denosumab

General

**REMS Drug**
Pronunciation
de-NO-su-mab

Trade Name(s)

• Prolia

• Xgeva

Pregnancy Category
Category C

Ther. class.
bone resorption inhibitors

Pharm. class.
monoclonal antibodies

Indications

• Prolia: Treatment of:

» Osteoporosis in postmenopausal women who are at high risk for fracture or those who have failed/are intolerant of conventional osteoporosis therapy,

» Men receiving androgen deprivation therapy for nonmetastatic prostate cancer who are at high risk for fracture,

» Women receiving adjuvant aromatase inhibitor therapy for breast cancer who are at high risk for fracture.

• Xgeva: Prevention of skeletal-related events in patients with bone metastases from solid tumors.

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 Effect(s):

• ↓ 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 subcutaneous administration.

Distribution: Unknown.

Metabolism and Excretion: Unknown.

Half-life: 25.4 days.

TIME/ACTION PROFILE (effects on bone resorption)

ROUTE	ONSET	PEAK	DURATION
Subcut	1 mo	unknown†	12 mo‡

†Maximum ↓ in serum calcium occurs at 10 days.
‡Following discontinuation.

Contraindication/Precautions

Contraindicated in:

• Hypocalcemia (correct before administering); adequate supplemental calcium and vitamin D required;

• Lactation: Avoid use; ↓ mammary gland development and lactation.

Use Cautiously in:

• Conditions associated with hypocalcemia including hypoparathyroidism, previous thyroid/parathyroid surgery, malabsorption syndromes, history of small intestinal excision, renal impairment/hemodialysis (CCr <30 mL/min); monitoring of calcium and other minerals recommended;

• Concurrent use of immunosuppressants or diseases resulting in immunosuppression (↑ risk of infection);

• Geri: May be more sensitive to drug effects;

• OB: Use only when potential benefit justifies potential risk to fetus;

• Pedi: Safety and effectiveness not established.

Adverse Reactions/Side Effects

CNS: headache.

GI: PANCREATITIS, diarrhea, nausea.

GU: cystitis.

Derm: dermatitis, eczema, rashes.

F and E: hypocalcemia, hypophosphatemia.

Metabolic: hypercholesterolemia.

MS: back pain, extremity pain, musculoskeletal pain, osteonecrosis of the jaw, suppression of bone turnover.

Resp: dyspnea, cough.

Misc: infection.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug
Concurrent use of immunosuppressants ↑ risk of infection.

Route/Dosage

Prolia

• SC (Adults): 60 mg every 6 mo..

Xgeva

• SC (Adults): 120 mg every 4 weeks..

Availability

• Injection (Prolia): 60 mg/1 mL in prefilled syringes and single-use vials.

• Injection (Xgeva): 120 mg/1.7 mL in single-use vials.

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.

Lab Test Considerations

• Assess serum calcium, phosphorous and magnesium levels before and periodically during therapy. Hypocalcemia and vitamin D deficiency should be treated before initiating therapy. May cause mild, transient ↑ of calcium and phosphate.

» May cause anemia.

» May cause hypercholesterolemia.

Potential Nursing Diagnoses

• Risk for injury (Indications)

Implementation

• Grey needle cap on single-use pre-filled syringe should not be handled by people sensitive to latex.

• 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 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 400 IU vitamin D daily.

Patient/Family Teaching

• Explain the purpose of denosumab to patient. If a dose is missed, administer injection as soon as possible; schedule injections every 6 mo from date of last injection.

• 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 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) 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.

• Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Encourage women who become pregnant during Xgeva treatment to enroll in Amgen's Pregnancy Surveillance Program. Patients or their health care professional should call 1-800-77-AMGEN (1-800-772-6436) to enroll.

Evaluation/Desired Outcomes

• Reversal of the progression of osteoporosis with ↓ fractures and other sequelae.

• ↑ bone mass.