Krazati (Adagrasib)

Krazati targets KRAS G12C‑mutated cancers, a molecular subset of solid tumors.

• KRAS G12C‑mutated non‑small cell lung cancer: provides targeted inhibition of tumor growth in adult patients.
• KRAS G12C‑mutated colorectal cancer: offers a molecularly targeted option for patients with this specific mutation.

• Adagrasib covalently binds to the cysteine residue of the mutant KRAS G12C protein, locking it in the inactive GDP‑bound state. This prevents downstream signaling through the MAPK and PI3K pathways, thereby inhibiting cellular proliferation and survival signals that drive tumor growth.

Adagrasib may cause a range of adverse reactions, which are categorized by frequency and severity.

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 of emesis.
• Elevated liver enzymes: mild transaminase increases.

Serious or Rare Side Effects

• Interstitial lung disease: inflammation of lung tissue requiring monitoring.
• Cardiac toxicity: arrhythmias or reduced ejection fraction.
• Severe hepatotoxicity: marked liver enzyme elevation or bilirubin rise.
• Hematologic abnormalities: anemia or neutropenia.
• Severe skin reactions: Stevens‑Johnson syndrome or toxic epidermal necrolysis.

When prescribing Adagrasib, clinicians should consider several safety precautions.

• Baseline assessment: obtain liver function tests before initiating therapy.
• Monitoring: perform regular CBC and liver enzyme panels during treatment.
• Drug interactions: review concomitant medications for CYP3A4 substrates.
• Pregnancy: avoid use unless potential benefit justifies risk; discuss with patient.
• Breastfeeding: discontinue if nursing due to unknown excretion in milk.
• Store at ambient temperature: keep below 25°C in original packaging, protect from moisture and light.

Adagrasib can affect and be affected by other medicines; interaction potential varies.

Major Interactions (Avoid)

• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): may markedly reduce adagrasib exposure.
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): may increase exposure and toxicity.
• Antacids containing aluminum or magnesium: may affect absorption if taken simultaneously.

Moderate Interactions (Monitor Closely)

• Moderate CYP3A4 inhibitors (e.g., fluconazole): may require dose adjustment.
• Warfarin: potential for altered anticoagulant effect, monitor INR.
• Statins metabolized by CYP3A4 (e.g., simvastatin): monitor for myopathy.