Adagrasib

What is Adagrasib?

• Adagrasib (Krazati) is an irreversible inhibitor of KRAS G12C and belongs to the RAS GTPase family.

Adagrasib

Adagrasib structure

Adagrasib CH3

What are the uses of this medicine?

Adagrasib (Krazati) is a prescription medicine used 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
• whose tumor has an abnormal KRAS G12C gene, and
• who have received at least one prior treatment for their cancer.

How does this medicine work?

• Adagrasib is an irreversible inhibitor of KRAS G12C that covalently binds to the mutant cysteine in KRAS G12C and locks the mutant KRAS protein in its inactive state that prevents downstream signaling without affecting wild-type KRAS protein.
• Adagrasib inhibits tumor cell growth and viability in cells harboring KRAS G12C mutations and results in tumor regression in KRAS G12C-mutated tumor xenograft models with minimal off-target activity.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
• Krazati can affect the way other medicines work, and other medicines can affect how Krazati works.

Be sure to mention any of the following:

• St. John's Wort. Be sure to let your doctor and pharmacist know that you are taking this medication before you start taking adagrasib.
• Strong CYP3A4 Inducers
• Strong CYP3A4 Inhibitors
• Sensitive CYP3A4 Substrates
• Sensitive CYP2C9 or CYP2D6 Substrates or P-gp Substrates
• Drugs That Prolong QT Interval

Is this medicine FDA approved?

• It was approved for medical use in the United States in December 2022.

How should this medicine be used?

• 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.

Recommended dosage:

• The recommended dosage of Krazati is 600 mg orally twice daily until disease progression or unacceptable toxicity.

Administration:

• Take Krazati exactly as your healthcare provider tells you to take it. Do not change your dose or stop taking Krazati unless your healthcare provider tells you to.
• Your healthcare provider may change your dose, or temporarily or permanently stop treatment with Krazati if you develop certain side effects.
• Take your prescribed dose of Krazati 2 times each day, at about the same time each day.
• Take Krazati either with food or without food.
• Swallow Krazati tablets whole.
• Do not chew, crush or split tablets.
• If you vomit after taking a dose of Krazati, do not take an extra dose.
• Take your next dose at your next scheduled time.
• If you miss a dose of Krazati, take the dose as soon as you remember.
• If it has been more than 4 hours, do not take the dose.
• Take your next dose of Krazati at your next scheduled time.
• Do not take 2 doses at the same time to make up for a missed dose.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 200 mg

This medicine is available in fallowing brand namesː

• Krazati

What side effects can this medication cause?

The most common side effects of this medicine include:

• nausea
• diarrhea
• vomiting
• tiredness
• muscle and bone pain
• kidney problems
• swelling
• breathing trouble
• decreased appetite

The most common laboratory abnormalities include:

• decreased lymphocytes
• decreased hemoglobin
• increased alanine aminotransferase
• increased aspartate aminotransferase
• hypokalemia, hyponatremia
• increased lipase
• decreased leukocytes
• decreased neutrophils
• increased alkaline phosphatase

Less common, but serious side effects may include:

• Stomach and intestinal (gastrointestinal) problems
• Changes in the electrical activity of your heart called QTc prolongation.
• Liver problems
• Lung or breathing problems

What special precautions should I follow?

• Krazati can cause severe gastrointestinal adverse reactions. Advise patients that Krazati can cause severe gastrointestinal adverse reactions and to contact their healthcare provider for signs or symptoms of severe or persistent gastrointestinal adverse reactions.
• Krazati can cause QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (e.g., torsades de pointes) or sudden death. Avoid concomitant use of Krazati with other products with a known potential to prolong the QTc interval. Monitor ECG and electrolytes in patients at risk, and in patients taking medications known to prolong the QT interval. Withhold, reduce the dose, or permanently discontinue based on severity.
• Krazati can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis. Monitor liver laboratory tests prior to the start of Krazati and monthly for 3 months after and as clinically indicated. Reduce the dose, withhold, or permanently discontinue based on severity.
• Krazati can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal. Monitor for new or worsening respiratory symptoms. Withhold Krazati for suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified.
• It is not known if Krazati passes into your breastmilk. Do not breast feed during treatment and for 1 week after your last dose of Krazati.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• There are no available data on the use of Krazati in pregnant women.
• It is not known if Krazati can harm your unborn baby.

Can this medicine be used in children?

• It is not known if Krazati is safe and effective in children.

What are the active and inactive ingredients in this medicine?

• Active ingredient: adagrasib
• Inactive ingredients: colloidal silicon dioxide, crospovidone, magnesium stearate (vegetable sourced), mannitol, and microcrystalline cellulose. The tablet film coating contains hypromellose, maltodextrin, medium chain triglycerides (vegetable sourced), polydextrose, talc, and titanium dioxide.

Who manufactures and distributes this medicine?

Manufactured for: Mirati Therapeutics, Inc. 3545 Cray Court San Diego, CA, U.S.A.

What should I know about storage and disposal of this medication?

• Store Krazati at room temperature between 68°F to 77°F (20°C to 25°C ).
• Krazati comes in a child-resistant container.
• Krazati comes with a desiccant in the container to keep the medicine dry. Do not remove the desiccant from the container after opening.
• Do not eat or swallow the desiccant.

• Dailymed label info on Adagrasib
• FDA Adagrasib

Adagrasib Resources
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