Sotorasib (AMG510) is a KRASG12C inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation.
How to Use Sotorasib (AMG510)
Recommended Dosage Regimen
The recommended dose of sotorasib is 960 mg (8 tablets of 120 mg each) administered orally once daily, until disease progression or the occurrence of unacceptable toxicity.
It can be taken with or without food, but must be taken at a fixed time every day.
For patients with swallowing difficulties, the tablets can be dispersed in 120 mL of non-carbonated room-temperature water (other liquids must not be used). Stir until the tablets break into small pieces, then administer the dispersion immediately or within 2 hours. After that, rinse the container with another 120 mL of water and have the patient drink the rinsing water.
Administration Precautions
Swallow whole: Do not chew, crush, or split the tablets.
Missed dose management: If a dose is missed by more than 6 hours, skip that dose and take the next dose as scheduled on the following day.
Vomiting management: If vomiting occurs after taking the dose, do not take an additional dose; take the next dose as scheduled on the following day.
Concomitant use with antacids: Avoid concomitant use with proton pump inhibitors (PPIs) and H2 receptor antagonists. If co-administration is necessary, sotorasib should be taken either 4 hours before or 10 hours after the administration of local antacids.
Dose Adjustment of Sotorasib (AMG510)
Dose Adjustment for Adverse Reactions
Sotorasib allows a maximum of two dose reductions: the first dose reduction to 480 mg (4 tablets) once daily, and the second dose reduction to 240 mg (2 tablets) once daily. If the patient cannot tolerate the minimum dose, permanent discontinuation of sotorasib is recommended.
Measures Based on the Severity of Adverse Reactions
Hepatotoxicity: For grade 2 symptomatic AST/ALT elevation or grade 3-4 AST/ALT elevation, suspend administration. Resume treatment at a reduced dose after AST/ALT levels return to ≤ grade 1. If AST > 3 × upper limit of normal (ULN) and total bilirubin > 2 × ULN without other identifiable causes, permanently discontinue sotorasib.
Interstitial lung disease (ILD)/pneumonitis: Suspend administration in suspected cases; permanently discontinue sotorasib upon confirmation of diagnosis.
Nausea/vomiting: For grade 3-4 nausea/vomiting that is unresponsive to supportive care, suspend administration. Resume treatment at a reduced dose after symptom resolution.
Diarrhea: For grade 3-4 diarrhea that is unresponsive to supportive care, suspend administration. Resume treatment at a reduced dose after symptom resolution.
Other adverse reactions: For grade 3-4 adverse reactions, suspend administration. Resume treatment at a reduced dose after symptom resolution.
Use of Sotorasib (AMG510) in Special Populations
Patients with Hepatic Impairment
No dose adjustment is required for patients with mild hepatic impairment (Child-Pugh A).
Use with caution in patients with moderate hepatic impairment (Child-Pugh B).
Data on the use of sotorasib in patients with severe hepatic impairment (Child-Pugh C) are insufficient.
Patients with Renal Impairment
No dose adjustment is required for patients with mild to moderate renal impairment (eGFR ≥ 30 mL/min/1.73 m²).
Data on the use of sotorasib in patients with end-stage renal disease are limited.
Pregnant and Lactating Women
There are no available data on the use of sotorasib in pregnant women. Animal studies did not show teratogenicity, but caution is still advised.
Females of reproductive potential should use contraceptive measures during treatment with sotorasib and for 1 week after the last dose.
Lactating women should not breastfeed during treatment with sotorasib and for 1 week after the last dose.
