Krazati (Adagrasib)

Krazati targets cancers driven by the KRAS G12C mutation and is indicated for the following conditions:

• KRAS G12C mutated non‑small cell lung cancer: improves disease control and progression‑free survival in eligible patients.
• KRAS G12C mutated colorectal cancer: offers therapeutic benefit after standard therapies have failed.
• KRAS G12C mutated solid tumours (investigational): being evaluated in clinical studies for potential efficacy.

• Adagrasib binds irreversibly and covalently to the cysteine residue of the KRAS G12C mutant protein, locking it in the inactive GDP‑bound state. This prevents downstream signaling through the MAPK pathway, thereby inhibiting tumor cell proliferation and survival associated with the KRAS G12C driver mutation.

Adagrasib may cause a range of adverse reactions, most of which are manageable with monitoring and supportive care.

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset.
• Diarrhea: frequent loose stools.
• Fatigue: reduced energy levels.
• Decreased appetite: reduced food intake.
• Vomiting: occasional episodes.
• Constipation: infrequent bowel movements.

Serious or Rare Side Effects

• Elevated liver enzymes: potential hepatotoxicity requiring monitoring.
• Interstitial lung disease: respiratory symptoms indicating lung inflammation.
• Cardiac toxicity: arrhythmias or QT prolongation.
• Severe hypertension: marked increase in blood pressure.
• Neutropenia: low neutrophil count increasing infection risk.
• Severe skin reactions: such as Stevens‑Johnson syndrome.

Before initiating therapy, clinicians should consider several safety measures.

• Monitor liver function: baseline and periodic LFTs are recommended.
• Assess cardiac status: watch for QT prolongation and arrhythmias.
• Evaluate for interstitial lung disease: monitor respiratory symptoms closely.
• Check for drug interactions: avoid concomitant strong CYP3A4 inhibitors.
• Pregnancy and lactation: use only if potential benefit justifies potential risk; data are limited.
• Store at ambient temperature below 25°C: keep in the original container, protect from moisture and light.

Adagrasib can interact with other medicines, requiring careful management.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): may increase Adagrasib exposure.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): may reduce therapeutic levels.
• Antacids containing aluminum or magnesium: can affect absorption if taken simultaneously.

Moderate Interactions (Monitor Closely)

• Moderate CYP3A4 inhibitors (e.g., erythromycin, fluconazole): may modestly raise plasma concentrations.
• Anticoagulants (e.g., warfarin): monitor INR for potential changes.
• Statins metabolized by CYP3A4 (e.g., simvastatin): observe for increased statin exposure and muscle toxicity.