Entrectinib Adverse Reaction Dose Modifications
1. Congestive Heart Failure
(1) Grade 2 or 3: Withhold until recovery to ≤ Grade 1; reduce dose upon resumption.
(2) Grade 4: Permanently discontinue.
2. Central Nervous System Effects
(1) Intolerable Grade 2: Withhold until recovery to ≤ Grade 1 or baseline; upon resumption, may maintain same dose or reduce dose.
(2) Grade 3: Withhold until recovery to ≤ Grade 1 or baseline. If the adverse reaction resolves within 4 weeks, resume at the same dose. If not resolved within 4 weeks, permanently discontinue. For recurrent Grade 3 events that resolve within 4 weeks, resume at a reduced dose.
(3) Grade 4: Withhold until recovery to ≤ Grade 1 or baseline. If the adverse reaction resolves within 4 weeks, resume at the same or reduced dose. If not resolved within 4 weeks, permanently discontinue. For recurrent Grade 4 events, permanently discontinue.
3. Hyperuricemia
(1) QTc interval >500 ms: Withhold until QTc returns to baseline. If the factor causing QTc prolongation is identified and corrected, resume at the same dose; if no other contributing factor is identified, resume at a reduced dose.
(2) Torsade de pointes, polymorphic ventricular tachycardia, or signs/symptoms of serious arrhythmia: Permanently discontinue.
4. Visual Disturbance
Grade 2 or higher: Withhold until improvement or stabilization; upon resumption, may maintain same dose or reduce dose (as appropriate).
5. Anemia or Neutropenia
Grade 3 or 4: Withhold until the adverse reaction resolves or improves to Grade 1 or baseline. If resolved within 4 weeks, resume at the same or reduced dose. If not resolved within 4 weeks, permanently discontinue. For recurrent Grade 4 events, permanently discontinue.
Entrectinib Coadministration with Moderate and Strong CYP450 3A Inhibitors
1. Adults and pediatric patients aged 12 years and older with body surface area >1.5 m²
Avoid concomitant use with moderate or strong CYP450 3A inhibitors. If coadministration is unavoidable, adjust the dose of entrectinib as follows:
(1) With moderate CYP450 3A inhibitors: 200 mg orally once daily.
(2) With strong CYP450 3A inhibitors: 100 mg orally once daily.
2. After discontinuation of the strong or moderate CYP450 3A inhibitor for 3 to 5 elimination half‑lives, resume the dose that was used before starting the inhibitor.
Entrectinib Storage
Store below 30°C (86°F).
