Denosumab (Prolia / Xgeva) - Injection Guide

Formulations & Doses

Step-by-Step Administration

Before You Begin

1. Remove from refrigerator 15-30 minutes before use - let the pre-filled syringe reach room temperature. Do not heat it or shake it.
2. Check the solution - it should be clear, colorless to pale yellow. Do not use if discolored, cloudy, or contains particles.
3. Gather supplies: pre-filled syringe, alcohol swabs, sterile gauze, sharps disposal container, gloves.
4. Wash hands thoroughly with soap and water.
5. Do not remove the needle cap until just before injection.

Choose the Injection Site

• Upper thigh (anterior/outer aspect) - most common
• Abdomen - at least 5 cm (2 inches) away from the navel
• Upper outer arm (deltoid region) - often used when a healthcare professional administers it

• Bruised, tender, red, or hard skin
• Areas with scars, stretch marks, or skin lesions
• Previous injection site (rotate sites each time)

Preparing the Injection

1. Clean the chosen site with an alcohol swab using a circular motion.
2. Allow the skin to air dry completely (about 30 seconds) - do not blow on it or fan it.
3. Remove the needle cap by pulling it straight off (do not twist).

Administering the Injection

1. Pinch the skin firmly between your thumb and forefinger to create a ~5 cm fold.
2. Hold the syringe like a pencil with your dominant hand.
3. Insert the needle at a 45-90 degree angle into the pinched skin fold. A 90-degree angle is standard for most patients with adequate subcutaneous tissue; use 45 degrees if the patient is very thin.
4. Release the skin pinch.
5. Inject slowly - push the plunger all the way down at a steady, even pace.
6. After the plunger bottoms out, hold for 5-10 seconds before withdrawing.
7. Withdraw the needle at the same angle it was inserted.
8. Activate the safety guard (on pre-filled syringes) by sliding it over the needle immediately after withdrawal.

After the Injection

1. Apply gentle pressure with a clean gauze pad - do not rub (rubbing can cause bruising).
2. Do not recap the needle.
3. Dispose of the used syringe immediately in a sharps container.
4. Document the injection site and date.
5. Observe the patient for at least a few minutes for any hypersensitivity reaction.

Key Clinical Points

• Calcium and Vitamin D supplementation is required in all patients on denosumab - give at least 1000 mg calcium and 400 IU Vitamin D daily to prevent hypocalcemia.
• Check serum calcium before each dose, especially in patients with renal impairment (CrCl < 30 mL/min).
• Dental review before starting therapy - invasive dental procedures should be avoided or completed before initiating denosumab due to risk of osteonecrosis of the jaw (ONJ).
• Do not stop abruptly - discontinuation leads to rapid bone turnover rebound and increased vertebral fracture risk (typically 12-18 months after last dose). Transition to a bisphosphonate if stopping.
• Missed dose - administer as soon as possible, then reschedule from that date.
• Storage - store in refrigerator at 2-8°C (36-46°F). Do not freeze. Protect from light. Once removed from refrigerator, use within 30 days.

Contraindications / Precautions

• Hypocalcemia - must be corrected before starting
• Hypersensitivity to denosumab or any excipient
• Pregnancy - avoid (fetal harm risk)
• Atypical femoral fractures - rare but possible with long-term use; counsel patients to report new thigh/groin pain

Zoledronic Acid (Reclast / Zometa) - IV Infusion Guide

Doses by Indication

Pre-Infusion Assessment (MANDATORY)

1. Check renal function - Calculate eGFR / creatinine clearance (CrCl) using Cockcroft-Gault formula before every dose:
   • Reclast: Do NOT give if CrCl < 35 mL/min
   • Zometa: Dose-adjust if CrCl ≤ 60 mL/min (see table below); avoid if CrCl < 30 mL/min
2. Check serum calcium - Correct hypocalcemia before infusion. Vitamin D deficiency must also be corrected first.
3. Hydration status - Patient must be adequately hydrated. Give 500 mL normal saline before or alongside the infusion in at-risk patients (elderly, on diuretics, reduced oral intake).
4. Dental review - Invasive dental procedures should be completed before starting therapy (ONJ risk).
5. Paracetamol/Acetaminophen pre-medication - Give 650-1000 mg paracetamol the day before, day of, and day after infusion to reduce acute-phase reaction (fever, myalgia, flu-like symptoms occur in ~5-10% of first-time recipients).

Preparation of the Infusion

Reclast (5 mg / 100 mL) - Ready-to-use

• Comes as a ready-to-use 100 mL solution - no dilution needed.
• Inspect visually for particulate matter or discoloration before use.
• Do not use if solution is discoloured or contains particles.

Zometa (4 mg / 5 mL concentrate) - Requires dilution

1. Withdraw 5 mL from the vial (= 4 mg).
2. Dilute immediately in 100 mL of 0.9% Normal Saline or 5% Dextrose (D5W).
3. Use aseptic technique throughout.
4. Do NOT dilute in Lactated Ringer's or any calcium-containing or divalent-cation-containing solution - precipitation will occur.
5. If not used immediately, refrigerate at 2-8°C and use within 24 hours.

Zometa dose reduction for renal impairment (CrCl 30-60 mL/min):

Administering the Infusion

1. Establish IV access - peripheral IV cannula is standard; ensure it is patent.
2. Dedicated IV line - run zoledronic acid through a separate IV line, not mixed with any other drug.
3. Infusion rate - infuse over no less than 15 minutes at a constant rate. (Harrison's states 30 minutes for Reclast in osteoporosis; FDA minimum is 15 minutes - many centres use 30 minutes as safer practice, especially in older patients.)
4. Do NOT give as IV bolus - rapid infusion increases nephrotoxicity risk significantly.
5. Flush the line after infusion with 10 mL of normal saline.
6. Monitor the patient during and for at least 30 minutes post-infusion.

After the Infusion

• Encourage oral hydration for 24-48 hours post-infusion.
• Advise patient about the acute-phase reaction - fever, myalgia, headache, arthralgia typically appear within 24-48 hours and last 1-3 days; usually milder or absent on subsequent doses.
• Ensure patient takes calcium (1000-1200 mg/day) and Vitamin D (800-1000 IU/day) supplements daily.
• Recheck renal function 1-2 weeks after infusion if there was pre-existing renal impairment.
• Document date, dose, batch number, and any reactions.

Key Contraindications / Precautions

Key Difference: Reclast vs Zometa