Wednesday, July 19, 2023

denosumab (de-no-su-mab) Prolia, Xgeva

 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.

Treatment of 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:pbone resorption withpoccurrence

of fractures (vertebral, nonvertebral, hip) or other

skeletal-related events (e.g., radiation therapy to bone,

surgery to bone, spinal cord compression).qbone

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‡

†Maximumpin serum calcium occurs at 10 days.

‡Following discontinuation.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Hypocalcemia

(correct before administering); adequate supplemental

calcium and vitamin D required; OB: May

cause fetal harm; Lactation: Avoid use;pmammary

gland development and 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

qrisk of jaw osteonecrosis); Concurrent use of immunosuppressants

or diseases resulting in immunosuppression

(qrisk of infection); Geri: May be more sensitive

to drug effects; Rep: Women of reproductive

potential (use effective contraception) (for Xgeva only);

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, hypercalcemia.

Metab: hypercholesterolemia. MS: back pain,

extremity pain, musculoskeletal pain, atypical femoral

fracture, osteonecrosis of the jaw, suppression of bone

turnover. Resp: dyspnea, cough. Misc: hypersensitivity

reactions including ANAPHYLAXIS, infection.

Interactions

Drug-Drug: Concurrent use of immunosuppressantsqrisk

of infection.

Route/Dosage

Prolia

Subcut (Adults): 60 mg every 6 mo.

Xgeva

Subcut (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 mo of therapy;

Hypercalcemia of malignancy—120 mg every 4

weeks, with additional doses of 120 mg given on Days 8

and 15 of first mo of therapy.

Availability

Solution for subcutaneous injection (Prolia)

(prefilled syringe): 60 mg/mL. Solution for subcutaneous

injection (Xgeva): 120 mg/1.7 mL.

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