Denosumab

Class
Antiresorptive agents
Subclass
Anti-RANKL monoclonal antibodies
Substance name
Denosumab, denosumab-dssb, denosumab-bmwo, denosumab-bbdz
Brand names
Prolia®, Xgeva®, Stoboclo®, Osenvelt®, Ospomyv®
Common formulations
Solution for injection
Dosage and administration
Adults patients
Treatment
Giant cell tumor of bone • Unresectable
•
120 mg SC q4 weeks, with additional 120 mg doses on days 8 and 15 of the first month of therapy
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Hypercalcemia of malignancy • Refractory to bisphosphonates
•
120 mg SC q4 weeks, with additional 120 mg doses on days 8 and 15 of the first month of therapy
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Osteoporosis • Corticosteroid-induced, high risk for fracture
•
60 mg SC q6 months
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Osteoporosis in females with breast cancer • Receiving adjuvant aromatase inhibitor therapy
•
60 mg SC q6 months
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Osteoporosis in males • High risk for fracture
•
60 mg SC q6 months
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Osteoporosis in males, if other osteoporosis therapies are ineffective or contraindicated
•
60 mg SC q6 months
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Osteoporosis in patients with prostate cancer • Receiving androgen-deprivation therapy, nonmetastatic
•
60 mg SC q6 months
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Osteoporosis in postmenopausal females, if other osteoporosis therapies are ineffective or contraindicated
•
60 mg SC q6 months
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Postmenopausal osteoporosis • High risk for fracture
•
60 mg SC q6 months
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Hypercalcemia of malignancy • Off-label
•
Start at: 120 mg SC weekly at weeks 0, 1, and 2, and one dose at week 4
•
Maintenance: 120 mg SC q4 weeks
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Prevention
Skeletal-related events in patients with bone metastasis • From solid tumors
•
120 mg SC q4 weeks
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Skeletal-related events in patients with multiple myeloma
•
120 mg SC q4 weeks
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Osteoporosis in postmenopausal females with osteopenia • Off-label
•
60 mg SC q6 months
Administered subcutaneously in the upper arm, upper thigh, or abdomen. Administer with calcium 1,000 mg daily and at least 400 IU vitamin D daily. Administered into the upper arm, upper thigh, or abdomen.
Indications for use
Labeled indications
Adults
•
Treatment of giant cell tumor of bone (unresectable)
•
Treatment of hypercalcemia of malignancy (refractory to bisphosphonates)
•
Treatment of osteoporosis (corticosteroid-induced, high risk for fracture)
•
Treatment of osteoporosis in females with breast cancer (receiving adjuvant aromatase inhibitor therapy) (high risk for fracture)
•
Treatment of osteoporosis in males
•
Treatment of osteoporosis in males (high risk for fracture)
•
Treatment of osteoporosis in patients with prostate cancer (receiving androgen-deprivation therapy, nonmetastatic) (high risk for fracture)
•
Treatment of osteoporosis in males, if other osteoporosis therapies are ineffective or contraindicated
•
Treatment of osteoporosis in postmenopausal females, if other osteoporosis therapies are ineffective or contraindicated
•
Treatment of postmenopausal osteoporosis (high risk for fracture)
•
Prevention of skeletal-related events in patients with bone metastasis (from solid tumors)
•
Prevention of skeletal-related events in patients with multiple myeloma
Off-label indications
Adults
•
Treatment of hypercalcemia of malignancy
•
Prevention of osteoporosis in postmenopausal females with osteopenia
Safety risks
Boxed warnings
Severe hypocalcemia
•
Use extreme caution in patients with advanced kidney disease. Evaluate patients with advanced CKD for CKD-mineral and bone disorder before initiating denosumab.
Contraindications
Hypersensitivity to denosumab or its components
Hypocalcemia
•
Correct pre-existing hypocalcemia before initiating denosumab. Administer calcium and vitamin D supplements for the prevention and treatment of hypocalcemia during denosumab treatment.
Warnings and precautions
Cutaneous adverse reactions
•
Maintain a high level of suspicion, as denosumab may cause dermatitis, eczema, and rashes.
Femoral fracture
•
Maintain a high level of suspicion, as denosumab has been associated with an increased risk of atypical subtrochanteric and diaphyseal femoral fractures.
Hypercalcemia
•
Use caution when discontinuing denosumab in patients with giant cell tumor of bone and in patients with growing skeletons. Monitor patients for signs and symptoms of hypercalcemia, measure serum calcium periodically, and re-evaluate the need for calcium and vitamin D supplementation after discontinuation.
Medication-related osteonecrosis of the jaw
•
Use caution in patients with poor oral hygiene, periodontal and/or other dental diseases, ill-fitting dentures, undergoing invasive dental procedures, having comorbid disorders (such as cancer, anemia, coagulopathy, infection), or receiving chemotherapy, corticosteroids, or angiogenesis inhibitors. Perform a dental examination with appropriate preventive dentistry before initiating denosumab.
Musculoskeletal pain
•
Maintain a high level of suspicion, as denosumab may cause bone, joint, and muscle pain.
Serious infections
•
Use caution in patients with immunosuppression, as denosumab has been associated with an increased risk of serious infections, including skin, intra-abdominal, urinary tract, ear infections, and endocarditis.
Suppression of bone turnover
•
Maintain a high level of suspicion, as denosumab has been associated with a significant suppression of bone turnover and bone remodeling.
Vertebral fracture
•
Use caution when discontinuing denosumab in patients with osteoporosis, as fracture risk increases after discontinuation. Switch to an alternative antiresorptive therapy when denosumab is being discontinued.
Specific populations
Renal impairment
eGFR ≥ 30 mL/min/1.73 m²
•
Use acceptable. No dose adjustment required.
eGFR < 30 mL/min/1.73 m²
•
Use with caution. Monitor serum calcium. Monitor serum magnesium. Monitor serum phosphate levels. Evaluate patients with advanced chronic kidney disease for chronic kidney disease-mineral and bone disorder before initiating denosumab. Ensure adequate intake of calcium and vitamin D.
Renal replacement therapy
Any modality
•
Use with caution. Monitor serum calcium. Monitor serum magnesium. Monitor serum phosphate. Evaluate patients with advanced chronic kidney disease for chronic kidney disease-mineral and bone disorder before initiating denosumab. Ensure adequate intake of calcium and vitamin D.
Hepatic impairment
Any severity
•
Use acceptable. No dose adjustment required.
Pregnancy and breastfeeding
Pregnancy
All trimesters • Australia Category: D
•
Do not use. Evidence of fetal harm in humans. Verify pregnancy status in females of reproductive potential before initiating treatment. Advise using effective contraception during treatment and for at least 5 months after the last dose.
Breastfeeding
Use only if benefits outweigh potential risks.
Unknown amount excreted in breastmilk.
Unknown drug levels in breastfed infants.
Adverse reactions
Very common > 10%
•
Anemia, ↓ platelet count, ↓ serum calcium, ↓ serum phosphate, peripheral edema, arthralgia, back pain, constipation, cough, diarrhea, dyspnea, fatigue, headache, loss of appetite, nausea, pain in extremity, skin rash, vomiting, upper respiratory tract infections
Common 1-10%
•
Bronchitis, cataract, ↓ serum magnesium, ↓ serum potassium, dermatitis, eczema, gastroesophageal reflux, herpes zoster, hypertension, ↑ serum cholesterol, nasopharyngitis, osteoradionecrosis of the jaw, pneumonia, angina pectoris, asthenia, dizziness, bone pain, dyspepsia, epigastric pain, falls, insomnia, musculoskeletal pain, myalgia, pruritus, flatulence, vertigo, sciatica, serious infections, urinary tract infections
Uncommon < 1%
•
Acute pancreatitis, erysipelas, cellulitis
Unknown frequency
•
Femoral fracture, vertebral fracture, anaphylaxis, vasculitis, DRESS syndrome, ↑ serum calcium, urticaria, facial edema, skin erythema, ↑ serum PTH, lichenoid drug eruption, hair loss
Interactions
Drug(s)
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