The following clinically significant adverse reactions are described elsewhere in the labeling: QT/QTc Interval Prolongation [see Warnings and Precautions ( 5.1 )] . The most common adverse reactions (≥ 10%) and laboratory abnormalities (≥ 15%) were hot flush, glucose increased, triglycerides increased, musculoskeletal pain, hemoglobin decreased, alanine aminotransferase (ALT) increased, fatigue, aspartate aminotransferase (AST) increased, constipation, and diarrhea ( 6.1 ).
To report SUSPECTED ADVERSE REACTIONS, contact Sumitomo Pharma America, at 1-833-696-8268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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. The safety of ORGOVYX was evaluated in HERO, a randomized (2:1), open-label, clinical study in patients with advanced prostate cancer [see Clinical Studies ( 14 )] .
Patients received orally administered ORGOVYX as a loading dose of 360 mg on the first day followed by 120 mg taken orally once daily (n = 622) or received leuprolide acetate administered by depot injection at doses of 22.5 mg (n = 264) or 11.25 mg (n = 44) per local guidelines every 12 weeks (n = 308). Leuprolide acetate 11.25 mg is a dosing regimen that is not recommended for this indication in the US. Among patients who received ORGOVYX, 91% were exposed for at least 48 weeks.
Ninety-nine (16%) patients received concomitant radiotherapy and 17 (3%) patients received concomitant enzalutamide with ORGOVYX. Serious adverse reactions occurred in 12% of patients receiving ORGOVYX. Serious adverse reactions in ≥ 0.5% of patients included myocardial infarction (0.8%), acute kidney injury (0.6%), arrhythmia (0.6%), hemorrhage (0.6%), and urinary tract infection (0.5%). Fatal adverse reactions occurred in 0.8% of patients receiving ORGOVYX including metastatic lung cancer (0.3%), myocardial infarction (0.3%), and acute kidney injury (0.2%).
Fatal and non-fatal myocardial infarction and stroke were reported in 2.7% of patients receiving ORGOVYX. Permanent discontinuation of ORGOVYX due to an adverse reaction occurred in 3.5% of patients. Adverse reactions which resulted in permanent discontinuation of ORGOVYX in ≥ 0.3 % of patients included atrioventricular block (0.3%), cardiac failure (0.3%), hemorrhage (0.3%), increased transaminases (0.3%), abdominal pain (0.3%), and pneumonia (0.3%).
Dosage interruptions of ORGOVYX due to an adverse reaction occurred in 2.7% of patients. Adverse reactions which required dosage interruption in ≥ 0.3% of patients included fracture (0.3%). The most common adverse reactions (≥ 10%) and laboratory abnormalities (≥ 15%) were hot flush (54%), glucose increased (44%), triglycerides increased (35%), musculoskeletal pain (30%), hemoglobin decreased (28%), alanine aminotransferase increased (ALT) (27%), fatigue (26%), aspartate aminotransferase increased (AST) (18%), constipation (12%), and diarrhea (12%).
Table 1 summarizes the adverse reactions in HERO. Table 1: Adverse Reactions ( ≥ 10%) of Patients with Advanced Prostate Cancer Who Received ORGOVYX in HERO a Includes arthralgia, back pain, pain in extremity, musculoskeletal pain, myalgia, bone pain, neck pain, arthritis, musculoskeletal stiffness, non-cardiac chest pain, musculoskeletal chest pain, spinal pain, and musculoskeletal discomfort. b Includes fatigue and asthenia. c Includes diarrhea and colitis.
Adverse Reaction ORGOVYX N = 622 Leuprolide Acetate N = 308 All Grades (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%) Vascular disorders Hot flush 54 0.6 52 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain a 30 1.1 29
1.6General
Fatigue b 26 0.3 24 0 Gastrointestinal disorders Diarrhea c 12 0.2 7 0 Constipation 12 0 10 0 Clinically relevant adverse reactions in < 10% of patients who received ORGOVYX included increased weight, insomnia, gynecomastia, hyperhidrosis, depression, decreased libido, and angioedema. Table 2 summarizes the laboratory abnormalities in HERO. Table 2: Select Laboratory Abnormalities ( ≥ 15%) That Worsened from Baseline in Patients with Advanced Prostate Cancer Who Received ORGOVYX in HERO Laboratory Test ORGOVYX a Leuprolide Acetate a All Grades (%) Grade 3-4 (%) All Grades (%) Grade 3-4 (%) a The denominator used to calculate the rate varied from 611 to 619 in the ORGOVYX arm and from 301 to 306 in the leuprolide arm based on the number of patients with a baseline value and at least one post-treatment value.
Chemistry Glucose increased 44 2.9 54 6 Triglycerides increased 35 2 36
