rm Prolia
(N = 3886)
n (%) Placebo
(N = 3876)
n (%)
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Anemia 129 (3.3) 107 (2.8)
CARDIAC DISORDERS
Angina pectoris 101 (2.6) 87 (2.2)
Atrial fibrillation 79 (2.0) 77 (2.0)
EAR AND LABYRINTH DISORDERS
Vertigo 195 (5.0) 187 (4.8)
GASTROINTESTINAL DISORDERS
Abdominal pain upper 129 (3.3) 111 (2.9)
Flatulence 84 (2.2) 53 (1.4)
Gastroesophageal reflux disease 80 (2.1) 66 (1.7)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Edema peripheral 189 (4.9) 155 (4.0)
Asthenia 90 (2.3) 73 (1.9)
INFECTIONS AND INFESTATIONS
Cystitis 228 (5.9) 225 (5.8)
Upper respiratory tract infection 190 (4.9) 167 (4.3)
Pneumonia 152 (3.9) 150 (3.9)
Pharyngitis 91 (2.3) 78 (2.0)
Herpes zoster 79 (2.0) 72 (1.9)
METABOLISM AND NUTRITION DISORDERS
Hypercholesterolemia 280 (7.2) 236 (6.1)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Back pain 1347 (34.7) 1340 (34.6)
Pain in extremity 453 (11.7) 430 (11.1)
Musculoskeletal pain 297 (7.6) 291 (7.5)
Bone pain 142 (3.7) 117 (3.0)
Myalgia 114 (2.9) 94 (2.4)
Spinal osteoarthritis 82 (2.1) 64 (1.7)
NERVOUS SYSTEM DISORDERS
Sciatica 178 (4.6) 149 (3.8)
PSYCHIATRIC DISORDERS
Insomnia 126 (3.2) 122 (3.1)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Rash 96 (2.5) 79 (2.0)
Pruritus 87 (2.2) 82 (2.1)
Hypocalcemia
Decreases in serum calcium levels to less than 8.5 mg/dL were reported in 0.4% women in the placebo group and 1.7% women in the Prolia group at the month 1 visit. The nadir in serum calcium level occurs at approximately day 10 after Prolia dosing in subjects with normal renal function.
In clinical studies, subjects with impaired renal function were more likely to have greater reductions in serum calcium levels compared to subjects with normal renal function. In a study of 55 patients with varying degrees of renal function, serum calcium levels < 7.5 mg/dL or symptomatic hypocalcemia were observed in 5 subjects. These included no subjects in the normal renal function group, 10% of subjects in the CrCL 50 to 80 mL/min group, 29% of subjects in the CrCL <30 mL/min group, and 29% of subjects in the hemodialysis group. These subjects did not receive calcium and vitamin D supplementation. In a study of 4,550 postmenopausal women with osteoporosis, the mean change from baseline in serum calcium level 10 days after Prolia dosing was -5.5% in subjects with creatinine clearance < 30 mL/min vs. -3.1% in subjects with CrCL ≥ 30 mL/min.
Serious Infections
Receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed on activated T and B lymphocytes and in lymph nodes. Therefore, a RANKL inhibitor such as Prolia may increase the risk of infection.
In the clinical study of 7808 postmenopausal women with osteoporosis, the incidence of infections resulting in death was 0.2% in both placebo and Prolia treatment groups. However, the incidence of nonfatal serious infections was 3.3% in the placebo group and 4.0% in the Prolia group. Hospitalizations due to serious infections in the abdomen (0.7% placebo vs. 0.9% Prolia), urinary tract (0.5% placebo vs. 0.7% Prolia), and ear (0.0% placebo vs. 0.1% Prolia) were reported. Endocarditis was reported in no placebo patients and 3 patients receiving Prolia.
Skin infections, including erysipelas and cellulitis, leading to hospitalization were reported more frequently in patients treated with Prolia (< 0.1% placebo vs. 0.4% Pro
