Rasonque

Daraxonrasib · Tablet, Film Coated · Oral

Prescription (Rx)

Uses

1 INDICATIONS AND USAGE RASONQUE is indicated for the treatment of adult patients with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy. RASONQUE is an inhibitor of the RAS GTPase family, indicated for the treatment of adult patients with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy. ( 1 )

Dosage and administration

Recommended dosage: 300 mg orally once daily. ( 2.2 ) Swallow tablets whole with or without food. ( 2.2 ) Administer prophylactic and concomitant medications to reduce the risk of dermatologic reactions. ( 2.1 ) 2.1 Prophylactic and Concomitant Medication When initiating RASONQUE and throughout treatment, prophylactic and concomitant medications are recommended to reduce the risk of dermatologic reactions [see Warnings and Precautions (5.1) ] : administer a topical corticosteroid (applied to the face and chest) and emollient creams advise patients to limit sun exposure and use broad-spectrum sunscreen (SPF 30 or higher) consider prophylactic oral antibiotics (e.g., doxycycline or minocycline) 2.2 Recommended Dosage The recommended dosage of RASONQUE is 300 mg orally once daily until disease progression or unacceptable toxicity. Take RASONQUE at the same time each day with or without food. Swallow tablets whole. Do not chew, crush, or split tablets. If a dose is missed for more than 4 hours, skip the missed dose, and take the next dose at the next regularly scheduled time. If vomiting occurs after taking the dose, do not take an additional dose. Resume dosing at the next regularly scheduled time. 2.3 Dosage Modifications for Adverse Reactions Recommended dosage reductions for adverse reactions are provided in Table 1 . Permanently discontinue RASONQUE in patients who are unable to tolerate 150 mg orally once daily. Table 1: Recommended Dosage Reductions for Adverse Reactions Dose Reduction Level Dosage First dose reduction 200 mg once daily Second dose reduction 150 mg once daily Recommended dosage modifications for adverse reactions are provided in Table 2 . Table 2: Recommended Dosage Modifications for Adverse Reactions Adverse Reaction Severity Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Dosage Modification Dermatologic Toxicity (rash) [see Warnings and Precautions (5.1) ] Grade 2 Consider withholding RASONQUE until recovery to ≤ Grade 1. Initiate supportive measures, as necessary. Resume RASONQUE at the same dose level or the next lower dose level. Grade 3 Withhold RASONQUE until recovery to ≤ Grade 1. Initiate supportive measures, as necessary, and consider consultation with a dermatologist. Resume RASONQUE at the next lower dose level. Grade 4 Permanently discontinue. Stomatitis [see Warnings and Precautions (5.2) ] Grade 2 Consider withholding RASONQUE until recovery to ≤ Grade 1. Initiate supportive measures, as necessary. Resume RASONQUE at the same dose level or the next lower dose level. Grade 3 Withhold RASONQUE until recovery to ≤ Grade 1. Initiate supportive measures, as necessary. Resume RASONQUE at the next lower dose level. Grade 4 Permanently discontinue. Diarrhea [see Warnings and Precautions (5.3) ] Grade 2 Consider withholding RASONQUE until recovery to ≤ Grade 1. Initiate antidiarrheal treatment. Resume RASONQUE at the same dose level or the next lower dose level. Grade 3 Withhold RASONQUE until recovery to ≤ Grade 1. Initiate antidiarrheal treatment. Resume RASONQUE at the next lower dose level. Grade 4 Permanently discontinue. Gastrointestinal Perforation [see Warnings and Precautions (5.4) ] Grade 3 Withhold RASONQUE until recovery to ≤ Grade 1. If appropriate, resume RASONQUE at the next lower dose level. Grade 4 Permanently discontinue. Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.5) ] Grade 2 Withhold RASONQUE until recovery to ≤ Grade 1. If appropriate, resume RASONQUE at the next lower dose level. Recurrent Grade 2, or Grade 3-4 Permanently discontinue. Nausea or Vomiting [see Adverse Reactions (6.1) ] Grade 3 Withhold RASONQUE until recovery to ≤ Grade 1. Initiate or modify anti-emetic regimen. Resume RASONQUE at the next lower dose level. Grade 4 Permanently discontinue. Other Adverse Reactions [see Adverse Reactions (6.1) ] Grade 3 Withhold RASONQUE until recovery to ≤ Grade 1 or baseline. Resume RASONQUE at the next lower dose level. Grade 4 Permanently discontinue. 2.4 Dosage Modifications for Drug Interactions Strong CYP3A Inhibitors without P-gp Inhibition Reduce the dosage of RASONQUE from 300 mg once daily to 150 mg once daily when used concomitantly with a strong CYP3A inhibitor without P-gp inhibition [see Drug Interactions (7.1) ] . After the strong CYP3A inhibitor without P-gp inhibition has been discontinued for 5 days or 3 to 5 half-lives, whichever is longer, resume the RASONQUE dosage taken prior to initiating the inhibitor. Moderate CYP3A Inhibitors with P-gp Inhibition Reduce the dosage of RASONQUE from 300 mg once daily to 100 mg once daily when used concomitantly with a moderate CYP3A inhibitor with P-gp inhibition [see Drug Interactions (7.1) ] . After the moderate CYP3A inhibitor with P-gp inhibition has been discontinued for 3 to 5 half-lives, resume the RASONQUE dosage taken prior to initiating the inhibitor. Moderate CYP3A Inhibitors without P-gp Inhibition Reduce the dosage of RASONQUE from 300 mg once daily to 200 mg once daily when used concomitantly with a moderate CYP3A inhibitor without P-gp inhibition [see Drug Interactions (7.1) ] . After the moderate CYP3A inhibitor without P-gp inhibition has been discontinued for 3 to 5 half-lives, resume the RASONQUE dosage taken prior to initiating the inhibitor. P-gp Inhibitors Reduce the dosage of RASONQUE from 300 mg once daily to 150 mg once daily when used concomitantly with a P-gp inhibitor [see Drug Interactions (7.1) ] . After the P-gp inhibitor has been discontinued, resume the RASONQUE dosage taken prior to initiating the inhibitor. Strong CYP3A Inducers If a strong CYP3A inducer cannot be avoided, increase the dosage of RASONQUE from 300 mg once daily to 400 mg once daily when used concomitantly with a strong CYP3A inducer [see Drug Interactions (7.1) ] .

Dosage forms and strengths

Tablets: 100 mg, blue, oval, biconvex, film-coated, debossed with “R” on one side and “100 M” on the other side. Tablets: 150 mg, blue, oval, biconvex, film-coated, debossed with “R” on one side and “150 M” on the other side. Tablets: 100 mg; 150 mg. ( 3 )

Contraindications

None. None. ( 4 )

Warnings and precautions

Dermatologic and Soft Tissue Toxicity : RASONQUE can cause dermatologic or soft tissue toxicities, including rash, pruritus, and dry skin. Advise patients to limit sun exposure, use sunscreen, and use emollient creams. Withhold, reduce the dose, or permanently discontinue based on severity. ( 2.3 , 5.1 ) Stomatitis and Oral Disorders : RASONQUE can cause stomatitis, including mouth ulcers and oral mucositis. Withhold, reduce the dose, or permanently discontinue based on severity. ( 2.3 , 5.2 ) Diarrhea : RASONQUE can cause diarrhea. Withhold, reduce the dose, or permanently discontinue based on severity. ( 2.3 , 5.3 ) Gastrointestinal Perforation : Monitor for gastrointestinal perforation. Withhold if suspected. If appropriate, reduce the dose or permanently discontinue if no other potential causes of gastrointestinal perforation are identified. ( 2.3 , 5.4 ) Interstitial Lung Disease (ILD)/Pneumonitis : Monitor for new or worsening pulmonary symptoms. Withhold if suspected. If appropriate, reduce the dose or permanently discontinue if no other potential causes of ILD/pneumonitis are identified. ( 2.3 , 5.5 ) Embryo-Fetal Toxicity : RASONQUE can cause fetal harm. Advise of the potential risk to the fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) 5.1 Dermatologic and Soft Tissue Toxicity RASONQUE can cause dermatologic toxicity, which may be severe. Clinical manifestations included, but were not limited to, rash, pruritus, paronychia, dry skin, and skin fissures. In clinical trials of patients with pancreatic adenocarcinoma, dermatologic toxicity occurred in 86% of patients treated with RASONQUE, of which 10% were Grade 3. The median time to first onset was 13 days (range: 1 to 106 days). The median time to improvement from Grade 3 to Grade 1 or resolution was 16 days (range: 8 to 218 days). Dermatologic toxicity led to interruption of RASONQUE in 24% of patients, dose reduction in 16% of patients, and dose discontinuation in 0.5% of patients. Monitor patients who develop dermatologic or soft tissue toxicities while receiving RASONQUE. Initiate prophylactic measures (e.g., topical corticosteroids, emollient creams, sunscreen, oral antibiotics) prior to the first dose of RASONQUE to reduce the risk of moderate to severe dermatologic reactions. Advise patients to limit sun exposure while taking RASONQUE. Initiate supportive measures (e.g., oral corticosteroids) as clinically indicated, and consider dermatologic consultation. Withhold, reduce the dose, or permanently discontinue RASONQUE based on severity [see Dosage and Administration (2.3) ]. 5.2 Stomatitis and Oral Disorders RASONQUE can cause stomatitis, including mouth ulcers and oral mucositis. In clinical trials of patients with pancreatic adenocarcinoma, stomatitis occurred in 57% of patients, of which 9% were Grade 3. The median time to first onset was 22 days (range: 1 to 343 days). The median time to improvement from Grade 3 to Grade 1 or resolution was 12 days (range: 1 to 127 days). Stomatitis led to interruption of RASONQUE in 17% of patients and dose reduction in 8% of patients. Monitor patients for signs and symptoms of stomatitis while receiving RASONQUE. Initiate a steroid-containing mouthwash for treatment of stomatitis and administer other topical treatments (e.g., chlorhexidine mouthwash, 2% lidocaine viscous) as clinically indicated. Withhold, reduce the dose, or permanently discontinue RASONQUE based on severity [see Dosage and Administration (2.3) ]. 5.3 Diarrhea RASONQUE can cause diarrhea. In clinical trials of patients with pancreatic adenocarcinoma, diarrhea occurred in 63% of patients, of which 6% were Grade 3. The median time to first onset was 3 days (range: 1 to 260 days). The median time to improvement from Grade 3 to Grade 1 or resolution was 3 days (range: 1 to 21 days). Diarrhea led to interruption of RASONQUE in 8% of patients and dose reduction in 4% of patients. If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue RASONQUE based on severity [see Dosage and Administration (2.3) ]. 5.4 Gastrointestinal Perforation RASONQUE can cause gastrointestinal perforation. In clinical trials of patients with pancreatic adenocarcinoma, gastrointestinal perforation occurred in 0.9% of patients treated with RASONQUE, of which 0.5% were Grade 3, one event was Grade 4, and one event was fatal. The median time to first onset was 134 days (range: 17 to 254 days). The median time to improvement from Grade ≥ 3 to resolution was 8 days (range: 7 to 9 days). Monitor patients for gastrointestinal perforation. Withhold RASONQUE if gastrointestinal perforation is suspected. Reduce the dose or permanently discontinue RASONQUE if no other potential causes of gastrointestinal perforation are identified [see Dosage and Administration (2.3) ]. 5.5 Interstitial Lung Disease (ILD)/Pneumonitis RASONQUE can cause interstitial lung disease or pneumonitis. In clinical trials of patients with pancreatic adenocarcinoma, ILD/pneumonitis occurred in 2.4% of patients treated with RASONQUE, of which 0.9% were Grade 3, and one event was fatal. The median time to first onset was 111 days (range: 22 to 242 days). The median time to improvement from Grade 3 to resolution was 12 days (range: 12 to 47 days). Monitor patients for new or worsening pulmonary symptoms. Withhold RASONQUE if ILD/pneumonitis is suspected. Reduce the dose or permanently discontinue RASONQUE if no other potential causes of ILD/pneumonitis are identified [see Dosage and Administration (2.3) ] . 5.6 Embryo-Fetal Toxicity Based on findings in animals, RASONQUE can cause fetal harm when administered to a pregnant woman.

Side effects

The following clinically significant adverse reactions are described elsewhere in the labeling: Dermatologic and Soft Tissue Toxicity [see Warnings and Precautions (5.1) ] Stomatitis and Oral Disorders [see Warnings and Precautions (5.2) ] Diarrhea [see Warnings and Precautions (5.3) ] Gastrointestinal Perforation [see Warnings and Precautions (5.4) ] Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.5 )] Most common adverse reactions (≥ 20%) were rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage. ( 6.1 ) Most common laboratory abnormalities (≥ 20%) were decreased albumin, decreased calcium, decreased hemoglobin, increased aspartate aminotransferase, decreased lymphocytes, decreased platelets, increased alanine aminotransferase, decreased sodium, decreased white blood cells, decreased magnesium, increased alkaline phosphatase, increased creatinine, and decreased potassium. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Revolution Medicines, Inc. at 1-844-2-REVMED (1-844-273-8633) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population of RASONQUE described in the WARNINGS AND PRECAUTIONS section reflects exposure to RASONQUE 300 mg once daily in 241 patients with pancreatic adenocarcinoma enrolled in RASolute 302 and 184 patients with pancreatic adenocarcinoma enrolled in the open-label trial RMC-6236-001. Metastatic Pancreatic Adenocarcinoma The safety of RASONQUE was evaluated in RASolute 302 [see Clinical Studies (14) ] . Patients with metastatic pancreatic adenocarcinoma received either RASONQUE 300 mg once daily (N = 241) or physician’s choice of standard of care (SOC) chemotherapy regimens (N = 214). Among patients who received RASONQUE, 52% were exposed for 6 months or longer and 2% were exposed for greater than one year. Serious adverse reactions occurred in 30% of patients treated with RASONQUE. Serious adverse reactions occurring in ≥ 2% of patients treated with RASONQUE were diarrhea (3.7%), pyrexia (3.3%), sepsis (2.9%), fatigue (2.1%), and hemorrhage (2.1%). Adverse reactions leading to permanent discontinuation of RASONQUE occurred in 2.9% of patients, including two patients who discontinued due to rash (0.8%). Adverse reactions leading to dose interruptions occurred in 69% of patients who received RASONQUE. Adverse reactions which required dose interruptions in ≥ 5% of patients were rash (27%), stomatitis (20%), fatigue (9%), diarrhea (8%), vomiting (8%), nausea (7%), and pyrexia (6%). Adverse reactions leading to dose reductions occurred in 37% of patients who received RASONQUE. Adverse reactions which required dose reductions in ≥ 5% of patients were rash (18%), stomatitis (8%), and diarrhea (5%). The most common (≥ 20%) adverse reactions in patients treated with RASONQUE were rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage. Table 3 and Table 4 summarize adverse reactions and laboratory abnormalities in RASolute 302, respectively. Table 3: Adverse Reactions (≥ 10%) in Patients Who Received RASONQUE in RASolute 302 Adverse Reaction Graded per NCI CTCAE Version 5.0. RASONQUE N = 241 Physician’s Choice SOC Chemotherapy Regimens Chemotherapy: mFOLFIRINOX, gemcitabine and nab-paclitaxel, FOLFOX, or nal-IRI+5-FU/LV. N = 214 All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Skin and subcutaneous tissue disorders Rash Includes multiple related terms. 87 13 9 0 Dry skin 14 0 3 0 Pruritus 11 0.4 4 0 Gastrointestinal disorders Diarrhea 67 7 44 8 Stomatitis 56 12 19 3 Nausea 52 3 42 2 Vomiting 42 1 25 1 Abdominal pain 27 2 26 2 Constipation 16 0.4 21 0.5 General disorders and administration site conditions Fatigue 47 5 61 10 Edema 25 0.8 22 0 Pyrexia 19 1 23 0.9 Metabolism and nutrition disorders Decreased appetite 24 2 27 0.9 Vascular disorders Hemorrhage 22 3 12 4 Musculoskeletal and connective tissue disorders Musculoskeletal pain 19 0.8 27 1 Infections and infestations Paronychia 17 0 0 0 Nervous system disorders Neuropathy peripheral 10 0 29 4 Other clinically important adverse reactions occurring in less than 10% of patients who received RASONQUE in RASolute 302 included renal-limited thrombotic microangiopathy (0.4%). Table 4: Select Laboratory Abnormalities (≥ 20%) that Worsened from Baseline in Patients Who Received RASONQUE in RASolute 302 The denominator used to calculate the percentage varied from 234 to 237 in the RASONQUE arm and from 207 to 208 in the SOC chemotherapy arm, based on the number of patients with a baseline value and at least one post-baseline value. Laboratory Abnormality Graded per NCI CTCAE Version 5.0. RASONQUE Physician’s Choice SOC Chemotherapy Regimens All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Chemistry Albumin decreased 71 3 51 1 Calcium (corrected) decreased 64 2 47 3 Aspartate aminotransferase increased 51 3 36 2 Alanine aminotransferase increased 36 4 39 0.5 Sodium decreased 36 6 30 5 Magnesium decreased 34 1 22 1 Alkaline phosphatase increased 29 2 24 0.5 Creatinine increased 24 0.8 9 0 Potassium decreased 20 3 33 7 Hematology Hemoglobin decreased 52 10 68 20 Lymphocyte cell count decreased 49 11 56 19 Platelet count decreased 45 3 58 10 White blood cell count decreased 35 3 58 17

Drug interactions

Strong CYP3A Inhibitors with P-gp Inhibition : Avoid concomitant use. ( 7.1 ) Strong CYP3A Inhibitors without P-gp Inhibition : Reduce RASONQUE dosage. ( 2.4 ) Moderate CYP3A Inhibitors with or without P-gp Inhibition : Reduce RASONQUE dosage. ( 2.4 ) P-gp Inhibitors : Reduce RASONQUE dosage. ( 2.4 ) Cyclosporine A : Avoid concomitant use. ( 7.1 ) Strong CYP3A Inducers : Avoid concomitant use. Increase RASONQUE dosage if concomitant use cannot be avoided. ( 2.4 , 7.1 ) Moderate CYP3A Inducers : Increase RASONQUE dosage. ( 2.4 ) P-gp Substrates : Take at least 4 hours apart from RASONQUE. ( 7.2 ) 7.1 Effects of Other Drugs on RASONQUE Table 5: Effects of Other Drugs on RASONQUE Strong or Moderate CYP3A Inhibitors with or without P-gp Inhibition Prevention or Management Strong CYP3A inhibitors with P-glycoprotein (P-gp) inhibition : Avoid concomitant use. Strong CYP3A inhibitors without P-gp inhibition : Reduce RASONQUE dosage to 150 mg once daily [see Dosage and Administration (2.4) ] . Moderate CYP3A inhibitors with P-gp inhibition : Reduce RASONQUE dosage to 100 mg once daily [see Dosage and Administration (2.4) ] . Moderate CYP3A inhibitors without P-gp inhibition : Reduce RASONQUE dosage to 200 mg once daily [see Dosage and Administration (2.4) ] . Mechanism and Clinical Effect Daraxonrasib is a CYP3A and P-gp substrate. Moderate or strong CYP3A inhibitors with or without P-gp inhibition increase daraxonrasib exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions. P-gp Inhibitors Prevention or Management Reduce RASONQUE dosage to 150 mg once daily [see Dosage and Administration (2.4) ] . Mechanism and Clinical Effect Daraxonrasib is a P-gp substrate. P-gp inhibitors increase daraxonrasib exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions. Cyclosporine A Prevention or Management Avoid concomitant use of RASONQUE with systemic cyclosporine A or its derivatives. Mechanism and Clinical Effect Cyclosporine A or its derivatives and daraxonrasib bind to cyclophilin A. Coadministration of systemic cyclosporine A or its derivatives and RASONQUE may have the potential to alter daraxonrasib pharmacokinetics, efficacy, and safety. Strong or Moderate CYP3A Inducers Prevention or Management Strong CYP3A inducers : Avoid concomitant use. If concomitant use cannot be avoided, increase RASONQUE dosage to 400 mg once daily [see Dosage and Administration (2.4) ] . Moderate CYP3A inducers : Increase RASONQUE dosage to 400 mg once daily [see Dosage and Administration (2.4) ] . Mechanism and Clinical Effect Daraxonrasib is a CYP3A substrate. Strong CYP3A inducers reduce daraxonrasib exposure [see Clinical Pharmacology (12.3) ] , which may reduce the effectiveness of RASONQUE. 7.2 Effects of RASONQUE on Other Drugs P-gp Substrates Take a P-gp substrate at least 4 hours apart from RASONQUE. Daraxonrasib is a P-gp inhibitor. Coadministration with RASONQUE increases exposure of P-gp substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates.

Use in specific populations

Lactation : Advise women not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings in animals, RASONQUE can cause fetal harm when administered to pregnant women. There are no available data on RASONQUE use in pregnant women to inform a drug-associated risk. In an animal reproduction study, oral administration of daraxonrasib to pregnant female mice during the period of organogenesis resulted in adverse developmental outcomes including mortality, alterations to growth, and structural abnormalities at exposures ≥ 2.5 times the recommended dose based on AUC (see Data ) . Advise pregnant women of the potential risk to a fetus. 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. Data Animal Data Daraxonrasib was administered orally to pregnant female mice during the period of organogenesis at doses of 25, 50, and 75 mg/kg/day. Daraxonrasib at a dose of ≥ 50 mg/kg/day (≥ 2.5 times the exposure at the recommended dose based on AUC) was associated with post-implantation loss, reduced number of live fetuses, decreased fetal body weights, and malformations including eyes, limbs, palate, gonads, great vessels, kidneys, and bones. 8.2 Lactation Risk Summary There are no data on the presence of daraxonrasib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with RASONQUE and for 1 week after the last dose. 8.3 Females and Males of Reproductive Potential RASONQUE can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating RASONQUE. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with RASONQUE and for 1 week after the last dose. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with RASONQUE and for 1 week after the last dose. 8.4 Pediatric Use The safety and effectiveness of RASONQUE have not been established in pediatric patients. 8.5 Geriatric Use Of the 248 patients with pancreatic adenocarcinoma randomized to the RASONQUE arm in the RASolute 302 study, 54% (134 patients) were ≥ 65 years of age and 18% (45 patients) were ≥ 75 years of age. No overall differences in safety or efficacy were observed between patients who were ≥ 65 years of age and younger patients.

Pregnancy

8.1 Pregnancy Risk Summary Based on findings in animals, RASONQUE can cause fetal harm when administered to pregnant women. There are no available data on RASONQUE use in pregnant women to inform a drug-associated risk. In an animal reproduction study, oral administration of daraxonrasib to pregnant female mice during the period of organogenesis resulted in adverse developmental outcomes including mortality, alterations to growth, and structural abnormalities at exposures ≥ 2.5 times the recommended dose based on AUC (see Data ) . Advise pregnant women of the potential risk to a fetus. 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. Data Animal Data Daraxonrasib was administered orally to pregnant female mice during the period of organogenesis at doses of 25, 50, and 75 mg/kg/day. Daraxonrasib at a dose of ≥ 50 mg/kg/day (≥ 2.5 times the exposure at the recommended dose based on AUC) was associated with post-implantation loss, reduced number of live fetuses, decreased fetal body weights, and malformations including eyes, limbs, palate, gonads, great vessels, kidneys, and bones.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of RASONQUE have not been established in pediatric patients.

Geriatric use

8.5 Geriatric Use Of the 248 patients with pancreatic adenocarcinoma randomized to the RASONQUE arm in the RASolute 302 study, 54% (134 patients) were ≥ 65 years of age and 18% (45 patients) were ≥ 75 years of age. No overall differences in safety or efficacy were observed between patients who were ≥ 65 years of age and younger patients.

Description

Daraxonrasib is an inhibitor of the RAS GTPase family. The molecular formula is C 44 H 58 N 8 O 5 S and the molecular weight is 811.06 g/mol. The chemical name is Cyclopropanecarboxamide, N -[(2 R ,14 S ,18 S )-1-ethyl-18,19,20,21-tetrahydro-2-[2-[(1 S )-1-methoxyethyl]-5-(4-methyl-1-piperazinyl)-3-pyridinyl]-25,25-dimethyl-15,22-dioxo-17 H -5,3-([4,2]- endo -thiazolopropano[1,3]- endo -pyridazinomethanoxypropano)-1 H -indol-14-yl]-2-methyl-, (1 S ,2 S )-. Daraxonrasib has the following chemical structure: Daraxonrasib is a white to yellow crystalline solid; formulated as a spray-dried dispersion (SDD) and incorporated into a tablet for oral use. Daraxonrasib shows a pH-dependent aqueous solubility across the physiological pH range. Daraxonrasib thermodynamic solubility at 24 hours is greater than 10 mg/mL at pH 1.2, while daraxonrasib solubility is approximately 0.009 mg/mL at pH 6.8. RASONQUE (daraxonrasib) is supplied as film-coated tablets for oral use containing 150 mg or 100 mg of daraxonrasib. Inactive ingredients in the tablet core are butylated hydroxytoluene, colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose acetate succinate, magnesium stearate, mannitol, and microcrystalline cellulose. The tablet film coating contains FD&C blue #2/indigo carmine aluminum lake, glyceryl mono and dicaprylocaprate, polyvinyl alcohol, sodium lauryl sulfate, talc, and titanium dioxide. chemical structure

Mechanism of action

12.1 Mechanism of Action Daraxonrasib is an inhibitor of the RAS GTPase family. Daraxonrasib binds to cyclophilin A, resulting in a binary complex that binds to the active, GTP-bound state of RAS. The tri-complex inhibits RAS signaling by blocking interactions with downstream effectors and promoting GTP hydrolysis to the inactive GDP-bound state of RAS. Daraxonrasib inhibition of wild-type and mutant variants of KRAS, NRAS, and HRAS induces tumor growth suppression and apoptosis. In RAS-dependent models of pancreatic adenocarcinoma, daraxonrasib treatment led to tumor growth inhibition and regression and is associated with antitumor immunity.

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING RASONQUE tablets are packaged in a bottle containing one desiccant and a child-resistant cap, available as follows: Strength Description Bottle NDC Number 100 mg blue, oval, biconvex, film-coated, debossed with “R” on one side and “100 M” on the other side 30 tablets 85219-101-01 150 mg blue, oval, biconvex, film-coated, debossed with “R” on one side and “150 M” on the other side 30 tablets 85219-104-01 Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

Patient information

Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Dermatologic Reactions Advise patients of the risk of dermatologic reactions including rash and to use prophylactic measures. Advise patients to limit sun exposure and contact their healthcare provider if they experience dermatologic reactions [see Dosage and Administration (2.1) and Warnings and Precautions (5.1) ] . Stomatitis Advise patients of the risk of stomatitis. Advise patients to contact their healthcare provider for new onset or worsening stomatitis [see Warnings and Precautions (5.2) ] . Diarrhea Advise patients to contact their healthcare provider if they experience new onset or worsening diarrhea [see Warnings and Precautions (5.3) ] . Gastrointestinal Perforation Advise patients to contact their healthcare provider immediately if they experience severe abdominal pain or other symptoms of gastrointestinal perforation [see Warnings and Precautions (5.4) ] . Interstitial Lung Disease (ILD)/Pneumonitis Advise patients to contact their healthcare provider immediately if they experience new or worsening respiratory symptoms [see Warnings and Precautions (5.5) ] . Embryo-Fetal Toxicity Advise females to inform their healthcare provider if they are pregnant or become pregnant. Inform females of the potential risk to a fetus [see Warnings and Precautions (5.6) ] . Advise females of reproductive potential to use effective contraception during treatment with RASONQUE and for 1 week after the last dose [see Warnings and Precautions (5.6) and Use in Specific Populations (8.3) ] . Advise males with female partners of reproductive potential to use effective contraception during treatment with RASONQUE and for 1 week after the last dose [see Warnings and Precautions (5.6) and Use in Specific Populations (8.3) ] . Lactation Advise women not to breastfeed during treatment with RASONQUE and for 1 week after the last dose [see Use in Specific Populations (8.2) ] . Drug Interactions Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products [see Drug Interactions (7.1) ] . Manufactured for: Revolution Medicines, Inc. Redwood City, CA 94063 USA RASONQUE ™ is a trademark of Revolution Medicines, Inc. © 2026 Revolution Medicines, Inc. Pat.: http://www.revmed.com/patents/

Label text from the FDA structured product label by Revolution Medicines, Inc. (revised Aug 27, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Daraxonrasib in 4 products

Rasonque NDC products (4)

NDC	Strength & form	Labeler	Type
85219-101	Daraxonrasib 100 mg/1 Tablet, Film Coated	Revolution Medicines, Inc.	NDA
85219-104	Daraxonrasib 150 mg/1 Tablet, Film Coated	Revolution Medicines, Inc.	NDA
24538-430	Daraxonrasib 100 mg/100mg Tablet, Film Coated	Shanghai SynTheAll Pharmaceutical Co., Ltd.	NDA
24538-435	Daraxonrasib 150 mg/150mg Tablet, Film Coated	Shanghai SynTheAll Pharmaceutical Co., Ltd.	NDA

Frequently asked questions

What is Rasonque used for?

What are the side effects of Rasonque?

Who makes Rasonque?

Rasonque is listed by 2 labelers in the FDA NDC directory, including Revolution Medicines, Inc., Shanghai SynTheAll Pharmaceutical Co., Ltd..