Xgeva Denosumab amgen

I. Basic Drug Information

Generic Name: Denosumab

Brand Name: Xgeva

Dosage Form: Solution for Injection (120 mg/1.7 mL, single-dose vial)

Manufacturer: Amgen Inc. (USA)

Pharmacological Class: Humanized IgG2 monoclonal antibody targeting RANK Ligand (RANKL); inhibits osteoclast activity and reduces bone resorption.

II. Indications

1. Bone Metastases from Solid Tumors: Prevention of skeletal-related events (e.g., pathological fractures, spinal cord compression) in patients with bone metastases from solid tumors (such as prostate cancer and breast cancer) or multiple myeloma. 

*Note: Not indicated for the prevention of skeletal-related events in multiple myeloma.*

2. Giant Cell Tumor of Bone (GCTB): Treatment of GCTB that is unresectable or where surgical resection is likely to result in severe functional impairment (in adults and skeletally mature adolescents weighing ≥ 45 kg).

3. Hypercalcemia of Malignancy (HCM): Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

III. Dosage and Administration

Route of Administration

Subcutaneous Injection Only: Administer via subcutaneous injection into the upper arm, upper thigh, or abdomen; do not administer intravenously, intramuscularly, or intradermally. Recommended Dosage:

| Indication                 | Dosing Regimen                                                              | Supplemental Requirements

| Solid Tumors with Bone Metastases | 120 mg subcutaneously every 4 weeks                                         | Calcium + Vitamin D (to prevent hypocalcemia)

| Giant Cell Tumor of Bone   | 120 mg subcutaneously every 4 weeks; with additional 120 mg doses on Days 8 and 15 of the first month | Calcium + Vitamin D (mandatory supplementation)

| Malignancy-Associated Hypercalcemia | Same regimen as for Giant Cell Tumor of Bone                                | Calcium + Vitamin D (monitor serum calcium levels)

Precautions for Use

1. Pre-treatment:

Correct pre-existing hypocalcemia prior to administration;

Monitor serum calcium, phosphorus, and creatinine levels every 4 weeks, particularly in patients with renal impairment (creatinine clearance <30 mL/min).

2. Administration Steps:

Allow refrigerated medication to reach room temperature (≤25°C) for 15–30 minutes prior to use;

Visually inspect prior to injection: the solution should be clear, colorless to pale yellow; discard if cloudy, discolored, or if particulate matter is present;

Withdraw using a 27-gauge needle; discard the vial after single use.

IV. Adverse Reactions

Common Adverse Reactions (≥25%)

- Fatigue/Asthenia (45%), Hypophosphatemia (32%), Nausea (31%).

- Others: Diarrhea (20%), Dyspnea (21%), Headache (13%).

Serious Adverse Reactions

1. Hypocalcemia:

Incidence: 18% (in the Xgeva group vs. 9% in the zoledronic acid group); severe hypocalcemia (serum calcium <7 mg/dL) occurred in 3.1% of patients.

*Management*: Mandatory supplementation with calcium and Vitamin D during treatment; monitor serum calcium levels regularly.

2. Osteonecrosis of the Jaw (ONJ):

Annual incidence increases with the duration of treatment (1.1% in Year 1, 3.7% in Year 2, 4.6% in Year ≥3).

*Prevention*: Perform an oral examination prior to administration; avoid invasive dental procedures during treatment. 3. Atypical Femoral Fractures:

Associated with long-term treatment; patients should be monitored for pain in the thigh or groin.

4. Risks Associated with Treatment Discontinuation:

May precipitate hypercalcemia (in adolescent patients with Giant Cell Tumor of Bone [GCTB]) or multiple vertebral fractures (MVF).

V. Contraindications

1. Hypersensitivity to Denosumab or any of its excipients;

2. Uncorrected hypocalcemia.

VI. Use in Specific Populations

Pregnancy/Lactation:

- Pregnancy Category C (animal studies indicate fetal risk); effective contraception is required during treatment, and pregnancy should be avoided for at least 5 months after discontinuing the drug;

- Contraindicated during lactation (may impair mammary gland development and milk production).

Pediatric Patients: Restricted to skeletally mature adolescents (who meet specific criteria for skeletal maturity); contraindicated in skeletally immature children (may inhibit bone growth and delay permanent tooth eruption).

Geriatric Patients/Renal Impairment:

- No dose adjustment is required for geriatric patients;

- Patients with renal failure (creatinine clearance <30 mL/min) or those undergoing dialysis require close monitoring for hypocalcemia.

VII. Drug Interactions

Bisphosphonates: Concomitant use is contraindicated (due to additive effects on bone suppression);

Immunosuppressants: May increase the risk of serious infections; a benefit-risk assessment should be performed.

VIII. Storage Conditions

Refrigerated Storage: Store in the original packaging at 2–8°C; do not freeze or shake;

After Opening: Use within 14 days if stored at room temperature (≤25°C); discard if the time limit is exceeded or if exposed to high temperatures or light.

IX. Packaging and Shelf Life

Presentation: 120 mg/1.7 mL/vial (single-dose vial);

Shelf Life: 36 months (expiration date indicated on the label).

> The information provided above is compiled based on the product prescribing information and clinical studies; specific usage should strictly follow a physician's instructions. During treatment, patients require periodic monitoring of serum calcium levels, oral health status, and renal function, and should promptly report any abnormal symptoms such as bone pain or numbness in the jaw. **Product Specifications**

**Product Name:** Xgeva (Denosumab) Injection 120 mg (1.7 mL) – 1 Vial

**Common Name:** Xgeva

**Active Ingredient:** Denosumab

**Dosage Form:** Solution for Injection

**Specification:** 120 mg/1.7 mL, single-dose vial

**Manufacturer:** Amgen Inc. (USA)

**Indications:**

1. **Bone Metastasis from Solid Tumors:** Prevention of skeletal-related events (such as pathological fractures and spinal cord compression) in patients with bone metastases from solid tumors (e.g., prostate cancer, breast cancer) and multiple myeloma.

*Note: Not indicated for the prevention of skeletal-related events in multiple myeloma.*

2. **Giant Cell Tumor of Bone (GCTB):** Treatment of GCTB that is unresectable or where surgical resection is likely to result in severe functional impairment (in adults and skeletally mature adolescents weighing ≥45 kg).

3. **Hypercalcemia of Malignancy (HCM):** Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

**Dosage and Administration:**

1. **Bone Metastasis from Solid Tumors / Multiple Myeloma**

**Dosage:** 120 mg administered once every 4 weeks via subcutaneous injection (into the upper arm, thigh, or abdomen).

**Administration Notes:** Hypocalcemia must be corrected prior to initiating therapy; serum calcium levels should be monitored during treatment, and calcium and Vitamin D supplements should be administered as necessary.

2. **Giant Cell Tumor of Bone (Unresectable or High Surgical Risk)**

**Dosage:** 120 mg administered once every 4 weeks via subcutaneous injection; during the first month of treatment, an additional dose may be administered on Day 8 and Day 15 (totaling 3 doses in the first month).

**Treatment Duration:** Continue until disease progression or the onset of unacceptable toxicity.