Adagrasib

Adagrasib is a prescription medication used for the treatment of  KRAS G12C–mutated locally advanced or metastatic non–small cell lung cancer (NSCLC) in adults who have received more than one systemic treatment.

• Adagrasib is available under the following different brand names: Krazati.

Common side effects of Adagrasib include:

• nausea
• diarrhea
• vomiting
• fatigue
• musculoskeletal pain
• liver toxicity
• kidney problems
• fluid retention (edema)
• shortness of breath
• decreased appetite
• decreased white blood cells (lymphocytes, leukocytes, neutrophils)
• decreased hemoglobin
• increased alanine aminotransferase
• increased aspartate aminotransferase
• low blood potassium (hypokalemia)
• low blood sodium (hyponatremia)
• increased lipase
• increased alkaline phosphatase

Serious side effects of Adagrasib include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• nausea
• vomiting
• diarrhea
• fainting
• seizures
• abnormal heart rhythm
• heart palpitations
• shortness of breath
• weakness
• fast, fluttering, or pounding heart rate
• rash
• abdominal pain
• dark-colored urine
• light-colored stools
• yellowing of the eyes and skin (jaundice)
• loss of appetite
• fever
• cough
• weight loss
• black or tarry stool
• bright red blood in the vomit
• blood mixed with stool
• tiredness
• dizziness
• constipation
• abdominal cramping
• swelling of the abdomen
• inability to have a bowel movement or pass gas, and
• watery diarrhea

Rare side effects of Adagrasib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 200 mg

Non–small cell lung cancer

Adult dosage

• 600 mg orally two times a day until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Adagrasib has severe interactions with no other drugs.
• Adagrasib has serious interactions with at least 161 other drugs.
• Adagrasib has moderate interactions with the following drugs:
  • lenacapavir
  • sparsentan
  • vardenafil
  • zanubrutinib
• Adagrasib has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Adagrasib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Adagrasib?”

Cautions

• Severe gastrointestinal (GI) adverse reactions (eg, GI bleeding, GI obstruction, colitis, ileus, stenosis, nausea, diarrhea, vomiting) reported; monitor and treat using supportive care (eg, antidiarrheals, antiemetics, fluid replacement) as indicated
• May cause interstitial lung disease (ILD)/pneumonitis; monitor for new or worsening respiratory symptoms (eg, dyspnea, cough, fever) during treatment; permanently discontinue therapy if no other potential causes of ILD/pneumonitis are identified
• QT interval prolongation
  • May cause QTc prolongation, which may increase the risk for ventricular tachyarrhythmias (eg, torsade de pointes) or sudden death
  • Avoid coadministration with other drugs that prolong QTc interval
  • Avoid use in patients with congenital long QT syndrome or with concurrent QTc prolongation
  • Monitor ECGs and electrolytes before initiating, during treatment, and as clinically indicated in patients with congestive heart failure, bradyarrhythmias, and electrolyte abnormalities and in patients who are unable to avoid drugs that are known to prolong the QT interval
• Hepatoxicity
  • Hepatoxicity reported, including drug-induced liver injury
  • Median time to the first onset of increased alanine transaminase/aspartate transaminase (ALT/AST) was 3 weeks
  • Monitor AST, ALT, alkaline phosphatase, and total bilirubin before initiating and monthly for 3 months or as clinically indicated; closely monitor patients who develop AST/ALT elevations
• Drug interaction overview
• CYP3A4 substrate
  • CYP3A4, CYP2C9, CYP2D6, and P-gp inhibitor
• Strong CYP3A4 inducers
  • Avoid coadministration
  • Strong CYP3A inducers reduce adagrasib exposure and efficacy
• Strong CYP3A4 inhibitors
  • Avoid coadministration until adagrasib concentrations reach a steady state
  • If adagrasib concentrations have not reached a steady state, strong CYP3A inhibitors will increase adagrasib concentrations and risk for adverse reactions
• Sensitive CYP3A4 substrates
  • Avoid coadministration
  • Adagrasib increases exposure and risk for adverse reactions of sensitive CYP3A4 substrates
• Sensitive CYP2C9 or CYP2D6 substrates or P-gp substrates
  • Avoid coadministration with sensitive CYP2C9 or CYP2D6 substrates or P-gp substrates where minimal concentration changes may lead to a serious adverse reaction
  • Adagrasib increases exposure and risk for adverse reactions of sensitive CYP2C9 or CYP2D6 substrates or P-gp substrates
• QT-prolonging drugs
  • Avoid coadministration
  • If unavoidable, closely monitor
  • Coadministration may cause additive QT prolongation

Pregnancy and Lactation

• No data are available on adagrasib in pregnant women
• Infertility
  • Based on animal findings, fertility impairment may occur in women and men of reproductive potential
• Lactation
  • There are no data on the presence of adagrasib or its metabolites in human milk, its effects on breastfed children, or milk production
  • Advise women not to breastfeed during treatment and for 1 week after the last dose