Augtyro®Repotrectinib Capsules

1. Indications and Usage
ROS1-Positive NSCLC: Treatment of adult patients with locally advanced or metastatic ROS1-positivenon-small cell lung cancer (NSCLC) .
2. Dosage and Administration
Administration: Oral administration. Swallow capsules whole. Do not chew, crush, or open the capsules .
Food Requirement: Can be taken with or without food .
Standard Dose:
Recommended Dose: 160 mg once daily for the first 14 days, followed by an increase to 160 mg twice daily thereafter .
Note: This titration schedule compensates for time-dependent auto-induction and helps manage early CNS-related adverse reactions .
Missed Dose or Vomiting: If a dose is missed or if vomiting occurs at any time after administration, do not make up for the missed dose. Take the next dose at the usual scheduled time .
Dose Reduction: Mandatory dose reduction (e.g., to 80 mg BID) for severe toxicities .
3. Mechanism of Action
Repotrectinib is a next-generation, oral, small-molecule inhibitor of ROS1, NTRK (TRKA/B/C), and ALK rearrangements.
It is structurally designed to penetrate the blood-brain barrier and overcome resistance mutations (such as ROS1 G2032R solvent front mutations) that typically limit the efficacy of earlier-generation TKIs .
4. Safety and Warnings
CNS Effects: Can cause dizziness, cognitive impairment, or ataxia. Patients should avoid driving or operating machinery if these symptoms occur .
Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for respiratory symptoms (dyspnea, cough). Interrupt or permanently discontinue based on severity .
Embryo-Fetal Toxicity: May cause fetal harm. Contraception is required for females and males during treatment and for at least 1 week after the final dose .
Muscle Damage: Monitor Creatine Kinase (CK) levels if muscle pain or weakness occurs .
5. Adverse Reactions
Common adverse reactions (incidence ≥20%) include:
CNS: Dizziness, cognitive impairment, ataxia, dysgeusia (taste disturbance), sleep disorders .
Gastrointestinal: Constipation, nausea, diarrhea.
General: Fatigue, dyspnea, pyrexia .
Laboratory Abnormalities: Increased CPK, anemia, increased uric acid .
6. Drug Interactions
CYP3A Inhibitors: Avoid co-administration with strong or moderate CYP3A inhibitors (e.g., itraconazole) as they increase Repotrectinib exposure. If unavoidable, reduce dose .
CYP3A Inducers: Avoid co-administration with strong or moderate CYP3A inducers (e.g., rifampin) as they significantly reduce efficacy .
CYP3A4 Substrates: Repotrectinib is a CYP3A4 inducer. It may decrease the exposure of co-administered CYP3A4 substrates (e.g., hormonal contraceptives) .
7. Pharmaceutical Information
Chemical Name: (3R,11S)-6-Fluoro-3,11-dimethyl-10-oxa-2,13,17,18,21-pentazabicyclo[13.5.2.049.01822]docosa-1(21),4,6,8,15(22),16,19-heptaen-14-one .
Molecular Formula: C18H18FN5O2 .
Storage: Store at 20°C to 25°C (68°F to 77°F) .