denosumab

(redirected from Xgeva)

denosumab

(de-no-su-mab) ,

Prolia

(trade name),

Xgeva

(trade name)

Classification

Therapeutic: bone resorption inhibitors
Pharmacologic: monoclonal antibodies
Pregnancy Category: X

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
  • 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
  • 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.
Xgeva:
  • Prevention of skeletal-related events 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

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 subcutaneous administration.
Distribution: Unknown.
Metabolism and Excretion: Unknown.
Half-life: 25.4 days.

Time/action profile (effects on bone resorption)

ROUTEONSETPEAKDURATION
Subcut1 mounknown†12 mo‡
†Maximum ↓ in serum calcium occurs at 10 days.‡Following discontinuation.

Contraindications/Precautions

Contraindicated in: HypersensitivityHypocalcemia (correct before administering); adequate supplemental calcium and vitamin D required; Obstetric: May cause fetal harm 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); Geriatric: May be more sensitive to drug effects; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

  • headache

Gastrointestinal

  • pancreatitis (life-threatening)
  • diarrhea
  • nausea

Genitourinary

  • cystitis (most frequent)

Dermatologic

  • dermatitis
  • eczema
  • rashes

Fluid and Electrolyte

  • hypocalcemia (most frequent)
  • hypophosphatemia (most frequent)

Metabolic

  • hypercholesterolemia (most frequent)

Musculoskeletal

  • back pain (most frequent)
  • extremity pain (most frequent)
  • musculoskeletal pain (most frequent)
  • atypical femoral fracture
  • osteonecrosis of the jaw
  • suppression of bone turnover

Respiratory

  • dyspnea (most frequent)
  • cough

Miscellaneous

  • hypersensitivity reactions including anaphylaxis (life-threatening)
  • infection

Interactions

Drug-Drug interaction

Concurrent use of immunosuppressants ↑ risk of infection.

Route/Dosage

Prolia
Subcutaneous (Adults) 60 mg every 6 mo.
Xgeva
Subcutaneous (Adults ) Bone metastasis from solid tumors—120 mg every 4 weeks; Giant cell tumor of bone—120 mg every 4 weeks, with additional doses of 120 mg given on Days 8 and 15 of first month of therapy.

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

Nursing implications

Nursing 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.
  • Monitor for signs and symptoms of hypersensitivity reactions (hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritis, urticaria). Treat symptomatically and discontinue medication if symptoms occur.
  • 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. Administer calcium, magnesium, and vitamin D as needed.
    • May cause anemia.
    • May cause hypercholesterolemia.

Potential Nursing Diagnoses

Risk for injury (Indications)

Implementation

  • Grey needle cap on single-use prefilled syringe should not be handled by people sensitive to latex.
  • Subcutaneous: 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.
  • Advise patient to eat a balanced diet and consult health care professional about the need for supplemental calcium and vitamin D (see ).
  • 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) 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 breast feeding. Instruct female patient to use highly effective contraception during and for at least 5 mo after therapy is completed. 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.
  • Decreased growth of giant cell tumors

denosumab

A monoclonal antibody drug that interferes with osteoclast production and function. The antibody binds to the receptor activator of a nuclear factor ligand RANKL, interfering with osteoclast differentiation, activation and survival. Given to post-menopausal women it increases bone mineral density and decreases the rate of bone reabsorption. The drug shows promise for the treatment of OSTEOPOROSIS.
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The Committee also recommended extensions of indications for Bosulif, Feraccru, Isentress, Kineret, Lynparza and Xgeva.
Amgen announced that the Committee for Medicinal Products for Human Use, or CHMP, of the European Medicines Agency has adopted a positive opinion to expand the current indication for XGEVA to cover skeletal-related events in patients with multiple myeloma.
He played a fundamental role in the discovery of the OPG/RANKL/RANK pathway that resulted in the therapeutics Prolia for osteoporosis, and Xgeva for cancer-related bone diseases.
M2 EQUITYBITES-January 9, 2018-US Food and Drug Administration grants Amgen's XGEVA approval for supplemental biologics license application
Amgen's sBLA for XGEVA (denosumab) to expand the currently approved indication for the prevention of skeletal-related events in patients with bone metastases from solid tumors, has been approved to include multiple myeloma.
Soft but Reliable Growth: Growth of a number of established products, XGEVA (bone metastases), Prolia (osteoporosis), Nplate (thrombocytopenia), Vectibix (metastatic colorectal cancer), and Sensipar (secondary hyperparathyroidism), should help to offset some of the risk of anticipated branded and biosimilar competition against Neulasta and Epogen and existing competition against Neupogen.
US-based biotechnology company Amgen (NASDAQ: AMGN) has entered into a definitive agreement with UK-based drugmaker GSK to reacquire all of its remaining rights to Prolia (denosumab), Xgeva (denosumab) and Vectibix (panitumumab) in 48 countries in Asia, South America, Europe, Australia and other regions throughout the world, the company said.
Its largest selling products include Neulasta for preventing infections in patients undergoing chemotherapy, Enbrel for rheumatoid arthritis, Epogen, Vectibix and XGEVA.
Food and Drug Administration (FDA) has approved a new indication for XGEVA (denosumab) for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone (GCTB) that is unresectable or where surgical resection is likely to result in severe morbidity.
The ODAC will review results from clinical studies in support of this new indication, including the pivotal '147 trial, a randomized, placebo-controlled, multi-center Phase 3 study that compared XGEVA to placebo in prolonging bone metastasis-free survival in men with non-metastatic CRPC who were at high risk for bone metastases based on prostate specific antigen criteria.
It is marketed as Xgeva and administered more frequently at a higher dose for this indication.