Denosumab (Prolia)

DENOSUMAB is a fully human, highly specific, monoclonal antibody to receptor activator of nuclear factor kappa-B ligand (RANKL). The antibody is produced in genetically engineered mammalian (Chinese hamster ovary) cells. Denosumab binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts; the cells responsible for bone resorption. Denosumab prevents RANKL from activating on its receptor, RANK, present on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone. Ultimately, denosumab blocks osteoclast activation, thereby resulting in decreased bone resorption (less bone breakdown).

Resources from Manufacturer

Patient Medication Guide
Full Prescribing Information

Indications and Dosing

Denosumab is indicated for:

  • 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.
  • 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.
  • Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for non-metastatic prostate cancer.
  • Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

Dosing:

  • Denosumab should be administered by a healthcare professional.
  • Administer 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh or abdomen.
  • All patients should receive calcium 1000 mg and at least 400 IU vitamin D daily.

Contraindications

  • Hypocalcemia
  • Pregnancy
  • Known hypersensitivity to denosumab

Warning and Precautions

  1. Same Active Ingredient: Patients receiving Prolia® should not receive XGEVA®
  2. Hypersensitivity including anaphylactic reactions may occur. Discontinue permanently if a clinically significant reaction occurs.
  3. Hypocalcemia: Must be corrected before initiating denosumab. Hypocalcemia may worsen, especially in patients with renal impairment. Adequately supplement patients with calcium and vitamin D.
  4. Serious infections including skin infections may occur, including severe infections requiring hospitalization. Advise patients to seek prompt medical attention, if they develop signs or symptoms of infection, including cellulitis.
  5. Dermatitis, eczema and rashes may occur.
  6. Pregnancy
  7. Osteonecrosis of the jaw (ONJ) has been reported with denosumab – monitor for symptoms.
  8. Atypical femoral fractures have been reported. Evaluate patients with thigh or groin pain for femoral fracture.
  9. Severe bone, joint, muscle pain may occur. Discontinue use if severe symptoms develop.
  10. Suppression of bone turnover: Significant suppression has been demonstrated. Monitor for consequences of bone oversuppression.

These risks should be discussed with patients. A non-promotional Patient Counseling Toolkit is available through 1-800-77-AMGEN (1-800-772-6436).

Adverse Reactions

  • Postmenopausal osteoporosis: Most common adverse reactions (>5%) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain and cystitis. Pancreatitis has been reported in clinical trials.
  • Male osteoporosis: Most common adverse reactions (>5%) were: back pain, arthralgia and nasopharyngitis.
  • Bone loss due to hormone ablation for cancer: Most common adverse reactions (>10%) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials.

Pre-Administration Checklist

  1. Calcium levels should be assessed prior to administration of denosumab. Hypocalcemia must be corrected prior to initiating therapy with denosumab.
  2. Patient cannot have any signs and symptoms of infection. Ensure patient is not on an antibiotic.
  3. May want repeat calcium level after injection in high risk populations.

Medication Administration and Monitoring

  1. Denosumab should be administered by a healthcare professional.
  2. Prior to administration, denosumab may be allowed to reach room temperature in the original carton. This generally takes 15 to 30 minutes. Do not warm by any other method. Once removed from the refrigerator, denosumab must be maintained at room temperature (up to 77°F [25°C]) in the original carton and must be used within 14 days.
  3. Visually inspect denosumab for particulate matter and discoloration prior to administration whenever solution and container permit. Denosumab is a clear, colorless to pale yellow solution that may contain trace amounts of translucent to white protein particles. Do not use if the solution is discolored or cloudy or if the solution contains many particles or foreign particulate matter.
  4. Latex Allergy: People sensitive to latex should not handle the grey needle cap on the single-use prefilled syringe, which contains dry natural rubber (a derivative of latex).

Instructions for Prefilled Syringe with Needle Safety Guard

  1. In order to minimize accidental needle sticks, the denosumab (Prolia®) single-use prefilled syringe has a green safety guard that may be activated after the injection is administered.
  2. Do not slide the safety guard forward over the needle before administering the injection – it will lock in place and prevent injection.

Instructions for Single-use Vial

  1. For administration of Prolia from the single-use vial, use a 27-gauge needle to withdraw and inject the 1 mL dose. Do not re-enter the vial. Discard vial and any liquid remaining in the vial.
  2. Administer 60mg every 6 months as a subcutaneous injection in the upper arm, upper thigh or abdomen.
  3. Instruct patients to take calcium 1000mg daily and at least 400 IU vitamin D daily.
  4. Recommend monitoring of serum creatinine, serum calcium, phosphorus and magnesium, signs and symptoms of hypocalcemia, especially in patients predisposed to hypocalcemia (severe renal impairment, thyroid/parathyroid surgery, malabsorption syndromes, hypoparathyroidism); infection, or dermatologic reactions; routine oral exam (prior to treatment); dental exam if risk factors for ONJ; monitor for sings/symptoms of hypersensitivity

Updated: January 2017 - ARHP Practice Committee

DISCLAIMER:The information contained in this biologic reference guide is offered solely for purposes of providing health care professionals with a quick and initial reference. Before prescribing or administering any drug contained in this biologic reference guide, health professionals should read the manufacturer’s complete prescribing information in order to be informed of the various clinical considerations to be taken into account. The American College of Rheumatology is providing this information as a benefit and service in furtherance of its educational mission. By providing this information, ACR is not endorsing or recommending any of the listed companies or any of their drugs or other products. The information contained in the biologic reference guides reflect the conclusions of the individual companies and not those of the ACR which specifically disclaims any responsibility or liability for the use of such information and/or for the performance of any of the drugs listed in this biologic reference guide.