Sotoprazib (AMG510), a specific inhibitor of KRASG12C, can cause various adverse reactions in the treatment of non-small cell lung cancer.
Common Side Effects and Incidence of Sotoprazib (AMG510)
Gastrointestinal Reactions
(1) Diarrhea: Incidence 42%, with 5% being grade 3-4.
(2) Nausea and Vomiting: Nausea 26% (1% severe), Vomiting 17% (1.5% severe).
(3) Others: Constipation (16%), Abdominal Pain (15%).
Hepatotoxicity
(1) Liver dysfunction in 25% of patients, with 12% reaching grade 3-4.
(2) Median time to onset: 9 weeks (range 0.3-42 weeks).
Other Frequent Reactions
(1) Musculoskeletal pain (35%, 8% severe).
(2) Fatigue (26%, 2% severe).
(3) Cough (20%), Dyspnea (16%).
(4) Abnormal laboratory indicators.
(5) Lymphopenia (48%), Decreased hemoglobin (43%).
(6) Elevated AST/ALT (39%/38%), Hypocalcemia (35%).
Sottorazib (AMG510) Side Effect Mitigation Strategy
Liver Toxicity Management
(1) Monitoring Protocol: ALT/AST/bilirubin are measured every 3 weeks before and during the initial stage of treatment, and monthly thereafter after 3 months. (2. Grade 2 with symptoms or grade 3-4 elevation: Discontinue medication until recovery to ≤ grade 1.
(3) When resuming medication, reduce the dose (initially to 480 mg/day).
(4) AST/ALT > 3 × ULN and bilirubin > 2 × ULN: Permanently discontinue medication.
Interstitial Lung Disease (ILD) Management
(1) New onset/worsening of dyspnea, cough, or fever.
(2) Immediately discontinue medication and investigate the cause.
(3) Permanent discontinuation after diagnosis. Discontinue use.
Control of digestive symptoms:
(1) Diarrhea: Antidiarrheal medication such as loperamide + fluid replacement; discontinue use if grade 3-4.
(2) Nausea and vomiting: 5-HT3 receptor antagonist for prevention; dose adjustment required if grade 3-4.
Management of other reactions:
(1) Muscle pain: Nonsteroidal anti-inflammatory drugs (NSAIDs); consider dose reduction if severe.
(2) Fatigue: Adjust activity level and provide nutritional support.
Precautions for Sotoprazib (AMG510) Patient Dosage Dosage and Administration
(1) Take 960mg (8 tablets) at the same time daily, swallowing whole.
(2) For those with difficulty swallowing, dissolve in 120mL of water and drink within 2 hours.
(3) Skip a missed dose if more than 6 hours have passed; do not take a missed dose after vomiting.
Drug Interactions
(1) Absolutely avoid: Proton pump inhibitors (e.g., omeprazole).
(2) Strong CYP3A4 inducers (e.g., rifampin).
(3) Use with caution: CYP3A4 substrates (dose adjustment required).
(4) P-gp substrates (e.g., digoxin).
Special Populations
(1) Lactation: Breastfeeding is prohibited during treatment and for one week after discontinuation.
(2) Patients with liver damage: Moderate damage requires close monitoring; severe damage is contraindicated.
(3) Elderly: No adjustment of starting dose is required.
Daily Monitoring
(1) Regularly check liver function and complete blood count.
(2) Record new respiratory symptoms, abnormal bleeding, or persistent vomiting.
