What are the gastrointestinal (GI) side effects of Ceftriaxone and how are they managed?

Ceftriaxone Gastrointestinal Side Effects

Diarrhea is the most common GI side effect of ceftriaxone, occurring in 2.7% of patients, with rare but serious complications including pseudomembranous colitis and pancreatitis. 1

Common GI Side Effects

Diarrhea/Loose Stools

• Incidence: 2.7% in FDA-reported cases, making it the most frequent GI adverse effect 1
• Pediatric populations show higher rates at 5.63% 2
• In most cases, diarrhea does not require discontinuation of therapy 3
• One study documented diarrhea development after 7 days of therapy in a patient with high biliary clearance of ceftriaxone 4

Nausea and Vomiting

• Reported in less than 1% of patients 1
• Generally mild and self-limiting 1

Other Less Common GI Effects

• Dysgeusia (altered taste): <1% 1
• Abdominal pain: <0.1% 1
• Dyspepsia: <0.1% 1
• Flatulence: <0.1% 1

Serious GI Complications

Pseudomembranous Colitis (C. difficile)

• Can occur during or after antibacterial treatment 1
• One documented case involved a toxin-producing Clostridium difficile isolated after 7 days of ceftriaxone therapy 4
• Ceftriaxone causes pronounced changes in colonic microflora with almost total disappearance of normal bacteria and overgrowth of yeasts and enterococci 4
• Requires immediate discontinuation of ceftriaxone if suspected 1

Pancreatitis

• Rare but documented complication, potentially due to ceftriaxone precipitation in bile 5
• Presents with dyspepsia, nausea, epigastric pain, and fever, typically around day 8 of treatment 5
• Laboratory findings include elevated lipase and amylase 5
• Prompt discontinuation results in normalization within 72 hours 5

Other Serious GI Events

• Colitis: <0.1% 1
• Pancreatitis: rare postmarketing reports 1
• Stomatitis and glossitis: rare postmarketing reports 1

Mechanism and Risk Factors

Biliary Excretion

• Ceftriaxone has significant biliary excretion with large individual variation (0-16 ml/min) 4
• High biliary clearance correlates with increased risk of diarrhea 4
• Biliary precipitation can lead to gallbladder sludge, biliary lithiasis, and potentially pancreatitis 1, 5

Microflora Disruption

• Marked disruption of intestinal microflora with disappearance of staphylococci, streptococci, and enterobacteria 4
• Overgrowth of yeasts and enterococci predisposes to secondary infections 4

Management Strategies

For Mild Diarrhea

• Continue ceftriaxone in most cases as diarrhea typically does not require therapy change 3
• Provide supportive care with hydration 3
• Monitor for progression to more severe symptoms 1

For Suspected C. difficile Colitis

• Immediately discontinue ceftriaxone 1
• Test for C. difficile toxin 4
• Initiate appropriate treatment for pseudomembranous colitis if confirmed 1

For Suspected Pancreatitis

• Discontinue ceftriaxone immediately 5
• Check lipase and amylase levels 5
• Obtain abdominal imaging if clinical suspicion is high 5
• Expect rapid improvement (within 72 hours) after drug discontinuation 5

Clinical Pitfalls to Avoid

• Do not ignore persistent diarrhea beyond day 7 of therapy, as this may signal C. difficile infection 4
• Do not overlook biliary complications in patients developing upper abdominal pain, as ceftriaxone can precipitate in bile 1, 5
• Do not assume all GI symptoms are benign - rare but serious complications like pancreatitis require prompt recognition 5
• Consider alternative antibiotics in patients with previous severe GI reactions to cephalosporins 6