For the treatment of postmenopausal women with osteoporosis at high risk for fracture
Prescribe Prolia® to Significantly Reduce Fracture Risk at Vertebral, Hip, and Nonvertebral Sites at 3 Years1,2
Prolia® was studied for 3 years in a pivotal phase 3 fracture trial of 7808 women with postmenopausal osteoporosis aged 60-91 years, with an average age of 72.1,2
- *Includes 7393 patients with a baseline and at least one post-baseline radiograph.1,2
- †Composite measurement excluding pathological fractures and those associated with severe trauma, fractures of the vertebrae, skull, face, mandible, metacarpals, fingers, and toes.1,2
- ‡Relative risk reduction.
- §Absolute risk reduction.
Pivotal Phase 3 Study Design: Multicenter, international, randomized, double-blind, placebo-controlled clinical trial. Patients were postmenopausal women between 60 and 91 years of age with a BMD T-score between -2.5 and -4.0 at the lumbar spine or total hip. 7808 patients were randomized to receive Prolia® 60 mg (n=3902) or placebo (n=3906) subcutaneously (SC) every 6 months (Q6M). All patients were supplemented with calcium and vitamin D. The primary endpoint was incidence of new vertebral fractures at 3 years, and secondary endpoints were time to first nonvertebral and hip fracture.1,2
Prolia® reduced the incidence of new vertebral fracture in patients with or without a baseline vertebral fracture.2
- In the pivotal phase 3 fracture trial, 1 in 4 patients had a baseline vertebral fracture.2
- In a pre-specified analysis of these patients, Prolia® (n = 883) reduced the relative risk of a new vertebral fracture by 66% vs placebo (n = 853).3§
No overall differences in the efficacy and safety of Prolia® were observed between younger patients and patients aged 75 or older.1
- Of the total number of patients in clinical studies of Prolia®, 9943 (76%) were ≥ 65 years old, and 3576 (27%) were ≥ 75 years old.1
Prolia® (denosumab) is contraindicated in patients with hypocalcemia, women who are pregnant, and patients with a history of systemic hypersensitivity to any component of the product.
§ARR = 9%; p=<0.0001.4
Prolia® Reduced the Incidence of Vertebral Fracture at Year 1, Year 2, and Year 31,2
- *Patients with a baseline and at least one post-baseline radiograph.1,2
- †Absolute Risk Reduction.
Prolia® significantly increased BMD vs placebo at lumbar spine (8.8%), total hip (6.4%), and femoral neck (5.2%), at 3 years.1
Prolia® increased bone mass and strength in both cortical and trabecular bone.1
Prolia® patient bone biopsies showed normal bone architecture and quality.1‡
‡53 bone biopsy specimens taken from transiliac crest.1
Important Safety Information
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, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of Prolia®.
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 within 14 days of Prolia® injection. 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 is recommended prior to treatment in patients with risk factors for ONJ such as invasive dental procedures, diagnosis of cancer, concomitant therapies (e.g. chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid disorders. Good oral hygiene practices should be maintained during treatment with Prolia®. The risk of ONJ may increase with duration of exposure to 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.
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 symptoms develop.
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® group. 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 www.proliasafety.com or call 1-800-772-6436 for more information.
Prolia® 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.
Prolia® is indicated for treatment to increase bone mass in men 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.
1. Prolia® (denosumab) prescribing information, Amgen. 2. 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. 3. McClung MR, Boonen S, Törring O, et al. Effect of denosumab treatment on risk of fractures in subgroups of women with postmenopausal osteoporosis [published online ahead of print December 22, 2011]. J Bone Miner Res. 2012;27:211-18. doi:10.1002/jbmr.536. 4. Data on file, Amgen. 2008.