Generic
Sotorasib
1 brands available in the market
At a glance
Sotorasib is a KRAS G12C inhibitor used for the treatment of KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients who have received at least one prior systemic therapy.
Description
Sotorasib is a potent and highly selective KRASG12C inhibitor that covalently and irreversibly binds to the unique cysteine of KRASG12C. Inactivation of KRASG12C by sotorasib blocks tumor cell signaling and survival, inhibits cell growth, and promotes apoptosis selectively in tumors harboring KRASG12C.
Indications
- KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) – with at least one prior systemic therapy
Therapeutic class
Cytotoxic Chemotherapy
Pharmacological class
KRAS G12C Inhibitor
Pharmacology
Sotorasib binds to both the P2 pocket and the His95 surface groove of KRASG12C, locking the protein in an inactive state that prevents downstream signaling. It inhibits oncogenic signaling in KRASG12C-harboring tumor cells, enhances antigen presentation and inflammatory cytokine production, and induces anti-tumor inflammatory responses.
Mechanism of action
Binds to KRASG12C protein to block tumor cell growth and signaling.
Dosage
Adult Dose (Oral):
- 960 mg (eight 120 mg tablets) once daily
- Continue until disease progression or unacceptable toxicity
- Take at the same time each day with or without food
Administration
- Swallow tablets whole; do not chew, crush, or split
- Take at the same time each day
- If missed by >6 hours, take the next dose as prescribed the next day
- If vomiting occurs, do not take an additional dose
Missed dose
If missed by >6 hours, take the next dose as prescribed the next day; do not take 2 doses at the same time; if vomiting occurs, do not take an additional dose.
Side effects
Serious Side Effects:
- Hepatotoxicity (elevated liver enzymes, bilirubin, drug-induced hepatitis) – 25% of patients
- Interstitial Lung Disease (ILD)/Pneumonitis – 0.8% (can be fatal)
Other:
- Diarrhea, nausea
- Fatigue, muscle pain
Precautions & warnings
- Hepatotoxicity: Monitor liver function tests (ALT, AST, bilirubin) at baseline, every 3 weeks for first 3 months, then monthly
- ILD/Pneumonitis: Monitor for new or worsening pulmonary symptoms (dyspnea, cough, fever); withhold if suspected
- Avoid acid-reducing agents (PPI, H2RA, antacids); if unavoidable, administer 4 hours before or 10 hours after
Contraindications
- Hypersensitivity to any component
Drug interactions
- Acid-reducing agents (PPI, H2RA, antacids): Decrease sotorasib concentrations; avoid
- Strong CYP3A4 inducers: Decrease sotorasib concentrations; avoid
- CYP3A4 substrates: Decrease plasma concentrations; dose increase may be needed
- P-gp substrates (digoxin): Increase plasma concentrations; dose reduction may be needed
Food interactions
Caution is advised when consuming alcohol with Sotorasib; consult your doctor.
Use in pregnancy
Use in Pregnancy: No data in pregnant women; animal studies show reproductive toxicity; advise potential risk to fetus; consult your doctor.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Unknown if excreted in human milk; decide whether to discontinue breastfeeding or sotorasib therapy; consult your doctor.
Pediatric use
Safety and efficacy not established in pediatric patients
Geriatric use
Applicable for elderly (age-specific differences not specified)
Renal / hepatic impairment
Renal Impairment: Specific information not available; consult your doctor.
Hepatic Impairment: Risk of hepatotoxicity; monitor liver function closely; consult your doctor.
Overdose effects
No clinical overdose experience; in overdose, provide symptomatic and supportive treatment.
Storage conditions
Store below 25°C in a cool and dry place, protected from light; keep out of reach of children.
Chemical structure
Sotorasib