TRUXIMA

What it is

Truxima is rituximab (rch) concentrate for solution for intravenous (IV) infusion. Truxima is supplied at a concentration of 10 mg/mL in either 100 mg (10 mL) or 500 mg (50 mL) single-use glass vials. Truxima 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

Dosing varies by indication. For relapsed or refractory low grade or follicular non-Hodgkin's lymphoma used 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. 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, a course consists of two 1000 mg IV infusions, with the recommended dosage being 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 Truxima 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, and if such symptoms occur, further administration of Truxima should be immediately suspended until a diagnosis of PML has been excluded. Rituximab is associated with infusion-related reactions, which may be related to release of cytokines and/or other chemical mediators. 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 and 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, angio-oedema and other symptoms. Patients with a high tumour burden or with a high number (>25 x 10⁹/L) of circulating malignant cells such as patients with chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma may be at higher risk of developing severe infusion-related reactions. 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. The majority of patients received rituximab in combination with chemotherapy. Isolated cases have been reported in patients who either had evidence of antibodies against Hepatitis B surface antigen before treatment or did not have any such antibodies. The median time to diagnosis of hepatitis was approximately 4 months after the initiation of rituximab and approximately one month after the last dose. HBV screening should be performed in all patients before initiation of treatment with Truxima, and at a minimum this should include HBsAg-status and HBcAb-status. Pulmonary events have included hypoxia, lung infiltration, and acute respiratory failure. Some of these events have been preceded by severe bronchospasm and dyspnoea. In some cases, symptoms worsened over time, while in others initial improvement was followed by clinical deterioration. Patients experiencing pulmonary events or other severe infusion-related symptoms should be closely monitored until complete resolution of their symptoms occurs.

Contraindications

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

PBS listing

The 500 mg in 50 mL solution for intravenous infusion is listed on the PBS with 4 items, unrestricted access, at an ex-manufacturer price of A$216.18.

Regulatory history

Truxima rituximab (rch) in both 500 mg/50 mL and 100 mg/10 mL concentrate solution for intravenous infusion strengths were first listed on the ARTG on 16 April 2018. In November 2015, the PBAC recommended a change to include the 100 mg vial for Section 100 (Highly Specialised Drugs Program) listing for remission induction in severe, active granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). In November 2017, the PBAC recommended listing as a new biosimilar brand for treatment of chronic lymphocytic leukaemia, non-Hodgkin lymphoma, and severe active rheumatoid arthritis.