ination with prednisone 5 mg twice daily in the active treatment arm (N = 791). Placebo plus prednisone 5 mg twice daily was given to control patients (N = 394). The median duration of treatment with ZYTIGA was 8 months.
The most common adverse drug reactions (≥5%) reported in clinical studies were joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia, fractures and upper respiratory tract infection.
The most common adverse drug reactions that resulted in drug discontinuation were aspartate aminotransferase increased, alanine aminotransferase increased, urosepsis and cardiac failure (each in <1% of patients taking ZYTIGA).
Adverse reactions and laboratory abnormalities related to mineralocorticoid effects were reported more commonly in patients treated with ZYTIGA than in patients treated with placebo: hypokalemia 28% versus 20%, hypertension 9% versus 7% and fluid retention (edema) 27% versus 18%, respectively (see Table 1). In patients treated with ZYTIGA, grades 3 to 4 hypokalemia occurred in 5% of patients and grades 3 to 4 hypertension was reported in 1% of patients [see Warnings and Precautions (5.1)].
Table 1 shows adverse reactions due to ZYTIGA that occurred with either a ≥ 2% absolute increase in frequency compared to placebo, or were events of special interest (mineralocorticoid excess, cardiac adverse reactions, and liver toxicities).
Table 1: Adverse Reactions due to ZYTIGA in a Placebo-Controlled Phase 3 Trial ZYTIGA with Prednisone (N=791) Placebo with Prednisone (N=394)
System/Organ Class
Adverse reaction All Grades*
% Grade 3–4
% All Grades
% Grade 3–4
%
*
Adverse events graded according to CTCAE version 3.0
†
Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness
‡
Includes terms Muscle spasms, Musculoskeletal pain, Myalgia, Musculoskeletal discomfort, and Musculoskeletal stiffness
§
Includes terms Edema, Edema peripheral, Pitting edema, and Generalized edema
¶
Includes all fractures with the exception of pathological fracture
#
Includes terms Arrhythmia, Tachycardia, Atrial fibrillation, Supraventricular tachycardia, Atrial tachycardia, Ventricular tachycardia, Atrial flutter, Bradycardia, Atrioventricular block complete, Conduction disorder, and Bradyarrhythmia
Þ
Includes terms Angina pectoris, Chest pain, and Angina unstable. Myocardial infarction or ischemia occurred more commonly in the placebo arm than in the ZYTIGA arm (1.3% vs. 1.1% respectively).
ß
Includes terms Cardiac failure, Cardiac failure congestive, Left ventricular dysfunction, Cardiogenic shock, Cardiomegaly, Cardiomyopathy, and Ejection fraction decreased
Musculoskeletal and connective tissue disorders
Joint swelling/ discomfort† 29.5 4.2 23.4 4.1
Muscle discomfort‡ 26.2 3.0 23.1 2.3
General disorders
Edema§ 26.7 1.9 18.3 0.8
Vascular disorders
Hot flush 19.0 0.3 16.8 0.3
Hypertension 8.5 1.3 6.9 0.3
Gastrointestinal disorders
Diarrhea 17.6 0.6 13.5 1.3
Dyspepsia 6.1 0 3.3 0
Infections and in |
