What are the liver impacts of Mavenclad (cladribine)?

Liver Impacts of Mavenclad (Cladribine)

Mavenclad (cladribine) can cause liver injury including drug-induced liver injury (DILI), which is rare but potentially serious, requiring liver function screening before treatment initiation but not routine monitoring during treatment. 1

Hepatic Safety Profile

Cladribine's impact on the liver includes:

• Drug-induced liver injury (DILI): Rare but potentially serious adverse reaction reported in post-marketing surveillance 1
• Common hepatobiliary adverse reactions: Abnormal hepatic function, ALT increases, liver disorders, hepatic failure, jaundice, hepatotoxicity, and hypertransaminasemia 2
• Clearance mechanism: Cladribine is cleared primarily by the liver, while its metabolites are excreted in the urine 3

Monitoring Recommendations

Based on current evidence:

• Pre-treatment screening: Patients should be screened for liver dysfunction before starting treatment 1
• Ongoing monitoring: Routine hepatic monitoring during treatment is not required according to recent expert consensus 1
• Action required: Cladribine must be withdrawn if signs and symptoms of DILI develop 1

Risk Factors and Special Populations

Hepatic Impairment

• Caution advised: There are inadequate data on dosing patients with hepatic insufficiency 3
• FDA guidance: Until more information is available, caution is advised when administering cladribine to patients with known or suspected hepatic impairment 3

Demographic Considerations

• Gender and age: The majority of cladribine-induced hepatic adverse reactions occur in female patients between 18-65 years of age 2
• Seriousness: 93% of reported hepatobiliary adverse reactions were classified as serious 2

Clinical Evidence of Liver Safety

Recent clinical evidence supports cladribine's relatively favorable liver safety profile:

• FinClad Study: In patients who discontinued fingolimod due to elevated liver enzymes (>3x upper limit of normal), AST and ALT levels normalized and remained within normal range after transition to cladribine (p<0.001) with no reports of liver-related adverse events 4

• Pharmacokinetic data: Cladribine pharmacokinetics are linear and time-independent, with a volume of distribution of 480-490 L and approximately 20% plasma protein binding 5

Comparison to Other MS Treatments

• Cladribine has demonstrated a more favorable hepatic safety profile compared to some other MS treatments:
  • Fingolimod has been associated with higher rates of transaminase elevations 4
  • Cladribine emerges as a safer option for patients with previous drug-induced liver injury from other MS medications 4

Practical Recommendations

1. Before starting Mavenclad:

   • Complete liver function testing
   • Screen for pre-existing liver conditions
   • Assess for other hepatotoxic medications

2. During treatment:

   • No routine liver monitoring is required
   • Educate patients about symptoms of liver injury (jaundice, dark urine, right upper quadrant pain, fatigue)
   • Immediately discontinue if signs of DILI develop

3. After treatment:

   • Monitor for any delayed hepatic effects, especially in high-risk patients

Conclusion

While cladribine can cause liver injury in rare cases, its overall hepatic safety profile is favorable compared to some other MS treatments. The risk of serious liver injury appears to be low, but pre-treatment screening and vigilance for symptoms of liver injury remain important aspects of patient management.