Adagrasib

Krazati (Adagrasib) is an inhibitor of the RAS GTPase family indicated for: 

Non-small cell lung cancer (NSCLC)

• As a single agent, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as detected by an FDA-approved test, who have received at least one prior systemic therapy.

Colorectal cancer (CRC)

• In combination with cetuximab, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC, as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

These indications are approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for these indications may be contingent upon verification and description of a clinical benefit in confirmatory trials. 

Strength:

Tablets: 200 mg.

Dosage:

The recommended dosage as a single agent for Non-Small Cell Lung Cancer (NSCLC) and in combination with cetuximab for Colorectal Cancer (CRC): 600 mg orally twice daily. 

Adverse Effects:  

• Interstitial Lung Disease / Pneumonitis (lung disease): Interstitial Lung disease can be fatal.
• Hepatotoxicity (Liver Problems): Elevated liver enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. This may lead to drug-induced liver injury and hepatitis.
• QTc interval prolongation (heart disease): symptoms like ventricular tachyarrhythmias (e.g., torsades de pointes) or sudden death can occur.
• Gastrointestinal tract problems: symptoms like nausea, vomiting, and diarrhoea.

Side Effects: 

Single-agent use in non-small cell lung cancer (NSCLC): The most common side effects are listed below: 

• Nausea, diarrhea, vomiting: Digestive tract-related issues are common.
• Fatigue: Feeling unusually tired.
• Musculoskeletal pain: Pain in muscles, bones, tendons, and ligaments.
• Hepatotoxicity: Liver damage.
• Renal impairment: Slight reduction in kidney function
• Edema: Swelling in the parts of the body.
• Dyspnea: Shortness of breath.
• Decreased appetite: Not feeling hungry.
• Decreased lymphocytes, increased leukocytes, decreased neutrophils: Variant levels of white blood cells
• Decreased hemoglobin: Low levels of red blood cells
• Increased alanine aminotransferase, increased aspartate aminotransferase, and increased alkaline phosphatase: an increase in blood levels of liver enzymes.
• Hypokalemia and hyponatremia: These are due to electrolyte imbalance.
• Increased lipase: It indicates an underlying issue in the pancreas, kidney, or salivary glands.

In combination with cetuximab: The most common side effects are:

• Rash 
• Nausea, diarrhea, vomiting, abdominal pain, decreased appetite: Digestive tract-related issues are common.
• Fatigue: Feeling unusually tired.
• Musculoskeletal pain: Pain in muscles, bones, tendons, and ligaments.
• Hepatotoxicity: Liver damage.
• Headache: Common discomfort.
• Dry skin: Various areas of skin.
• Edema: Swelling in the parts of the body.
• Anemia: Reduced amounts of red blood cells.
• Cough: Respiratory symptom.
• Decreased lymphocytes: Reduced amounts of white blood cells.
• Decreased potassium and decreased magnesium: Electrolyte imbalance in blood.
• Decreased hemoglobin: Reduced amounts of red blood cells.
• Increased aspartate aminotransferase and increased alanine aminotransferase:
• Increased lipase: A digestive metabolism problem.
• Decreased albumin: A reduction of albumin in the blood.

Storage:

(20°C to 25°C).