| AEs . | AEs by grade . | Guidance . |
|---|---|---|
| GI toxicities | Grade 1/2 AEs | Interrupt/modify dose at healthcare provider and patient discretion |
| Grade 3 nausea >72h Grade 3/4 vomiting >24h Grade 3 diarrhea >48h | Interrupt adagrasib until ≤ grade 1 or return to baseline, and decrease one dose level | |
| Symptomatic grade 3/4 amylase or lipase elevation | CT scan to rule in/out acute pancreatitis. Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume one dose level lower | |
| Other grade 3 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same dose level or one dose level lower | |
| Grade 4 diarrhea Grade 3/4 pancreatitis Other grade 4 AEs | Discontinue adagrasib | |
| Hepatic toxicities | Grade 1/2 AEs (not including grade 2 ALT/AST increase) | Interrupt/modify dose at healthcare provider and patient discretion |
| Grade 2 ALT/AST increase | Decrease one dose level | |
| Grade 3 ALT/AST increase Grade 3 increased bilirubin ≤22 days | Interrupt adagrasib until ≤ grade 1 or return to baseline, and decrease one dose level | |
| Grade 4 ALT/AST increase Hy’s Law Case Grade 3 increased bilirubin >22 days | Discontinue adagrasib | |
| Other Grade 3/4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same dose level or one dose level lower | |
| Cardiac toxicities | QTcF prolongation >500 ms and increase >60 ms on at least 2 ECGs ≤22 days | Interrupt adagrasib until ≤ grade 1 or return to baseline (<15 ms above baseline), check electrolytes, and decrease one or two dose levels |
| QTcF prolongation >500 ms and increase >60 ms on at least 2 ECGs >22 days Decrease in LVEF ≥20% from baseline and below LLN Symptomatic left ventricular systolic dysfunction | Discontinue adagrasib | |
| Other grade 3/4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at one dose level lower | |
| Other toxicities | Grade 1/2 AEs | Interrupt/modify dose at healthcare provider and patient discretion |
| Grade 3/4 fatigue or asthenia ≤8 days | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same or lower dose level | |
| Grade 3/4 creatinine increased ≤22 days Other lab-based grade 3/4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same dose level or one dose level lower | |
| Grade 3/4 creatinine increased >22 days | Discontinue adagrasib | |
| Other grade 3 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and resume one or more dose levels lower | |
| Other grade 4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at a lower dose level (only if not life-threatening and can be managed; otherwise permanently discontinue adagrasib) |
| AEs . | AEs by grade . | Guidance . |
|---|---|---|
| GI toxicities | Grade 1/2 AEs | Interrupt/modify dose at healthcare provider and patient discretion |
| Grade 3 nausea >72h Grade 3/4 vomiting >24h Grade 3 diarrhea >48h | Interrupt adagrasib until ≤ grade 1 or return to baseline, and decrease one dose level | |
| Symptomatic grade 3/4 amylase or lipase elevation | CT scan to rule in/out acute pancreatitis. Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume one dose level lower | |
| Other grade 3 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same dose level or one dose level lower | |
| Grade 4 diarrhea Grade 3/4 pancreatitis Other grade 4 AEs | Discontinue adagrasib | |
| Hepatic toxicities | Grade 1/2 AEs (not including grade 2 ALT/AST increase) | Interrupt/modify dose at healthcare provider and patient discretion |
| Grade 2 ALT/AST increase | Decrease one dose level | |
| Grade 3 ALT/AST increase Grade 3 increased bilirubin ≤22 days | Interrupt adagrasib until ≤ grade 1 or return to baseline, and decrease one dose level | |
| Grade 4 ALT/AST increase Hy’s Law Case Grade 3 increased bilirubin >22 days | Discontinue adagrasib | |
| Other Grade 3/4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same dose level or one dose level lower | |
| Cardiac toxicities | QTcF prolongation >500 ms and increase >60 ms on at least 2 ECGs ≤22 days | Interrupt adagrasib until ≤ grade 1 or return to baseline (<15 ms above baseline), check electrolytes, and decrease one or two dose levels |
| QTcF prolongation >500 ms and increase >60 ms on at least 2 ECGs >22 days Decrease in LVEF ≥20% from baseline and below LLN Symptomatic left ventricular systolic dysfunction | Discontinue adagrasib | |
| Other grade 3/4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at one dose level lower | |
| Other toxicities | Grade 1/2 AEs | Interrupt/modify dose at healthcare provider and patient discretion |
| Grade 3/4 fatigue or asthenia ≤8 days | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same or lower dose level | |
| Grade 3/4 creatinine increased ≤22 days Other lab-based grade 3/4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same dose level or one dose level lower | |
| Grade 3/4 creatinine increased >22 days | Discontinue adagrasib | |
| Other grade 3 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and resume one or more dose levels lower | |
| Other grade 4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at a lower dose level (only if not life-threatening and can be managed; otherwise permanently discontinue adagrasib) |
Sequential dose reduction steps: 400 mg BID, 600 mg once daily (may be split into BID dosing for tolerability).
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ECG, electrocardiogram; GI, gastrointestinal; LLN, lower limit of normal; LVEF, left ventricular ejection fraction; QTcF, QT corrected interval by Fredericia.
| AEs . | AEs by grade . | Guidance . |
|---|---|---|
| GI toxicities | Grade 1/2 AEs | Interrupt/modify dose at healthcare provider and patient discretion |
| Grade 3 nausea >72h Grade 3/4 vomiting >24h Grade 3 diarrhea >48h | Interrupt adagrasib until ≤ grade 1 or return to baseline, and decrease one dose level | |
| Symptomatic grade 3/4 amylase or lipase elevation | CT scan to rule in/out acute pancreatitis. Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume one dose level lower | |
| Other grade 3 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same dose level or one dose level lower | |
| Grade 4 diarrhea Grade 3/4 pancreatitis Other grade 4 AEs | Discontinue adagrasib | |
| Hepatic toxicities | Grade 1/2 AEs (not including grade 2 ALT/AST increase) | Interrupt/modify dose at healthcare provider and patient discretion |
| Grade 2 ALT/AST increase | Decrease one dose level | |
| Grade 3 ALT/AST increase Grade 3 increased bilirubin ≤22 days | Interrupt adagrasib until ≤ grade 1 or return to baseline, and decrease one dose level | |
| Grade 4 ALT/AST increase Hy’s Law Case Grade 3 increased bilirubin >22 days | Discontinue adagrasib | |
| Other Grade 3/4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same dose level or one dose level lower | |
| Cardiac toxicities | QTcF prolongation >500 ms and increase >60 ms on at least 2 ECGs ≤22 days | Interrupt adagrasib until ≤ grade 1 or return to baseline (<15 ms above baseline), check electrolytes, and decrease one or two dose levels |
| QTcF prolongation >500 ms and increase >60 ms on at least 2 ECGs >22 days Decrease in LVEF ≥20% from baseline and below LLN Symptomatic left ventricular systolic dysfunction | Discontinue adagrasib | |
| Other grade 3/4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at one dose level lower | |
| Other toxicities | Grade 1/2 AEs | Interrupt/modify dose at healthcare provider and patient discretion |
| Grade 3/4 fatigue or asthenia ≤8 days | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same or lower dose level | |
| Grade 3/4 creatinine increased ≤22 days Other lab-based grade 3/4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same dose level or one dose level lower | |
| Grade 3/4 creatinine increased >22 days | Discontinue adagrasib | |
| Other grade 3 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and resume one or more dose levels lower | |
| Other grade 4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at a lower dose level (only if not life-threatening and can be managed; otherwise permanently discontinue adagrasib) |
| AEs . | AEs by grade . | Guidance . |
|---|---|---|
| GI toxicities | Grade 1/2 AEs | Interrupt/modify dose at healthcare provider and patient discretion |
| Grade 3 nausea >72h Grade 3/4 vomiting >24h Grade 3 diarrhea >48h | Interrupt adagrasib until ≤ grade 1 or return to baseline, and decrease one dose level | |
| Symptomatic grade 3/4 amylase or lipase elevation | CT scan to rule in/out acute pancreatitis. Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume one dose level lower | |
| Other grade 3 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same dose level or one dose level lower | |
| Grade 4 diarrhea Grade 3/4 pancreatitis Other grade 4 AEs | Discontinue adagrasib | |
| Hepatic toxicities | Grade 1/2 AEs (not including grade 2 ALT/AST increase) | Interrupt/modify dose at healthcare provider and patient discretion |
| Grade 2 ALT/AST increase | Decrease one dose level | |
| Grade 3 ALT/AST increase Grade 3 increased bilirubin ≤22 days | Interrupt adagrasib until ≤ grade 1 or return to baseline, and decrease one dose level | |
| Grade 4 ALT/AST increase Hy’s Law Case Grade 3 increased bilirubin >22 days | Discontinue adagrasib | |
| Other Grade 3/4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same dose level or one dose level lower | |
| Cardiac toxicities | QTcF prolongation >500 ms and increase >60 ms on at least 2 ECGs ≤22 days | Interrupt adagrasib until ≤ grade 1 or return to baseline (<15 ms above baseline), check electrolytes, and decrease one or two dose levels |
| QTcF prolongation >500 ms and increase >60 ms on at least 2 ECGs >22 days Decrease in LVEF ≥20% from baseline and below LLN Symptomatic left ventricular systolic dysfunction | Discontinue adagrasib | |
| Other grade 3/4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at one dose level lower | |
| Other toxicities | Grade 1/2 AEs | Interrupt/modify dose at healthcare provider and patient discretion |
| Grade 3/4 fatigue or asthenia ≤8 days | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same or lower dose level | |
| Grade 3/4 creatinine increased ≤22 days Other lab-based grade 3/4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at same dose level or one dose level lower | |
| Grade 3/4 creatinine increased >22 days | Discontinue adagrasib | |
| Other grade 3 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and resume one or more dose levels lower | |
| Other grade 4 AEs | Interrupt adagrasib until ≤ grade 1 or return to baseline, and may resume at a lower dose level (only if not life-threatening and can be managed; otherwise permanently discontinue adagrasib) |
Sequential dose reduction steps: 400 mg BID, 600 mg once daily (may be split into BID dosing for tolerability).
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ECG, electrocardiogram; GI, gastrointestinal; LLN, lower limit of normal; LVEF, left ventricular ejection fraction; QTcF, QT corrected interval by Fredericia.
This PDF is available to Subscribers Only
View Article Abstract & Purchase OptionsFor full access to this pdf, sign in to an existing account, or purchase an annual subscription.
