What are the recommendations for a patient experiencing elevated Alanine Transaminase (ALT) levels, dizziness, and fatigue while on Tivdak (tisotumab vedotin)?

Management of ALT Elevation, Dizziness, and Fatigue in a Patient on Tivdak

For a patient experiencing elevated ALT (38), dizziness, and fatigue while on Tivdak (tisotumab vedotin), treatment should be continued with close monitoring as these symptoms do not meet criteria for drug discontinuation based on current guidelines.

Assessment of Current Symptoms

• ALT elevation to 38 is considered mild (<3× ULN) and does not meet discontinuation criteria for Tivdak therapy 1
• The combination of ALT elevation with fatigue and dizziness requires careful evaluation but does not automatically warrant drug discontinuation unless ALT reaches ≥3× ULN with symptoms 1
• Fatigue is a common adverse reaction reported in 36% of patients on Tivdak, while dizziness may be related to other factors 2

Monitoring Recommendations

• Confirm ALT elevation with repeat testing within 7-10 days to assess trend and reproducibility 1
• Monitor for additional symptoms such as nausea, vomiting, right upper quadrant pain, fever, or rash which would increase concern for drug-induced liver injury 1
• Implement accelerated monitoring of liver enzymes (every 2-5 days) if ALT continues to rise 3
• Evaluate for other potential causes of liver enzyme elevation and symptoms (medications, alcohol, viral hepatitis) 1

Specific Management Algorithm

For Current ALT Level (38):

• Continue Tivdak at current dose with close monitoring 4
• Repeat liver function tests within 7-10 days 1
• Assess for other causes of liver enzyme elevation 1

Criteria for Dose Modification:

• Consider dose interruption if:
  • ALT increases to ≥3× ULN with symptoms (severe fatigue, nausea, vomiting, right upper quadrant pain) 1
  • ALT increases to ≥5× ULN for more than 2 weeks 1
  • ALT increases to ≥8× ULN 1

Management of Dizziness and Fatigue:

• Evaluate for potential causes of dizziness (vestibular issues, medication effects, dehydration) 5
• Consider supportive measures for fatigue (adequate hydration, rest periods, nutrition assessment) 2, 6
• Monitor for worsening symptoms that may indicate more serious adverse effects 2

Specific Tivdak-Related Considerations

• Fatigue is one of the most common adverse reactions (36% of patients) with Tivdak, with grade 3-4 fatigue occurring in 6% of patients 2
• Monitor for other common adverse reactions including peripheral neuropathy (38%), conjunctival adverse reactions (37%), and hemorrhage (21%) 2
• Be vigilant for ocular adverse reactions which require specific management according to the FDA label 2

Important Pitfalls to Avoid

• Do not automatically discontinue Tivdak for mild, asymptomatic ALT elevations as this may be transient 3
• Do not ignore the combination of symptoms (ALT elevation, fatigue, dizziness) even if mild, as this requires closer monitoring 1
• Do not fail to implement the required eye care protocol for patients on Tivdak, as ocular adverse reactions are common 2, 6
• Do not overlook the potential for peripheral neuropathy which may present with dizziness and requires dose modification if it progresses 2

Follow-up Plan

• If ALT remains stable or decreases: continue current dosing with regular monitoring 4
• If ALT increases to ≥3× ULN with persistent symptoms: consider dose interruption per FDA guidelines 1, 2
• If symptoms resolve but ALT remains elevated: consider resuming at a reduced dose level (from 2 mg/kg to 1.3 mg/kg) 2
• If symptoms worsen or new symptoms develop: reevaluate immediately for potential drug discontinuation 2