lls
Infection
Asthenia
Headache
Abdominal Pain
Pain
Back Pain
Throat Irritation
Flushing
Heme and Lymphatic System
Lymphopenia
Leukopenia
Neutropenia
Thrombocytopenia
Anemia
Skin and Appendages
Night Sweats
Rash
Pruritus
Urticaria
Respiratory System
Increased Cough
Rhinitis
Bronchospasm
Dyspnea
Sinusitis
Metabolic and Nutritional Disorders
Angioedema
Hyperglycemia
Peripheral Edema
LDH Increase
Digestive System
Nausea
Diarrhea
Vomiting
Nervous System
Dizziness
Anxiety
Musculoskeletal System
Myalgia
Arthralgia
99
86
53
33
31
26
19
14
12
10
9
5
67
48
14
14
12
8
44
15
15
14
8
38
13
12
8
7
6
38
11
9
8
7
37
23
10
10
32
10
5
26
10
10
57
10
1
3
4
1
1
1
1
1
0
0
48
40
4
6
2
3
2
1
1
1
1
4
1
1
1
1
0
3
1
1
0
0
2
1
1
1
1
1
1
3
1
1
6.2 Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity. The detection ofantibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity inan assay may be influenced by several factors including assay methodology, sample handling,timing of sample collection, concomitant medications, and underlying disease. For thesereasons, comparison of the incidence of antibodies to rituximab in the studies described belowwith the incidence of antibodies in other studies or to other products may be misleading.
Using an ELISA assay, anti-rituximab antibody was detected in 4 of 356 (1.1%) patientswith low-grade or follicular NHL receiving single-agent rituximab. Three of the fourpatients had an objective clinical response.
6.3 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of rituximab.
Because these reactions are reported voluntarily from a population of uncertain size, it is notalways possible to reliably estimate their frequency or establish a causal relationship to drugexposure.
•Hematologic: prolonged pancytopenia, marrow hypoplasia, Grade 3-4 prolongedor late-onset neutropenia, hyperviscosity syndrome in Waldenstrom’smacroglobulinemia, prolonged hypogammaglobulinemia [see Warnings andPrecautions (5.6)].
•Cardiac: fatal cardiac failure.
•Immune/Autoimmune Events: uveitis, optic neuritis, systemic vasculitis, pleuritis,lupus-like syndrome, serum sickness, polyarticular arthritis, and vasculitis with
rash.
•Infection: viral infections, including progressive multifocal leukoencephalopathy(PML), increase in fatal infections in HIV-associated lymphoma, and a reported
increased incidence of Grade 3 and 4 infections [see Warnings and Precautions(5.6)].
•Neoplasia: disease progression of Kaposi’s sarcoma.
•Skin: severe mucocutaneous reactions.
•Gastrointestinal: bowel obstruction and perforation.
•Pulmonary: fatal bronchiolitis obliterans and fatal interstitial lung disease.
•Nervous system: Posterior Reversible Encephalopathy Syndrome (PRES)/Reversible Posterior |
