Description of the risk of drug interactions when using adagrasib (Krazati) with digoxin

Adagrasib (Krazati) is a selective KRAS G12C inhibitor, used to treat patients with advanced non-small cell lung cancer (NSCLC) carrying KRAS G12C mutations. Digoxin is a cardiac glycoside commonly used for the long-term management of heart failure and arrhythmias. Due to the potential overlap between the two in drug metabolism and body distribution, special attention needs to be paid to the risk of drug interaction when used together.

Adagorasib is mainly metabolized byCYP3A4 enzyme, while digoxin is not dependent on CYP3A4 metabolism, but its concentration in the body is susceptible to inhibition or induction by the drug transporter P-glycoprotein (P-gp). Adagrasiib may slightly inhibit P-gp activity, which may lead to an increase in digoxin plasma concentration. Elevated levels of digoxin in the blood will increase the risk of poisoning, which may manifest as arrhythmia, nausea, vomiting, blurred vision and other symptoms.

Clinically, if adagrasib and digoxin must be used together, strict monitoring measures should be taken. It is recommended to measure the baseline digoxin blood concentration before coadministration and to review it regularly during treatment. If elevated digoxin levels or signs of toxicity are found, the digoxin dose should be adjusted promptly or separate dosing intervals should be considered. At the same time, closely observe changes in heart rate, blood pressure and electrocardiogram to prevent potential heart rhythm abnormalities.

In addition, doctors should assess the patient's renal function during prescription, because digoxin is mainly excreted through the kidneys, and blood concentrations are more likely to increase when renal function is impaired. For elderly patients or patients with multiple chronic diseases, the dose needs to be adjusted individually and patients should be educated to pay attention to poisoning symptoms. Once palpitations, fatigue, or abnormal vision occur, you should seek medical attention immediately to ensure the therapeutic effect of adagrasib and reduce digoxin-related risks.

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