Can meropenem cause cholestasis?

Meropenem Can Cause Cholestasis

Yes, meropenem can cause cholestasis, though it is an uncommon adverse effect that requires prompt recognition and discontinuation of the drug to prevent serious liver injury.

Evidence of Meropenem-Induced Cholestasis

The FDA drug label for meropenem explicitly lists "cholestatic jaundice/jaundice" among its adverse effects in the digestive system category 1. This official documentation confirms that cholestasis is a recognized adverse reaction to meropenem therapy.

Recent case reports provide further evidence of this association:

• A 2021 case report described an 83-year-old female who developed mixed hepatocellular and cholestatic liver injury with jaundice and pruritus within just three days of starting meropenem therapy 2.

• Multiple cases of meropenem-induced vanishing bile duct syndrome (VBDS), a severe form of drug-induced cholestasis, have been documented. In one case, a 60-year-old woman developed mixed hepatocellular and cholestatic liver injury with jaundice and pruritus three weeks after starting meropenem 3.

• A 2018 case report described a 63-year-old man who developed elevated liver enzymes with a mixed hepatocellular/cholestatic pattern within 48 hours of receiving meropenem, with recurrence upon rechallenge 4.

Mechanism and Clinical Presentation

According to the European Association for the Study of the Liver (EASL) guidelines, drug-induced cholestatic injury can occur through two major mechanisms 5:

1. Inhibition of hepatocellular transporter expression and/or function with alteration of bile secretion at the hepatocellular level
2. Induction of an idiosyncratic inflammatory or hypersensitive reaction at the bile ductular/cholangiocellular level

The clinical presentation typically includes:

• Elevated alkaline phosphatase (AP) >2× upper limit of normal (ULN)
• ALT/AP ratio (both elevated above ULN) <2
• Jaundice
• Pruritus
• In severe cases, progression to vanishing bile duct syndrome

Management Recommendations

When cholestasis is suspected during meropenem therapy:

1. Immediately discontinue meropenem - This is the primary and most effective treatment for drug-induced cholestasis 6.

2. Monitor liver function tests - Repeat blood tests within 7-10 days and continue monitoring until normalization (typically within 3 months) 6.

3. Consider alternative antibiotics - Based on culture results and antibiotic susceptibility testing, switch to an alternative antibiotic with a different mechanism of action.

4. Supportive care - For symptomatic management of pruritus, consider cholestyramine 4g up to four times daily as first-line treatment 5.

5. Consider ursodeoxycholic acid (UDCA) - May benefit approximately two-thirds of cases of drug-induced cholestasis, though evidence is limited 6.

Risk Factors and Prevention

Certain factors may increase the risk of meropenem-induced cholestasis:

• Pre-existing liver disease
• Advanced age
• Concomitant hepatotoxic medications
• Genetic variations in hepatobiliary transporters

To prevent serious outcomes:

• Obtain baseline liver function tests before starting meropenem in high-risk patients
• Monitor liver function tests during therapy, especially in prolonged courses
• Educate patients to report symptoms such as jaundice, dark urine, or pruritus immediately

Conclusion

While meropenem is generally well-tolerated with a favorable safety profile 7, clinicians should maintain awareness of its potential to cause cholestasis. Early recognition of drug-induced liver injury is crucial, and a high index of suspicion should be maintained, especially when other causes of cholestasis have been excluded.