Rituzena (Previously Tuxella)

For CLL patients whose lymphocyte counts are > 25 x 109/L it is recommended to administer prednisone/prednisolone 100 mg intravenous shortly before infusion with Rituzena to decrease the rate and severity of acute infusion reactions and/or cytokine release syndrome.

The recommended dosage of Rituzena in combination with chemotherapy for previously untreated and relapsed/refractory patients is 375 mg/m2 body surface area administered on day 0 of the first treatment cycle followed by 500 mg/m2 body surface area administered on day 1 of each subsequent cycle for 6 cycles in total.

The chemotherapy should be given after Rituzena infusion. Granulomatosis with polyangiitis and microscopic polyangiitis Patients treated with Rituzena must be given the patient alert card with each infusion. The recommended dosage of Rituzena for induction of remission therapy of granulomatosis with polyangiitis and microscopic polyangiitis is 375 mg/m2 body surface area, administered as an intravenous infusion once weekly for 4 weeks (four infusions in total).

Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with granulomatosis with polyangiitis or microscopic polyangiitis during and following Rituzena treatment, as appropriate. Special populations Elderly No dose adjustment is required in elderly patients (aged >65 years).

Paediatric population The safety and efficacy of Rituzena in children below 18 years has not been established. No data are available. Method of administration The prepared Rituzena solution should be administered as an intravenous infusion through a dedicated line.

It should not be administered as an intravenous push or bolus. 4). Patients who develop evidence of severe reactions, especially severe dyspnoea, bronchospasm or hypoxia should have the infusion interrupted immediately. Patients with non-Hodgkin’s lymphoma should then be evaluated for evidence of tumour lysis syndrome including appropriate laboratory tests and, for pulmonary infiltration, with a chest X-ray.

In all patients, the infusion should not be restarted until complete resolution of all symptoms, and normalisation of laboratory values and chest X-ray findings. At this time, the infusion can be initially resumed at not more than one-half the previous rate.

8) usually respond to a reduction in the rate of infusion. The infusion rate may be increased upon improvement of symptoms. First infusion The recommended initial rate for infusion is 50 mg/h; […]

Regular full blood counts, including neutrophil and platelet counts, should be performed during rituximab therapy. 8). g. 3). 8). Cases of hepatitis B reactivation have been reported in subjects receiving rituximab including fulminant hepatitis with fatal outcome.

The majority of these subjects were also exposed to cytotoxic chemotherapy. Limited information from one study in relapsed/refractory CLL patients suggests that rituximab treatment may also worsen the outcome of primary hepatitis B infections.

Hepatitis B virus (HBV) screening should be performed in all patients before initiation of treatment with rituximab. At minimum this should include HBsAg-status and HBcAb-status. These can be complemented with other appropriate markers as per local guidelines.

Patients with active hepatitis B disease should not be treated with rituximab. Patients with positive hepatitis B serology (either HBsAg or HBcAb) should consult liver disease experts before start of treatment and should be monitored and managed following local medical standards to prevent hepatitis B reactivation.

8). The majority of patients hadMedicinal product no longer authorised 8 received rituximab in combination with chemotherapy or as part of a haematopoietic stem cell transplant. Immunisations The safety of immunisation with live viral vaccines, following rituximab therapy has not been studied for NHL and CLL patients and vaccination with live virus vaccines is not recommended.

Patients treated with rituximab may receive non-live vaccinations. However, with non-live vaccines response rates may be reduced. In a non-randomised study, patients with relapsed low-grade NHL who received rituximab monotherapy when compared to healthy untreated controls had a lower rate of response to vaccination with tetanus recall antigen (16% vs.

81%) and Keyhole Limpet Haemocyanin (KLH) neoantigen (4% vs. 76% when assessed for >2-fold increase in antibody titer). For CLL patients similar results are assumable considering similarities between both diseases but that has not been investigated in clinical trials.

Mean pre-therapeutic antibody titres against a panel of antigens (Streptococcus pneumoniae, influenza A, mumps, rubella, varicella) were maintained for at least 6 months after treatment with rituximab. 8). In case of such an event, with a suspected relationship to rituximab, treatment should be permanently discontinued.

Rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis Methotrexate (MTX) naïve populations with rheumatoid arthritis The use of rituximab is not recommended in MTX-naïve patients since a favourable benefit risk relationship has not been established.

Infusion related reactions Rituximab is associated with infusion related reactions (IRRs), which may be related to release of cytokines and/or other chemical mediators. Premedication consisting of an analgesic/anti-pyretic medicinal product and an anti-histaminic medicinal product, should always be […]

Non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia Infusion related reactions Rituximab is associated with infusion-related reactions, which may be related to release of cytokines and/or other chemical mediators. Cytokine release syndrome may be clinically indistinguishable from acute hypersensitivity reactions.

This set of reactions which includes syndrome of cytokine release, tumour lysis syndrome and anaphylactic and hypersensitivity reactions are described below. Severe infusion-related reactions with fatal outcome have been reported during post-marketing use of the rituximab intravenous formulation, with an onset ranging within 30 minutes to 2 hours after starting the first rituximab intravenous infusion.

8). Severe cytokine release syndrome is characterised by severe dyspnoea, often accompanied by bronchospasm and hypoxia, in addition to fever, chills, rigors, urticaria, and angioedema. This syndrome may be associated with some features of tumour lysis syndrome such as hyperuricaemia, hyperkalaemia, hypocalcaemia, hyperphosphataemia, acute renal failure, elevated lactate dehydrogenase (LDH) and may be associated with acute respiratory failure and death.

The acute respiratory failure may be accompanied by events such as pulmonary interstitial infiltration or oedema, visible on a chest X-ray. The syndrome frequently manifests itself within one or two hours of initiating the first infusion.

Patients with a history of pulmonary insufficiency or those with pulmonary tumour infiltration may be at greater risk of poor outcome and should be treated with increased caution. 2) and should receive aggressive symptomatic treatment.

Since initial improvement of clinical symptoms may be followed by deterioration, these patients should be closely monitored until tumour lysis syndrome and pulmonary infiltration have been resolved or ruled out. Further treatment of patients after complete resolution of signs and symptoms has rarely resulted in repeated severe cytokine release syndrome.

Patients with a high tumour burden or with a high number (≥25 x 109/L) of circulating malignant cells such as patients with CLL, who may be at higher risk of especially severe cytokine release syndrome, should only be treated with extreme caution.

These patients should be very closely monitored throughout the first infusion. Consideration should be given to the use of a reduced infusion rate for the first infusion in these patients or a split dosing over two days during the first cycle and any subsequent cycles if the lymphocyte count is still >25 x 109/L.

8. These symptoms are usually reversible with interruption of rituximab infusion and administration of an anti-pyretic, an antihistaminic, and, occasionally, oxygen, intravenous saline or bronchodilators, and glucocorticoids if required.

Please see cytokine release syndrome above for severe reactions. Anaphylactic and other hypersensitivity reactions have been reported following the intravenous administration of proteins to patients. In contrast to cytokine release syndrome, true hypersensitivity reactions typically occur within minutes after starting infusion.

, epinephrine (adrenaline), antihistamines and glucocorticoids, should be available for immediate use in the event of an allergic reaction during […]