What cardiac monitoring and safety measures are required when initiating KRAZATI (adagrasib) for KRAS G12C‑mutated non‑small cell lung cancer?

Cardiac Monitoring and Safety Measures for KRAZATI (Adagrasib)

KRAZATI requires baseline ECG assessment and ongoing cardiac monitoring due to its concentration-dependent QTc prolongation risk, with 6% of patients developing QTc ≥501 msec and 11% experiencing increases >60 msec from baseline. 1

Pre-Treatment Cardiac Assessment

Obtain a baseline ECG and comprehensive electrolyte panel (potassium, magnesium) before initiating KRAZATI. 1 This is critical because adagrasib causes dose-dependent QTc interval prolongation that increases the risk of ventricular tachyarrhythmias, including torsades de pointes and sudden death. 1

Absolute Contraindications

• Congenital long QT syndrome 1
• Concurrent QTc prolongation at baseline 1

High-Risk Populations Requiring Enhanced Monitoring

Patients with the following conditions warrant more frequent ECG surveillance: 1

• Congestive heart failure
• Bradyarrhythmias
• Baseline electrolyte abnormalities (hypokalemia, hypomagnesemia)
• Inability to avoid concomitant QT-prolonging medications

Ongoing Cardiac Monitoring Protocol

Monitor ECGs and electrolytes (particularly potassium and magnesium) during treatment as clinically indicated, with mandatory reassessment when adding any new medications or if cardiac symptoms develop. 1

Drug Interaction Management

Avoid all concomitant medications with known QT-prolonging potential. 1 This is a critical safety measure because the combination of multiple QT-prolonging agents dramatically increases torsades de pointes risk. 2

Electrolyte Management

Correct any electrolyte abnormalities immediately before continuing KRAZATI. 1 Hypokalemia and hypomagnesemia are independent risk factors for QT prolongation and must be normalized to reduce arrhythmia risk. 3, 2

Dose Modification Algorithm for QTc Prolongation

The FDA label provides specific thresholds for intervention: 1

• QTc ≥501 msec or increase >60 msec from baseline:

  • Withhold KRAZATI immediately
  • Correct electrolyte abnormalities
  • Repeat ECG within 1 week
  • Resume at reduced dose (400 mg twice daily) only after QTc returns to <481 msec

• Recurrent QTc prolongation despite dose reduction:

  • Permanently discontinue KRAZATI 1

Additional Cardiovascular Considerations

While the primary cardiac concern is QTc prolongation, clinicians should maintain awareness of the comprehensive cardiovascular risk assessment framework recommended by ASCO for cancer patients receiving potentially cardiotoxic therapies. 3 This includes:

• Screening for cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity, smoking) before treatment initiation 3
• Active management of modifiable risk factors throughout therapy 3

Clinical Pearls and Common Pitfalls

Do not assume a normal baseline ECG eliminates the need for ongoing monitoring—adagrasib causes concentration-dependent QTc prolongation that develops during treatment. 1 The median time to first onset of adverse events with adagrasib is typically within the first few weeks, making early monitoring particularly important. 1

Patients with multiple cardiovascular risk factors (≥2 risk factors including smoking, hypertension, diabetes, dyslipidemia, obesity) or age ≥60 years require heightened vigilance, as these populations have increased baseline cardiac dysfunction risk. 3

Avoid the common error of continuing KRAZATI when QTc exceeds 500 msec—this threshold mandates immediate drug interruption regardless of symptoms. 1 Waiting for symptoms before acting significantly increases the risk of life-threatening arrhythmias.