A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Vidaza Side Effects, and Drug Interactions - Azacitidine
Vidaza Side Effects, and Drug Interactions - Azacitidine
SIDE EFFECTS
Overview
Adverse Reactions Described in Other Labeling Sections:
neutropenia, thrombocytopenia, elevated serum creatinine, renal failure,
renal tubular acidosis, hypokalemia, hepatic coma.
Most Commonly Occurring Adverse Reactions (SC Route): nausea,
anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, fatigue,
injection site erythema, constipation, neutropenia, ecchymosis.
Adverse Reactions Most Frequently (>2%) Resulting in Clinical
Intervention (SC Route):
Discontinuation: leukopenia (5.0%), thrombocytopenia
(3.6%), neutropenia (2.7%). Dose Held: leukopenia (4.5%), neutropenia (4.5%),
febrile neutropenia (2.7%). Dose Reduced: leukopenia (4.5%), neutropenia
(4.1%), thrombocytopenia (3.2%).
Discussion of Adverse Reactions Information
The data described below reflect exposure to Vidaza in 268
patients, including 116 exposed for 6 cycles (approximately 6 months)
or more and 60 exposed for greater than 12 cycles (approximately one year).
Vidaza was studied primarily in supportive care-controlled and uncontrolled
trials (n= 150 and n=118, respectively). The population in the subcutaneous
studies (n = 220) was 23 to 92 years old (mean 66.4 years), 68% male,
and 94% white, and had MDS or AML. The population in the IV study (n = 48) was
35 to 81 years old (mean 63.1 years), 65% male, and 100% white. Most patients
received average daily doses between 50 and 100 mg/m2.
The following table presents the most common adverse events,
whether or not considered drug related by investigators, occurring in at least
5% of patients treated with Vidaza in the supportive care-controlled trial and
the uncontrolled subcutaneous trial combined. It is important to note that duration
of exposure was longer for the Vidaza-treated group than for the observation
group: patients received Vidaza for a mean of 11.4 months while mean time in
the observation arm was 6.1 months.
|
Table 4: Most Frequently Observed Adverse Events ( ³
5% in All Vidaza)*
|
|
|
All Vidaza‡
|
Observation†
|
|
Preferred Term**
|
(N=220)
|
(N=92)
|
|
At least 1 TEAE
|
219 (99.5)
|
89 (96.7)
|
|
Nausea
|
155 (70.5)
|
16 (17.4)
|
|
Anemia
|
153 (69.5)
|
59 (64.1)
|
|
Thrombocytopenia
|
144 (65.5)
|
42 (45.7)
|
|
Vomiting
|
119 (54.1)
|
5 (5.4)
|
|
Pyrexia
|
114 (51.8)
|
28 (30.4)
|
|
Leukopenia
|
106 (48.2)
|
27 (29.3)
|
|
Diarrhea
|
80 (36.4)
|
13 (14.1)
|
|
Fatigue
|
79 (35.9)
|
23 (25.0)
|
|
Injection site erythema
|
77 (35.0)
|
0
|
|
Constipation
|
74 (33.6)
|
6 (6.5)
|
|
Neutropenia
|
71 (32.3)
|
10 (10.9)
|
|
Ecchymosis
|
67 (30.5)
|
14 (15.2)
|
|
Cough
|
65 (29.5)
|
14 (15.2)
|
|
Dyspnea
|
64 (29.1)
|
11 (12.0)
|
|
Weakness
|
64 (29.1)
|
19 (20.7)
|
|
Rigors
|
56 (25.5)
|
10 (10.9)
|
|
Petechiae
|
52 (23.6)
|
8 (8.7)
|
|
Injection site pain
|
50 (22.7)
|
0
|
|
Arthralgia
|
49 (22.3)
|
3 (3.3)
|
|
Headache
|
48 (21.8)
|
10 (10.9)
|
|
Anorexia
|
45 (20.5)
|
6 (6.5)
|
|
Pain in limb
|
44 (20.0)
|
5 (5.4)
|
|
Pharyngitis
|
44 (20.0)
|
7 (7.6)
|
|
Back pain
|
41 (18.6)
|
7 (7.6)
|
|
Contusion
|
41 (18.6)
|
9 (9.8)
|
|
Dizziness
|
41 (18.6)
|
5 (5.4)
|
|
Edema peripheral
|
41 (18.6)
|
10 (10.9)
|
|
Erythema
|
37 (16.8)
|
4 (4.3)
|
|
Chest pain
|
36 (16.4)
|
5 (5.4)
|
|
Epistaxis
|
36 (16.4)
|
9 (9.8)
|
|
Febrile neutropenia
|
36 (16.4)
|
4 (4.3)
|
|
Myalgia
|
35 (15.9)
|
2 (2.2)
|
|
Weight decreased
|
35 (15.9)
|
10 (10.9)
|
|
Abdominal pain
|
34 (15.5)
|
12 (13.0)
|
|
Pallor
|
34 (15.5)
|
7 (7.6)
|
|
Nasopharyngitis
|
32 (14.5)
|
3 (3.3)
|
|
Pitting edema
|
32 (14.5)
|
9 (9.8)
|
|
Skin lesion
|
32 (14.5)
|
8 (8.7)
|
|
Dyspnea exertional
|
31 (14.1)
|
15 (16.3)
|
|
Injection site bruising
|
31 (14.1)
|
0
|
|
Rash
|
31 (14.1)
|
9 (9.8)
|
|
Injection site reaction
|
30 (13.6)
|
0
|
|
Anxiety
|
29 (13.2)
|
3 (3.3)
|
|
Appetite decreased
|
28 (12.7)
|
8 (8.7)
|
|
Fatigue aggravated
|
28 (12.7)
|
4 (4.3)
|
|
Hypokalemia
|
28 (12.7)
|
12 (13.0)
|
|
Upper respiratory tract infection
|
28 (12.7)
|
4 (4.3)
|
|
Pruritus
|
27 (12.3)
|
11 (12.0)
|
|
Abdominal tenderness
|
26 (11.8)
|
1 (1.1)
|
|
Depression
|
26 (11.8)
|
7 (7.6)
|
|
Productive cough
|
25 (11.4)
|
4 (4.3)
|
|
Insomnia
|
24 (10.9)
|
4 (4.3)
|
|
Malaise
|
24 (10.9)
|
1 (1.1)
|
|
Pain
|
24 (10.9)
|
3 (3.3)
|
|
Pneumonia
|
24 (10.9)
|
5 (5.4)
|
|
Abdominal pain upper
|
23 (10.5)
|
3 (3.3)
|
|
Crackles lung
|
23 (10.5)
|
8 (8.7)
|
|
Sweating increased
|
23 (10.5)
|
2 (2.2)
|
|
Cardiac murmur
|
22 (10.0)
|
8 (8.7)
|
|
Rhinorrhea
|
22 (10.0)
|
2 (2.2)
|
|
Gingival bleeding
|
21 (9.5)
|
4 (4.3)
|
|
Lymphadenopathy
|
21 (9.5)
|
3 (3.3)
|
|
Herpes simplex
|
20 (9.1)
|
5 (5.4)
|
|
Hematoma
|
19 (8.6)
|
0
|
|
Night sweats
|
19 (8.6)
|
3 (3.3)
|
|
Rales
|
19 (8.6)
|
8 (8.7)
|
|
Tachycardia
|
19 (8.6)
|
6 (6.5)
|
|
Wheezing
|
19 (8.6)
|
2 (2.2)
|
|
Cellulitis
|
18 (8.2)
|
4 (4.3)
|
|
Dysuria
|
18 (8.2)
|
2 (2.2)
|
|
Breath sounds decreased
|
17 (7.7)
|
1 (1.1)
|
|
Lethargy
|
17 (7.7)
|
2 (2.2)
|
|
Oral mucosal petechiae
|
17 (7.7)
|
3 (3.3)
|
|
Stomatitis
|
17 (7.7)
|
0
|
|
Urinary tract infection
|
17 (7.7)
|
5 (5.4)
|
|
Peripheral swelling
|
16 (7.3)
|
5 (5.4)
|
|
Dyspepsia
|
15 (6.8)
|
4 (4.3)
|
|
Hemorrhoids
|
15 (6.8)
|
1 (1.1)
|
|
Hypotension
|
15 (6.8)
|
2 (2.2)
|
|
Injection site pruritus
|
15 (6.8)
|
0
|
|
Transfusion reaction
|
15 (6.8)
|
0
|
|
Pleural effusion
|
14 (6.4)
|
6 (6.5)
|
|
Abdominal distension
|
13 (5.9)
|
4 (4.3)
|
|
Muscle cramps
|
13 (5.9)
|
3 (3.3)
|
|
Post procedural hemorrhage
|
13 (5.9)
|
1 (1.1)
|
|
Postnasal drip
|
13 (5.9)
|
3 (3.3)
|
|
Rhonchi
|
13 (5.9)
|
2 (2.2)
|
|
Syncope
|
13 (5.9)
|
5 (5.4)
|
|
Urticaria
|
13 (5.9)
|
1 (1.1)
|
|
Anemia aggravated
|
12 (5.5)
|
5 (5.4)
|
|
Loose stools
|
12 (5.5)
|
0
|
|
Nasal congestion
|
12 (5.5)
|
1 (1.1)
|
|
Atelectasis
|
11 (5.0)
|
2 (2.2)
|
|
Chest wall pain
|
11 (5.0)
|
0
|
|
Dry skin
|
11 (5.0)
|
1 (1.1)
|
|
Dysphagia
|
11 (5.0)
|
2 (2.2)
|
|
Dyspnea exacerbated
|
11 (5.0)
|
3 (3.3)
|
|
Hypoesthesia
|
11 (5.0)
|
1 (1.1)
|
|
Injection site granuloma
|
11 (5.0)
|
0
|
|
Injection site pigmentation changes
|
11 (5.0)
|
0
|
|
Injection site swelling
|
11 (5.0)
|
0
|
|
Mouth hemorrhage
|
11 (5.0)
|
1 (1.1)
|
|
Post procedural pain
|
11 (5.0)
|
2 (2.2)
|
|
Sinusitis
|
11 (5.0)
|
3 (3.3)
|
|
Skin nodule
|
11 (5.0)
|
1 (1.1)
|
|
Tongue ulceration
|
11 (5.0)
|
2 (2.2)
|
|
* Mean Vidaza exposure = 11.4 months. Mean
time in observation arm = 6.1 months.
|
|
** Multiple reports of the same preferred
terms for a patient are only counted once within each treatment group.
|
|
† Includes events from observation period only; excludes
any events after crossover to Vidaza.
|
|
‡ Includes events from all patients exposed to Vidaza,
including patients after crossing over from observation.
|
Nausea, vomiting, diarrhea, and constipation all tended to
increase in incidence with increasing doses of Vidaza. Nausea, vomiting, injection
site erythema, constipation, rigors, petechiae, injection site pain, dizziness,
injection site bruising, anxiety, hypokalemia, insomnia, epistaxis, and rales
tended to be more pronounced during the first 1-2 cycles of SC Vidaza treatment
compared with later cycles of treatment. There did not appear to be any adverse
events that increased in frequency over the course of treatment. There did not
appear to be any relevant differences in adverse events by gender.
In clinical studies of either SC or IV Vidaza, the following
serious treatment-related adverse events occurring at a rate of <5% (not
described in Table 4) were reported:
Blood and lymphatic system disorders: agranulocytosis,
bone marrow depression, splenomegaly.
Cardiac disorders: atrial fibrillation, cardiac failure,
cardiac failure congestive, cardio-respiratory arrest, congestive cardiomyopathy.
Gastrointestinal disorders: diverticulitis, gastrointestinal
hemorrhage, melena, perirectal abscess.
General disorders and administration site conditions:
catheter site hemorrhage, general physical health deterioration, systemic inflammatory
response syndrome.
Hepatobiliary disorders: cholecystitis.
Immune system disorders: anaphylactic shock, hypersensitivity.
Infections and infestations: abscess limb, bacterial
infection, blastomycosis, injection site infection, Klebsiella sepsis, pharyngitis
streptococcal, pneumonia Klebsiella, sepsis, Staphylococcal bacteremia, Staphylococcal
infection, toxoplasmosis.
Metabolism and nutrition disorders: dehydration.
Musculoskeletal and connective tissue disorders: bone
pain aggravated, muscle weakness, neck pain.
Neoplasms benign, malignant and unspecified: leukemia
cutis.
Nervous system disorders: convulsions, intracranial
hemorrhage.
Psychiatric disorders: confusion.
Renal and urinary disorders: hematuria, loin pain, renal
failure.
Respiratory, thoracic and mediastinal disorders: hemoptysis,
lung infiltration, pneumonitis, respiratory distress.
Skin and subcutaneous tissue disorders: pyoderma gangrenosum,
rash pruritic, skin induration.
Surgical and medical procedures: cholecystectomy.
Vascular disorders: orthostatic hypotension.
DRUG INTERACTIONS
No formal assessments of drug-drug interactions between Vidaza
and other agents have been conducted. (See CLINICAL
PHARMACOLOGY.)
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