Repotrectinib, an innovative ROS1 and NTRK-targeting inhibitor, can simultaneously inhibit multiple oncogenic targets, exhibiting broad-spectrum anti-cancer effects.
Common Dosage for Adults with Non-Small Cell Lung Cancer
Initial Dose
160 mg of repotrectinib orally daily for 14 days.
Maintenance Dose
160 mg of repotrectinib orally twice daily.
Duration of Treatment
Until disease progression or unacceptable toxicity occurs.
Repotrectinib Dose Adjustment
1. Dose Reduction for Adverse Reactions
(1) Dosage Regimen 1
If the dose is 160 mg of repotrectinib orally once daily:
Initial Dose Reduction: 120 mg of repotrectinib orally once daily.
Second Dose Reduction: 80 mg of repotrectinib orally once daily.
(2) Dosage Regimen Two
If the dosage is 160 mg orally twice daily:
Initial dose reduction: 120 mg orally twice daily.
Second dose reduction: 80 mg orally twice daily.
2. Dosage Adjustment for Renal Impairment
Mild to moderate renal impairment (estimated glomerular filtration rate - modified diet for kidney disease [eGFR-MDRD] 30 to 90 mL/min): Dosage adjustment of Repotrectinib is not recommended.
Severe renal impairment (eGFR-MDRD < 30 mL/min): No data available.
3. Dosage Adjustment for Hepatic Impairment
Mild hepatic impairment (total bilirubin > 1 to 1.5 times the upper limit of normal [1 to 1.5 × ULN] or aspartate aminotransferase > the upper limit of normal): Dosage adjustment of Repotrectinib is not recommended.
Moderate to severe hepatic impairment (total bilirubin >1.5 to 3 × ULN, with any aspartate aminotransferase level): No data available.
If hepatotoxicity occurs during treatment:
Grade 3: Discontinue treatment until it decreases to Grade 1 or below, or to baseline levels. If the condition resolves within 4 weeks, treatment can be resumed at the original dose; for recurrent Grade 3 events that resolve within 4 weeks, treatment can be resumed at a reduced dose.
Grade 4: Discontinue treatment until it decreases to Grade 1 or below, or to baseline levels; resume treatment at a reduced dose. If adverse reactions do not resolve within 4 weeks or a recurrent Grade 4 event occurs, treatment should be permanently discontinued.
Alanine aminotransferase or aspartate aminotransferase >3 × ULN, and total bilirubin >1.5 × ULN (without cholestasis or hemolysis): This drug should be permanently discontinued.
Adjustments for Other Adverse Reactions to Repotrectinib
Central Nervous System
Grade 2 (Intolerable): Discontinue use until grade 1 or below, or baseline levels; resume repotrectinib at the same or reduced dose, depending on clinical condition.
Grade 3: Discontinue use until grade 1 or below, or baseline levels; resume use at a reduced dose.
Grade 4: Permanently discontinue repotrectinib.
Interstitial Lung Disease (ILD)/Pneumonia
Any grade: Discontinue use if ILD/pneumonia is suspected; permanently discontinue use if ILD/pneumonia is confirmed.
Elevated Creatine Phosphokinase (CPK)
CPK elevation greater than 5 × ULN: Discontinue repotrectinib until it returns to baseline levels or 2.5 × ULN or below, then resume use at the same dose.
CPK elevation greater than 10 × ULN or a second occurrence of CPK elevation greater than 5 × ULN: Discontinue use until it returns to baseline or 2.5 × ULN or below, then resume use at a reduced dose.
Hyperuricemia
Grade 3 or 4: Discontinue Repotrectinib until symptoms improve; resume use at the same or reduced dose.
Other Clinically Relevant Adverse Reactions
Grade 3 or 4 or intolerable Grade 2: Discontinue use until it decreases to Grade 1 or below or baseline; if it resolves within 4 weeks, resume use at the same or reduced dose. If the adverse reaction does not resolve within 4 weeks or a recurrent Grade 4 event occurs, the medication should be permanently discontinued.
