KRAZATI 200 MG TAB (ADAGRASIB)

🧬 Introduction

          Krazati® is an oral targeted therapy developed by Mirati Therapeutics, now part of Bristol Myers Squibb. It is designed to treat specific cancers

           harboring the KRAS G12C mutation, a genetic alteration found in certain tumor types.

           Krazati FDA approval is to treat adults with:

• non-small cell lung cancer (NSCLC) that has spread to other parts of the body or cannot be removed by surgery and has a KRAS G12C mutation determined by an FDA-approved test. Patients must have tried at least one prior systemic therapy. In NSCLC this medicine is used as a single agent.
• metastatic colorectal cancer (CRC) that has spread to other parts of the body or cannot be removed by surgery and has a KRAS G12C mutation determined by an FDA-approved test. Krazati is used in combination with Erbitux (cetuximab). Patients must already tried a prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

💊 Composition & Mechanism

• Active Ingredient: Adagrasib

• Drug Class: KRAS G12C inhibitor

• Mechanism of Action: Adagrasib selectively and irreversibly binds to the KRAS G12C mutant protein, inhibiting its activity and thereby impeding cancer cell growth.

📋 Indications

Krazati is approved for the treatment of:

1. Non-Small Cell Lung Cancer (NSCLC): For adults with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy.

2. Colorectal Cancer (CRC): In combination with cetuximab, for adults with KRAS G12C-mutated locally advanced or metastatic CRC who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

🧪 Dosage & Administration

• Recommended Dosage: 600 mg orally twice daily (total of 1200 mg per day)

• Administration: Take three 200 mg tablets in the morning and three in the evening, with or without food. Swallow tablets whole; do not chew, crush, or split them.

⚠️ Warnings & Precautions

1. Gastrointestinal (GI) Toxicity
Krazati may cause severe GI side effects, including nausea, diarrhea, vomiting, and, in rare cases, serious conditions like bleeding, obstruction, colitis, and ileus. Patients should be monitored for these symptoms, and supportive care should be provided as needed.

2. QTc Interval Prolongation
Treatment with Krazati can lead to QTc interval prolongation, increasing the risk of life-threatening arrhythmias such as torsades de pointes. Regular monitoring of ECGs and electrolytes is recommended, especially in patients with existing heart conditions.

3. Hepatotoxicity
Krazati has been associated with liver toxicity, including elevated liver enzymes and, in rare cases, drug-induced liver injury. Liver function tests should be conducted prior to and during treatment.

4. Interstitial Lung Disease (ILD)/Pneumonitis
Cases of ILD/pneumonitis have been reported, some of which were fatal. Patients should be monitored for respiratory symptoms, and treatment should be discontinued if ILD/pneumonitis is suspected.

5. Embryo-Fetal Toxicity
Krazati may cause fetal harm. Effective contraception is advised during treatment and for a period after the last dose

Krazati (adagrasib) offers a targeted treatment option for patients with KRAS G12C-mutated NSCLC and CRC, addressing a previously unmet medical need. Its oral administration and specific mechanism provide a convenient and effective therapy. However, due to potential serious side effects, including liver toxicity, heart rhythm disturbances, and lung inflammation, careful patient selection and regular monitoring are essential. Consultation with an oncologist is crucial to determine the appropriateness of this therapy for individual patients.