genitourinary Effects

• Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure 2
• Darkened urine has been reported in approximately one patient in 100,000, likely due to a metabolite of metronidazole with no clinical significance 2
• Proliferation of Candida in the vagina, dyspareunia, and decrease of libido 2

Other Notable Effects

• Proctitis and fleeting joint pains sometimes resembling "serum sickness" 2
• Rare cases of pancreatitis, which generally abate on withdrawal of the drug 2
• Rare psychiatric effects including mania have been documented, though this is an uncommon side effect 6

Duration-Related Safety Concerns

The standard recommended duration for metronidazole treatment is 10 days for most indications, with prolonged courses beyond 14 days avoided due to safety concerns 4

• Extension to 14 days may be considered only in cases where patients have shown improvement but not complete symptom resolution by 10 days 4
• The risk of cumulative neurotoxicity increases significantly with repeated or prolonged courses 7, 4

Critical Clinical Pitfall

Clinicians must remain vigilant for evidence of neurotoxicity in metronidazole-treated patients, especially those on prolonged or high-dose therapy, as peripheral neuropathy can be persistent and potentially irreversible even after drug discontinuation 2, 5. Patients should be instructed to immediately report any neurologic symptoms such as numbness, tingling, or paresthesias 2.