What are the prescribing guidelines for Prolia (Denosumab)?

From the Guidelines

Prolia (Denosumab) Prescribing Guidelines: Prolia (Denosumab) should be prescribed every 4 weeks, with a dose of 120 mg subcutaneously, for patients with castration-resistant prostate cancer (CRPC) and bone metastases to prevent or delay disease-associated skeletal-related events (SREs) 1.

Key Considerations

• Indications: Denosumab is recommended for patients with CRPC and bone metastases, as well as for men undergoing androgen deprivation therapy (ADT) who are at increased risk of osteoporosis 1.
• Dosing and Administration: The recommended dose of denosumab is 120 mg subcutaneously every 4 weeks 1.
• Monitoring and Precautions: Patients should be monitored for hypocalcemia, and supplemental calcium and vitamin D are recommended to prevent hypocalcemia 1. Oral hygiene and baseline dental evaluation are also recommended to reduce the risk of osteonecrosis of the jaw (ONJ) 1.
• Renal Impairment: Denosumab may be administered to patients with impaired renal function, but the risk of severe hypocalcemia and hypophosphatemia is greater, and the dose, schedule, and safety of denosumab have not yet been defined in this population 1.

Special Populations

• Men with Osteoporosis: Denosumab is recommended as a treatment option for men with osteoporosis who are at increased risk of fracture 1.
• Patients with Breast Cancer: Denosumab is recommended for patients with breast cancer who have evidence of bone metastases, with a dose of 120 mg subcutaneously every 4 weeks 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Pregnancy must be ruled out prior to administration of Prolia. (2.1) Before initiating Prolia in patients with advanced chronic kidney disease, including dialysis patients, evaluate for the presence of chronic kidney disease mineral and bone disorder with intact parathyroid hormone, serum calcium, 25(OH) vitamin D, and 1,25(OH)2 vitamin D. (2.2,5.1,8. 6) Prolia should be administered by a healthcare professional. (2.3) Administer 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. (2.3) Instruct patients to take calcium 1000 mg daily and at least 400 IU vitamin D daily. (2. 3)

The prescribing guidelines for Prolia (Denosumab) are as follows:

• Administration: 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen by a healthcare professional.
• Supplementation: Patients should take calcium 1000 mg daily and at least 400 IU vitamin D daily.
• Evaluation: Evaluate patients with advanced chronic kidney disease for the presence of chronic kidney disease mineral and bone disorder before initiating Prolia.
• Contraindications: Prolia is contraindicated in patients with hypocalcemia, pregnancy, and known hypersensitivity to Prolia. 2

From the Research

Prescribing Guidelines for Prolia (Denosumab)

• Denosumab (Prolia) is a fully human monoclonal antibody against the receptor activator of the nuclear factor kappaB ligand, used to improve bone mineral density and reduce the incidence of new fractures in postmenopausal women and men 3.
• It is also used in the treatment of glucocorticoid-induced osteoporosis, as well as for the prevention of bone loss and reduction of fracture risk in men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer 3.
• Denosumab may be an appropriate initial therapy in patients at high risk for fracture, including older patients who have difficulty with the dosing requirements of oral bisphosphonates, as well as patients who are intolerant of, unresponsive to, or have contraindications to other therapies 3, 4.

Administration and Dosage

• Denosumab is administered once every 6 months via subcutaneous injection 4.
• The dose-specific effects of denosumab on serum calcium levels have been studied, and it has been found that the initial dose of denosumab reduces serum calcium levels more significantly than subsequent doses, especially in patients with advanced chronic kidney disease (CKD) 5.

Special Considerations

• Patients with CKD are at increased risk of fragility fractures and associated consequences, and denosumab may be considered as a treatment option after optimizing CKD-mineral and bone disorders (CKD-MBD) and supplementing with calcium and vitamin D 6.
• The long-term safety and efficacy of denosumab have been assessed in a 10-year study, which found that denosumab treatment was associated with low rates of adverse events, low fracture incidence, and continued increases in bone mineral density (BMD) without plateau 7.

Safety Monitoring

• Safety concerns with denosumab include infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures, although further study and experience provide reassurance on these issues 3.
• Denosumab-induced hypocalcemia has been reported, especially in patients with advanced CKD, and risk factors include lower baseline serum calcium and 25 hydroxyvitamin D and both low and high bone turnover 6, 5.