Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: BeiGene Ireland Limited., 10 Earlsfort Terrace, Dublin 2, D02 T380, Ireland, Tel. +353 1 566 7660, E-mail bg.ireland@beigene.com
BRUKINSA as monotherapy is indicated for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy.
BRUKINSA as monotherapy is indicated for the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based therapy.
BRUKINSA as monotherapy is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL).
BRUKINSA in combination with obinutuzumab is indicated for the treatment of adult patients with refractory or relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies.
Treatment with this medicinal product should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
The recommended total daily dose of zanubrutinib is 320 mg. The daily dose may be taken either once daily (four 80 mg capsules) or divided into two doses of 160 mg twice daily (two 80 mg capsules). Treatment with BRUKINSA should be continued until disease progression or unacceptable toxicity.
Zanubrutinib must be administered orally before obinutuzumab infusion. The recommended dose is obinutuzumab 1,000 mg intravenously on Days 1, 8, and 15 of Cycle 1, and on Day 1 of every 28-day cycle from Cycles 2 to 6. At the discretion of the physician, obinutuzumab may be administered 100 mg on Day 1 and 900 mg on Day 2 of Cycle 1 instead of 1,000 mg on Day 1 of Cycle 1. Obinutuzumab maintenance (one infusion every two months for up to two years) may be prescribed. Refer to the obinutuzumab SmPC for additional dosing information, including premedication before each infusion.
Recommended dose modifications of zanubrutinib for Grade 3 or greater adverse reactions are provided in Table 1.
Table 1. Recommended dose modifications for adverse reactions:
| Adverse reaction | Adverse reaction occurrence | Dose modification (starting dose: 320 mg once daily or 160 mg twice daily) |
|---|---|---|
| ≥Grade 3 non-haematological toxicities Grade 3 febrile neutropenia Grade 3 thrombocytopenia with significant bleeding Grade 4 neutropenia (lasting >10 consecutive days) Grad 4 thrombocytopenia (lasting >10 consecutive days) | First | Interrupt BRUKINSA Once toxicity has resolved to ≤Grade 1 or baseline: Resume at 320 mg once daily or 160 mg twice daily |
| Second | Interrupt BRUKINSA Once toxicity has resolved to ≤Grade 1 or baseline: Resume at 160 mg once daily or 80 mg twice daily | |
| Third | Interrupt BRUKINSA Once toxicity has resolved to ≤Grade 1 or baseline: Resume at 80 mg once daily | |
| Fourth | Discontinue BRUKINSA |
Asymptomatic lymphocytosis should not be regarded as an adverse reaction, and these patients should continue taking BRUKINSA.
For dose modification of obinutuzumab for adverse reactions, refer to the SmPC of obinutuzumab.
Dose modifications for use with CYP3A inhibitors or inducers are shown in Table 2 (see also sections 4.4, 4.5 and 5.2):
Table 2. Recommended dose modifications when co-administered with other medicinal products:
| CYP3A | co-administered medicinal product | recommended dose |
|---|---|---|
| Inhibition | Strong CYP3A inhibitor (e.g., posaconazole, voriconazole, ketoconazole, itraconazole, clarithromycin, indinavir, lopinavir, ritonavir, telaprevir) | 80 mg once daily |
| Moderate CYP3A inhibitor (e.g., erythromycin, ciprofloxacin, diltiazem, dronedarone, fluconazole, verapamil, aprepitant, imatinib, grapefruit juice, Seville oranges) | 80 mg twice daily | |
| Induction | Strong CYP3A inducer (e.g., carbamazepine, phenytoin, rifampin, St. John’s wort) Moderate CYP3A inducer (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) | Avoid concomitant use; Consider alternative agents with less CYP3A induction |
A double dose should not be taken to make up for a forgotten dose. If a dose is not taken at the scheduled time, the next dose should be taken according to the normal schedule.
No specific dose adjustment is required for elderly patients (aged ≥65 years).
No dose modification is recommended in patients with mild to moderate renal impairment (creatinine clearance (CrCl) ≥30 mL/min, estimated by Cockcroft-Gault). There is limited data on patients with severe renal impairment and end-stage renal disease (n=12). Patients with severe renal impairment (CrCl <30 mL/min) or on dialysis should be monitored for adverse reactions (see section 5.2).
Dose modifications are not needed in patients with mild (Child-Pugh class A) or moderate hepatic impairment (Child-Pugh class B). Patients with mild or moderate hepatic impairment were treated in BRUKINSA clinical studies. The recommended dose of BRUKINSA for patients with severe hepatic impairment (Child-Pugh class C) is 80 mg orally twice daily. The safety of BRUKINSA has not been evaluated in patients with severe hepatic impairment. Monitor these patients closely for adverse events of BRUKINSA (see section 5.2).
The safety and efficacy of BRUKINSA in children and adolescents below 18 years of age have not been established. No data are available.
BRUKINSA is for oral use. The hard capsules can be taken with or without food. Patients should be instructed to swallow the capsules whole with water, and not to open, break or chew the capsules.
There is no specific antidote for BRUKINSA. For patients who experience overdose, closely monitor and provide appropriate supportive treatment.
3 years.
This medicinal product does not require any special storage conditions.
HDPE bottles with a child-resistant polypropylene closure. Each bottle contains 120 hard capsules.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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