What are the side effects of Flagyl (metronidazole)?

Side Effects of Flagyl (Metronidazole)

Metronidazole is associated with gastrointestinal side effects, a disulfiram-like reaction with alcohol, peripheral neuropathy with prolonged therapy, and rare but serious neuropsychiatric effects including seizures and encephalopathy. 1, 2

Common Side Effects

Gastrointestinal Effects

• Nausea occurs in approximately 12% of patients, sometimes accompanied by headache, anorexia, and vomiting 2
• Diarrhea, epigastric distress, abdominal cramping, and constipation are frequently reported 2, 3
• These gastrointestinal effects are generally mild to moderate in severity 3

Oral and Taste Disturbances

• A sharp, unpleasant metallic taste is common and not unusual 2
• Furry tongue, glossitis, and stomatitis may occur, often associated with sudden Candida overgrowth during therapy 2
• Dryness of the mouth has been reported 2

Urine Discoloration

• Darkened urine occurs in approximately 1 in 100,000 patients 2
• Reddish discoloration of urine has been documented and typically resolves within 24 hours of discontinuing metronidazole 4
• This pigmentation is likely a metabolite of metronidazole and has no clinical significance 2

Serious Neurological Side Effects

Peripheral Neuropathy

• Peripheral neuropathy is characterized mainly by numbness or paresthesia of an extremity 2
• Persistent peripheral neuropathy has been reported with prolonged administration 1, 2
• Patients should be specifically warned about this reaction and told to stop the drug immediately if any neurologic symptoms occur 2

Central Nervous System Effects

• Convulsive seizures represent one of the two most serious adverse reactions 2
• Dizziness, vertigo, incoordination, ataxia, confusion, irritability, depression, weakness, and insomnia have been reported 2
• Serious neurotoxicity, optic neuropathy, and encephalopathy occur in rare cases 3
• Neuropsychiatric effects appear to be dose- and serum concentration-related, with symptoms resolving within 24-48 hours after discontinuation 5
• Higher doses increase the likelihood of anxiety symptoms 5

Critical Safety Warning

• Repeated or prolonged courses of metronidazole should be avoided due to the risk of cumulative and potentially irreversible neurotoxicity 5, 6, 7
• This risk is particularly dangerous in patients with impaired drug clearance states 5

Alcohol Interaction (Disulfiram-Like Reaction)

• If patients drink alcoholic beverages while taking metronidazole, they may experience abdominal distress, nausea, vomiting, flushing, or headache 1, 2
• This reaction is similar to disulfiram (Antabuse) and results from accumulation of acetaldehyde in the blood 8
• A modification of the taste of alcoholic beverages has also been reported 2
• One case of sudden death has been documented due to cardiac dysrhythmia from acetaldehyde toxicity in a patient taking metronidazole with ethanol 8

Hematologic Effects

• Reversible neutropenia (leukopenia) can occur 2
• Reversible thrombocytopenia occurs rarely 2
• Metronidazole lacks the predictable irreversible hematologic toxicity seen with chloramphenicol 9

Cardiovascular Effects

• Flattening of the T-wave may be seen on electrocardiographic tracings 2
• Acetaldehyde (from alcohol interaction) is cardiotoxic and arrhythmogenic 8

Hypersensitivity Reactions

• Urticaria, erythematous rash, flushing, nasal congestion, dryness of mouth/vagina/vulva, and fever have been reported 2

Genitourinary Effects

• Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure 2
• Proliferation of Candida in the vagina, dyspareunia, and decrease of libido 2

Other Rare Effects

• Rare cases of pancreatitis, which generally abate on withdrawal of the drug 2
• Proctitis and fleeting joint pains sometimes resembling "serum sickness" 2

Important Clinical Considerations

Monitoring Requirements

• Patients should be specifically warned about neurologic reactions and instructed to stop the drug and report immediately if any neurologic symptoms occur 2
• Assess neurological status at each clinical encounter when using metronidazole 7

Common Pitfall to Avoid

• Do not prescribe repeated or prolonged courses due to cumulative neurotoxicity risk 5, 6, 7
• Avoid use during intercurrent illness in patients with chronic kidney disease to prevent further kidney damage 7

Tolerability Profile

• Metronidazole is generally well tolerated with mild to moderate side effects 3
• The limited side effects are generally tolerable, transient, or reversible 9
• Serious adverse effects, while documented, remain rare 3