Entretinib is an oral multi-target tyrosine kinase inhibitor used for NTRK fusion positive solid tumors and ROS1 positive non-small cell lung cancer. Correctly mastering the medication method, dosage adjustment, and discontinuation principles is the key to ensuring efficacy and safety.

1、 Fasting or with meals?

1.1 Recommended methods

It is recommended to take it with meals as a priority to reduce gastrointestinal adverse reactions such as nausea and vomiting.

High fat meals can increase drug exposure (AUC increases by about twice), and it is recommended to maintain relatively consistent dietary conditions each time medication is taken to maintain stable blood drug concentrations.

1.2 Specific Operations

Choose to take it with the main meal (morning/evening) to avoid stomach discomfort caused by taking medication on an empty stomach.

If taken on an empty stomach, ensure at least 1 hour before meals or at least 2 hours after meals.

2、 Dose adjustment strategy

2.1 Standard Dose

Adults: 600mg, once daily (orally).

Children (≥ 1 month): Calculated based on body surface area (BSA ≥ 1.5m ²: 600mg/day); 1.1-1.5m ²: 500mg/day; 0.9-1.1m ²: 400mg/day).

2.2 Adjustments related to adverse reactions

Adverse reactions ≥ grade 3: Suspend medication and consider reducing dosage (adult: 400mg/day) or permanently stopping medication after recovery to ≤ grade 1.

Abnormal liver function: When transaminase>5 times ULN or bilirubin>3 times ULN, pause until recovery, and reduce to 400mg/day when re administering medication.

Cardiac toxicity (QTc interval prolongation): If QTc>500ms, administration should be suspended, electrolyte correction should be performed, and restart and dose reduction should be evaluated.

2.3 Combined use with other drugs

Strong CYP3A4 inhibitor: Enkinib should be reduced to 400mg/day (if currently 600mg/day), or the use of the inhibitor should be suspended.

Strong CYP3A4 inducer: Avoid co administration as it may significantly reduce the efficacy of emtricinib.

3、 Principle of discontinuation of medication

3.1 Disease progression

When imaging confirms disease progression (RECIST 1.1 criteria) and there is no clear clinical benefit, the medication should be permanently discontinued.

3.2 Intolerable toxicity

After two dose reductions (600mg → 400mg → 200mg), a grade ≥ 3 adverse reaction still occurred and the medication needs to be permanently discontinued.

Severe toxicity such as interstitial lung disease (ILD)/pneumonia, life-threatening arrhythmias, and liver failure should be immediately discontinued and no longer used.

3.3 Planned discontinuation of medication (surgery/operation)

Stop using Enqutinib at least 3 days before surgery, and wait for the wound to heal well (usually ≥ 1 week) before recovery after surgery.