Adverse Reactions Most Frequently (>2%) Resulting in Clinical Intervention (SC or IV Route):

Discontinuation: leukopenia, thrombocytopenia, neutropenia.

Dose Held: leukopenia, neutropenia, thrombocytopenia, pyrexia, pneumonia, febrile neutropenia.

Dose Reduced: leukopenia, neutropenia, thrombocytopenia.

6.2 Adverse Reactions in Clinical Trials
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to VIDAZA in 443 MDS patients from 4 clinical studies. Study 1 was a supportive-care controlled trial (SC administration), Studies 2 and 3 were single arm studies (one with SC administration and one with IV administration), and Study 4 was an international randomized trial (SC administration) [see Clinical Studies (14)].

In Studies 1, 2 and 3, a total of 268 patients were exposed to VIDAZA, 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 100mg/m2.

In Study 4, a total of 175 patients with higher-risk MDS (primarily RAEB and RAEB-T subtypes) were exposed to VIDAZA. Of these patients, 119 were exposed for 6 or more cycles, and 63 for at least 12 cycles. The mean age of this population was 68.1 years (ranging from 42 to 83 years), 74% were male, and 99% were white. Most patients received daily VIDAZA doses of 75mg/m2.

Table 1 presents adverse reactions occurring in at least 5% of patients treated with VIDAZA (SC) in Studies 1 and 2. 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.

Table1: Most Frequently Observed Adverse Reactions (≥ 5.0% in All SC VIDAZA Treated Patients; Studies 1 and 2)  Number (%) of Patients
System Organ Class
Preferred Terma All VIDAZAb
(N=220) Observationc
(N=92)
a Multiple terms of the same preferred terms for a patient are only counted once within each treatment group.
 
b Includes adverse reactions from all patients exposed to VIDAZA, including patients after crossing over from observations.
 
c Includes adverse reactions from observation period only; excludes any adverse events after crossover to VIDAZA.
 
Blood and lymphatic system disorders  
Anemia 153 (69.5) 59 (64.1)
Anemia aggravated 12 (5.5) 5 (5.4)
Febrile neutropenia 36 (16.4) 4 (4.3)
Leukopenia 106 (48.2) 27 (29.3)
Neutropenia 71 (32.3) 10 (10.9)
Thrombocytopenia 144 (65.5) 42 (45.7)
Gastr