Gastrointestinal Side Effects of Cefixime
Cefixime commonly causes gastrointestinal side effects, with diarrhea and stool changes being the most frequent adverse reactions, occurring in approximately 6.6% of patients, though these effects are typically mild to moderate, transient, and resolve within the first few days of treatment. 1, 2
Common GI Side Effects
The FDA-approved labeling for cefixime identifies the following gastrointestinal adverse reactions 1:
- Diarrhea and loose stools - most frequently reported, particularly in pediatric patients receiving suspension formulations 1
- Nausea 1
- Abdominal pain 1
- Vaginitis and genital candidiasis (related to GI flora disruption) 1
Severity and Time Course
- Most GI adverse effects are mild to moderate in severity and do not require discontinuation of therapy 3, 2
- Symptoms typically occur within the first few days of treatment and are transient in nature 3
- The incidence of GI disturbances in pediatric patients is comparable to that seen in adults 1
Serious GI Complications
Pseudomembranous colitis has been reported with cefixime use, as with other cephalosporins, and should be considered in any patient who develops diarrhea during or after treatment 4. This represents a potentially life-threatening complication requiring immediate discontinuation and appropriate management 1.
Dosing-Related Considerations
The once-daily 400 mg dose shows a higher incidence of gastrointestinal adverse effects compared to 200 mg administered twice daily 5. Therefore:
- Administer the total daily dose in two divided doses (200 mg twice daily) rather than as a single 400 mg dose to minimize GI side effects 5
- This dosing strategy maintains therapeutic efficacy while improving tolerability 5
Management Strategies
To minimize gastrointestinal side effects 1:
- Administer cefixime with food - absorption is not significantly affected (40-50% bioavailability maintained), but time to peak concentration increases by approximately 0.8 hours, which may reduce GI irritation 1
- Use divided dosing (200 mg twice daily instead of 400 mg once daily) 5
- Monitor for severe or persistent diarrhea that could indicate pseudomembranous colitis 4
Clinical Pitfalls to Avoid
- Do not dismiss persistent or severe diarrhea as a benign side effect - always consider Clostridioides difficile infection, particularly if symptoms worsen or persist beyond the first few days 1, 4
- Do not assume all GI symptoms are drug-related - rule out other causes of diarrhea, especially in immunocompromised patients or those with recent healthcare exposure 1
- Avoid single daily dosing when GI tolerability is a concern - split the dose to 200 mg twice daily 5