Prolia® (denosumab) injection

For treatment of postmenopausal women with osteoporosis at high risk for fracture

INTOLERANT TO OTHER THERAPY

Prolia® may be appropriate for your patients at high risk for fracture who are intolerant to other osteoporosis therapy

What are you hearing from your patients with postmenopausal osteoporosis at high risk for fracture who are intolerant to other available osteoporosis therapy?

Hypothetical patient statements after taking oral osteoporosis therapy.

Consider Prolia® for this patient:*

  • Has been taking an oral bisphosphonate for the past 3 months
  • Complains of frequent GI symptoms after taking her osteoporosis therapy

Important Safety Information

Clinically significant hypersensitivity including anaphylaxis has been reported with Prolia®. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of Prolia®.

PRIOR FRACTURE

Prolia® may reduce the risk of fracture for your patients with a prior osteoporotic fracture

Are there osteoporotic postmenopausal women in your practice who have had a prior fracture?

In women, prior osteoporotic fracture increases the relative risk of a subsequent hip fracture by 77%.1*

Images of vertebral and hip fractures.

Only 25% of women who suffered an osteoporotic fracture received treatment during the following year.2†

Consider Prolia® for this patient:

  • Prior osteoporotic fracture
  • Family history of fracture
  • Patient complaints related to the spine
  • *Compared to women without a prior fracture.
  • According to the 2012 HEDIS measures. Data are drawn from Medicare health maintenance organizations.
  • Hypothetical patient.

Important Safety Information

Hypocalcemia may worsen with the use of Prolia®, especially in patients with severe renal impairment. Adequately supplement all patients with calcium and vitamin D.

FAILED OTHER OSTEOPOROSIS THERAPY

Prolia® may be appropriate for your postmenopausal osteoporosis patients at high risk for fracture who have failed other osteoporosis therapy

Do you have patients with postmenopausal osteoporosis at high risk for fracture with a significant decline in BMD despite osteoporosis therapy whom you consider a treatment failure?

Hypothetical patient bone mineral density and T-score (-2.5 at diagnosis, and -2.9 at two years postdiagnosis).

Consider Prolia® for this patient:*

  • Diagnosed with postmenopausal osteoporosis 2 years ago; prescribed osteoporosis therapy
  • At diagnosis, lumbar spine T-score = -2.5
  • Decline in T-score seen 2 years after diagnosis despite osteoporosis therapy
  • Further evaluation did not show underlying causes of bone loss

Important Safety Information

ONJ and atypical femoral fracture have been reported in patients with Prolia®. Patients should be monitored for adverse outcomes.

MULTIPLE RISK FACTORS

Prolia® may be appropriate for your postmenopausal osteoporosis patients with multiple risk factors for fracture who are naive to treatment

Are there postmenopausal osteoporosis patients with multiple risk factors for fracture in your practice?

1 in 2 women over the age of 50 will have a fracture related to osteoporosis in their lifetime.3

Risk factors for fracture:4

  • Age
  • BMD
  • Prior fracture as an adult
  • Falling
  • Excessive thinness
  • Parental history of hip fracture
  • Low calcium intake
  • Cigarette smoking
  • Vitamin D insufficiency
  • Inadequate physical activity
  • Immobilization

Consider Prolia® for this patient:*

  • 65-year old woman naive to osteoporosis therapy
  • T-score: -2.5
  • Very low body weight
  • Smoker

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.

Indications

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.

References

1. Kanis JA, Johnell O, De Laet C, et al. A meta-analysis of previous fracture and subsequent fracture risk. Bone. 2004;35(2):375-382. 2. National Committee for Quality Assurance. Improving Quality and Patient Experience: The State of Health Care Quality 2013. Washington DC: National Committee for Quality Assurance; October 2013. 3. US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: Department of Health and Human Services, Office of the Surgeon General; 2004. 4. National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013.