IMBRUVICA® (ibrutinib) capsules
IMBRUVICA® (ibrutinib) capsules
Table 7: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with
Waldenström’s Macroglobulinemia (N=63) (continued)
Table 4: Treatment-Emergent* Decrease of Hemoglobin, Platelets,
or Neutrophils in Patients with CLL (N=48) in Study 1
Percent of Patients (N=48)
All Grades
Grade 3 or 4
(%)
(%)
71
10
54
27
44
0
Platelets Decreased
Neutrophils Decreased
Hemoglobin Decreased
* Based on laboratory measurements per IWCLL criteria and adverse reactions
Study 2: Adverse reactions and laboratory abnormalities described below in Tables 5 and 6 reflect
exposure to IMBRUVICA with a median duration of 8.6 months and exposure to ofatumumab with a
median of 5.3 months in Study 2.
Table 5: Non-Hematologic Adverse Reactions ≥ 10% Reported in Study 2
System Organ Class
ADR Term
Gastrointestinal disorders
Diarrhea
Nausea
Stomatitis*
Constipation
Vomiting
General disorders and
administration site conditions
Fatigue
Pyrexia
Infections and infestations
Upper respiratory tract
infection
Pneumonia*
Sinusitis*
Urinary tract infection
Skin and subcutaneous tissue
disorders
Rash*
Petechiae
Bruising*
Musculoskeletal and
connective tissue disorders
Musculoskeletal Pain*
Arthralgia
Nervous system disorders
Headache
Dizziness
Injury, poisoning and
procedural complications
Contusion
Eye disorders
Vision blurred
IMBRUVICA
(N=195)
All Grades
Grade 3 or 4
(%)
(%)
Ofatumumab
(N=191)
All Grades
Grade 3 or 4
(%)
(%)
48
26
17
15
14
4
2
1
0
0
18
18
6
9
6
2
0
1
0
1
28
24
2
2
30
15
2
1
16
15
11
10
1
10
1
4
11
13
6
5
2
9
0
1
24
14
12
3
0
0
13
1
1
0
0
0
28
17
2
1
18
7
1
0
14
11
1
0
6
5
0
0
11
0
3
0
10
0
3
0
Subjects with multiple events for a given ADR term are counted once only for each ADR term.
The system organ class and individual ADR terms are sorted in descending frequency order in the
IMBRUVICA arm.
* Includes multiple ADR terms
Table 6: Treatment-Emergent* Decrease of Hemoglobin, Platelets,
or Neutrophils in Study 2
Neutrophils Decreased
Platelets Decreased
Hemoglobin Decreased
IMBRUVICA
(N=195)
All Grades
Grade 3 or 4
(%)
(%)
51
23
52
5
36
0
Ofatumumab
(N=191)
All Grades
Grade 3 or 4
(%)
(%)
57
26
45
10
21
0
* Based on laboratory measurements per IWCLL criteria
Waldenström’s Macroglobulinemia
The data described below reflect exposure to IMBRUVICA in an open label clinical trial that included
63 patients with previously treated WM.
The most commonly occurring adverse reactions in the WM trial (≥ 20%) were neutropenia,
thrombocytopenia, diarrhea, rash, nausea, muscle spasms, and fatigue.
Six percent of patients receiving IMBRUVICA in the WM trial discontinued treatment due to adverse
events. Adverse events leading to dose reduction occurred in 11% of patients.
Adverse reactions and laboratory abnormalities described below in Tables 7 and 8 reflect exposure
to IMBRUVICA with a median duration of 11.7 months in the WM trial.
Table 7: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with
Waldenström’s Macroglobulinemia (N=63)
System Organ Class
Gastrointestinal
disorders
Skin and
subcutaneous tissue
disorders
Preferred Term
Diarrhea
Nausea
Stomatitis*
Gastroesophageal reflux disease
Rash*
Bruising*
Pruritus
All Grades
(%)
37
21
16
13
22
16
11
Grade 3 or 4
(%)
0
0
0
0
0
0
0
System Organ Class
Preferred Term
Fatigue
All Grades
(%)
21
Grade 3 or 4
(%)
0
General disorders and
administrative site
conditions
Musculoskeletal and
connective tissue
disorders
Infections and
infestations
Muscle spasms
Arthropathy
21
13
0
0
Respiratory, thoracic
and mediastinal
disorders
Nervous system
disorders
Neoplasms benign,
malignant, and
unspecified (including
cysts and polyps)
Upper respiratory tract infection
Sinusitis
Pneumonia*
Skin infection*
Epistaxis
Cough
19
19
14
14
19
13
0
0
6
2
0
0
Dizziness
Headache
Skin cancer*
14
13
11
0
0
0
The syste