Indication
Adarasib (adagrasib) is indicated for the treatment of adults with advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation, following prior systemic therapy failure.

Mechanism of Action

Adagrasib is an irreversible inhibitor of the KRAS G12C protein, which drives uncontrolled cancer cell growth. It binds to the abnormal protein, blocking its activity and slowing or stopping tumor progression.

Dosage and Administration

• Recommended dose: 600 mg (three 200 mg tablets) twice daily, approximately 12 hours apart.

• Administration:

• Swallow tablets whole with water, with or without food.

• For patients unable to swallow whole: Dissolve tablets in 120 mL of room-temperature water, swirl gently, drink immediately, and rinse the glass with another 120 mL of water.

• Missed dose: Take as soon as possible if within 4 hours; otherwise, skip and resume the next scheduled dose. Do not double dose.

• Vomiting: Do not take an extra dose; resume the next scheduled dose.

Contraindications

• Hypersensitivity to adagrasib or excipients.

• Concomitant use with specific drugs (risk of severe interactions):

• Alfuzosin, amiodarone, cisapride, pimozide, quinidine, ergot derivatives, simvastatin/lovastatin, sildenafil (for PAH), triazolam, sirolimus/tacrolimus, ticagrelor.

Key Warnings and Precautions

1. Hepatotoxicity:

• Monitor liver function (ALT, AST, bilirubin) before treatment, monthly for 3 months, and as needed. Dose adjustments or discontinuation may be required.

2. QT Prolongation:

• Risk of life-threatening arrhythmias. Monitor ECG in patients with cardiac conditions or on QT-prolonging medications.

3. Severe Skin Reactions:

• Discontinue immediately if symptoms of Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS occur (e.g., rash, mucosal ulcers, fever).

4. Drug Interactions:

• Avoid strong CYP3A4 inducers (e.g., rifampicin, St. John’s Wort) and CYP3A4 inhibitors (e.g., itraconazole, clarithromycin).

• Use caution with drugs metabolized by CYP3A4, CYP2C9, or CYP2D6 (e.g., warfarin).

5. Pregnancy/Breastfeeding:

• Contraindicated in pregnancy. Use effective contraception during treatment and for ≥5 days after the last dose.

• Avoid breastfeeding.

Common Side Effects

• Very common (≥10%): Fatigue, nausea, diarrhea, vomiting, dizziness, edema, anemia, lymphopenia, hyponatremia, elevated creatinine, hyperamylasemia/hyperlipasemia.

• Serious: QT prolongation, hepatotoxicity, pneumonitis.

Storage

• Store in the original container with desiccant packs. Protect from moisture.

• Do not use after the expiration date.