IMBRUVICA® (ibrutinib) capsules
IMBRUVICA® (ibrutinib) capsules
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 (%)
Platelets Decreased
71
10
Neutrophils Decreased
54
27
Hemoglobin Decreased
44
0
* Based on laboratory measurements per IWCLL criteria and adverse reactions.
Table 7: Adverse Reactions Reported in ≥ 10% of Patients and at Least 2% Greater in the
IMBRUVICA Treated Arm in Patients in Study 3 (continued)
IMBRUVICA
Chlorambucil
(N=135)
(N=132)
Body System
All Grades
Grade 3 or 4
All Grades
Grade 3 or 4
Adverse Reaction
(%)
(%)
(%)
(%)
Infections and infestations
Skin infection*
15
2
3
1
Pneumonia*
14
8
7
4
Urinary tract infections
10
1
8
1
Respiratory, thoracic and
mediastinal disorders
Cough
22
0
15
0
General disorders and
administration site conditions
Peripheral edema
19
1
9
0
Pyrexia
17
0
14
2
Vascular Disorders
Hypertension*
14
4
1
0
Nervous System Disorders
Headache
12
1
10
2
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
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: Adverse Reactions Reported in ≥ 10% of Patients and at Least 2% Greater in the
IMBRUVICA Treated Arm in Patients in Study 2
Body System
Adverse Reaction
Gastrointestinal disorders
Diarrhea
Nausea
Stomatitis*
Constipation
Vomiting
General disorders and
administration site conditions
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
24
2
15
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
IMBRUVICA
Ofatumumab
(N=195)
(N=191)
All Grades
Grade 3 or 4
All Grades
Grade 3 or 4
(%)
(%)
(%)
(%)
Neutrophils Decreased
51
23
57
26
Platelets Decreased
52
5
45
10
Hemoglobin Decreased
36
0
21
0
* Based on laboratory measurements per IWCLL criteria.
Study 3: Adverse reactions described below in Table 7 reflect exposure to IMBRUVICA with a median
duration of 17.4 months. The median exposure to chlorambucil was 7.1 months in Study 3.
Table 7: Adverse Reactions Reported in ≥ 10% of Patients and at Least 2% Greater in the
IMBRUVICA Treated Arm in Patients in Study 3
IMBRUVICA
Chlorambucil
(N=135)
(N=132)
Body System
All Grades
Grade 3 or 4
All Grades
Grade 3 or 4
Adverse Reaction
(%)
(%)
(%)
(%)
Gastrointestinal disorders
Diarrhea
42
4
17
0
Stomatitis*
14
1
4
1
Musculoskeletal and connective
tissue disorders
Musculoskeletal pain*
36
4
20
0
Arthralgia
16
1
7
1
Muscle spasms
11
0
5
0
Eye Disorders
Dry eye
17
0
5
0
Lacrimation increased
13
0
6
0
Vision blurred
13
0
8
0
Visual acuity reduced
11
0
2
0
Skin and subcutaneous tissue
disorders
Rash*
21
4
12
2
Bruising*
19
0
7
0
Waldenström’s Macroglobulinemia: The data described below reflect exposure to IMBRUVICA in an openlabel 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 8 and 9 reflect exposure to
IMBRUVICA with a median duration of 11.7 months in the WM trial.
Table 8: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with
Waldenström’s Macroglobulinemia (N=63)
All Grades
Grade 3 or 4
Body System
Adverse Reaction
(%)
(%)
Gastrointestinal disorders
Diarrhea
37
0
Nausea
21
0
Stomatitis*
16
0
Gastroesophageal reflux disease
13
0
Skin and subcutaneous tissue
Rash*
22
0
disorders
Bruising*
16
0
Pruritus
11
0
General disorders and
Fatigue
21
0
administrative site conditions
Musculoskeletal and connective Muscle spasms
21
0
tissue disorders
Arthropathy
13
0
Infections and infestations
Upper respiratory tract infection
19
0
Sinusitis
19
0
Pneumonia*
14
6
Skin infection*
14
2
Respiratory, thoracic and
Epistaxis
19
0
mediastinal disorders
Cough
13
0
Nervous system disorders
Dizziness
14
0
Headache
13
0
Neoplasms benign, malignant, and Skin cancer*
11
0
unspecified (including cysts and
polyps)
The system organ class and individual ADR preferred terms are sorted in descending frequency order.
* Includes multiple ADR terms.
Table 9: Treatment-Emergent* Decrease of Hemoglobin, Platelets, or Neutrophils
in Patients with WM (N=63)
Percent of Patients (N=63)
All Grades (%)
Grade 3 or 4 (%)
Platelets Decreased
43
13
Neutrophils Decreased
44
19
Hemoglobin Decreased
13
8
* Based on laboratory measurements.
Additional Important Adverse Reactions: Diarrhea: Diarrhea of any grade occurred at a rate of 47% (range,
37% to 63%) of patients treated with IMBRUVICA. Grade 2 diarrhea occurred in 9% (range, 3% to 15%) and
Grad R2