Overview
Repotrex 40 mg contains Repotrectinib, an advanced, next-generation tyrosine kinase inhibitor (TKI) designed to target specific genetic drivers of cancer. Manufactured by Everest Pharmaceuticals Ltd. and supplied by Saif Pharma, Repotrex represents a breakthrough for patients with ROS1-positive and NTRK-positive advanced solid tumors. Its compact molecular structure is specifically engineered to overcome resistance mutations that often develop with earlier-generation treatments, while also providing superior penetration into the central nervous system (CNS) to treat brain metastases.
Therapeutic Applications
Repotrex is indicated for the following conditions:
ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): For adult patients with locally advanced or metastatic NSCLC that is positive for the ROS1 gene rearrangement. It is effective for both treatment-naïve patients and those previously treated with other ROS1 TKIs.
NTRK Gene Fusion-Positive Solid Tumors: For adult and pediatric patients (12 years and older) with advanced or metastatic solid tumors (such as lung, thyroid, or soft tissue cancers) that harbor a neurotrophic tyrosine receptor kinase (NTRK) gene fusion.
Mechanism of Action
Repotrectinib is a multi-targeted inhibitor that focuses on ROS1 and the TRK (TRK-A, TRK-B, TRK-C) protein families.
Direct Inhibition: It blocks the signaling pathways that tell cancer cells to multiply rapidly.
Overcoming Resistance: Unlike older TKIs, its “macrocyclic” design allows it to bind tightly to the target even when the cancer cell has developed “solvent-front” mutations (like the G2032R mutation in ROS1) intended to block drug entry.
CNS Efficacy: Its small size allows it to cross the blood-brain barrier effectively, making it a critical option for patients whose cancer has spread to the brain.
Pharmacokinetic Profile
Absorption: Peak plasma concentrations are reached after oral administration, with stable levels achieved through a gradual dose-escalation schedule.
Metabolism: Primarily processed by the CYP3A4 enzyme system. It exhibits time-dependent autoinduction, meaning its clearance changes slightly over the first few weeks of therapy.
Elimination: Excreted through both fecal and urinary pathways, with a half-life that supports twice-daily maintenance dosing.
Dosage & Administration
Repotrex 40 mg capsules must be taken exactly as prescribed.
Initial Dose (Days 1–14): 160 mg (four 40 mg capsules) once daily.
Maintenance Dose (Day 15 onwards): 160 mg (four 40 mg capsules) twice daily.
Instructions: Capsules must be swallowed whole. Do not open, crush, or chew. Can be taken with or without food.
Missed Dose: If a dose is missed or if vomiting occurs, skip that dose and take the next scheduled dose at the normal time.
Clinical Considerations & Safety
CNS Effects: Dizziness is the most common side effect (approx. 60%). Other effects include ataxia (balance issues), cognitive impairment, and mood changes.
Liver Function: Monitoring of ALT/AST levels is required every two weeks during the first month.
Pulmonary Health: Patients should be monitored for signs of interstitial lung disease (ILD) or pneumonitis.
Interactions: Avoid grapefruit and strong/moderate CYP3A inhibitors/inducers, as these can significantly alter drug levels.