Risk Evaluation and Mitigation Strategy (REMS)
Surveillance Program | Safety Profile
Prolia® (denosumab) is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, Prolia® reduces the incidence of vertebral, nonvertebral, and hip fractures.
Hypocalcemia
Prolia® is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia
must be corrected prior to initiating Prolia®. Hypocalcemia may worsen, especially
in patients with severe renal impairment. In patients predisposed to hypocalcemia
and disturbances of mineral metabolism, clinical monitoring of calcium and mineral
levels is highly recommended. Adequately supplement all patients with calcium and
vitamin D.
Same Active Ingredient
Prolia® contains the same active ingredient (denosumab) found in XGEVA®. Patients receiving Prolia® should not receive XGEVA®.
Serious Infections
In a clinical trial (N = 7808), serious infections leading to hospitalization were reported
more frequently in the Prolia® (denosumab) group than in the placebo group. Serious skin infections,
as well as infections of the abdomen, urinary tract and ear, were more frequent in patients
treated with Prolia®. Endocarditis was also reported more frequently in Prolia®-treated
subjects. The incidence of opportunistic infections was balanced and the overall incidence
of infections was similar between the treatment groups. Advise patients to seek prompt medical
attention if they develop signs or symptoms of severe infection, including cellulitis.
Patients on concomitant immunosuppressant agents or with impaired immune systems may be at increased risk for serious infections. In patients who develop serious infections while on Prolia®, prescribers should assess the need for continued Prolia® therapy.
Dermatologic Adverse Reactions
Epidermal and dermal adverse events such as dermatitis, eczema and rashes occurred at a significantly
higher rate in the Prolia® group compared to the placebo group. Most of these events were not
specific to the injection site. Consider discontinuing Prolia® if severe symptoms develop.
Osteonecrosis of the Jaw (ONJ)
ONJ, which can occur spontaneously, is generally associated with tooth extraction and/or local infection
with delayed healing, and has been reported in patients receiving Prolia®. An oral exam should be
performed by the prescriber prior to initiation of Prolia®. A dental examination with appropriate
preventive dentistry should be considered prior to treatment in patients with risk factors for ONJ.
Good oral hygiene practices should be maintained during treatment with Prolia®.
For patients requiring invasive dental procedures, clinical judgment should guide the management plan of each patient. Patients who are suspected of having or who develop ONJ should receive care by a dentist or an oral surgeon. Extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of Prolia® should be considered based on individual benefit-risk assessment.
Suppression of Bone Turnover
Prolia® (denosumab) resulted in significant suppression of bone remodeling as evidenced by markers of bone
turnover and bone histomorphometry. The significance of these findings and the effect of
long-term treatment are unknown. Monitor patients for consequences, including ONJ, atypical
fractures, and delayed fracture healing.
Adverse Reactions
The most common adverse reactions (> 5% and more common than placebo) are back pain, pain in extremity,
musculoskeletal pain, hypercholesterolemia, and cystitis. Pancreatitis has been reported with Prolia®.
The overall incidence of new malignancies was 4.3% in the placebo and 4.8% in the Prolia® groups. A causal relationship to drug exposure has not been established. Denosumab is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity.
Prolia® Postmarketing Active Safety Surveillance Program
The Prolia® Postmarketing Active Safety Surveillance Program is available to collect information from prescribers
on specific adverse events. Please see www.proliasafety.com
or call 1-800-772-6436 for more information about this program.
Prolia® (denosumab) prescribing information, Amgen.
Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal
women with osteoporosis. N Engl J Med. 2009;361:756-765.
