Adagrasib
Generic Name: adagrasib
Brand Names:
Krazati
11 DESCRIPTION Adagrasib is an irreversible inhibitor of KRAS G12C and belongs to the RAS GTPase family. The molecular formula is C 32 H 35 ClFN 7 O 2 and the molecular weight is 604.1 g/mol. The chemical name is {(2 S )-4-[7-(8-chloronaphthalen-1-yl)-2-{[(2 S )-1-methylpyrrolidin-2-yl]- methoxy}-5,6,7,8-tetrahydropyrido[3,4- d ]pyrimidin-4-yl]-1-(2-fluoroprop-2-enoyl)piperazin-2-yl}acetonitrile. Adagrasib has the following chemical structure: Adagrasib is a crystalline solid.
Overview
11 DESCRIPTION Adagrasib is an irreversible inhibitor of KRAS G12C and belongs to the RAS GTPase family. The molecular formula is C 32 H 35 ClFN 7 O 2 and the molecular weight is 604.1 g/mol. The chemical name is {(2 S )-4-[7-(8-chloronaphthalen-1-yl)-2-{[(2 S )-1-methylpyrrolidin-2-yl]- methoxy}-5,6,7,8-tetrahydropyrido[3,4- d ]pyrimidin-4-yl]-1-(2-fluoroprop-2-enoyl)piperazin-2-yl}acetonitrile. Adagrasib has the following chemical structure: Adagrasib is a crystalline solid.
Uses
1 INDICATIONS AND USAGE KRAZATI is an inhibitor of the RAS GTPase family indicated for: Non-small cell lung cancer (NSCLC)* • As a single agent, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. ( 1.1 ) Colorectal cancer (CRC)* • In combination with cetuximab, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC, as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. ( 1.2 ) *These indications are approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR).
Dosage
2 DOSAGE AND ADMINISTRATION • Recommended dosage as a single agent for NSCLC and in combination with cetuximab for CRC: 600 mg orally twice daily. ( 2.2 ) • Swallow tablets whole with or without food. ( 2.2 ) 2.1 Patient Selection Non-Small Cell Lung Cancer 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 [see Clinical Studies (14.1) ] . If no mutation is detected in a plasma specimen, test tumor tissue. Colorectal Cancer Select patients for treatment of locally advanced or metastatic CRC with KRAZATI based on the presence of KRAS G12C mutation in tumor specimens [see Clinical Studies (14.2) ] .
Side Effects
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.1) ] • QTc Interval Prolongation [see Warnings and Precautions (5.2) ] • Hepatotoxicity [see Warnings and Precautions (5.3) ] • Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.4) ] • Single agent use in NCSLC: The most common adverse reactions (≥ 25%) were nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea, and decreased appetite.
Interactions
7 DRUG INTERACTIONS See full prescribing information for clinically significant drug interactions with KRAZATI. ( 7 ) • Strong CYP3A4 Inducers : Avoid concomitant use. ( 7.1 ) • Strong CYP3A4 Inhibitors : Avoid concomitant use until adagrasib concentrations have reached steady state. ( 7.1 ) • Sensitive CYP3A4 Substrates : Avoid concomitant use with sensitive CYP3A4 substrates. ( 7.2 ) • Sensitive CYP2C9 or CYP2D6 Substrates or P-gp Substrates : Avoid concomitant use with sensitive CYP2C9 or CYP2D6 substrates or P-gp substrates where minimal concentration changes may lead to serious adverse reactions. ( 7.2 ) • Drugs That Prolong QT Interval : Avoid concomitant use with KRAZATI.
Warnings
5 WARNINGS AND PRECAUTIONS • Gastrointestinal Adverse Reactions : Monitor patients for diarrhea, nausea and vomiting and provide supportive care as needed. Withhold, reduce the dose or permanently discontinue based on severity. ( 2.3 , 5.1 ) • QTc Interval Prolongation: Avoid concomitant use of KRAZATI with other products with a known potential to prolong the QTc interval. Monitor ECG and electrolytes particularly potassium and magnesium, in patients at risk, and in patients taking medications known to prolong the QT interval. Correct electrolyte abnormalities. Withhold, reduce the dose, or permanently discontinue based on severity. ( 2.3 , 5.2 ) • Hepatotoxicity: Monitor liver laboratory tests prior to the start of KRAZATI and monthly for 3 months after and as clinically indicated. 4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy
8.1 Pregnancy Risk Summary 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.
Storage
Storage and Handling Store tablets at room temperature, 20°C to 25°C (68°F to 77°F). Temperature excursions between 15°C and 30°C (59°F to 86°F) are permitted [see USP Controlled Room Temperature] .
Frequently Asked Questions
What is Adagrasib used for?▼
1 INDICATIONS AND USAGE KRAZATI is an inhibitor of the RAS GTPase family indicated for: Non-small cell lung cancer (NSCLC)* • As a single agent, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. ( 1.1 ) Colorectal cancer (CRC)* • In combination with cetuximab, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC, as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. ( 1.2 ) *These indications are approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR).
What are the side effects of Adagrasib?▼
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.1) ] • QTc Interval Prolongation [see Warnings and Precautions (5.2) ] • Hepatotoxicity [see Warnings and Precautions (5.3) ] • Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.4) ] • Single agent use in NCSLC: The most common adverse reactions (≥ 25%) were nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea, and decreased appetite.
Can I take Adagrasib during pregnancy?▼
8.1 Pregnancy Risk Summary 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.
What are the important warnings for Adagrasib?▼
5 WARNINGS AND PRECAUTIONS • Gastrointestinal Adverse Reactions : Monitor patients for diarrhea, nausea and vomiting and provide supportive care as needed. Withhold, reduce the dose or permanently discontinue based on severity. ( 2.3 , 5.1 ) • QTc Interval Prolongation: Avoid concomitant use of KRAZATI with other products with a known potential to prolong the QTc interval. Monitor ECG and electrolytes particularly potassium and magnesium, in patients at risk, and in patients taking medications known to prolong the QT interval. Correct electrolyte abnormalities. Withhold, reduce the dose, or permanently discontinue based on severity. ( 2.3 , 5.2 ) • Hepatotoxicity: Monitor liver laboratory tests prior to the start of KRAZATI and monthly for 3 months after and as clinically indicated. 4 CONTRAINDICATIONS None. None. ( 4 )
Related Medications
Vespa Crabro
vespa crabro
Pain and itching from bee or wasp stings*
Dl-epinephrine Hcl
dl-epinephrine hcl
Dosage form: POWDER. Active ingredients: RACEPINEPHRINE HYDROCHLORIDE (100 g/100g). Category: BULK INGREDIENT.
Calendula Officinalis, Kali Phosphoricum, Natrum Muriaticum, Arnica Montana, Agave Americana, Cistus Canadensis, Kreosotum, Myrrha, Calcarea Fluorica, Aconitum Napellus, Bismuthum Subnitricum, Sepia, Hepar Sulphuris Calcareum, Mercurius Vivus
calendula officinalis, kali phosphoricum, natrum muriaticum, arnica montana, agave americana, cistus canadensis, kreosotum, myrrha, calcarea fluorica, aconitum napellus, bismuthum subnitricum, sepia, hepar sulphuris calcareum, mercurius vivus
HOMEOPATHIC INDICATIONS: For temporary relief of symptoms related to gingivitis, inflamed and bleeding gums and minor pain.** **These statements are based upon traditional homeopathic principles. They have not been reviewed by the Food and Drug Administration.
Medical Disclaimer
This drug information is for educational purposes only and should not replace professional medical advice. Drug information is sourced from the FDA National Drug Code Directory and Structured Product Labeling. Always consult with a healthcare provider before starting, stopping, or changing any medication.