denosumab

Treatment of osteoporosis in postmenopausal women who are at high risk for fracture or those who have failed/are intolerant of conventional osteoporosis therapy.
To increase bone mass in men with osteoporosis who are at high risk for fracture or those who have failed/are intolerant of conventional osteoporosis therapy.
Treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture who are initiating or continuing systemic glucocorticoids at a daily dosage of ≥7.5 mg of prednisone and are expected to remain on glucocorticoids for ≥6 mo.
To increase bone mass in men receiving androgen deprivation therapy for nonmetastatic prostate cancer who are at high risk for fracture.
To increase bone mass in women receiving adjuvant aromatase inhibitor therapy for breast cancer who are at high risk for fracture.

Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.
Giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

REMS

Prolia

Xgeva

Hypercalcemia of malignancy that is refractory to bisphosphonate therapy.

Action ⬆ ⬇

A monoclonal antibody that binds specifically to the human receptor activator of nuclear factor kappa-B-ligand (RANKL), which is required for formation, function, and survival of osteoclasts. Binding inhibits osteoclast formation, function, and survival.

Therapeutic effects:

↓bone resorption with ↓ occurrence of fractures (vertebral, nonvertebral, hip) or other skeletal-related events (e.g., radiation therapy to bone, surgery to bone, spinal cord compression).
↑bone mass.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following SUBQ administration.

Distribution: Unknown.

Metabolism/Excretion: Unknown.

Half-Life: 25.4 days.

Time/Action Profile ⬆ ⬇

(effects on bone resorption)

ROUTE	ONSET	PEAK	DURATION
SUBQ	1 mo	unknown‡	12 mo‡

‡Maximum ↓ in serum calcium occurs at 10 days.

‡Following discontinuation.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Hypocalcemia (correct before administration); adequate supplemental calcium and vitamin D required;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Conditions associated with hypocalcemia including hypoparathyroidism, previous thyroid/parathyroid surgery, malabsorption syndromes, history of small intestinal excision, inadequate/no calcium supplementation, renal impairment/hemodialysis (CCr <30 mL/min and/or on dialysis); monitoring of calcium levels and calcium and vitamin D intake recommended;
Invasive dental procedures, cancer, receiving chemotherapy, corticosteroids, or angiogenesis inhibitors, poor oral hygiene, diabetes, gingival infections, periodontal disease, dental disease, anemia, coagulopathy, infection, or poorly-fitting dentures (may ↑ risk of jaw osteonecrosis);
History of osteoporosis or prior fractures (↑ risk of multiple vertebral fractures upon drug discontinuation);
Concurrent use of immunosuppressants or diseases resulting in immunosuppression (↑ risk of infection);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may be more sensitive to drug effects.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: dermatitis, eczema, rashes

F and E: hypocalcemia, hypophosphatemia, hypercalcemia

GI: diarrhea, nausea, PANCREATITIS

GU: cystitis

Metab: hypercholesterolemia

MS: back pain, extremity pain, musculoskeletal pain, atypical femoral fracture, osteonecrosis of the jaw, suppression of bone turnover

Neuro: headache

Resp: dyspnea, cough

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), infection

Interactions ⬆ ⬇

Drug-drug:

Concurrent use of immunosuppressants↑ risk of infection.
Concurrent use of calcimimetic drugs may ↑ risk of hypocalcemia.

Route/Dosage ⬆ ⬇

Prolia

SC (Adults ): 60 mg every 6 mo.

Xgeva

SC (Adults ): Multiple myeloma or bone metastasis from solid tumors: 120 mg every 4 wk; Giant cell tumor of bone: 120 mg every 4 wk, with additional doses of 120 mg given on Days 8 and 15 of first mo of therapy; Hypercalcemia of malignancy: 120 mg every 4 wk, with additional doses of 120 mg given on Days 8 and 15 of first mo of therapy.

Availability ⬆ ⬇

Solution for injection (Prolia) (prefilled syringe): 60 mg/mL
Solution for injection (Xgeva): 120 mg/1.7 mL

Assessment ⬆ ⬇

Assess patients via bone density study for low bone mass before and periodically during therapy.
Perform a routine oral exam prior to initiation of therapy. Dental exam with appropriate preventative dentistry should be considered prior to therapy. Patients with history of tooth extraction, poor oral hygiene, gingival infections, diabetes, or use of a dental appliance or those taking immunosuppressive therapy, angiogenesis inhibitors, or systemic corticosteroids are at greater risk for osteonecrosis of the jaw.
Monitor for signs and symptoms of hypersensitivity reactions (hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, urticaria). Treat symptomatically and discontinue medication if symptoms occur.

Lab Test Considerations:

Verify negative pregnancy status of patient before starting therapy.
- Assess serum calcium, phosphorous, and magnesium levels before and periodically during therapy, especially during first wk of therapy. Correct hypocalcemia and vitamin D deficiency before starting therapy. May cause mild, transient ↑ of calcium and phosphate. Supplement with calcium, magnesium, and vitamin D as needed.
- May cause hypercalcemia within the yr following discontinuation. Monitor for signs and symptoms of hypercalcemia, assess serum calcium periodically, reevaluate the patient’s calcium and vitamin D supplementation requirements and manage as clinically.
- May cause anemia.
- May cause hypercholesterolemia.

Implementation ⬆ ⬇

SC: Remove from refrigerator and bring to room temperature by standing in original container for 15–30 min prior to administration; do not warm in any other way. Do not shake. Administer using a 27-gauge needle in the upper arm, upper thigh, or abdomen. Solution is clear and colorless to pale yellow, and may contain trace amounts of translucent to white proteinaceous particles. Do not use if solution is discolored or contains many particles. Manually activate the green safety guard after the injection is given, not before.
- Patients should receive calcium 1000 mg and vitamin D 400 IU daily.

Patient/Family Teaching ⬆ ⬇

Explain the purpose of denosumab to patient. If a dose is missed, administer injection as soon as possible.
Advise patient once treatment is stopped there may be an increased risk of having broken bones in the spine, especially in patients who have had a fracture or who have had osteoporosis. Advise patients not to interrupt therapy without their health care professional advice.
Advise patient to eat a balanced diet and consult health care professional about the need for supplemental calcium and vitamin D (see Food Sources for Specific Nutrients).
Advise patient to notify health care professional immediately if signs of hypersensitivity, hypocalcemia (spasms, twitches, or cramps in muscles; numbness or tingling in fingers, toes, or around mouth), infection (fever, chills, skin that is red, swollen, hot, or tender to touch; severe abdominal pain, frequent or urgent need to urinate or burning during urination), or skin reactions (redness, itching, rash, dry or leathery feeling, blisters that ooze or become crusty, peeling), or osteonecrosis of the jaw (pain, numbness, swelling of or drainage from the jaw, mouth, or teeth) occur.
Encourage patient to participate in regular exercise and to modify behaviors that ↑ the risk of osteoporosis (stop smoking, reduce alcohol consumption).
Advise patient to take good care of teeth and gums (brush and floss regularly) and to inform health care professional of therapy prior to dental surgery.
Inform patient of increased risk of fractures upon discontinuation. If denosumab is discontinued, consider another bone resorption inhibitor.
Rep: Instruct female of reproductive potential to use highly effective contraception during and for at least 5 mo after therapy is completed. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇