Adagrasib – Uses, Dosage, Side Effects, Interaction

Mechanism of Action

In normal cells, KRAS is activated by binding to guanosine triphosphate (GTP), and this promotes the activation of the MAP kinase pathway and intracellular signal transduction. When GTP is hydrolyzed to guanosine diphosphate (GDP), KRAS is inactivated. This mechanism works as an “on”/”off” system that regulates cell growth. The substitution of Gly12 by cysteine in KRAS (KRASG12C) impairs GTP hydrolysis and maintains KRAS in its active form. Therefore, the presence of this mutation leads to uncontrolled cellular proliferation and growth, as well as malignant transformation. Adagrasib is a covalent inhibitor of KRASG12C that irreversibly and selectively binds and locks KRASG12C in its inactive, guanosine diphosphate–bound state. Therefore, the use of adagrasib inhibits tumor cell growth and viability in cancers with KRASG12C mutations with minimal off-target activity.

The exposure-response relationship and pharmacodynamic response time course of adagrasib have not been elucidated. The use of adagrasib can cause QTc interval prolongation. The increase in QTc is concentration-dependent. In patients given 600 mg of adagrasib twice daily, the mean QTcF change from baseline (ΔQTcF) was 18 ms at the mean steady-state maximum concentration. The use of adagrasib can also lead to severe gastrointestinal adverse reactions, hepatotoxicity, and interstitial lung disease/pneumonitis.


  • Adagrasib is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).
  • Adagrasib is a KRAS inhibitor indicated for the treatment of locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer in patients who have received at least one prior systemic therapy.
  • This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).[rx]
  • Locally Advanced Non-Small Cell Lung Cancer
  • Metastatic Non-Small Cell Lung Cancer

Use in Cancer

Adagrasib is approved to treat:

Adagrasib is approved under FDA’s Accelerated Approval Program. As a condition of approval, confirmatory trial(s) must show that it provides a clinical benefit in these patients.

Adagrasib is also being studied in the treatment of other types of cancer.


  • low amount of magnesium in the blood
  • low amount of calcium in the blood
  • low amount of potassium in the blood
  • torsades de pointes, a type of abnormal heart rhythm
  • slow heartbeat
  • prolonged QT interval on EKG
  • chronic heart failure
  • abnormal EKG with QT changes from birth
  • abnormal liver function tests
  • pregnancy
  • a patient who is producing milk and breastfeeding
  • lung tissue problem


Strength: Tablets: 200 mg

  • Recommended dosage: 600 mg orally twice daily.
  • Swallow tablets whole with or without food.

Select patients for treatment of locally advanced or metastatic NSCLC with KRAZATI based on the presence of KRAS G12C mutation in plasma or tumor specimens. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection of a KRAS G12C mutation is available at:

Recommended Dosage

  • The recommended dosage of KRAZATI is 600 mg orally twice daily until disease progression or unacceptable toxicity. Take KRAZATI at the same time every day with or without food. Swallow tablets whole. Do not chew, crush or split tablets. If vomiting occurs after taking KRAZATI, do not take an additional dose. Resume dosing at the next scheduled time.
  • If a dose is inadvertently missed, it should be skipped if greater than 4 hours have elapsed from the expected dosing time. Resume dosing at the next scheduled time.
  • Recommended dose reductions for adverse reactions are outlined in Table 1. If adverse reactions occur, a maximum of two dose reductions are permitted. Permanently discontinue KRAZATI in patients who are unable to tolerate 600 mg once daily.

Side Effects

The Most Common

  • diarrhea,
  • nausea,
  • fatigue,
  • vomiting,
  • musculoskeletal pain,
  • hepatotoxicity,
  • renal impairment,
  • dyspnea,
  • edema,
  • decreased appetite,
  • cough,
  • pneumonia,
  • dizziness,
  • constipation,
  • abdominal pain, and QTc interval prolongation.

More Common

  • decreased lymphocytes,
  • increased aspartate aminotransferase,
  • decreased sodium,
  • decreased hemoglobin,
  • increased creatinine,
  • decreased albumin,
  • increased alanine aminotransferase,
  • increased lipase,
  • decreased platelets,
  • decreased magnesium, and
  • decreased potassium.


  • your skin or the white part of your eyes turns yellow (jaundice)
  • dark or “tea-colored” urine
  • light-colored stools (bowel movements)
  • tiredness or weakness
  • nausea or vomiting
  • bleeding or bruising
  • loss of appetite
  • pain, aching or tenderness on the right side of your stomach area (abdomen)
  • muscle and bone pain
  • kidney problems
  • swelling
  • breathing trouble
  • decreased appetite

Drug Interaction

Pregnancy and Lactation

FDA Pregnancy Category : Not Assign


There are no available data on the use of KRAZATI in pregnant women. In animal reproduction studies, oral administration of adagrasib to pregnant rats and rabbits during the period of organogenesis did not cause adverse development effects or embryo-fetal lethality at exposures below the human exposure at the recommended dose of 600 mg twice daily (see DATA).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.


There are no data on the presence of adagrasib or its metabolites in human milk, the effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with KRAZATI and for 1 week after the last dose.