地诺单抗详细说明书

Detailed instructions

Generic name: denosumab

Product name: Xgeva

Full names: denosumab, denosumab, denosumab, Xgeva, Denosumab

Indications:

Denosumab is a RANK ligand (RANKL) inhibitor indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. Important limitations of use: Denosumab is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.

[Dosage and Administration]

(1) Administer 120 mg subcutaneously/injection into the upper arm, upper thigh, or abdomen once every 4 weeks

(2) Give calcium and vitamin D when necessary to treat or prevent hypocalcemia

[Contraindications for denosumab] None

[Denosumab Warnings and Precautions]

(1) Hypocalcemia, severe hypocalcemia, may occur in patients receiving denosumab. Correct hypocalcemia before initiating denosumab. Monitor calcium levels and appropriately supplement all patients with calcium and vitamin D

(2) Osteonecrosis of the jaw may occur in patients receiving denosumab. Perform an oral examination before starting denosumab. Monitor for symptoms. Avoid invasive dental procedures during treatment with denosumab

[Adverse reactions of denosumab]

The most common adverse reactions (incidence per case-patient greater than or equal to 25%) in patients receiving denosumab were fatigue/asthenia, hypophosphatemia, and nausea

[Use of denosumab in special populations]

(1) Pregnancy: According to animal data, it may cause fetal damage. Pregnancy monitoring programs available

(2) Nursing mothers: Mammary gland development and lactation may be impaired. Discontinue medication or breastfeeding

(3) Pediatric patients: Solace and effectiveness have not been determined

(4) Renal impairment: Patients with creatinine clearance less than 30 mL/min or receiving dialysis are at risk for hypocalcemia. Appropriate supplement of calcium and vitamin D.

【Pharmacological effects】

This product is the first approved monoclonal antibody specifically targeting RANK ligand. RANK ligand is a transmembrane or soluble protein that is necessary for osteoclasts to maintain their structure, function, and survival. Human RANKL mRNA is mainly found in bones, bone marrow and lymphoid tissues. Its main function in bones is to stimulate the differentiation and activity of osteoclasts and inhibit the apoptosis of osteoclasts. Osteoclasts are responsible for bone resorption, and osteoclast precursors must have low levels of macrophage colony-stimulating factor and RANKL during their differentiation into mature osteoclasts. This product has a high affinity with RANKL, preventing RANK ligand from activating RANK on the surface of osteoclasts, inhibiting osteoclast activation and development, reducing bone resorption, increasing bone density and bone strength of both cortical bone and trabecular bone, promoting bone reconstruction, and reducing the incidence of vertebral, non-vertebral and hip fractures in postmenopausal women with osteoporosis.

The effect of this product on bone reconstruction can be evaluated by measuring some bone turnover markers (BTMs), such as the bone resorption marker N-telopeptide (NTX), the bone formation marker bone-specific alkaline phosphatase (BSAP), etc. A phase I clinical study conducted in healthy postmenopausal women showed that a dose-dependent decrease in morning urine NTX levels was observed on day 2 after administration. This decrease lasted for 6 months, with the maximum decrease reaching 84% compared with baseline. This effect is reversible. When serum denosumab levels disappear, NTX levels can be seen to rise again, which reflects the reversibility of its effect on bone reconstruction. As treatment continues, these effects will persist for a new cycle.

[Storage and Handling] Store denosumab in the original box in the refrigerator at 2°C-8°C. Do not freeze. Once removed from the refrigerator, denosumab must not be exposed to temperatures above 25°C or direct light and must be used within 14 days. Discard denosumab if it has not been used for 14 days. Do not use denosumab that has expired after the label expiry date. Protect denosumab from light and heat. Avoid vigorous shaking of denosumab.