Adagrasib has clear contraindications for patients with severe liver injury and QTc prolongation, and strict risk assessment and monitoring of relevant indicators are necessary. The following will explain from three aspects: classification of taboo populations, key points of clinical management, and special precautions.

1. Severe liver injury patient

(1) Contraindications: The liver is the main metabolic organ for drugs, and severe liver dysfunction (Child Pugh C grade) can lead to drug accumulation toxicity.

(2) Alternative plan: Other anti-tumor drugs metabolized by the kidneys need to be used, or a dosage adjustment plan (with the participation of clinical pharmacists for evaluation) needs to be adopted.

Patients with QTc prolongation

(1) Risk mechanism: The drug may prolong myocardial repolarization, and is contraindicated in patients with baseline QTc>500ms or a history of long QT syndrome.

(2) Monitoring requirements: An electrocardiogram should be performed before medication, and electrolytes (especially potassium and magnesium) should be regularly monitored during treatment to avoid the use of other QT prolonging drugs in combination.

3 Special Management Points

(1) Dynamic assessment of liver function: Patients with mild liver damage need to undergo ALT/AST testing every 2 weeks, while those with moderate to severe liver damage need to be monitored weekly and considered for dose reduction.

(2) Cardiac event prevention: When QTc>480ms occurs, medication should be suspended until baseline values are restored and the concomitant medication regimen adjusted.

4 Other Taboo Related Factors

(1) Drug interactions: Strong CYP3A4 inhibitors (such as ketoconazole) can increase blood drug concentrations and should be avoided in combination or adjusted in dosage.

(2) Underlying diseases: Uncontrolled heart failure and recent myocardial infarction patients require additional assessment of cardiovascular risk benefit ratio.