Active Ingredient: Repotrectinib
Repotrectinib is indicated for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that:
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 160 milligrams repotrectinib, once daily, over the duration of 14 days. Afterwards, oral, 160 milligrams repotrectinib, 2 times daily.
Select patients for the treatment of solid tumors with repotrectinib based on the presence of NTRK1/2/3 rearrangements in tumor specimens.
In patients with secretory breast cancer or mammary analogue secretory cancer, consider treatment without confirmation of NTRK rearrangements in tumor specimens.
Select patients for the treatment of locally advanced or metastatic NSCLC with repotrectinib based on the presence of ROS1 rearrangement(s) in tumor specimens.
Prior to initiating repotrectinib, discontinue strong and moderate CYP3A inhibitors for 3 to 5 elimination half-lives of the CYP3A inhibitor.
Prior to initiation of repotrectinib, evaluate:
The recommended dosage of repotrectinib is 160 mg taken orally once daily with or without food for 14 days, then increase to 160 mg twice daily and continue until disease progression or unacceptable toxicity.
The recommended dosage reductions of repotrectinib for the management of adverse reactions are provided in Table 1.
Table 1. Recommended dose reductions for repotrectinib adverse reactions:
| Dose | Dose Reduction | |
|---|---|---|
| First | Second | |
| 160 mg Once Daily | 120 mg Once Daily | 80 mg Once Daily |
| 160 mg Twice Daily | 120 mg Twice Daily | 80 mg Twice Daily |
Recommended dosage modifications of repotrectinib for the management of adverse reactions are provided in Table 2.
Table 2. Recommended dosage modifications for repotrectinib adverse reactions:
| Adverse Reaction | Severity* | Dosage Modification |
|---|---|---|
| Central Nervous System Effects | Intolerable Grade 2 | • Withhold repotrectinib until ≤Grade 1 or baseline. • Resume at same or reduced dose, as clinically appropriate. |
| Grade 3 | • Withhold repotrectinib until ≤Grade 1 or baseline. • Resume at reduced dose. | |
| Grade 4 | • Permanently discontinue repotrectinib. | |
| Interstitial Lung Disease (ILD)/Pneumonitis | Any Grade | • Withhold repotrectinib if ILD/pneumonitis is suspected. • Permanently discontinue if ILD/pneumonitis is confirmed. |
| Hepatotoxicity | Grade 3 | • Withhold repotrectinib until ≤Grade 1 or baseline. • Resume at same dose if resolution occurs within 4 weeks. • Resume at a reduced dose for recurrent Grade 3 events that resolve within 4 weeks. |
| Grade 4 | • Withhold repotrectinib until ≤Grade 1 or baseline. • Resume at reduced dose. • Permanently discontinue if adverse reaction does not resolve within 4 weeks. • Permanently discontinue for recurrent Grade 4 events. | |
| ALT or AST greater than 3 times ULN with concurrent total bilirubin greater than 1.5 times ULN (in the absence of cholestasis or hemolysis) | • Permanently discontinue repotrectinib. | |
| Creatine Phosphokinase (CPK) Elevation | CPK elevation greater than 5 times ULN | • Withhold until recovery to baseline or to less than or equal to 2.5 times ULN, then resume at same dose. |
| CPK elevation greater than 10 times ULN or second occurrence of CPK elevation of greater than 5 times ULN | • Withhold until recovery to baseline or to less than or equal to 2.5 times ULN, then resume at reduced dose. | |
| Hyperuricemia | Grade 3 or Grade 4 | • Withhold repotrectinib until improvement of signs or symptoms. • Resume repotrectinib at same or reduced dose. |
| Other Clinically Relevant Adverse Reactions | Intolerable Grade 2 or Grade 3 or Grade 4 | • Withhold repotrectinib until ≤Grade 1 or baseline. • Resume at the same or reduced dose if resolution occurs within 4 weeks. • Permanently discontinue if adverse reaction does not resolve within 4 weeks. • Permanently discontinue for recurrent Grade 4 events. |
* Graded per Common Terminology Criteria for Adverse Events v4.03
Take repotrectinib at approximately the same time each day with or without food.
If a dose of repotrectinib is missed or if vomiting occurs at any time after taking a dose, skip the dose and resume repotrectinib at its regularly scheduled time.
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