Does cefixime or fluconazole cause gastritis?

Gastrointestinal Side Effects of Cefixime and Fluconazole

Fluconazole can cause gastrointestinal side effects including nausea and vomiting, but it is not specifically associated with gastritis, while cefixime commonly causes gastrointestinal adverse effects including diarrhea and stool changes which may be mistaken for gastritis symptoms. 1, 2, 3

Fluconazole and Gastrointestinal Effects

• Fluconazole is associated with gastrointestinal adverse effects, primarily nausea and vomiting, but these are generally less severe than those seen with other azole antifungals like ketoconazole 1
• According to FDA labeling, the most common side effects of fluconazole include headache, diarrhea, nausea, and upset stomach, but gastritis is not specifically listed as a common adverse effect 3
• Gastrointestinal symptoms with fluconazole are typically mild to moderate and transient, occurring in approximately 10-40% of patients, though this is significantly less than with ketoconazole 1

Cefixime and Gastrointestinal Effects

• Cefixime has a well-documented association with gastrointestinal adverse effects, with the FDA label specifically noting that gastrointestinal events were reported in 30% of adult patients 2
• The most common gastrointestinal side effects of cefixime include diarrhea (16%), loose or frequent stools (6%), abdominal pain (3%), nausea (7%), dyspepsia (3%), and flatulence (4%) 2
• In comparative studies, cefixime was associated with a significantly higher incidence of drug-related gastrointestinal adverse events (18%) compared to other cephalosporins like cefuroxime axetil (10%) 4

Comparison of Gastrointestinal Effects

• In clinical trials, approximately 5% of patients discontinued cefixime therapy due to drug-related adverse reactions, primarily gastrointestinal in nature 2, 5
• The incidence of gastrointestinal adverse events with cefixime varies widely across studies, ranging from 1.4% to 38.6%, with higher rates reported in US clinical trials compared to studies conducted in other countries 5
• Dosing frequency affects the incidence of gastrointestinal side effects with cefixime, with once-daily dosing (400 mg) showing a higher incidence of gastrointestinal adverse effects than twice-daily dosing (200 mg) 6

Specific Concerns About Gastritis

• While neither drug is specifically indicated to cause gastritis in the FDA labeling, the gastrointestinal symptoms from either medication could be mistaken for or exacerbate existing gastritis 2, 3
• One study specifically examining cefixime in combination with cimetidine for Helicobacter pylori suppression in gastric ulcer patients did not report worsening of gastritis as an adverse effect 7
• Clostridium difficile-associated diarrhea has been reported with cefixime use, which can present with symptoms that might be confused with gastritis but represents a different pathological process 2

Clinical Recommendations

• For patients with a history of gastritis or gastrointestinal sensitivity, cefixime should be used with caution and potentially at a lower twice-daily dosing schedule rather than once daily to minimize gastrointestinal effects 5, 6
• If gastrointestinal symptoms develop during treatment with either medication, they should be monitored closely, as symptoms are usually mild and transient but occasionally can indicate more serious conditions like pseudomembranous colitis 2
• For patients requiring either medication who have a history of gastritis, fluconazole may be better tolerated from a gastrointestinal perspective than cefixime, though individual patient responses may vary 1, 5

Monitoring and Management

• Patients taking cefixime should be monitored for gastrointestinal symptoms, particularly during the first few days of treatment when such effects are most likely to occur 8
• If severe gastrointestinal symptoms develop during treatment with either medication, consideration should be given to discontinuing the drug and selecting an alternative agent 2, 3
• For patients with pre-existing gastrointestinal conditions who require these medications, administering cefixime with food may help reduce gastrointestinal irritation, while fluconazole can be taken with or without food 3, 8