Side Effects of Metronidazole and Cefuroxime
Metronidazole (Flagyl) Side Effects
Metronidazole is generally well-tolerated but carries important neurologic risks that require immediate discontinuation if symptoms develop. 1
Common Side Effects (Gastrointestinal)
- Nausea occurs in approximately 12% of patients, sometimes accompanied by headache, anorexia, and occasionally vomiting 1
- Diarrhea, epigastric distress, abdominal cramping, and constipation are frequently reported 1
- Sharp, unpleasant metallic taste is common and not unusual 1
- Furry tongue, glossitis, and stomatitis may occur, potentially associated with Candida overgrowth during therapy 1
Serious Neurologic Side Effects (Require Immediate Discontinuation)
- Peripheral neuropathy characterized mainly by numbness or paresthesia of an extremity 1
- Convulsive seizures 1
- Persistent peripheral neuropathy has been reported with prolonged administration; patients must stop the drug immediately and report any neurologic symptoms 1
- Dizziness, vertigo, incoordination, ataxia, confusion, irritability, depression, weakness, and insomnia 1
- Rare cases of neurotoxicity, optic neuropathy, and encephalopathy have been documented 2
Hematologic Effects
Other Notable Side Effects
- Cardiovascular: Flattening of the T-wave on electrocardiographic tracings 1
- Hypersensitivity: Urticaria, erythematous rash, flushing, nasal congestion, dryness of mouth/vagina/vulva, and fever 1
- Genitourinary: Dysuria, cystitis, polyuria, incontinence, pelvic pressure, and darkened urine (occurs in approximately 1 in 100,000 patients) 1
- Disulfiram-like reaction: If patients consume alcohol, they may experience abdominal distress, nausea, vomiting, flushing, or headache 1
- Rare cases of pancreatitis that generally resolve upon drug withdrawal 1
Long-Term Concerns
- Repeated or prolonged courses should be avoided due to risk of cumulative and potentially irreversible neurotoxicity 3
- Metronidazole is carcinogenic in animals and mutagenic in vitro, though increased cancer incidence has not been demonstrated in humans followed for relatively short periods 4
- The carcinogenic potential in humans remains uncertain due to long latency periods involved in carcinogenesis 4
Cefuroxime (Ceftin) Side Effects
Cefuroxime is generally well-tolerated with primarily mild to moderate adverse effects that are reversible upon discontinuation. 5, 6
Common Side Effects
- Local reactions: Thrombophlebitis occurs in approximately 1 in 60 patients with IV administration 5
- Gastrointestinal symptoms occur in 1 in 150 patients, including diarrhea (1 in 220 patients) and nausea (1 in 440 patients) 5
- The majority of adverse events are mild to moderate in intensity and reversible upon discontinuation 6
Hypersensitivity Reactions
- Rash occurs in approximately 1 in 125 patients 5
- Pruritus, urticaria, and positive Coombs' test each occur in fewer than 1 in 250 patients 5
- Rare cases of anaphylaxis, drug fever, erythema multiforme, interstitial nephritis, toxic epidermal necrolysis, and Stevens-Johnson syndrome have been reported 5
Hematologic Effects
- Decrease in hemoglobin and hematocrit observed in 1 in 10 patients 5
- Transient eosinophilia in 1 in 14 patients 5
- Transient neutropenia (fewer than 1 in 100 patients) and leukopenia (1 in 750 patients) 5
- Rare reports of thrombocytopenia 5
Hepatic Effects
- Transient rise in SGOT and SGPT (1 in 25 patients) 5
- Elevated alkaline phosphatase (1 in 50 patients) 5
- Elevated LDH (1 in 75 patients) 5
- Elevated bilirubin (1 in 500 patients) 5
Serious Adverse Effects
- Pseudomembranous colitis may occur during or after antibacterial treatment 5
- Seizures, particularly in patients with renal impairment when dosage is not reduced; if seizures occur, the drug should be discontinued 5
- Cutaneous vasculitis, angioedema, acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction 5
Renal Effects
- Elevations in serum creatinine and/or blood urea nitrogen and decreased creatinine clearance have been observed, though their relationship to cefuroxime is unknown 5
Cephalosporin Class Effects
- Vomiting, abdominal pain, colitis, vaginitis including vaginal candidiasis 5
- Toxic nephropathy, hepatic dysfunction including cholestasis 5
- Aplastic anemia, hemolytic anemia, hemorrhage 5
- Prolonged prothrombin time, pancytopenia, agranulocytosis 5
Combined Use of Metronidazole and Cefuroxime
When used together for surgical prophylaxis or treatment of intra-abdominal infections, the combination is generally well-tolerated with no significant additional adverse effects beyond those of each individual agent. 7, 8
Clinical Evidence on Combined Safety
- In a prospective cohort study of 5,279 women undergoing hysterectomy, cefuroxime combined with metronidazole showed no significant increase in adverse effects compared to cefuroxime alone 8
- The combination is endorsed by international surgical prophylaxis guidelines (WHO, NICE) and IDSA for clean-contaminated procedures 7
- In brain abscess treatment, cefotaxime (similar third-generation cephalosporin) combined with metronidazole was highly effective but associated with a high frequency of reversible side effects, with 38 of 66 patients experiencing reversible adverse reactions 9
Important Caveats for Combined Use
- The combination does not cover Pseudomonas aeruginosa, MRSA, or ESBL-producing Enterobacteriaceae; broader agents are required when these pathogens are suspected 7
- Prophylactic courses should not exceed 24 hours post-operatively; longer durations constitute therapeutic treatment rather than prophylaxis 7
- Patients with severe β-lactam allergy should receive alternative regimens such as fluoroquinolone plus metronidazole or clindamycin plus aminoglycoside 7
- Monitor specifically for neurologic symptoms with metronidazole and instruct patients to report immediately 1
- Avoid alcohol consumption during metronidazole therapy to prevent disulfiram-like reactions 1