RUXIENCE

What it is

RUXIENCE is rituximab (rch) concentrate for solution for intravenous infusion, containing the active ingredient rituximab. RUXIENCE is supplied at a concentration of 10 mg/mL in either 100 mg (10 mL) or 500 mg (50 mL) single-use glass vials. RUXIENCE concentrate for solution for IV infusion is a sterile, clear, colourless, preservative-free, concentrated solution.

Approved indications

— CD20 positive, previously untreated, Stage III/IV follicular, B-cell non-Hodgkin's lymphoma. — CD20 positive, relapsed or refractory low grade or follicular, B-cell non-Hodgkin's lymphoma. — CD20 positive, diffuse large B-cell non-Hodgkin's lymphoma, in combination with chemotherapy. — CD20 positive chronic lymphocytic leukaemia (CLL) in combination with chemotherapy. — Severe, active rheumatoid arthritis in adult patients who have had an inadequate response or intolerance to at least one tumour necrosis factor (TNF) inhibitor therapy, in combination with methotrexate. — Induction of remission in patients with severely active Granulomatosis with polyangiitis (GPA, also known as Wegener's granulomatosis) and Microscopic polyangiitis (MPA), in combination with glucocorticoids.

Dosing overview

For relapsed or refractory low grade or follicular non-Hodgkin's lymphoma as monotherapy, the recommended dosage is 375 mg/m² administered as an intravenous infusion once weekly for four weeks. When used in combination with CHOP chemotherapy, the recommended dosage is 375 mg/m² administered on day 1 of each chemotherapy cycle (6 cycles). For previously untreated stage III/IV follicular non-Hodgkin's lymphoma in combination with chemotherapy, the recommended dosage is 375 mg/m² administered on day 1 of each chemotherapy cycle for up to 8 cycles as induction therapy. Previously untreated patients who have responded to induction treatment may receive maintenance therapy with RUXIENCE at 375 mg/m² body surface area once every 2 months until disease progression or for a maximum period of two years. Relapsed/refractory patients who have responded to induction treatment may receive maintenance therapy with RUXIENCE at 375 mg/m² body surface area once every 3 months until disease progression or for a maximum period of two years. For diffuse large B-cell non-Hodgkin's lymphoma in combination with CHOP chemotherapy, the recommended dosage is 375 mg/m², administered as an intravenous infusion on day 1 of each chemotherapy cycle, for up to 8 cycles. For chronic lymphocytic leukaemia in combination with chemotherapy, the recommended dosage is 375 mg/m² administered on day 1 of the first treatment cycle followed by 500 mg/m² administered on day 1 of each subsequent cycle, for a total of 6 cycles. For rheumatoid arthritis, the recommended dosage is 1000 mg by IV infusion followed by a second 1000 mg IV infusion two weeks later. For Granulomatosis with polyangiitis and Microscopic polyangiitis, the recommended dosage is 375 mg/m² body surface area, administered as an IV infusion once weekly for 4 weeks.

Key safety warnings

Use of RUXIENCE may be associated with an increased risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Patients must be monitored for any new or worsening neurological symptoms or signs suggestive of PML. RUXIENCE is associated with infusion-related reactions, which may be related to release of cytokines and/or other chemical mediators. Cytokine release syndrome may be indistinguishable from acute hypersensitivity reactions. Severe infusion-related reactions with fatal outcome have been reported during post-marketing use. Severe reactions usually manifested within 30 minutes to 2 hours after starting the first rituximab infusion, were characterised by pulmonary events and included, in some cases, rapid tumour lysis and features of tumour lysis syndrome in addition to fever, chills, rigors, hypotension, urticaria, angioedema and other symptoms. RUXIENCE mediates the rapid lysis of benign and malignant CD20-positive cells. Signs and symptoms (such as hyperuricaemia, hyperkalaemia, hypocalcaemia, acute renal failure, elevated LDH) consistent with tumour lysis syndrome have been reported to occur after the first rituximab infusion in patients with high numbers of circulating malignant lymphocytes. Cases of Hepatitis B virus (HBV) reactivation, occasionally with fulminant hepatitis, hepatic failure, and death have been reported in some patients with haematologic malignancies treated with rituximab. HBV screening should be performed in all patients before initiation of treatment with RUXIENCE. At a minimum this should include HBsAg-status and HBcAb-status. Cases of enteroviral meningoencephalitis, including fatal cases, have been reported following use of rituximab.

Contraindications

RUXIENCE is contraindicated in patients with known hypersensitivity to rituximab, to any of its excipients or to murine proteins.

PBS listing

RUXIENCE solution for IV infusion 100 mg in 10 mL is listed on the PBS with 2 items under unrestricted restriction, with an ex-manufacturer price of A$43.24.

Regulatory history

RUXIENCE was first listed on the ARTG on 2021-03-03, with two registrations: ARTG 330537 (100 mg/10 mL concentrated solution for injection vial) and ARTG 330536 (500 mg/50 mL concentrated solution for injection vial). In November 2021, the PBAC recommended RUXIENCE for listing for non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukaemia (CLL), rheumatoid arthritis (RA), Granulomatosis with polyangiitis (Wegener's granulomatosis) (GPA), and Microscopic polyangiitis (MPA).