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Rash
Rash / dermatologic toxicity. 87% overall; Grade 3–4 13% Assess extent, symptoms, skin integrity and impact on daily activities Dermatologic toxicity may include rash, pruritus, paronychia, dry skin and skin fissures Median time to first onset: 13 days
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Stomatitis / oral toxicity
Stomatitis / oral toxicity. 56% overall; Grade 3–4 12%. Assess grade and impact: mouth pain, mouth soreness, dysgeusia, oral mucositis, oral intake and hydration. Median time to first onset: 22 days.
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Stomatitis: start dexamethasone mouthwash
Continue oral care. Supportive regimen: Dexamethasone 0.5 mg/5 mL mouthwash: 10 mL TID; swish and spit. No food or drink for 30 minutes after use Reserve clotrimazole for suspected or confirmed candidiasis Daraxonrasib modification: Grade 2: consider withholding until recovery to ≤Grade 1; resume at the same or next lower dose Grade 3: withhold until recovery to ≤Grade 1; resume at the next lower dose Grade 4: permanently discontinue
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Grade toxicity and apply AE-specific dose modification
Most toxicity-specific restart criteria require recovery to ≤Grade 1. For rash, stomatitis and diarrhea, the label permits some Grade 2 events to resume at the same or next lower dose after improvement. For other Grade 3 adverse reactions, recovery to ≤Grade 1 or baseline is required.
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Continue daraxonrasib at current dose
Applicable to selected Grade 2 rash, stomatitis or diarrhea after recovery to ≤Grade 1 when resumption at the same dose is clinically appropriate.
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Ongoing daraxonrasib monitoring at the tolerated dose
Continue clinical toxicity assessment and appropriate laboratory monitoring throughout treatment. Re-enter the toxicity pathway promptly if new or worsening adverse reactions develop.
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Resume at next lower dose: 300 → 200 → 150 mg once daily
How to dose reduce daraxonrasib: Starting dose: 300 mg once daily First reduction: 200 mg once daily (one 100 mg + one 100 mg) Second reduction: 150 mg once daily (one 150 mg) No further reduction below 150 mg Permanently discontinue if unable to tolerate 150 mg This ladder applies to adverse reactions; drug-interaction dose adjustments are different.
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Ongoing daraxonrasib monitoring at the tolerated dose
Continue clinical toxicity assessment and appropriate laboratory monitoring throughout treatment. Re-enter the toxicity pathway promptly if new or worsening adverse reactions develop.
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Permanently discontinue daraxonrasib when required by toxicity-specific label guidance
Permanent discontinuation is required for specified severe or recurrent toxicities and when 150 mg once daily cannot be tolerated. Follow the toxicity-specific prescribing information.
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Implement withhold and restart plan
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Ongoing daraxonrasib monitoring at the tolerated dose
Continue clinical toxicity assessment and appropriate laboratory monitoring throughout treatment. Re-enter the toxicity pathway promptly if new or worsening adverse reactions develop.
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Diarrhea
Diarrhea. 67% overall; Grade 3–4 7% Assess stool frequency, duration, oral intake, hydration and clinically relevant electrolyte or renal abnormalities. Median time to first onset: 3 days.
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Start loperamide (4 mg initially, then 2 mg) + hydration
Start antidiarrheal therapy promptly. Supportive regimen: Loperamide 4 mg initially, then 2 mg after each loose stool; maximum 16 mg/day Maintain oral or IV hydration and replace electrolytes as clinically indicated Add antiemetics as needed Daraxonrasib modification: Grade 2 persistent or intolerable: consider withholding until recovery to ≤Grade 1; resume at the same or next lower dose Grade 3: withhold until recovery to ≤Grade 1; resume at the next lower dose Grade 4: permanently discontinue
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Grade toxicity and apply AE-specific dose modification
Most toxicity-specific restart criteria require recovery to ≤Grade 1. For rash, stomatitis and diarrhea, the label permits some Grade 2 events to resume at the same or next lower dose after improvement. For other Grade 3 adverse reactions, recovery to ≤Grade 1 or baseline is required.
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Continue daraxonrasib at current dose
Applicable to selected Grade 2 rash, stomatitis or diarrhea after recovery to ≤Grade 1 when resumption at the same dose is clinically appropriate.
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Ongoing daraxonrasib monitoring at the tolerated dose
Continue clinical toxicity assessment and appropriate laboratory monitoring throughout treatment. Re-enter the toxicity pathway promptly if new or worsening adverse reactions develop.
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Resume at next lower dose: 300 → 200 → 150 mg once daily
How to dose reduce daraxonrasib: Starting dose: 300 mg once daily First reduction: 200 mg once daily (one 100 mg + one 100 mg) Second reduction: 150 mg once daily (one 150 mg) No further reduction below 150 mg Permanently discontinue if unable to tolerate 150 mg This ladder applies to adverse reactions; drug-interaction dose adjustments are different.
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Ongoing daraxonrasib monitoring at the tolerated dose
Continue clinical toxicity assessment and appropriate laboratory monitoring throughout treatment. Re-enter the toxicity pathway promptly if new or worsening adverse reactions develop.
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Permanently discontinue daraxonrasib when required by toxicity-specific label guidance
Permanent discontinuation is required for specified severe or recurrent toxicities and when 150 mg once daily cannot be tolerated. Follow the toxicity-specific prescribing information.
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Implement withhold and restart plan
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Ongoing daraxonrasib monitoring at the tolerated dose
Continue clinical toxicity assessment and appropriate laboratory monitoring throughout treatment. Re-enter the toxicity pathway promptly if new or worsening adverse reactions develop.
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Suspected ILD/pneumonitis or GI perforation. HOLD daraxonrasib and urgently evaluate
New or worsening dyspnea, cough or fever: Withhold daraxonrasib and evaluate for ILD/pneumonitis Severe or persistent abdominal pain or clinical concern for perforation: Withhold daraxonrasib and urgently evaluate for gastrointestinal perforation ILD/pneumonitis: Frequency 2.4%; typically ~4 months after starting treatment (median 111 days; range 22–242) Grade 2: hold to ≤Grade 1; if appropriate, resume one dose lower Recurrent Grade 2 or Grade 3–4: permanently discontinue GI perforation: Frequency 0.9%; typically ~4–5 months after starting treatment (median 134 days; range 17–254). Grade 3: hold to ≤Grade 1; if appropriate, resume one dose lower Grade 4: permanently discontinue
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ILD/pneumonitis: Grade 2 → hold to ≤Grade 1; if appropriate, resume one dose lower
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Permanently discontinue daraxonrasib when required by toxicity-specific label guidance
Permanent discontinuation is required for specified severe or recurrent toxicities and when 150 mg once daily cannot be tolerated. Follow the toxicity-specific prescribing information.
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GI perforation: Grade 3 → hold to ≤Grade 1; if appropriate, resume one dose lower
This approach follows the label, although rechallenge after perforation is clinically high risk and should be individualized after full recovery.
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Permanently discontinue daraxonrasib when required by toxicity-specific label guidance
Permanent discontinuation is required for specified severe or recurrent toxicities and when 150 mg once daily cannot be tolerated. Follow the toxicity-specific prescribing information.
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Recurrent Grade 2 or Grade 3–4
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Permanently discontinue daraxonrasib when required by toxicity-specific label guidance
Permanent discontinuation is required for specified severe or recurrent toxicities and when 150 mg once daily cannot be tolerated. Follow the toxicity-specific prescribing information.
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Grade ≥3 laboratory or other clinically significant toxicity. Evaluate cause and severity
Evaluate relevant laboratory abnormalities and alternative/contributing causes, including disease-related factors, dehydration and concomitant medications. Grade according to CTCAE v5.0. Transaminase ↑, bilirubin ↑, cytopenias. Assess grade and trends.
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Other Grade 3 toxicity: hold to ≤G1/baseline + lower dose; Grade 4: discontinue
Grade 3: Withhold daraxonrasib until recovery to ≤Grade 1 or baseline Resume at the next lower dose Grade 4: Permanently discontinue Address reversible or competing causes before resumption when clinically appropriate.
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Grade toxicity and apply AE-specific dose modification
Most toxicity-specific restart criteria require recovery to ≤Grade 1. For rash, stomatitis and diarrhea, the label permits some Grade 2 events to resume at the same or next lower dose after improvement. For other Grade 3 adverse reactions, recovery to ≤Grade 1 or baseline is required.
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Continue daraxonrasib at current dose
Applicable to selected Grade 2 rash, stomatitis or diarrhea after recovery to ≤Grade 1 when resumption at the same dose is clinically appropriate.
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Ongoing daraxonrasib monitoring at the tolerated dose
Continue clinical toxicity assessment and appropriate laboratory monitoring throughout treatment. Re-enter the toxicity pathway promptly if new or worsening adverse reactions develop.
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Resume at next lower dose: 300 → 200 → 150 mg once daily
How to dose reduce daraxonrasib: Starting dose: 300 mg once daily First reduction: 200 mg once daily (one 100 mg + one 100 mg) Second reduction: 150 mg once daily (one 150 mg) No further reduction below 150 mg Permanently discontinue if unable to tolerate 150 mg This ladder applies to adverse reactions; drug-interaction dose adjustments are different.
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Ongoing daraxonrasib monitoring at the tolerated dose
Continue clinical toxicity assessment and appropriate laboratory monitoring throughout treatment. Re-enter the toxicity pathway promptly if new or worsening adverse reactions develop.
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Permanently discontinue daraxonrasib when required by toxicity-specific label guidance
Permanent discontinuation is required for specified severe or recurrent toxicities and when 150 mg once daily cannot be tolerated. Follow the toxicity-specific prescribing information.
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Implement withhold and restart plan
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Ongoing daraxonrasib monitoring at the tolerated dose
Continue clinical toxicity assessment and appropriate laboratory monitoring throughout treatment. Re-enter the toxicity pathway promptly if new or worsening adverse reactions develop.
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Nausea/Vomiting
Nausea: 52% | Grade 3–4: 3%; Vomiting: 42% | Grade 3–4: 1%
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Start antiemetic (e.g., ondansetron); maintain hydration and correct electrolyte abnormalities
Supportive treatment Ondansetron 8 mg PO every 8–12 hours PRN is a reasonable first-line option If persistent despite a 5-HT3 antagonist, add or switch antiemetic therapy based on symptoms, e.g. prochlorperazine 10 mg PO every 6 hours PRN or olanzapine 2.5–5 mg PO daily/at bedtime Daraxonrasib modification: Grade 1–2 Continue daraxonrasib; supportive antiemetic therapy and monitoring Grade 3 Hold daraxonrasib until recovery to ≤Grade 1; initiate/modify antiemetic therapy; resume at the next lower dose Grade 4 Permanently discontinue daraxonrasib
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Grade toxicity and apply AE-specific dose modification
Most toxicity-specific restart criteria require recovery to ≤Grade 1. For rash, stomatitis and diarrhea, the label permits some Grade 2 events to resume at the same or next lower dose after improvement. For other Grade 3 adverse reactions, recovery to ≤Grade 1 or baseline is required.
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Continue daraxonrasib at current dose
Applicable to selected Grade 2 rash, stomatitis or diarrhea after recovery to ≤Grade 1 when resumption at the same dose is clinically appropriate.
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Ongoing daraxonrasib monitoring at the tolerated dose
Continue clinical toxicity assessment and appropriate laboratory monitoring throughout treatment. Re-enter the toxicity pathway promptly if new or worsening adverse reactions develop.
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Resume at next lower dose: 300 → 200 → 150 mg once daily
How to dose reduce daraxonrasib: Starting dose: 300 mg once daily First reduction: 200 mg once daily (one 100 mg + one 100 mg) Second reduction: 150 mg once daily (one 150 mg) No further reduction below 150 mg Permanently discontinue if unable to tolerate 150 mg This ladder applies to adverse reactions; drug-interaction dose adjustments are different.
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Ongoing daraxonrasib monitoring at the tolerated dose
Continue clinical toxicity assessment and appropriate laboratory monitoring throughout treatment. Re-enter the toxicity pathway promptly if new or worsening adverse reactions develop.
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Permanently discontinue daraxonrasib when required by toxicity-specific label guidance
Permanent discontinuation is required for specified severe or recurrent toxicities and when 150 mg once daily cannot be tolerated. Follow the toxicity-specific prescribing information.
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Implement withhold and restart plan
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Ongoing daraxonrasib monitoring at the tolerated dose
Continue clinical toxicity assessment and appropriate laboratory monitoring throughout treatment. Re-enter the toxicity pathway promptly if new or worsening adverse reactions develop.
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Paronychia
Paronychia is included among the dermatologic manifestations of daraxonrasib toxicity, although this node does not provide a distinct treatment pathway.