Source: Health Products Regulatory Authority (ZA) Publisher: Dr. Reddys Laboratories (Pty) Ltd., Block B, 204 Rivonia Road, Morningside, Sandton, 2057
REDDITUX is indicated for:
Non Hodgkin lymphoma (NHL):
Chronic lymphocytic leukaemia (CLL):
Granulomatosis with polyangiitis and microscopic polyangiitis:
Pemphigus vulgaris:
REDDITUX should be administered under the close supervision of an experienced healthcare professional, and in an environment where full resuscitation facilities are immediately available (see Section 4.4).
Premedication consisting of an anti-pyretic and an antihistaminic, e.g., paracetamol and diphenhydramine, should always be administered before each infusion of REDDITUX. Premedication with glucocorticoids should be considered if REDDITUX is not given in combination with glucocorticoid-containing chemotherapy for treatment of non Hodgkin lymphoma and chronic lymphocytic leukaemia.
Prophylaxis with adequate hydration and administration of uricostatics starting 48 hours prior to start of therapy is recommended for CLL patients to reduce the risk of tumour lysis syndrome. For CLL patients whose lymphocyte counts are >25 × 109/ℓ it is recommended to administer prednisone/prednisolone 100 mg intravenous shortly before infusion with rituximab to decrease the rate and severity of acute infusion reactions and/or cytokine release syndrome.
In patients with granulomatosis with polyangiitis (Wegener’s) or microscopic polyangiitis in disease remission or pemphigus vulgaris, premedication with 100 mg intravenous methylprednisolone should be completed 30 minutes prior to REDDITUX infusions to decrease the incidence and severity of infusion related reactions (IRRs).
In patients with granulomatosis with polyangiitis (Wegener’s) or microscopic polyangiitis, methylprednisolone given intravenously for 1 to 3 days at a dose of 1000 mg per day is recommended prior to the first infusion of REDDITUX (the last dose of methylprednisolone may be given on the same day as the first infusion of REDDITUX). This should be followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day, and tapered as rapidly as possible based on clinical need) during and after the 4-week induction course of REDDITUX treatment. Pneumocystis jirovecii pneumonia (PCP) prophylaxis is recommended for patients with GPA/MPA or PV during and following REDDITUX treatment.
a) Initial treatment, weekly for 4 doses: The recommended dosage of REDDITUX used as a single agent/mono-therapy for adult patients is 375 mg/m² body surface area (BSA), administered as an intravenous infusion once weekly for four doses.
b) Initial treatment, bulky disease, weekly for 4 doses: The recommended dosage of REDDITUX used as a single agent/monotherapy for adult patients is 375 mg/m² body surface area (BSA), administered as an intravenous infusion once weekly for four doses.
c) Re-treatment following relapse, weekly for 4 doses: Patients who have responded to REDDITUX initially have been treated again with REDDITUX at a dose of 375 mg/m² body surface area, administered as an IV infusion once weekly for 4 weeks.
e) Combination therapy: The recommended dosage of REDDITUX in combination with chemotherapy for induction treatment of previously untreated or relapsed/refractory patients with follicular NHL is 375 mg/m² body surface area per cycle for 8 cycles (21 days/cycle). REDDITUX should be administered on day 1 of each chemotherapy cycle, after IV administration of the glucocorticoid component of the chemotherapy, if applicable.
f) Maintenance therapy: Previously untreated patients after response to induction treatment may receive maintenance therapy with REDDITUX given at 375 mg/m² body surface area once every 2 months until disease progression or for a maximum period of two years (12 infusions).
Relapsed/refractory patients after response to induction treatment may receive maintenance therapy with REDDITUX given at 375 mg/m² body surface area once every 3 months until disease progression or for a maximum period of two years.
REDDITUX should be used in combination with CHOP chemotherapy (R-CHOP). The recommended dosage is 375 mg/m² body surface area, administered on day 1 of each chemotherapy cycle for 8 cycles after IV administration of the glucocorticoid component of CHOP. The other components of CHOP should be given after the administration of REDDITUX.
First infusion: The recommended initial rate for infusion is 50 mg/hr; which can subsequently be escalated in 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr.
Subsequent infusions: Subsequent doses of REDDITUX can be infused at an initial rate of 100 mg/hr, and increased by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr.
No dose reductions of REDDITUX are recommended. When REDDITUX is given in combination with CHOP or CVP chemotherapy, standard dose reductions for the chemotherapeutic agents should be applied.
For CLL patients whose lymphocyte counts are >25 × 109/ℓ it is recommended to administer prednisone/prednisolone 100 mg IV shortly before infusion with REDDITUX to decrease the rate and severity of acute infusion reactions and/or cytokine release syndrome.
The recommended dosage of REDDITUX in combination with chemotherapy for previous untreated and relapsed/refractory patients is 375 mg/m² body surface area administered on day 0 of the first treatment cycle (the day before chemotherapy) 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 REDDITUX infusion.
The recommended dosage of REDDITUX for treatment of GPA and MPA is 375 mg/m² body surface area, administered as an IV infusion once weekly for 4 weeks. Methylprednisolone 1 000 mg IV per day for 1 to 3 days is recommended in combination with REDDITUX to treat severe vasculitis symptoms, followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day, and tapered as rapidly as possible per clinical need) during and after REDDITUX treatment.
First infusion: The recommended initial infusion rate for REDDITUX is 50 mg/h; subsequently, the rate can be escalated in 50 mg/h increments every 30 minutes to a maximum of 400 mg/h. Subsequent infusions: Subsequent infusions of REDDITUX can be started at a rate of 100 mg/h and increased by 100 mg/h increments every 30 minutes to a maximum of 400 mg/h.
Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with GPA and MPA during and following REDDITUX treatment, as appropriate.
The recommended dosage of REDDITUX for the treatment of pemphigus vulgaris is 1000 mg administered as an IV infusion followed two weeks later by a second 1000 mg IV infusion in combination with a tapering course of glucocorticoids.
A maintenance infusion of 500 mg IV should be administered at months 12 and 18, and then every 6 months thereafter if needed, based on clinical evaluation.
In the event of relapse, patients may receive 1000 mg IV. The healthcare provider should also consider resuming or increasing the patient’s glucocorticoid dose based on clinical evaluation. Subsequent infusions may be administered no sooner than 16 weeks following the previous infusion.
The safety and efficacy of REDDITUX in children below 18 years has not yet been established.
No dose adjustment is required in elderly patients (aged > 65 years).
The prepared REDDITUX solution should be administered as an intravenous (IV) infusion through a dedicated line. It should not be administered as an intravenous injection or bolus infusion.
REDDITUX infusions should be administered in an environment where full resuscitation facilities are immediately available and under the close supervision of an experienced physician.
REDDITUX is compatible with 0,9 % sodium chloride (normal saline) or 5% dextrose (D5W) solutions for infusion.
The recommended initial rate for infusion is 50 mg/hr; after the first 30 minutes, it can be escalated in 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr.
Subsequent doses of REDDITUX can be infused at an initial rate of 100 mg/hr, and increased by 100 mg/hr increments at 30 minutes intervals, to a maximum of 400 mg/hr.
Limited experience with doses higher than the approved dose of intravenous rituximab is available from clinical trials in humans. The highest intravenous dose of rituximab tested in humans to date is 5000 mg (2250 mg/m²), tested in a dose escalation study in patients with chronic lymphocytic leukaemia. No additional safety signals were identified.
Patients who experience overdose should have immediate interruption of their infusion and be closely monitored.
In the post-marketing setting five cases of rituximab overdose have been reported. Three cases had no reported adverse event. The two adverse events that were reported were flu-like symptoms, with a dose of 1,8 g of rituximab and fatal respiratory failure, with a dose of 2 g of rituximab.
Unopened vial: 3 years.
Storage of reconstituted vials: The prepared infusion solution is physically and chemically stable for 48 hours at 2°C to 8°C and subsequently 48 hours at room temperature (25°C).
From a microbiological point of view, the prepared infusion solution should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should normally not be longer than 48 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
Storage of unopened vials: Store vials in a refrigerator between 2°C to 8°C. Protect vials from light. Do not freeze. Store in the outer carton until required for use.
Storage of reconstituted vials: See Section 6.3.
REDDITUX 100: clear USP Type I 10 ml glass vials. The vials are closed with 20 mm grey butyl rubber stoppers laminated with a fluoro-polymer coating. The stoppers are smooth-finished, with a small cavity at the centre. Stoppered vials are capped with 20 mm, flip-off seals. The aluminium seal completely covers the rubber stopper and is capped with an orange polypropylene disc.
REDDITUX 500: clear USP Type I 50 ml glass vials. The vials are closed with 20 mm grey butyl rubber stoppers laminated with a fluoro-polymer coating. The stoppers are smooth-finished, with a small cavity at the centre. Stoppered vials are capped with 20 mm, flip-off seals. The aluminium seal completely covers the rubber stopper and is capped with an orange polypropylene disc.
Withdraw the required amount of REDDITUX under aseptic conditions and dilute to a calculated rituximab concentration of 1 to 4 mg/ml in an infusion bag containing sterile, non-pyrogenic 0,9% normal saline solution or 5% dextrose solution (D5W) for infusion. To mix the solution, gently invert the bag to avoid foaming. Care must be taken to ensure the sterility of prepared solutions. Since the medicine does not contain any anti-microbial preservative or bacteriostatic agents, aseptic technique must be observed. Parental medications should be inspected visually for particulate matter or discolouration prior to administration.
Any unused medicinal product or waste material should be disposed of.
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