Contraindications: Prolia® is contraindicated in patients with hypocalcemia. Pre-existing
hypocalcemia must be corrected prior to initiating Prolia®. Prolia® is contraindicated in women who are pregnant
and may cause fetal harm. Prolia® is contraindicated in patients with a history of systemic hypersensitivity to any component
of the product. Reactions have included anaphylaxis, facial swelling and urticaria.
Same Active Ingredient: Prolia® contains the same active ingredient (denosumab) found in
XGEVA®. Patients receiving Prolia® should not receive XGEVA®.
Hypersensitivity: Clinically significant hypersensitivity including anaphylaxis has been reported with
Prolia®. Symptoms have included hypotension, dyspnea, throat tightness, facial and upper airway edema, pruritis, and urticaria.
If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of
Hypocalcemia: Hypocalcemia may worsen with the use of Prolia®, 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.
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
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.
Atypical Femoral Fractures: Atypical low-energy, or low trauma fractures of the shaft have been reported
in patients receiving Prolia®. Causality has not been established as these fractures also occur in osteoporotic patients who
have not been treated with anti-resorptive agents.
During Prolia® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents
with thigh or groin pain should be evaluated to rule out an incomplete femur fracture. Interruption of Prolia® therapy should be
considered, pending a risk/benefit assessment, on an individual basis.
Serious Infections: In a clinical trial (N = 7808) in women with postmenopausal osteoporosis, serious
infections leading to hospitalization were reported more frequently in the Prolia® 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 patients. The incidence of opportunistic infections and the
overall incidence of infections were 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: In the same clinical trial in women with postmenopausal osteoporosis,
epidermal and dermal adverse events such as dermatitis, eczema and rashes occurred at a significantly higher rate with Prolia®
compared to placebo. Most of these events were not specific to the injection site. Consider discontinuing Prolia® if severe
Musculoskeletal Pain: Severe and occasionally incapacitating bone, joint, and/or muscle pain has been
reported in patients taking Prolia®. Consider discontinuing use if severe symptoms develop.
Suppression of Bone Turnover: In clinical trials in women with postmenopausal osteoporosis,
Prolia® 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) in women with
postmenopausal osteoporosis are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis.
The most common adverse reactions (> 5% and more common than placebo) in men with osteoporosis are back pain, arthralgia, and nasopharyngitis.
Pancreatitis has been reported with Prolia®.
In women with postmenopausal osteoporosis, the overall incidence of new malignancies was 4.3% in the placebo group and 4.8% in the
Prolia® groups. In men with osteoporosis, new malignancies were reported in no patients in the placebo group and 4 (3.3%)
patients in the Prolia® group. 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 surveillance program is
available to collect information from prescribers on specific adverse events. Please see
or call 1-800-772-6436 for more information.