RUXIENCE- rituximab injection, solution
Pfizer Laboratories Div Pfizer Inc
WARNING: FATAL INFUSION-RELATED REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
Administration of rituximab products can result in serious, including fatal, infusion-related reactions. Deaths within 24 hours of rituximab infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Monitor patients closely. Discontinue RUXIENCE infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion-related reactions [see Warnings and Precautions (5.1), Adverse Reactions (6.1)].
Severe Mucocutaneous Reactions
Severe, including fatal, mucocutaneous reactions can occur in patients receiving rituximab products [see Warnings and Precautions (5.2)].
Hepatitis B Virus (HBV) Reactivation
HBV reactivation can occur in patients treated with rituximab products, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with RUXIENCE. Discontinue RUXIENCE and concomitant medications in the event of HBV reactivation [see Warnings and Precautions (5.3)].
Progressive Multifocal Leukoencephalopathy (PML)
RUXIENCE (rituximab-pvvr) is indicated for the treatment of adult patients with:
- Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent.
- Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy.
- Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.
- Previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens.
RUXIENCE is indicated, in combination with fludarabine and cyclophosphamide (FC), for the treatment of adult patients with previously untreated and previously treated CD20-positive CLL.
1.3 Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA)
RUXIENCE, in combination with glucocorticoids, is indicated for the treatment of adult patients with Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA).
Administer only as an intravenous infusion [see Dosage and Administration (2.7)].
Do not administer as an intravenous push or bolus. RUXIENCE should only be administered by a healthcare professional with appropriate medical support to manage severe infusion-related reactions that can be fatal if they occur [see Warnings and Precautions (5.1)].
Premedicate before each infusion [see Dosage and Administration (2.6)].
Prior to First Infusion: Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with RUXIENCE [see Warnings and Precautions (5.3)]. Obtain complete blood counts including platelets (CBC) prior to the first dose.
During RUXIENCE Therapy: In patients with lymphoid malignancies, during treatment with RUXIENCE monotherapy, obtain complete blood counts (CBC) with differential and platelet counts prior to each RUXIENCE course. During treatment with RUXIENCE and chemotherapy, obtain CBC with differential and platelet counts at weekly to monthly intervals and more frequently in patients who develop cytopenias [see Adverse Reactions (6.1)]. In patients with GPA or MPA, obtain CBC with differential and platelet counts at two to four month intervals during RUXIENCE therapy. Continue to monitor for cytopenias after final dose and until resolution.
- First Infusion: Initiate infusion at a rate of 50 mg/hour. In the absence of infusion toxicity, increase infusion rate by 50 mg/hour increments every 30 minutes, to a maximum of 400 mg/hour.
- Subsequent Infusions:
Standard Infusion: Initiate infusion at a rate of 100 mg/hour. In the absence of infusion toxicity, increase rate by 100 mg/hour increments at 30-minute intervals, to a maximum of 400 mg/hour.
For previously untreated follicular NHL and DLBCL patients:
If patients did not experience a Grade 3 or 4 infusion-related adverse event during Cycle 1, a 90-minute infusion can be administered in Cycle 2 with a glucocorticoid-containing chemotherapy regimen.
Initiate at a rate of 20% of the total dose given in the first 30 minutes and the remaining 80% of the total dose given over the next 60 minutes. If the 90-minute infusion is tolerated in Cycle 2, the same rate can be used when administering the remainder of the treatment regimen (through Cycle 6 or 8).
Patients who have clinically significant cardiovascular disease or who have a circulating lymphocyte count ≥5,000/mm3 before Cycle 2 should not be administered the 90-minute infusion [see Clinical Studies (14.4)].
- Interrupt the infusion or slow the infusion rate for infusion-related reactions [see Boxed Warning, Warnings and Precautions (5.1)]. Continue the infusion at one-half the previous rate upon improvement of symptoms.
The recommended dose is 375 mg/m2 as an intravenous infusion according to the following schedules:
- Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell NHL
Administer once weekly for 4 or 8 doses.
- Retreatment for Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell NHL
Administer once weekly for 4 doses.
- Previously Untreated, Follicular, CD20-Positive, B-Cell NHL
Administer on Day 1 of each cycle of chemotherapy, for up to 8 doses. In patients with complete or partial response, initiate RUXIENCE maintenance eight weeks following completion of a rituximab product in combination with chemotherapy. Administer RUXIENCE as a single-agent every 8 weeks for 12 doses.
- Non-progressing, Low-Grade, CD20-Positive, B-Cell NHL, after first-line CVP chemotherapy
Following completion of 6–8 cycles of CVP chemotherapy, administer once weekly for 4 doses at 6-month intervals to a maximum of 16 doses.
- Diffuse Large B-Cell NHL Administer on Day 1 of each cycle of chemotherapy for up to 8 infusions.
The recommended dose is:
- 375 mg/m2 the day prior to the initiation of FC chemotherapy, then 500 mg/m2 on Day 1 of Cycles 2–6 (every 28 days).
- Infuse RUXIENCE 250 mg/m2 within 4 hours prior to the administration of Indium-111-(In-111-) Zevalin and within 4 hours prior to the administration of Yttrium-90- (Y-90-) Zevalin.
- Administer RUXIENCE and In-111-Zevalin 7–9 days prior to RUXIENCE and Y-90- Zevalin.
- Refer to the Zevalin package insert for full prescribing information regarding the Zevalin therapeutic regimen.
2.5 Recommended Dose for Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA)
Induction Treatment of Patients with Active GPA/MPA
- Administer RUXIENCE as a 375 mg/m2 intravenous infusion once weekly for 4 weeks for patients with active GPA or MPA.
- Glucocorticoids administered as methylprednisolone 1,000 mg intravenously per day for 1 to 3 days followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day and tapered per clinical need) are recommended to treat severe vasculitis symptoms. This regimen should begin within 14 days prior to or with the initiation of RUXIENCE and may continue during and after the 4 week induction course of RUXIENCE treatment.
Follow up Treatment of Patients with GPA/MPA who have achieved disease control with induction treatment
- Administer RUXIENCE as two 500 mg intravenous infusions separated by two weeks, followed by a 500 mg intravenous infusion every 6 months thereafter based on clinical evaluation.
- Patients should receive 100 mg intravenous methylprednisolone to be completed 30 minutes prior to each RUXIENCE infusion.
- If induction treatment of active disease was with a rituximab product, follow up treatment with RUXIENCE should be initiated within 24 weeks after the last induction infusion with a rituximab product or based on clinical evaluation, but no sooner than 16 weeks after the last induction infusion with a rituximab product.
- If induction treatment of active disease was with other standard of care immunosuppressants, RUXIENCE follow up treatment should be initiated within the 4 week period that follows achievement of disease control.
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