Adagrasib
KRAS G12C inhibitors
KRAS G12C inhibitorsHigh alert
An error with this medicine can cause serious harm: double checks and protocols are used.
Oral covalent KRAS G12C inhibitor for lung cancer and, with cetuximab, colorectal cancer. Watch the liver, the lungs and the heart rhythm (QT).
Also called: MRTX849
Quick facts
- Group
- KRAS G12C inhibitors
- Target
- Mutant KRAS G12C (small GTPase)
- Used for
- Locally advanced · Metastatic colorectal cancer
- Key effects
- Nausea · Fatigue · Musculoskeletal pain
- Monitor
- Test showing KRAS G12C before starting · Liver tests
- ATC
- L01XX77
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal structure shows adagrasib (MRTX849) covalently bound to human KRAS G12C with GDP.
Like sotorasib, adagrasib binds covalently to the mutant cysteine of KRAS G12C and keeps the protein in its inactive GDP-bound form, so it cannot signal to the RAF-MEK-ERK growth pathway. Tumours can escape through new KRAS mutations or amplification, activation of the pathway downstream, or change of histology.
- KRAS G12C drives the tumour
- Adagrasib bonds covalently to cysteine 12
- KRAS stays in its inactive GDP state
- Growth signalling stops
Indications
- Locally advanced or metastatic non-small cell lung cancer with KRAS G12C after at least one systemic therapy. Lung cancer →
- Metastatic colorectal cancer with KRAS G12C, with cetuximab, after fluoropyrimidine, oxaliplatin and irinotecan chemotherapy. Colorectal cancer →
Adverse effects
Common
- Nausea, vomiting, diarrhoea, constipation
- Fatigue, decreased appetite
- Musculoskeletal pain
- Rash, dry skin
- Numbness or tingling in the hands or feet
Contraindications
- Caution in long QT syndrome, heart failure, low potassium or magnesium
- Caution in liver or kidney disease
Key interactions
- St John's wort
- Can lower adagrasib levels; avoided.
- Other QT-prolonging drugs
- Add to the risk of dangerous heart rhythms.
What is monitored
- Test showing KRAS G12C before starting
- ECG and potassium and magnesium, especially with heart disease or other QT-prolonging drugs
- Liver tests
- Breathing symptoms
- Kidney function
Administration and safety
- Oral, on a regular schedule, with or without food.
- Swallowed whole; not crushed, chewed or split unless the product instructions allow it.
- Hazardous oral chemotherapy: handled with gloves and kept away from children; caregivers who are pregnant avoid handling it.
Pregnancy and breastfeeding
Pregnancy is discussed with the doctor and reported at once if it occurs; breastfeeding is avoided during treatment and for a short time after.
Nursing care
- Ask about palpitations, dizziness or fainting and report them.
- Review liver and kidney tests and electrolytes before refills.
- Ask about black stools, vomiting blood, cough or breathlessness.
- Teaching: report new medicines (including herbal ones) before starting them; report bleeding or yellow skin.
Pharmacokinetics
- Absorption
- Oral, with or without food.
Test yourself
Think of the answer, then tap the question to see it.
Which KRAS mutation does adagrasib target?
KRAS G12C.
Which antibody accompanies adagrasib in colorectal cancer?
Cetuximab.
Which heart test is relevant with adagrasib and why?
The ECG, because it can prolong the QT interval and cause rhythm problems.
Connections
← Back to the class: KRAS G12C inhibitors
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Adagrasib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Adagrasib - NCI (National Cancer Institute, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.