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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 Grade 1 and 2 rash management: Face: Hydrocortisone 2.5% cream — apply a thin layer to the face twice daily Chest: Triamcinolone acetonide 0.1% cream — apply a thin layer to the chest twice daily Moisturizer: Apply a fragrance-free emollient moisturizing cream (e.g., CeraVe Moisturizing Cream, Vanicream Moisturizing Cream, or equivalent) liberally to dry skin at least twice daily and after bathing Sun protection: Apply broad-spectrum SPF ≥30 sunscreen to exposed skin ≥30 minutes before sun exposure; reapply every 2 hours while outdoors. Limit sun exposure and use protective clothing/hat. Oral antibiotic: Doxycycline 100 mg PO twice daily or minocycline 50 mg PO twice daily. Initiate before the first daraxonrasib dose and continue for ≥8 weeks. Skin antiseptic (optional): Hypochlorous acid spray 0.014–0.018% AM/PM, applied to dry cleansed skin before other topical treatment
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Grade 2: Optimize dermatologic therapy; consider dermatology consultation if atypical, extensive, painful, infected, or refractory
Dermatology input is reasonable for atypical, extensive, painful, infected, or refractory Grade 2 toxicity. The label specifically recommends considering dermatology consultation for Grade 3 rather than routinely for every Grade 2 event.
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Topical corticosteroid ± doxycycline/minocycline
Continue or intensify topical corticosteroid and emollient therapy. For scalp involvement, consider betamethasone dipropionate 0.05% lotion or fluocinolone 0.01% oil. For Grade 3 rash, oral corticosteroid may be used, give a prednisone taper of 40 mg ×5 days → 20 mg ×5 days → 10 mg ×5 days. If not already receiving an oral antibiotic, consider doxycycline or minocycline as clinically appropriate. RASolute protocol prophylaxis used doxycycline 100 mg twice daily or minocycline 50 mg twice daily. Grade 2: Consider withholding daraxonrasib until recovery to ≤Grade 1 Resume at the same or next lower dose Grade 3: Withhold until recovery to ≤Grade 1 Consider dermatology consultation 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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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 and patient education: Oral hygiene at least BID, brushing/flossing, bland saline or salt-and-soda rinses, avoid rough/sharp foods, tobacco, alcohol, and alcohol-containing mouthwash. 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 Severe stomatitis, additional rescue/supportive options Add as clinically indicated: 2% viscous lidocaine, chlorhexidine mouthwash, oral antifungal therapy such as nystatin when appropriate, and systemic steroids for severe cases.
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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 What to do when initial loperamide fails? No improvement after 24h? → intensify loperamide; no improvement after 48h? → add another antidiarrheal such as diphenoxylate/atropine Persistent symptoms despite combination treatment → further evaluation. When to stop loperamide? Discontinue after the patient has been diarrhea-free for 12 hours; maximum remains 16 mg/24h.
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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
This is an agent-specific dose-modification rule from the 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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ILD/pneumonitis: Recurrent Grade 2 or Grade 3–4
The label identifies these events as permanent-discontinuation criteria.
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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 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.
-
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.
-
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.
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Grade 2: Optimize dermatologic therapy; consider dermatology consultation if atypical, extensive, painful, infected, or refractory
Dermatology input is reasonable for atypical, extensive, painful, infected, or refractory Grade 2 toxicity. The label specifically recommends considering dermatology consultation for Grade 3 rather than routinely for every Grade 2 event.
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Topical corticosteroid ± doxycycline/minocycline
Continue or intensify topical corticosteroid and emollient therapy. For scalp involvement, consider betamethasone dipropionate 0.05% lotion or fluocinolone 0.01% oil. For Grade 3 rash, oral corticosteroid may be used, give a prednisone taper of 40 mg ×5 days → 20 mg ×5 days → 10 mg ×5 days. If not already receiving an oral antibiotic, consider doxycycline or minocycline as clinically appropriate. RASolute protocol prophylaxis used doxycycline 100 mg twice daily or minocycline 50 mg twice daily. Grade 2: Consider withholding daraxonrasib until recovery to ≤Grade 1 Resume at the same or next lower dose Grade 3: Withhold until recovery to ≤Grade 1 Consider dermatology consultation 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.
-
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.
-
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.
-
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.
-
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.