地诺单抗注意事项有哪些？

(denosumab, also known as AMC-162, trade name XGeva) is a bone resorption inhibitor with a unique mechanism of action. It specifically targets the receptor activator of NF-kB ligand (RANKL), inhibits osteoclast activation and development, reduces bone resorption, and increases bone density. The FDA approved this product for use in postmenopausal women with osteoporosis who are at high risk of fracture. It can help reduce the incidence of vertebral, non-vertebral and hip fractures in postmenopausal women with osteoporosis. This product is also used in patients for whom other current treatments are ineffective or intolerable to reduce the risk of fractures.

What are the precautions for denosumab?

1. Hypocalcemia. Use of denosumab can cause severe hypocalcemia. Correct pre-existing hypocalcemia before denosumab treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when denosumab is administered with other drugs that can also reduce calcium levels. Advise patients to seek medical attention for symptoms of hypocalcemia.

2. According to clinical trials using lower doses of denosumab, patients with creatinine clearance less than 30 mL/min or receiving dialysis are at higher risk of severe hypocalcemia than patients with normal renal function. In a trial of 55 patients, free of cancer and with varying degrees of renal impairment, receiving a single dose of 60 mg denosumab, 8/17 patients had a creatinine clearance less than 30 mL/min or underwent dialysis and had a corrected serum calcium level less than 8.0 mg/dL compared with 0/12 patients with normal renal function. The risk of hypocalcemia with the recommended dosing regimen of 120 mg every 4 weeks has not been evaluated in patients with creatinine clearance less than 30 mL/min or receiving dialysis.

3. Osteonecrosis of the jaw (ONJ). Osteonecrosis of the jaw, manifested by jaw pain, osteomyelitis, osteitis, bone erosion, dental or periodontal infection, toothache, gingival ulceration, or gingival erosion, may occur in patients receiving denosumab. Persistent pain or slow healing of the back of the mouth or jawbone from dental surgery may also be signs of ONJ. In clinical trials, ONJ occurred in 2.2% of patients receiving denosumab, and of these patients, 79% had a history of tooth extraction, poor oral hygiene, or use of dental instruments. Perform oral examinations and appropriate preventive dentistry before starting denosumab and periodically during denosumab treatment. Remind patients about oral hygiene habits. Avoid invasive dental procedures during treatment with denosumab.

4. The risk of hypercalcemia increases after stopping treatment. For patients with giant cell tumors of bone and those with immature bone development, there is an increased risk of hypercalcemia after discontinuation of treatment, which can be very serious. Tell your doctor right away if you have symptoms of hypercalcemia, such as nausea, vomiting, headache, and decreased alertness.