Can ciprofloxacin (Cipro) cause Drug-Induced Liver Injury (DILI)?

Can Ciprofloxacin Cause Drug-Induced Liver Injury (DILI)?

Yes, ciprofloxacin can cause drug-induced liver injury, though it occurs rarely; the FDA-approved drug label reports liver function test abnormalities in 1.3% of patients, and while most cases are mild and self-limited, severe hepatotoxicity including fatal hepatic failure has been documented in post-marketing surveillance. 1

Incidence and Clinical Significance

• Ciprofloxacin-associated liver injury is uncommon but well-documented, with liver function test abnormalities occurring in approximately 1.3% of treated patients in clinical trials 1
• The drug was discontinued due to adverse events in only 1% of orally treated patients, indicating most hepatic reactions are mild 1
• Post-marketing surveillance has identified more severe cases, including hepatic failure with fatal outcomes, though these remain rare 1, 2
• As of 2004, only 14 cases of ciprofloxacin-associated liver injuries had been reported in the literature, though this number has increased with continued use 3

Pattern and Presentation of Hepatotoxicity

• Ciprofloxacin can cause various patterns of liver injury, including hepatocellular, cholestatic, and mixed patterns 4, 5, 2
• The hepatocellular pattern (elevated ALT/AST) is more commonly reported, though cholestatic injury with jaundice and elevated alkaline phosphatase also occurs 5, 2
• Onset typically ranges from 2 days to 2 weeks after starting treatment, though delayed presentations up to several weeks have been documented 5, 3
• Clinical manifestations include asymptomatic transaminase elevations, symptomatic hepatitis with nausea/vomiting/abdominal pain, jaundice, and rarely acute liver failure 5, 2

FDA-Labeled Adverse Effects

• The FDA drug label specifically lists "changes in liver function tests" as a common side effect and "yellowing of the skin or eyes" as a serious reaction requiring immediate discontinuation 1
• Hepatic failure (including fatal cases) and hepatic necrosis are explicitly mentioned in post-marketing adverse event reports 1
• Patients should stop ciprofloxacin immediately if they develop unexplained yellowing of skin/eyes or dark urine, as these indicate serious liver injury 1

Clinical Context and Risk Factors

• Ciprofloxacin is mentioned in guidelines as an alternative antibiotic for spontaneous bacterial peritonitis, though the EASL guidelines note concern about amoxicillin-clavulanate being "associated with a high rate of drug induced liver injury" without specifically highlighting ciprofloxacin as problematic 6
• Patients with pre-existing liver disease may be at higher risk for adverse outcomes if DILI occurs, though susceptibility to developing DILI is not necessarily increased 6
• Idiosyncratic DILI from ciprofloxacin is more likely in patients with comorbidities 5

Management Approach

• Immediate discontinuation of ciprofloxacin is essential when DILI is suspected, particularly if ALT is ≥3 times upper limit of normal with symptoms or ≥5 times upper limit of normal without symptoms 6, 7
• Exclude other causes of liver injury including viral hepatitis (A, B, C, E), biliary disease, alcohol, acetaminophen, other hepatotoxic drugs, and herbal supplements before attributing injury to ciprofloxacin 6, 7
• Most cases resolve with drug cessation alone, though some severe cases have required corticosteroid therapy 3
• Timely diagnosis and discontinuation can prevent progression to severe liver damage and reduce mortality 5

Important Clinical Pitfalls

• Do not rechallenge with ciprofloxacin after documented DILI, as recurrent drug-induced liver injury can occur and may be more severe 4
• Cross-reactivity with other antibiotics of different chemical structures (such as amoxicillin-clavulanate) has been documented, so careful antibiotic selection is needed after ciprofloxacin-induced DILI 4
• The rarity of severe ciprofloxacin hepatotoxicity may lead to delayed recognition; maintain high clinical suspicion in patients with unexplained liver injury who recently received ciprofloxacin 2, 3
• Liver biopsy findings may show extensive hepatocellular necrosis with eosinophilic infiltration or cholestatic hepatitis, but biopsy is not required for diagnosis 3, 2