Detailed instructions for ibrutinib/ibrutinib capsules

1. Common names: ibrutinib, Ibrutinib, ibrutinib

Product name: Yike, IMBRUVICA

2. Indications:

1. Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Ibrutinib/ibrutinib is indicated for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, including adult patients with CLL or SLL with 17p deletion

2. Waldenström's macroglobulinemia (WM): Ibrutinib is suitable for the treatment of adult patients with Waldenström's macroglobulinemia.

3. Chronic graft-versus-host disease (cGVHD): Ibrutinib is suitable for the treatment of adult and pediatric patients 1 year old and older with chronic graft-versus-host disease after failure of one or more systemic therapies.

3. Usage and dosage:

1. Recommended dosage:

For the treatment ofCLL/SLL and WM, the recommended dose of ibrutinib is 420 mg orally once daily until disease progression or unacceptable toxicity. For patients 12 years of age and older with cGVHD, the recommended dose is 420 mg orally once daily, and for patients 1 to less than 12 years of age with cGVHD, the recommended dose is 240 mg/m2 orally once daily (maximum dose 420 mg) until progression of cGVHD, recurrence of underlying malignancy, or unacceptable toxicity. When a patient no longer requires treatment for cGVHD, discontinuation should be based on the patient's individual medical assessment.

2. Combination medication: For CLL/SLL, it can be used as a single drug in combination with rituximab or obinutuzumab, or in combination with bendamustine and rituximab (BR). When coadministered with rituximab or obinutuzumab, consider administering it before rituximab or obinutuzumab on the same day. For WM, it can be used as a single agent or in combination with rituximab.

3. Medication management: Take ibrutinib at approximately the same time every day; swallow the tablets or capsules with a glass of water. Do not open, break or chew capsules. If a dose of ibrutinib is not taken at the scheduled time, it can be taken as soon as possible that day and resume the normal schedule the next day. Do not take extra doses to make up for a missed dose.

4. Dose adjustment for special groups:

(1) Adult patients with B-cell malignancies: The recommended dose for patients with mild hepatic impairment (Child-Pugh Class A) is 140 mg daily; for patients with moderate hepatic impairment (Child-Pugh Class B), the recommended dose is 70 mg daily; for patients with severe hepatic impairment (Child-Pugh Class C), avoid the use of ibrutinib.

(2) Patients with cGVHD: For patients 12 years and older with total bilirubin levels >1.5 to 3 times the upper limit of normal (ULN), the recommended dose is 140 mg daily (unless non-hepatic or due to Gilbert syndrome); for patients 1 year to younger than 12 years (unless non-hepatic or due to Gilbert syndrome), the recommended dose is 80 mg/m2 daily. Avoid use of ibrutinib in patients with total bilirubin levels >3xULN (unless nonhepatic in origin or due to Gilbert syndrome).

4. Adverse reactions:

In clinical studies of ibrutinib, the most common adverse reactions in patients with CLL/SLL were thrombocytopenia, diarrhea, fatigue, musculoskeletal pain, neutropenia, rash, anemia, bruising and nausea; in patients with cGVHD, the most common adverse reactions were fatigue, bruising, diarrhea, thrombocytopenia, stomatitis, muscle spasm, nausea, bleeding, anemia and pneumonia.

5. Storage:

Store vials containing ibrutinib capsulesAt room temperature between 20°C and 25°C (68°F to 77°F), allow brief exposure to temperatures between 15°C and 30°C (59°F and 86°F). Keep in original packaging until dispensed.

6. Special groups:

1. Women: It is recommended that women of childbearing potential use effective contraceptive measures during treatment with ibrutinib and within 1 month after the last dose.

2. Men: It is recommended that men with female partners of potential reproductive potential use effective contraception during treatment with ibrutinib and for 1 month after the last dose.

7. Mechanism of action:

Ibrutinib is a small molecule inhibitor of Bruton's tyrosine kinase (BTK). Ibrutinib forms a covalent bond with the cysteine u200bu200bresidue in the active site of BTK, thereby inhibiting BTK enzyme activity. BTK is a signaling molecule of the B cell antigen receptor (BCR) and cytokine receptor pathways. The role of BTK in signaling through B cell surface receptors results in the activation of pathways required for B cell trafficking, chemotaxis, and adhesion. Non-clinical studies have shown that ibrutinib inhibits malignant B cell proliferation and survival in vivo and inhibits cell migration and matrix adhesion in vitro.