Krazati
Krazati (adagrasib) is a KRAS inhibitor that's FDA approved to treat advanced and metastatic non-small cell lung cancer (NSCLC) and colorectal cancer in adults with the KRAS G12C mutation. It’s typically used when previous treatments stop working. This medication is used alone to treat NSCLC. But for colorectal cancer, it's used with Erbitux (cetuximab), an infusion given once a week or every other week. Krazati (adagrasib) is conveniently available as an oral tablet which is taken by mouth twice a day. But it can commonly cause bothersome side effects such as diarrhea, nausea, and fatigue.
What is Krazati (adagrasib)?
What is Krazati (adagrasib) used for?
Locally advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS G12C mutation, after having tried at least one previous cancer treatment
Locally advanced or metastatic colorectal cancer with a KRAS G12C mutation, together with Erbitux (cetuximab), after having tried certain previous cancer treatments
How Krazati (adagrasib) works
Krazati (adagrasib) is a KRAS G12C inhibitor. KRAS is a protein in your body that sends signals to your cells to grow and divide. In certain cancers, a mutation in KRAS called G12C leads to uncontrolled cell growth. Krazati (adagrasib) works by attaching to KRAS proteins with the G12C mutation. By doing so, the medication helps block tumor growth.
Drug Facts
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What are the side effects of Krazati (adagrasib)?
Common Side Effects
- Diarrhea (70%)
- Nausea (69%)
- Lower blood cell counts (up to 64%)
- Fatigue (59%)
- Vomiting (56%)
- Signs of stress to the liver or kidney on blood tests (up to 52%)
- Muscle or bone pain (41%)
- Liver injury (37%)
- Kidney injury (36%)
- Shortness of breath (35%)
- Swelling (32%)
- Loss of appetite (30%)
Other Side Effects
- Cough
- Lung infection
- Dizziness
- Constipation
- Stomach pain
- Abnormal heart rhythm
Serious Side Effects
- Severe digestive system problems: stomach pain, black or bloody bloody stools, severe constipation
- Life-threatening abnormal heart rhythm: chest pain, shortness of breath, dizziness, fluttering or pounding heart beat
- Liver injury: pain in the right side of the stomach, yellowing of the eyes or skin, dark or brown urine
- Lung damage: cough, shortness of breath, fever
Source: DailyMed
The following side effects have also been reported
Side effects that you should report to your care team as soon as possible:
- Allergic reactions—skin rash, itching, hives, swelling of the face, lips, tongue, or throat
- Bowel blockage—stomach cramping, unable to have a bowel movement or pass gas, loss of appetite, vomiting
- Dry cough, shortness of breath or trouble breathing
- Heart rhythm changes—fast or irregular heartbeat, dizziness, feeling faint or lightheaded, chest pain, trouble breathing
- Kidney injury—decrease in the amount of urine, swelling of the ankles, hands, or feet
- Liver injury—right upper belly pain, loss of appetite, nausea, light-colored stool, dark yellow or brown urine, yellowing skin or eyes, unusual weakness or fatigue
- Stomach bleeding—bloody or black, tar-like stools, vomiting blood or brown material that looks like coffee grounds
- Sudden or severe stomach pain, bloody diarrhea, fever, nausea, vomiting
Side effects that usually do not require medical attention (report these to your care team if they continue or are bothersome):
- Diarrhea
- Fatigue
- Loss of appetite
- Muscle pain
- Nausea
- Vomiting
Pros and cons of Krazati (adagrasib)
Pros
Oral tablet that’s taken by mouth
Can be taken with or without food
Targeted therapy option for people with NSCLC or colorectal cancer with a KRAS G12C mutation
Cons
Has to be taken twice a day
Commonly causes diarrhea, nausea, vomiting, and fatigue
Only recommended after other treatments haven’t worked
Pharmacist tips for Krazati (adagrasib)
Krazati (adagrasib) is available as 200 mg tablets, so you’ll need 3 tablets to make one 600 mg dose. You can take your dose with or without food. Don’t chew, crush, or cut the tablets since it can affect how well the medication works.
If you vomit after taking your dose, don’t take a dose to make up for the vomited dose. If you forget to take a dose, only take it if you remember within 4 hours of the normal time. Otherwise, skip the dose and take your next dose at the regular time.
The Krazati (adagrasib) bottle contains a drying agent. After opening the bottle, leave the drying agent in the bottle to keep moisture out.
Krazati (adagrasib) frequently causes digestive system side effects, like nausea, vomiting, and diarrhea. Let your oncologist know if they become bothersome, they will be able to provide treatment recommendations to help ease those symptoms.
Try keeping a meal diary to track which foods agree with you and which ones upset you. If Krazati (adagrasib) is causing stomach issues, let your cancer care team know so they can suggest treatments or adjust your dose.
Krazati (adagrasib) can interact with other medications and supplements, causing more side effects or reducing how well it works. For example, taking antibiotics like levofloxacin (Levaquin) or azithromycin (Zithromax) with Krazati (adagrasib) puts you at higher risk of having an abnormal heart rhythm that could be life-threatening. Be sure to review all your medications and supplements with your cancer care team before and during treatment to make sure they are safe to take together.
Krazati (adagrasib) might affect fertility, or your ability to have a baby, based on animal studies. If you or your partner are trying to become pregnant, talk with your oncologist before starting this medication.
Krazati (adagrasib) hasn’t been studied during pregnancy or breastfeeding. Talk to your oncologist if you become pregnant or are planning to while taking this medication. Avoid breastfeeding while on Krazati (adagrasib) and for 1 week after stopping it.
Frequently asked questions about Krazati (adagrasib)
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What are the risks and warnings for Krazati (adagrasib)?
Krazati (adagrasib) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.
Severe digestive system problems
Krazati (adagrasib) commonly causes digestive system side effects like nausea, vomiting, or diarrhea. In studies, these side effects happened within the first couple weeks of starting Krazati (adagrasib) and were treated successfully with other medications. But in rare situations, Krazati (adagrasib) can cause more severe digestive system side effects like bleeding, blockages, or inflammation in the gut that could be life-threatening. If you have severe stomach upset, pain in the stomach that doesn’t go away, or are having trouble keeping food down, let your oncologist know. They might recommend medications or have you take a break from Krazati (adagrasib) while checking for problems.
Life-threatening abnormal heart rhythm
Risk factors: Personal or family history of abnormal heart rhythms (arrhythmias) | Low potassium or magnesium in the blood | Taking other medications that cause QT prolongation
[EDITOR|DRUG_DISPLAY_NAME|||title]] can affect your heart rhythm and lead to QT prolongation, which could be serious or life-threatening. Your risk for QT prolongation depends on genetics, electrolyte levels, and other medications that can also cause QT prolongation. In studies, the abnormal heart rhythm was found early on after starting treatment, and went back to normal in a little over 2 weeks later. Your oncologist will order an electrocardiogram (EKG) and check on your electrolyte levels before starting Krazati (adagrasib) and regularly during treatment to make sure the medication is safe to take.
Share your medication list, including supplements and herbal products, with your care team so they can make sure those medications are safe to take with Krazati (adagrasib). If you notice new pounding or fluttering heartbeat, lightheadedness, dizziness, or chest pain, tell your cancer care team right away. They can check your heart and might have you take a break from Krazati (adagrasib). Once your heart rhythm returns to normal, you might be able to restart the medication at a lower dose.
Liver injury
Krazati (adagrasib) might cause damage to your liver. Sometimes, people don’t feel any symptoms when their liver is having problems, so you’ll need to get blood tests done to track how well your liver is working. You’ll typically need these blood tests before starting Krazati (adagrasib), and then every month for the first 3 months after starting Krazati (adagrasib). In studies of people taking this medication for lung cancer, some people had higher levels of liver enzymes on their blood tests (a sign of potential liver injury) within the first month of starting Krazati (adagrasib), which went away about 2 to 3 weeks later.
Let your oncologist know if you notice signs of liver damage, such as pain in the right side of the stomach, yellowing of the eyes or skin, or dark or brown urine. If your oncologist suspects that you have liver damage, they might have you take a break from Krazati (adagrasib). Once your liver test results return to normal, you might be able to restart the medication at a lower dose.
Lung damage
Although rare, Krazati (adagrasib) can cause damage to the lungs, which can sometimes be life-threatening. In studies, the median time to the start of those lung problems was 3 months. So half of people who had lung problems while on the medication noticed those problems within the first 3 months of starting, while the other half developed lung problems after the 3 month mark. Let your oncologist know if you experience new or worsened cough, shortness of breath, or fevers. You’ll probably need to stop the medication while your care team checks your lungs for problems.
Krazati (adagrasib) dosage forms
Typical dosing for Krazati (adagrasib)
The typical dose is 600 mg (3 tablets) by mouth twice a day.
Your dose might change if you have certain side effects from the medication.
How much does Krazati (adagrasib) cost?
What are alternatives to Krazati (adagrasib)?
Locally advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS G12C mutation, after having tried at least one previous cancer treatment
Locally advanced or metastatic colorectal cancer with a KRAS G12C mutation, together with Erbitux (cetuximab), after having tried certain previous cancer treatments
Metastatic non-small cell lung cancer (NSCLC) with a KRAS G12C mutation, after having tried at least one previous cancer treatment
Krazati (adagrasib) images
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References
Best studies we foundAmerican Cancer Society. (2024). What Are Advanced and Metastatic Cancers?
American Cancer Society (n.d.). Chemotherapy.
American Cancer Society (n.d.). Targeted Therapy.
American Lung Association. (2022). KRAS and lung cancer.
Mirati Therapeutics, Inc. (2024). Krazati- adagrasib tablet, coated [package insert]. DailyMed.
Zhang, J., et al. (2023). Practical guidance for the management of adverse events in patients with KRASG12C-mutated non-small cell lung cancer receiving adagrasib. The Oncologist.
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