Vincristine Dose Modification for Abnormal Liver Function Tests

A 50% reduction in the dose of vincristine is recommended for patients having a direct serum bilirubin value above 3 mg/100 mL. 1

Rationale for Dose Adjustment

Vincristine is primarily metabolized by the liver, and impaired hepatic function can lead to decreased drug clearance, resulting in increased drug exposure and potential toxicity 2
Elevated serum alkaline phosphatase has been significantly associated with increased vincristine plasma concentration and greater neurotoxicity, suggesting impaired drug elimination when liver function is compromised 2
Hepatotoxicity following vincristine therapy has been documented, with transient elevations in liver enzymes (transaminases rising 2-6 times normal values) observed within days of administration 3

For patients with direct bilirubin >3 mg/dL: Reduce vincristine dose by 50% 1
For patients with milder liver dysfunction (bilirubin <3 mg/dL but elevated transaminases):
- Monitor liver function tests more frequently 4
- Consider dose reduction based on the degree of liver dysfunction and baseline liver function 4

Assess liver function before each cycle of vincristine administration 4
Increase monitoring frequency when liver test elevations are detected 4
Monitor for clinical signs of neurotoxicity, which may be exacerbated in patients with liver dysfunction 2
Pay particular attention to:
- Serum alkaline phosphatase levels, as elevations correlate with increased risk of neurotoxicity even without other evidence of liver dysfunction 2
- Transaminase levels, which may rise 2-6 times normal values within 6 days of vincristine administration 3

Age is a risk factor for chemotherapy-induced hepatopathy with vincristine-containing regimens, with children under 36 months having a significantly higher risk (15% vs 4% in older children) 5
Patients receiving concurrent hepatotoxic medications or radiation therapy that includes the liver may be at increased risk for vincristine-related hepatotoxicity 3
Vincristine should not be given to patients while they are receiving radiation therapy through ports that include the liver 1

If significant hepatotoxicity develops during vincristine treatment:
- Hold chemotherapy until improvement if ALT ≥8-10× ULN in patients with normal baseline liver function 4
- For patients with pre-existing abnormal liver function, use multiples of individual baseline values rather than fixed ULN thresholds to guide management decisions 4
- Consider rechallenge at reduced doses once liver function improves, based on benefit-risk assessment 4

Using the same action thresholds for patients with normal and abnormal baseline liver function tests is inadequate 4
Failing to monitor alkaline phosphatase levels, which may predict neurotoxicity even when other liver function tests are normal 2
Administering vincristine to patients receiving radiation therapy that includes the liver 1