BRUKINSA

What it is

BRUKINSA is the brand name for zanubrutinib, supplied as capsules containing 80 mg and tablets containing 160 mg. Zanubrutinib is a small-molecule inhibitor of Bruton's tyrosine kinase (BTK) that forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK activity. BTK is a signalling molecule of the B-cell antigen receptor and cytokine receptor pathways; in B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. This medicinal product is subject to additional monitoring in Australia.

Approved indications

— Waldenström's macroglobulinaemia in adult patients who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy. — Mantle cell lymphoma in adult patients who have received at least one prior therapy. — Marginal zone lymphoma in adult patients who have received at least one prior anti-CD20-based therapy. — Chronic lymphocytic leukaemia or small lymphocytic lymphoma as monotherapy in adult patients, including patients with deletion 17p and/or TP53 mutation.

Dosing overview

The recommended total daily oral dose of BRUKINSA is 320 mg. Capsules may be taken as either 320 mg (four 80 mg capsules) once daily, or as 160 mg (two 80 mg capsules) twice daily; tablets may be taken as either 320 mg (two 160 mg tablets) once daily or as 160 mg (one 160 mg tablet) twice daily. BRUKINSA can be taken with or without food. No dosage modification is recommended for elderly patients aged 65 years or older. No dosage modification is recommended in patients with mild to moderate renal impairment (creatinine clearance ≥30 mL/min). For patients with severe hepatic impairment, the recommended dose is 80 mg orally twice daily. Dose reduction is required when coadministered with strong CYP3A inhibitors (reduced to 80 mg once daily) or moderate CYP3A inhibitors (reduced to 80 mg twice daily).

Key safety warnings

Serious and fatal haemorrhagic events have occurred in patients with haematological malignancies treated with zanubrutinib monotherapy, with Grade 3 or higher bleeding events occurring in 4.6% of patients, including intracranial and gastrointestinal haemorrhage, haematuria, and haemothorax reported uncommonly. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of haemorrhage and patients should be monitored for signs of bleeding. Fatal and non-fatal infections, including bacterial, viral, or fungal infections, sepsis, and opportunistic infections, have occurred in patients with haematological malignancies treated with zanubrutinib monotherapy, with Grade 3 or higher infections occurring; the most common Grade 3 or higher infection was pneumonia. Infections due to hepatitis B virus or herpes zoster virus reactivation have occurred; consider prophylaxis according to standard of care in patients at increased risk for infections. Grade 3 or 4 cytopenias including neutropenia, thrombocytopenia, and anaemia have been reported in patients with haematological malignancies treated with zanubrutinib monotherapy; complete blood counts should be monitored during treatment. Second primary malignancies have occurred in 14.7% of patients with haematological malignancies treated with zanubrutinib monotherapy, with skin cancer reported in 8.8% of patients (basal cell carcinoma in 5.0% and squamous cell carcinoma of skin in 3.5%). Atrial fibrillation and atrial flutter have occurred in 4.6% of patients with haematological malignancies treated with zanubrutinib monotherapy, with Grade 3 or higher events occurring in 1.9% of patients, particularly in patients with cardiac risk factors, hypertension, and acute infections.

Contraindications

There are no contraindications listed.

PBS listing

The 80 mg capsule formulation has four PBS items with authority required restriction and an ex-manufacturer price of A$7769.96.

Regulatory history

BRUKINSA zanubrutinib 80 mg capsules were first listed on the ARTG on 7 October 2021. Brukinsa was approved for provisional registration on 8 October 2021 for the treatment of adult patients with mantle cell lymphoma who have received at least one prior therapy, based on objective response rate, with continued registration contingent on verification of clinical benefit in confirmatory trials. In July 2021, the PBAC recommended BRUKINSA for relapsed and/or refractory mantle cell lymphoma; however, in July 2021, the PBAC did not recommend it for Waldenström macroglobulinaemia. In March 2022, the PBAC recommended BRUKINSA for Waldenström macroglobulinaemia in treatment-naïve patients unsuitable for chemo-immunotherapy and relapsed/refractory patients who have received at least one prior chemo-immunotherapy. In March 2023, the PBAC recommended BRUKINSA for chronic lymphocytic leukaemia/small lymphocytic leukaemia in both relapsed or refractory patients unsuitable for treatment or retreatment with a purine analogue, and treatment-naïve patients. The 160 mg tablet formulation was first listed on the ARTG on 9 October 2025.