Before the first administration of Ziditnib, the following baseline assessments must be completed: serum creatine phosphokinase level, electrocardiogram, blood electrolytes (potassium, magnesium, calcium, etc.), lipase and amylase levels. This assessment aims to establish individualized baseline reference values, provide a basis for subsequent safety monitoring, and prevent potential cardiac repolarization abnormalities, muscle injury, and pancreatic toxicity.
Recommended Dosage
The recommended dose of Ziditnib is 100 mg once daily, taken orally, with or without food, until disease progression or unacceptable toxicity occurs.
Tablet administration instructions: The tablet should be swallowed whole and must not be split, chewed, crushed, or dissolved before intake.
Missed Dose Management
If a dose is missed and the time since the missed dose is less than 12 hours from the usual scheduled time, the missed dose should be taken as soon as possible.
If the missed dose is 12 hours or more, the missed dose should be skipped, and the next dose should be taken at the regularly scheduled time.
Vomiting management: If vomiting occurs after taking the dose, no additional dose should be taken; the next scheduled dose should be taken on time.
Dose Adjustment Strategy for Adverse Reactions
To manage adverse reactions occurring during treatment, Ziditnib may be dose‑reduced in a stepwise manner. The recommended dose reduction steps are as follows:
First dose reduction: 75 mg once daily.
Second dose reduction: 50 mg once daily.
If the patient cannot tolerate the 50 mg once‑daily dose, Ziditnib treatment should be permanently discontinued. It is important to note that after dose reduction due to adverse reactions, subsequent re‑escalation of the dose is not recommended.
Specific dose adjustment measures (including dose interruption, resumption, and permanent discontinuation) and core management principles for different types and severities of adverse reactions are as follows:
Central Nervous System Adverse Reactions
For grade 2 intolerable or grade 3 reactions, interrupt dosing until symptoms recover to ≤ grade 1 or baseline; after recovery, dosing may be resumed at the same or a reduced dose. For grade 4 reactions, permanently discontinue treatment.
QTc Interval Prolongation
For QTc 481‑500 ms (grade 2), interrupt dosing, correct electrolyte disturbances or adjust concomitant medications; after recovery, dosing may be resumed at the same dose. For QTc ≥ 501 ms or an increase from baseline of > 60 ms (grade 3), resume at a reduced dose. For torsade de pointes or severe arrhythmia (grade 4), permanently discontinue treatment.
Interstitial Lung Disease / Pneumonitis
For confirmed or suspected grade 1 or 2 ILD, interrupt dosing until recovery to grade 0 or baseline; if recovery occurs within 6 weeks, resume at the same dose (grade 1) or a reduced dose (grade 2); if recovery does not occur within 6 weeks or if ILD recurs, permanently discontinue. For grade 3 or 4 ILD, permanently discontinue treatment.
Creatine Phosphokinase Elevation
For CPK > 5 × ULN, interrupt dosing until recovery to baseline or ≤ 2.5 × ULN; after recovery, resume at the same dose. For CPK > 10 × ULN or recurrent > 5 × ULN, reduce the dose upon resumption.
Lipase or Amylase Elevation
For grade 3 laboratory abnormalities, interrupt dosing until recovery to ≤ grade 2 or baseline; if recovery occurs within 14 days, resume at a reduced dose; otherwise, permanently discontinue. For grade 4 abnormalities, permanently discontinue. Once grade 3 or 4 pancreatitis is confirmed, permanently discontinue treatment.
Other Adverse Reactions
For intolerable grade 2, grade 3, or grade 4 adverse reactions, interrupt dosing until recovery to ≤ grade 1 or baseline; if recovery occurs within 4 weeks, grade 2 or 3 reactions may be resumed at the same dose, whereas grade 4 reactions should be resumed at a reduced dose. If recovery does not occur within 4 weeks, permanently discontinue treatment.
