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TRUXIMA(rituximab-abbs) injection, for intravenous(八)
of 375 mg/m2 per infusion, given as a single agent weekly for up to 8 doses, in combinationwith chemotherapy for up to 8 doses, or following chemotherapy for up to 16 doses.
The most common adverse reactions of rituximab (incidence ≥25%) observed in clinical trialsof patients with NHL were infusion reactions, fever, lymphopenia, chills, infection, andasthenia.
Infusion Reactions
In the majority of patients with NHL, infusion reactions consisting of fever, chills/rigors,nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting,myalgia, dizziness, or hypertension occurred during the first rituximab infusion.
Infusionreactions typically occurred within 30 to 120 minutes of beginning the first infusion andresolved with slowing or interruption of the rituximab infusion and with supportive care(diphenhydramine, acetaminophen, and intravenous saline). The incidence of infusionreactions was highest during the first infusion (77%) and decreased with each subsequentinfusion. [see Warnings and Precautions (5.1)]. In patients with previously untreated follicularNHL or another indication, who did not experience a Grade 3 or 4 infusion reaction in Cycle 1and received a 90-minute infusion of rituximab at Cycle 2, the incidence of Grade 3-4 infusion
reactions on the day of, or day after the infusion was 1.1% (95% CI [0.3%, 2.8%]). For Cycles2-8, the incidence of Grade 3-4 infusion reactions on the day of or day after the 90-minuteinfusion, was 2.8% (95% CI [1.3%, 5.0%]). [see Warnings and Precautions (5.1), Clinical
Studies (14.3)].
Infections
Serious infections (NCI CTCAE Grade 3 or 4), including sepsis, occurred in less than 5% ofpatients with NHL in the single-arm studies. The overall incidence of infections was 31%(bacterial 19%, viral 10%, unknown 6%, and fungal 1%). [see Warnings and Precautions(5.6)].
In randomized, controlled studies where rituximab was administered following chemotherapyfor the treatment of follicular or low-grade NHL, the rate of infection was higher amongpatients who received rituximab.
Cytopenias and hypogammaglobulinemiaIn patients with NHL receiving rituximab monotherapy, NCI-CTC Grade 3 and 4 cytopeniaswere reported in 48% of patients. These included lymphopenia (40%), neutropenia (6%),leukopenia (4%), anemia (3%), and thrombocytopenia (2%). The median duration oflymphopenia was 14 days (range, 1−588 days) and of neutropenia was 13 days (range, 2−116days). A single occurrence of transient aplastic anemia (pure red cell aplasia) and twooccurrences of hemolytic anemia following rituximab therapy occurred during the single-armstudies.
In studies of monotherapy, rituximab-induced B-cell depletion occurred in 70% to 80% ofpatients with NHL. Decreased IgM and IgG serum levels occurred in 14% of these patients.
Relapsed or Refractory, Low-Grade NHLAdverse reactions presented in Table 1 occurred in 356 patients with relapsed or refractory,low-grade or follicular, CD20-positive, B-cell NHL treated in single-arm studies of rituximabadministered as a single agent [see Clinical Studies (14.1)]. Most patients received rituximab375 mg/m2 weekly for 4 doses.
Table 1
Incidence of Adverse Reactions in ≥5% of Patients with Relapsed or Refractory, Low-Grade or
Follicular NHL, Receiving Single-agent Rituximab (N=356)*, †
All Grades (%) Grade 3 and 4 (%)
Any Adverse Reactions
Body as a Whole
Fever
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