Adagrasib is an orally available, small-molecule inhibitor that targets the oncogenic KRAS substitution mutation, G12C, with potential antineoplastic activity. Upon oral administration adagrasib covalently binds to cytosine 12 within the switch II pocket of GDP-bound KRAS G12C, thereby inhibiting mutant KRAS-dependent signaling. KRAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division, and differentiation. Mutations of KRAS may induce constitutive signal transduction leading to tumor cell growth, proliferation, invasion, and metastasis.
Adagrasib (MRTX849) is an oral, small-molecule KRAS inhibitor developed by Mirati Therapeutics. KRAS mutations are highly common in cancer and account for approximately 85% of all RAS family mutations.[rx] However, the development of KRAS inhibitors has been challenging due to their high affinity for guanosine triphosphate (GTP) and guanosine diphosphate (GDP), as well as the lack of a clear binding pocket.[rx] Adagrasib targets KRASG12C, one of the most common KRAS mutations, at the cysteine 12 residue and inhibits KRAS-dependent signalling. In a phase I/IB clinical study that included patients with KRASG12C-mutated advanced solid tumors (NCT03785249), adagrasib exhibited anti-tumor activity. The phase II of the same study showed that in patients with KRASG12C-mutated non-small-cell lung cancer (NSCLC), adagrasib was efficient without new safety signals.[rx]
In February 2022, the FDA accepted a new drug application (NDA) for adagrasib for the treatment of patients with previously treated KRASG12C–positive NSCLC.[rx] In December 2022, the FDA granted accelerated approval to adagrasib for the treatment of KRASG12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy. Adagrasib joins sotorasib as another KRASG12C inhibitor approved by the FDA.[rx]
Adagrasib (MRTX849) is an oral, small-molecule KRAS inhibitor developed by Mirati Therapeutics. KRAS mutations are highly common in cancer and account for approximately 85% of all RAS family mutations. However, the development of KRAS inhibitors has been challenging due to their high affinity for guanosine triphosphate (GTP) and guanosine diphosphate (GDP), as well as the lack of a clear binding pocket. Adagrasib targets KRASG12C, one of the most common KRAS mutations, at the cysteine 12 residue and inhibits KRAS-dependent signaling. In phase I/IB clinical study that included patients with KRASG12C-mutated advanced solid tumors (NCT03785249), adagrasib exhibited anti-tumor activity. Phase II of the same study showed that in patients with KRASG12C-mutated non-small-cell lung cancer (NSCLC), adagrasib was efficient without new safety signals. In February 2022, the FDA accepted a new drug application (NDA) for adagrasib for the treatment of patients with previously treated KRASG12C–positive NSCLC. In December 2022, the FDA granted accelerated approval to adagrasib for the treatment of KRASG12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy. Adagrasib joins [sotorasib] as another KRASG12C inhibitor approved by the FDA.
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.
Indications
- 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:
- Non-small cell lung cancer (NSCLC) that has spread and has a KRAS p.G12C mutation. It is used in adults who have received at least one other systemic therapy.
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.
Contraindications
- 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
Dosage
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: https://www.fda.gov/CompanionDiagnostics
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.
Rare
- 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
| DRUG | INTERACTION |
|---|---|
| Alfentanil | The serum concentration of Alfentanil can be increased when it is combined with Adagrasib. |
| Alprazolam | The serum concentration of Alprazolam can be increased when it is combined with Adagrasib. |
| Amiodarone | The serum concentration of Adagrasib can be increased when it is combined with Amiodarone. |
| Amprenavir | The serum concentration of Adagrasib can be increased when it is combined with Amprenavir. |
| Apalutamide | The serum concentration of Adagrasib can be decreased when it is combined with Apalutamide. |
| Aprepitant | The serum concentration of Aprepitant can be increased when it is combined with Adagrasib. |
| Articaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Articaine. |
| Atazanavir | The serum concentration of Adagrasib can be increased when it is combined with Atazanavir. |
| Atomoxetine | The serum concentration of Atomoxetine can be increased when it is combined with Adagrasib. |
| Atorvastatin | The serum concentration of Atorvastatin can be increased when it is combined with Adagrasib. |
| Avanafil | The serum concentration of Avanafil can be increased when it is combined with Adagrasib. |
| Benzocaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Benzocaine. |
| Benzyl alcohol | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Benzyl alcohol. |
| Boceprevir | The serum concentration of Adagrasib can be increased when it is combined with Boceprevir. |
| Budesonide | The serum concentration of Budesonide can be increased when it is combined with Adagrasib. |
| Bupivacaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Bupivacaine. |
| Buspirone | The serum concentration of Buspirone can be increased when it is combined with Adagrasib. |
| Butacaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Butacaine. |
| Butamben | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Butamben. |
| Capsaicin | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Capsaicin. |
| Carbamazepine | The serum concentration of Adagrasib can be decreased when it is combined with Carbamazepine. |
| Celecoxib | The serum concentration of Celecoxib can be increased when it is combined with Adagrasib. |
| Chloroprocaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Chloroprocaine. |
| Cinchocaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Cinchocaine. |
| Clarithromycin | The serum concentration of Adagrasib can be increased when it is combined with Clarithromycin. |
| Clozapine | The risk or severity of QTc prolongation can be increased when Adagrasib is combined with Clozapine. |
| Cobicistat | The serum concentration of Adagrasib can be increased when it is combined with Cobicistat. |
| Cocaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Cocaine. |
| Colchicine | The serum concentration of Colchicine can be increased when it is combined with Adagrasib. |
| Conivaptan | The serum concentration of Conivaptan can be increased when it is combined with Adagrasib. |
| Curcumin | The serum concentration of Adagrasib can be increased when it is combined with Curcumin. |
| Danazol | The serum concentration of Adagrasib can be increased when it is combined with Danazol. |
| Darbepoetin alfa | The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Adagrasib. |
| Darifenacin | The serum concentration of Darifenacin can be increased when it is combined with Adagrasib. |
| Darunavir | The serum concentration of Darunavir can be increased when it is combined with Adagrasib. |
| Dasatinib | The serum concentration of Dasatinib can be increased when it is combined with Adagrasib. |
| Delamanid | Adagrasib may increase the QTc-prolonging activities of Delamanid. |
| Delavirdine | The serum concentration of Adagrasib can be increased when it is combined with Delavirdine. |
| Desipramine | The serum concentration of Desipramine can be increased when it is combined with Adagrasib. |
| Dexamethasone | The serum concentration of Adagrasib can be decreased when it is combined with Dexamethasone. |
| Dextromethorphan | The serum concentration of Dextromethorphan can be increased when it is combined with Adagrasib. |
| Diphenhydramine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Diphenhydramine. |
| Dronedarone | The serum concentration of Dronedarone can be increased when it is combined with Adagrasib. |
| Dyclonine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Dyclonine. |
| Ebastine | The serum concentration of Ebastine can be increased when it is combined with Adagrasib. |
| Econazole | The serum concentration of Adagrasib can be increased when it is combined with Econazole. |
| Efavirenz | The serum concentration of Adagrasib can be increased when it is combined with Efavirenz. |
| Eletriptan | The serum concentration of Eletriptan can be increased when it is combined with Adagrasib. |
| Eliglustat | The serum concentration of Eliglustat can be increased when it is combined with Adagrasib. |
| Elvitegravir | The serum concentration of Adagrasib can be increased when it is combined with Elvitegravir. |
| Encainide | The serum concentration of Encainide can be increased when it is combined with Adagrasib. |
| Entrectinib | The risk or severity of QTc prolongation can be increased when Adagrasib is combined with Entrectinib. |
| Enzalutamide | The serum concentration of Adagrasib can be decreased when it is combined with Enzalutamide. |
| Eplerenone | The serum concentration of Eplerenone can be increased when it is combined with Adagrasib. |
| Ergotamine | The serum concentration of Adagrasib can be increased when it is combined with Ergotamine. |
| Erythropoietin | The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Adagrasib. |
| Ethyl chloride | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Ethyl chloride. |
| Etidocaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Etidocaine. |
| Everolimus | The serum concentration of Everolimus can be increased when it is combined with Adagrasib. |
| Felodipine | The serum concentration of Felodipine can be increased when it is combined with Adagrasib. |
| Fexinidazole | The risk or severity of adverse effects can be increased when Adagrasib is combined with Fexinidazole. |
| Fluoxetine | The risk or severity of QTc prolongation can be increased when Fluoxetine is combined with Adagrasib. |
| Fosphenytoin | The serum concentration of Adagrasib can be decreased when it is combined with Fosphenytoin. |
| Glimepiride | The serum concentration of Glimepiride can be increased when it is combined with Adagrasib. |
| Haloperidol | The risk or severity of QTc prolongation can be increased when Adagrasib is combined with Haloperidol. |
| Hydroxyzine | The risk or severity of QTc prolongation can be increased when Adagrasib is combined with Hydroxyzine. |
| Ibrutinib | The serum concentration of Ibrutinib can be increased when it is combined with Adagrasib. |
| Imipramine | The serum concentration of Imipramine can be increased when it is combined with Adagrasib. |
| Indinavir | The serum concentration of Indinavir can be increased when it is combined with Adagrasib. |
| Isavuconazole | The serum concentration of Isavuconazole can be increased when it is combined with Adagrasib. |
| Itraconazole | The serum concentration of Adagrasib can be increased when it is combined with Itraconazole. |
| Ivabradine | The serum concentration of Ivabradine can be increased when it is combined with Adagrasib. |
| Ketoconazole | The serum concentration of Adagrasib can be increased when it is combined with Ketoconazole. |
| Lefamulin | Lefamulin may increase the QTc-prolonging activities of Adagrasib. |
| Lemborexant | The serum concentration of Lemborexant can be increased when it is combined with Adagrasib. |
| Levobupivacaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Levobupivacaine. |
| Levoketoconazole | The serum concentration of Adagrasib can be increased when it is combined with Levoketoconazole. |
| Lidocaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Lidocaine. |
| Lomitapide | The serum concentration of Lomitapide can be increased when it is combined with Adagrasib. |
| Lonafarnib | The serum concentration of Adagrasib can be increased when it is combined with Lonafarnib. |
| Lopinavir | The serum concentration of Adagrasib can be increased when it is combined with Lopinavir. |
| Lovastatin | The serum concentration of Lovastatin can be increased when it is combined with Adagrasib. |
| Lumacaftor | The serum concentration of Adagrasib can be decreased when it is combined with Lumacaftor. |
| Lurasidone | The serum concentration of Lurasidone can be increased when it is combined with Adagrasib. |
| Maraviroc | The serum concentration of Maraviroc can be increased when it is combined with Adagrasib. |
| Meloxicam | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Meloxicam. |
| Mepivacaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Mepivacaine. |
| Methimazole | The serum concentration of Adagrasib can be increased when it is combined with Methimazole. |
| Methoxy | The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Adagrasib. |
| Metoprolol | The serum concentration of Metoprolol can be increased when it is combined with Adagrasib. |
| Midazolam | The serum concentration of Midazolam can be increased when it is combined with Adagrasib. |
| Midostaurin | The serum concentration of Adagrasib can be decreased when it is combined with Midostaurin. |
| Mitotane | The serum concentration of Adagrasib can be decreased when it is combined with Mitotane. |
| Mobocertinib | The risk or severity of QTc prolongation can be increased when Adagrasib is combined with Mobocertinib. |
| Naloxegol | The serum concentration of Naloxegol can be increased when it is combined with Adagrasib. |
| Nebivolol | The serum concentration of Nebivolol can be increased when it is combined with Adagrasib. |
| Nefazodone | The serum concentration of Adagrasib can be increased when it is combined with Nefazodone. |
| Nelfinavir | The serum concentration of Adagrasib can be increased when it is combined with Nelfinavir. |
| Nilotinib | The serum concentration of Adagrasib can be increased when it is combined with Nilotinib. |
| Nisoldipine | The serum concentration of Nisoldipine can be increased when it is combined with Adagrasib. |
| Nortriptyline | The serum concentration of Nortriptyline can be increased when it is combined with Adagrasib. |
| Oxetacaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Oxetacaine. |
| Oxybuprocaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Oxybuprocaine. |
| Peginesatide | The risk or severity of Thrombosis can be increased when Peginesatide is combined with Adagrasib. |
| Pentobarbital | The serum concentration of Adagrasib can be decreased when it is combined with Pentobarbital. |
| Perphenazine | The serum concentration of Perphenazine can be increased when it is combined with Adagrasib. |
| Phenobarbital | The serum concentration of Adagrasib can be decreased when it is combined with Phenobarbital. |
| Phenol | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Phenol. |
| Phenytoin | The serum concentration of Adagrasib can be decreased when it is combined with Phenytoin. |
| Pimozide | The serum concentration of Pimozide can be increased when it is combined with Adagrasib. |
| Pitolisant | Adagrasib may increase the QTc-prolonging activities of Pitolisant. |
| Ponesimod | The risk or severity of bradycardia can be increased when Ponesimod is combined with Adagrasib. |
| Posaconazole | The serum concentration of Adagrasib can be increased when it is combined with Posaconazole. |
| Pramocaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Pramocaine. |
| Prilocaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Prilocaine. |
| Primidone | The serum concentration of Adagrasib can be decreased when it is combined with Primidone. |
| Procaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Procaine. |
| Propafenone | The serum concentration of Propafenone can be increased when it is combined with Adagrasib. |
| Proparacaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Proparacaine. |
| Propoxycaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Propoxycaine. |
| Propranolol | The serum concentration of Propranolol can be increased when it is combined with Adagrasib. |
| Quetiapine | The serum concentration of Quetiapine can be increased when it is combined with Adagrasib. |
| Ribociclib | The serum concentration of Adagrasib can be increased when it is combined with Ribociclib. |
| Rifampicin | The serum concentration of Adagrasib can be decreased when it is combined with Rifampicin. |
| Rifamycin | The serum concentration of Adagrasib can be decreased when it is combined with Rifamycin. |
| Rifapentine | The serum concentration of Adagrasib can be decreased when it is combined with Rifapentine. |
| Rilpivirine | The serum concentration of Rilpivirine can be increased when it is combined with Adagrasib. |
| Rimexolone | The serum concentration of Adagrasib can be decreased when it is combined with Rimexolone. |
| Ritonavir | The serum concentration of Adagrasib can be increased when it is combined with Ritonavir. |
| Rivaroxaban | The serum concentration of Rivaroxaban can be increased when it is combined with Adagrasib. |
| Ropivacaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Ropivacaine. |
| Saquinavir | The serum concentration of Saquinavir can be increased when it is combined with Adagrasib. |
| Sildenafil | The serum concentration of Sildenafil can be increased when it is combined with Adagrasib. |
| Simvastatin | The serum concentration of Simvastatin can be increased when it is combined with Adagrasib. |
| Sirolimus | The serum concentration of Sirolimus can be increased when it is combined with Adagrasib. |
| St. John’s Wort | The serum concentration of Adagrasib can be decreased when it is combined with St. John’s Wort. |
| Stiripentol | The serum concentration of Adagrasib can be increased when it is combined with Stiripentol. |
| Tacrolimus | The serum concentration of Tacrolimus can be increased when it is combined with Adagrasib. |
| Tadalafil | The serum concentration of Tadalafil can be increased when it is combined with Adagrasib. |
| Telaprevir | The serum concentration of Adagrasib can be increased when it is combined with Telaprevir. |
| Telithromycin | The serum concentration of Adagrasib can be increased when it is combined with Telithromycin. |
| Terfenadine | The serum concentration of Adagrasib can be increased when it is combined with Terfenadine. |
| Tetracaine | The risk or severity of methemoglobinemia can be increased when Adagrasib is combined with Tetracaine. |
| Ticagrelor | The serum concentration of Ticagrelor can be increased when it is combined with Adagrasib. |
| Tipranavir | The serum concentration of Tipranavir can be increased when it is combined with Adagrasib. |
| Tolbutamide | The serum concentration of Tolbutamide can be increased when it is combined with Adagrasib. |
| Tolterodine | The serum concentration of Tolterodine can be increased when it is combined with Adagrasib. |
| Tolvaptan | The serum concentration of Tolvaptan can be increased when it is combined with Adagrasib. |
| Tramadol | The serum concentration of Tramadol can be increased when it is combined with Adagrasib. |
| Trazodone | The risk or severity of QTc prolongation can be increased when Trazodone is combined with Adagrasib. |
| Triazolam | The serum concentration of Triazolam can be increased when it is combined with Adagrasib. |
| Trimipramine | The serum concentration of Trimipramine can be increased when it is combined with Adagrasib. |
| Troleandomycin | The serum concentration of Adagrasib can be increased when it is combined with Troleandomycin. |
| Vardenafil | The serum concentration of Vardenafil can be increased when it is combined with Adagrasib. |
| Venetoclax | The serum concentration of Venetoclax can be increased when it is combined with Adagrasib. |
| Venlafaxine | The serum concentration of Venlafaxine can be increased when it is combined with Adagrasib. |
| Voriconazole | The serum concentration of Adagrasib can be increased when it is combined with Voriconazole. |
| Ziprasidone | The risk or severity of QTc prolongation can be increased when Adagrasib is combined with Ziprasidone. |
Pregnancy and Lactation
FDA Pregnancy Category : Not Assign
Pregnancy
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.
Lactation
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.