Precautions of Repotrectinib

1. Central Nervous System Adverse Reactions

Repotrectinib can cause central nervous system adverse reactions.

Advise patients and caregivers of the risk of CNS adverse reactions with Repotrectinib. Advise patients not to drive or use machines if they are experiencing CNS adverse reactions. Withhold and then resume at same or reduced dose upon improvement, or permanently discontinue  Repotrectinib based on severity.

2. Interstitial Lung Disease/Pneumonitis

Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Immediately withhold Repotrectinib in patients with suspected ILD/pneumonitis and permanently discontinue Repotrectinib if ILD/pneumonitis is confirmed.

3. Hepatotoxicity

Monitor liver function tests, including ALT, AST and bilirubin, every 2 weeks during the first month of treatment, then monthly thereafter and as clinically indicated. Withhold and then resume at the same or reduced dose upon improvement, or permanently discontinue Repotrectinib based on  the severity.

4. Myalgia with Creatine Phosphokinase Elevation

Advise patients to report any unexplained muscle pain, tenderness, or weakness.

Monitor serum CPK levels during Repotrectinib treatment and monitor CPK levels every 2 weeks during the first month of treatment and as needed in patients reporting unexplained muscle pain,  tenderness, or weakness. Initiate supportive care as clinically indicated. Based on severity,  withhold and then resume Repotrectinib at the same or reduced dose upon improvement.

5. Hyperuricemia

Monitor serum uric acid levels prior to initiating Repotrectinib and periodically during treatment. Initiate treatment with urate-lowering medications as clinically indicated. Withhold and then resume at the same or reduced dose upon improvement, or permanently discontinue Repotrectinib  based on severity.

from FDA，2023.11