Brukinsa

Treatment with this medicinal product should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. Posology 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 should be continued until disease progression or unacceptable toxicity. BRUKINSA in combination with obinutuzumab 3 Zanubrutinib must be administered 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. Dose modifications for adverse reactions 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) Grade 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. , carbamazepine, phenytoin, rifampicin, St. , bosentan, efavirenz, etravirine, modafinil, nafcillin) Avoid concomitant use; Consider alternative agents with less CYP3A induction.

Summary of the safety profile Zanubrutinib monotherapy The most commonly occurring adverse reactions (≥20%) of zanubrutinib monotherapy were upper respiratory tract infection§ (36%), bruising§ (32%), haemorrhage/haematoma§ (30%), neutropenia§ (30%), musculoskeletal pain§ (27%), rash§ (25%), pneumonia§ (24%), diarrhoea (21%) and cough§ (21%) (Table 3).

The most common Grade 3 or higher adverse reactions (>3%) of zanubrutinib monotherapy were neutropenia§ (21%), pneumonia§ (14%), hypertension§ (8%), thrombocytopenia§ (6%), anaemia (6%) and haemorrhage /haematoma§ (4%). 8% of patients discontinued treatment due to adverse reactions.

6%). 0% of patients. Zanubrutinib in combination with obinutuzumab The most commonly occurring adverse reactions (≥20%) of zanubrutinib in combination with obinutuzumab were thrombocytopenia§ (37%), neutropenia§ (31%) and fatigue§ (27%) (Table 4).

9 The most common Grade 3 or higher adverse reactions (>3%) of zanubrutinib in combination with obinutuzumab were neutropenia§ (25%), thrombocytopenia§ (16%), pneumonia§ (15%) and anaemia (5%). 9% of patients discontinued treatment due to adverse reactions.

2%). 0% of patients. Platelet count decreased† (based on laboratory values) was observed in 65% (all grade) and 12% (grade 3 or 4) patients receiving zanubrutinib in combination with obinutuzumab compared to 43% (all grade) and 11% (grade 3 or 4) in patients receiving obinutuzumab.

8% patients who received zanubrutinib monotherapy. 41 months. 35 months. Adverse reactions in patients treated with BRUKINSA as monotherapy or in combination with obinutuzumab for B-cell malignancies are listed in Table 3 and Table 4, respectively, by system organ class and frequency grouping.

Frequencies are defined as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Haemorrhage Serious and fatal haemorrhagic events have occurred in patients treated with BRUKINSA. 8). Bleeding events of any grade including purpura and petechiae occurred in patients with haematological malignancies. The mechanism for the bleeding events is not well understood.

BRUKINSA may increase the risk of haemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. 2). Warfarin or other vitamin K antagonists should not be administered concomitantly with BRUKINSA.

Patients should be monitored for signs and symptoms of bleeding and complete blood counts should be monitored. The risks and benefits of anticoagulant or antiplatelet therapy when co-administered with BRUKINSA should be considered. The benefit-risk of withholding zanubrutinib for 3 to 7 days pre- and post- surgery depending upon the type of surgery and the risk of bleeding should be considered.

, herpes viral, cryptococcal, aspergillus and pneumocystis jiroveci infections) have occurred in patients treated with BRUKINSA. 8). The most common Grade 3 or higher infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation have also occurred.

Before initiating treatment with BRUKINSA, patients’ HBV status should be established. Consultation with a liver disease expert physician is recommended for patients who test positive for HBV or have positive hepatitis B serology, before initiating treatment.

Patients should be monitored and managed according to the medical standards to prevent hepatitis B reactivation. Consider prophylaxis according to standard of care in patients who are at increased risk for infections. Patients should be monitored for signs and symptoms of infection and treat appropriately.

8). 2). Second primary malignancies Second primary malignancies, including non-skin carcinoma have occurred in patients treated with BRUKINSA. The most frequent second primary malignancy was skin cancer (basal cell carcinoma and squamous cell carcinoma of skin).

1.