What are the side effects of metronidazole?

Side Effects of Metronidazole

Metronidazole causes gastrointestinal side effects in approximately 12% of patients, peripheral neuropathy with prolonged use, and a disulfiram-like reaction with alcohol—patients must be warned to stop the drug immediately if neurologic symptoms develop. 1

Gastrointestinal Side Effects

• Nausea is the most common adverse reaction, occurring in about 12% of patients, sometimes accompanied by headache, anorexia, and vomiting 1
• Diarrhea, epigastric distress, abdominal cramping, and constipation are frequently reported 1
• A sharp, unpleasant metallic taste is common and not unusual 1
• Furry tongue, glossitis, and stomatitis may occur, often associated with Candida overgrowth during therapy 1
• The high frequency of gastrointestinal side effects prompts some providers to prefer intravaginal routes when available to avoid systemic effects 2

Neurological Side Effects (Most Serious)

Peripheral Neuropathy

• Peripheral neuropathy is characterized mainly by numbness or paresthesia of an extremity and can be persistent 1
• The prevalence ranges from 21-39% in some populations 3
• Prolonged or repeated courses of metronidazole should be avoided due to cumulative risk of neurotoxicity, which is typically reversible upon discontinuation 2, 4
• The risk increases significantly with high doses (>140 grams cumulative) or prolonged therapy (>10 weeks) 5

Central Nervous System Effects

• Convulsive seizures can occur as a serious adverse reaction 1
• Dizziness, vertigo, incoordination, ataxia, confusion, irritability, depression, weakness, and insomnia have been reported 1
• Metronidazole-induced encephalopathy is rare but can cause dysarthria, ataxic gait, and altered mental status 6, 5
• MRI findings in encephalopathy show symmetric hyperintense dentate nuclei lesions and T2/FLAIR hyperintensities in the corpus callosum 6, 5
• Neurotoxic effects including seizures have been reported after 5-7 days of high doses (6-10.4 g every other day) 1

Disulfiram-Like Reaction with Alcohol

• Patients must avoid alcohol during metronidazole treatment and for 24 hours after completion to prevent disulfiram-like reaction 3, 2, 4
• If patients drink alcoholic beverages while on metronidazole, they may experience abdominal distress, nausea, vomiting, flushing, or headache 1
• A modification of the taste of alcoholic beverages has also been reported 1

Hematologic Effects

• Reversible neutropenia (leukopenia) can occur 1
• Reversible thrombocytopenia is rare 1

Cardiovascular Effects

• Flattening of the T-wave may be seen in electrocardiographic tracings 1

Hypersensitivity Reactions

• Urticaria, erythematous rash, flushing, nasal congestion, dryness of the mouth (or vagina or vulva), and fever have been reported 1

Genitourinary Effects

• Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure can occur 1
• Darkened urine has been reported in approximately one patient in 100,000, likely due to a metabolite with no clinical significance 1
• Proliferation of Candida in the vagina, dyspareunia, and decrease of libido have been noted 1

Other Adverse Effects

• Proctitis and fleeting joint pains sometimes resembling "serum sickness" 1
• Rare cases of pancreatitis, which generally abate on withdrawal of the drug 1

Critical Clinical Warnings

• Patients should be specifically warned about neurologic reactions and told to stop the drug and report immediately to their physicians if any neurologic symptoms occur 1
• There is no specific antidote for metronidazole overdose; management consists of symptomatic and supportive therapy 1
• Symptoms of overdose include nausea, vomiting, and ataxia 1
• Symptoms of metronidazole-induced neurotoxicity typically improve rapidly after cessation of the drug, often resolving within days 6, 7, 5