Can Meropenem Cause Jaundice?
Yes, meropenem can cause jaundice through drug-induced liver injury, including severe cholestatic hepatitis and vanishing bile duct syndrome (VBDS), though this is a rare adverse effect.
Mechanism and Clinical Presentation
Meropenem-induced liver injury typically manifests as:
- Mixed hepatocellular and cholestatic pattern with jaundice and pruritus developing within 2-3 days to 3 weeks after initiation 1, 2, 3
- Vanishing bile duct syndrome (VBDS), a rare but potentially life-threatening complication characterized by progressive destruction and disappearance of intrahepatic bile ducts 2, 4
- Rapid onset: Elevated liver enzymes can appear within 48 hours of starting meropenem, with peak elevations occurring at 3-5 days 1, 3
Evidence Quality and Strength
The evidence consists of multiple case reports documenting meropenem-induced hepatotoxicity with jaundice 1, 2, 3, 4. While case reports represent lower-level evidence, the consistent pattern across multiple reports—including positive rechallenge cases where jaundice recurred upon meropenem reintroduction—strongly supports causality 3, 4. The Naranjo adverse drug reaction probability scale indicated a "probable relationship" (score of 6) between meropenem and VBDS in documented cases 2.
Risk Factors and Special Populations
Renal impairment increases risk considerations:
- Meropenem is primarily eliminated renally (approximately 70% renal clearance), with 70% recovered unchanged in urine over 12 hours 5
- Renal dysfunction alters drug clearance predictably, though hepatotoxicity risk specifically in renal impairment is not well-characterized 5
Hepatic impairment:
- Baseline hepatic functional impairment does not alter meropenem disposition and no dosing adjustments are required 5
- However, pre-existing liver disease may complicate recognition of drug-induced injury
Context from general jaundice epidemiology:
- Drug-induced liver injury accounts for 0.5-7% of severe jaundice cases depending on the clinical setting 6
- Medication toxicity is recognized as one of the four most common causes of jaundice in the United States 6
Clinical Recognition and Management
Monitor for these specific findings:
- Jaundice with pruritus appearing within days to weeks of meropenem initiation 1, 2
- Elevated transaminases (ALT >1000 U/L documented), alkaline phosphatase, and bilirubin 3
- Mixed hepatocellular/cholestatic pattern on liver function tests 1, 2, 3
Diagnostic approach:
- Exclude other causes of cholestasis including biliary obstruction, infectious etiologies, and autoimmune conditions 2, 4
- Consider liver biopsy if cholestasis persists despite drug discontinuation to evaluate for VBDS 2
Management algorithm:
- Immediately discontinue meropenem upon suspicion of drug-induced liver injury 1, 2, 3, 4
- Symptomatic and laboratory improvement typically occurs within days to weeks after cessation 1, 4
- Do not rechallenge with meropenem if drug-induced liver injury is confirmed 3, 4
- Switch to alternative antibiotic therapy (e.g., ciprofloxacin, other non-carbapenem agents) 4
Critical Pitfalls
Delayed recognition: The rapid onset (within 48 hours possible) requires high clinical suspicion when liver enzymes rise shortly after meropenem initiation 3.
Rechallenge risk: Documented cases show immediate recurrence of liver injury upon meropenem reintroduction, with even more severe elevations 3, 4. Avoid rechallenge once drug-induced injury is suspected.
VBDS consideration: Persistent cholestasis beyond several weeks after drug discontinuation should prompt evaluation for VBDS, which may require months for resolution and carries significant morbidity 2, 4.
Cross-reactivity: Beta-lactam cross-reactivity for hepatotoxicity has been documented, suggesting caution with other carbapenems if meropenem-induced liver injury occurs 3.