e
As bioequivalence has been established only when TEMODAR for Injection was given over 90 minutes, infusion over a shorter or longer period of time may result in suboptimal dosing. Additionally, the possibility of an increase in infusion-related adverse reactions cannot be ruled out.
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
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.
Newly Diagnosed Glioblastoma Multiforme:
During the concomitant phase (TEMODAR+radiotherapy), adverse reactions including thrombocytopenia, nausea, vomiting, anorexia, and constipation were more frequent in the TEMODAR+RT arm. The incidence of other adverse reactions was comparable in the two arms. The most common adverse reactions across the cumulative TEMODAR experience were alopecia, nausea, vomiting, anorexia, headache, and constipation (see Table 7). Forty-nine percent (49%) of patients treated with TEMODAR reported one or more severe or life-threatening reactions, most commonly fatigue (13%), convulsions (6%), headache (5%), and thrombocytopenia (5%). Overall, the pattern of reactions during the maintenance phase was consistent with the known safety profile of TEMODAR.
TABLE 7: Number (%) of Patients with Adverse Reactions: All and Severe/Life Threatening (Incidence of 5% or Greater) Concomitant Phase
RT Alone
(n=285) Concomitant Phase
RT+TMZ
(n=288)* Maintenance Phase
TMZ
(n=224)
All Grade ≥3 All Grade ≥3 All Grade ≥3
RT+TMZ=radiotherapy plus temozolomide; NOS=not otherwise specified.
Note: Grade 5 (fatal) adverse reactions are included in the Grade ≥3 column.
*
One patient who was randomized to RT only arm received RT+temozolomide.
Subjects Reporting any Adverse Reaction 258 (91) 74 (26) 266 (92) 80 (28) 206 (92) 82 (37)
Body as a Whole - General Disorders
Anorexia 25 (9) 1 (<1) 56 (19) 2 (1) 61 (27) 3 (1)
Dizziness 10 (4) 0 12 (4) 2 (1) 12 (5) 0
Fatigue 139 (49) 15 (5) 156 (54) 19 (7) 137 (61) 20 (9)
Headache 49 (17) 11 (4) 56 (19) 5 (2) 51 (23) 9 (4)
Weakness 9 (3) 3 (1) 10 (3) 5 (2) 16 (7) 4 (2)
Central and Peripheral Nervous System Disorders
Confusion 12 (4) 6 (2) 11 (4) 4 (1) 12 (5) 4 (2)
Convulsions 20 (7) 9 (3) 17 (6) 10 (3) 25 (11) 7 (3)
Memory Impairment 12 (4) 1 (<1) 8 (3) 1 (<1) 16 (7) 2 (1)
Disorders of the Eye
Vision Blurred 25 (9) 4 (1) 26 (9) 2 (1) 17 (8) 0
Disorders of the Immune System
Allergic Reaction 7 (2) 1 (<1) 13 (5) 0 6 (3 |