How is Prolia (denosumab) administered?

How Prolia is Administered

Prolia (denosumab) is administered as a 60 mg subcutaneous injection once every 6 months by a healthcare professional, with injection sites including the upper arm, upper thigh, or abdomen. 1

Administration Route and Technique

• Subcutaneous injection is the only approved route for Prolia administration, distinguishing it from intravenous bisphosphonates like zoledronic acid 2, 1
• The injection must be administered by a healthcare professional, not self-administered by patients 1
• Three acceptable injection sites are available: upper arm, upper thigh, or abdomen 1
• The injection should not be administered into muscle or blood vessels 1

Dosing Schedule

• Standard dose is 60 mg every 6 months for osteoporosis indications 1, 2
• If a dose is missed, administer as soon as the patient is available, then resume the every-6-month schedule from that date 1
• For bone metastases from cancer, a higher dose of 120 mg monthly is used, but this is a different indication than osteoporosis 3

Preparation Before Injection

• Allow the prefilled syringe to reach room temperature (up to 25°C/77°F) by removing from refrigerator 15-30 minutes before injection 1
• Do not warm the medication by any other method 1
• Inspect the solution visually - it should be clear, colorless to pale yellow, and may contain trace amounts of translucent to white proteinaceous particles 1
• Do not use if the solution is discolored, cloudy, or contains many particles 1

Safety Guard Activation (Critical Step)

• Do NOT activate the green safety guard before injection - this will lock the syringe and prevent administration 1
• After completing the injection, immediately slide the green safety guard forward over the needle until it locks with an audible "click" 1
• Hold the clear finger grip with one hand and gently slide the safety guard base with the other hand 1
• Dispose immediately in a sharps container; never recap the needle 1

Mandatory Pre-Treatment Requirements

Before First Dose:

• Pregnancy testing is required in all females of reproductive potential before each administration 1
• Correct pre-existing hypocalcemia before initiating therapy - this is a contraindication 1
• For patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m²), evaluate for CKD-MBD by measuring intact PTH, serum calcium, 25(OH) vitamin D, and 1,25(OH)₂ vitamin D 1
• Dental examination is recommended before starting therapy to minimize osteonecrosis of the jaw risk 4, 5

Concurrent Supplementation:

• All patients must receive calcium 1000 mg daily and at least 400 IU vitamin D daily throughout treatment 1
• Some guidelines recommend higher supplementation: calcium 1,200-1,500 mg daily and vitamin D3 400-800 IU daily 3

Clinical Advantages of This Administration Method

• The 6-month dosing interval improves adherence compared to weekly or monthly oral bisphosphonates, with studies showing high continuation rates due to convenience and rapid BMD improvements 6, 7
• Subcutaneous administration avoids gastrointestinal side effects common with oral bisphosphonates 7, 8
• The route allows uniform distribution in both trabecular and cortical bone regardless of renal function 7

Common Pitfalls to Avoid

• Never activate the safety guard before injection - this is the most common administration error 1
• Do not warm the medication using heat sources or hot water 1
• Ensure calcium and vitamin D supplementation is started before or concurrent with the first injection to prevent hypocalcemia 1
• Do not confuse the 60 mg every-6-month osteoporosis dose with the 120 mg monthly dose used for bone metastases 3, 1