Formulation and Specifications: Capsules: 80mg
Indications:
1. Adult patients with condylomatous lymphoma (MCL) who have received at least one prior therapy.
2. Adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who have received at least one prior therapy.
Rational dosing points:
1. Zebutinib for CLL treatment should be preceded by a rigorous clinical evaluation, and if the patient has a clear del (17p), select BTK inhibitor therapy.
2. Baseline assessment should be done prior to treatment according to relevant disease guidelines, and treatment response and toxicity should be monitored regularly during treatment, with attention to tumor lysis syndrome (especially in patients with CLL).
3. The recommended dose for both MCL and CLL/SLL is 160 mg twice daily until disease progression or intolerable toxicity occurs.
4. No dose adjustment is required in patients with mild to moderate hepatic impairment (Child-Pugh class A and B). The recommended dose for patients with severe hepatic impairment (Child-Pugh Class B and C) is 80 mg twice daily.
5. Administer orally at an approximately fixed daily dosing schedule. The entire capsule should be delivered with water and may be taken before or after a meal. Opening, breaking or chewing the capsule is prohibited. If this product is not taken at the scheduled time, the patient should take it as soon as possible based on an interval of at least 8 hours between adjacent doses and resume the normal dosing schedule at a later date. Do not take additional doses of this product to make up for missed doses.
6. Granulocytopenia, thrombocytopenia, and anemia are common adverse reactions. Blood monitoring is required during dosing. Watch for dose adjustments in the presence of grade 3 hematologic toxicity and above. ≥In case of grade 3 neutropenia with infection or fever or grade 4 hematologic toxicity, treatment should be interrupted and restarted at the starting dose when symptoms of toxicity subside to grade 1 or baseline levels (recovery). If the toxicity reoccurs, treatment should be interrupted again and restarted at a dose of 80 mg/dose twice daily when the toxicity subsides to Grade 1 or baseline (recovery). If the toxicity occurs a third time after a dose reduction, treatment should be interrupted again and restarted at 80 mg/dose once daily when the toxicity subsides to Grade 1 or baseline level (recovery). If this toxicity occurs for the fourth time after two dose reductions, treatment with this product should be discontinued.
7. Dose adjustment when co-administered with CYP3A inhibitors or inducers.
Table 4 Dose adjustments when co-administered with CYP3A inhibitors or inducers.
| Dose adjustment recommendations | |
| Potent CYP3A inhibitors | 80mg/dose once daily Interruption of dosing recommended by dose adjustment in case of adverse reactions |
| 80 mg/dose twice daily Re-dose adjustment in case of adverse reactions |
|
| Avoid concurrent use |
8. Risk of hepatitis B virus reactivation: The risk of hepatitis B virus activation needs to be noted during the use of Zebutinib. Hepatitis B virus status should be clarified prior to use. For patients with current or previous hepatitis B virus infection, a hepatitis specialist needs to be consulted prior to initiating therapy and monitored during treatment.
9. Dose adjustment is not recommended for patients with renal impairment. The use of this product in patients with severe renal impairment (creatinine clearance <30 ml/min) or dialysis requires careful monitoring for adverse reactions.
※10. Other indications: first-line treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (based on data from the global multicenter phase II clinical study AU003 and data from the 17p-subgroup of the global multicenter phase III clinical study SEQUOIA study), primary and relapsed Walden’s macroglobulin hemophagocytic lymphoma (Phase III clinical study). relapsed/refractory marginal zone lymphoma (Phase I-II clinical studies only), relapsed/refractory follicular lymphoma (Phase I-II clinical studies only).