Xgeva Special Precautions

Calcium and Vitamin D supplementation: Supplementation with calcium and vitamin D is required in all patients unless hypercalcaemia is present (see Dosage & Administration).
Hypocalcaemia: Pre-existing hypocalcaemia must be corrected prior to initiating therapy with XGEVA. Hypocalcaemia can occur at any time during therapy with XGEVA. Monitoring of calcium levels should be conducted (i) prior to the initial dose of XGEVA, (ii) within two weeks after the initial dose, (iii) if suspected symptoms of hypocalcaemia occur (see Adverse Reactions for symptoms). Additional monitoring of calcium level should be considered during therapy in patients with risk factors for hypocalcaemia, or if otherwise indicated based on the clinical condition of the patient.
Patients should be encouraged to report symptoms indicative of hypocalcaemia. If hypocalcaemia occurs while receiving XGEVA, additional calcium supplementation and additional monitoring may be necessary.
In the post-marketing setting, severe symptomatic hypocalcaemia (including fatal cases) has been reported (see Adverse Reactions), with most cases occurring in the first weeks of initiating therapy, but can occur later.
Renal impairment: Patients with severe renal impairment (creatinine clearance < 30 mL/min) or receiving dialysis are at greater risk of developing hypocalcaemia. The risk of developing hypocalcaemia and accompanying elevations in parathyroid hormone increases with increasing degree of renal impairment. Regular monitoring of calcium levels is especially important in these patients.
Osteonecrosis of the Jaw (ONJ): ONJ has been reported commonly in patients receiving XGEVA (see Adverse Reactions).
The start of treatment/new treatment course should be delayed in patients with unhealed open soft tissue lesions in the mouth. A dental examination with preventive dentistry and an individual benefit-risk assessment is recommended prior to treatment with denosumab.
The following risk factors should be considered when evaluating a patient's risk of developing ONJ: potency of the medicinal product that inhibits bone resorption (higher risk for highly potent compounds), route of administration (higher risk of parenteral administration) and cumulative dose of bone resorption therapy; cancer, co-morbid conditions (e.g. anaemia, coagulopathies, infection), smoking; concomitant therapies: corticosteroids, chemotherapy, angiogenesis inhibitors, radiotherapy to head and neck; poor oral hygiene, periodontal disease, poorly fitting dentures, pre-existing dental disease, invasive dental procedures (e.g. tooth extractions).
All patients should be encouraged to maintain good oral hygiene, receive routine dental check-ups, and immediately report any oral symptoms such as dental mobility, pain or swelling, or non-healing of sores or discharge during treatment with denosumab. While on treatment, invasive dental procedures should be performed only after careful consideration and be avoided in close proximity to XGEVA administration.
The management plan of the patients who develop ONJ should be set up in close collaboration between the treating physician and a dentist or oral surgeon with expertise in ONJ. Temporary interruption of XGEVA treatment should be considered until the condition resolves and contributing risk factors are mitigated where possible.
Osteonecrosis of the external auditory canal: Osteonecrosis of the external auditory canal has been reported with denosumab. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving denosumab who present with ear symptoms including chronic ear infections.
Atypical fractures of the femur: Atypical femoral fractures have been reported in patients receiving denosumab (see Adverse Reactions). Atypical femoral fractures may occur with little or no trauma in the subtrochanteric and diaphyseal regions of the femur. Specific radiographic findings characterise these events. Atypical femoral fractures have also been reported in patients with certain co-morbid conditions (e.g., vitamin D deficiency, rheumatoid arthritis, hypophosphatasia) and with use of certain pharmaceutical agents (e.g., bisphosphonates, glucocorticoids, proton pump inhibitors). These events have also occurred without antiresorptive therapy. Similar fractures reported in association with bisphosphonates are often bilateral; therefore the contralateral femur should be examined in denosumab-treated patients who have sustained a femoral shaft fracture. Discontinuation of XGEVA therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient based on an individual benefit-risk assessment. During denosumab treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Patients presenting with such symptoms should be evaluated for an incomplete femoral fracture.
Hypercalcaemia following treatment discontinuation in patients with giant cell tumour of bone and in patients with growing skeletons: Clinically significant hypercalcaemia requiring hospitalisation and complicated by acute renal injury has been reported in XGEVA-treated patients with giant cell tumour of bone weeks to months following treatment discontinuation.
After treatment is discontinued, monitor patients for signs and symptoms of hypercalcaemia, consider periodic assessment of serum calcium and re-evaluate the patient's calcium and vitamin D supplementation requirements (see Adverse Reactions).
XGEVA is not recommended in patients with growing skeletons (see Dosage & Administration). Clinically significant hypercalcaemia has also been reported in this patient group weeks to months following treatment discontinuation.
Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation: Multiple vertebral fractures (MVF), not due to bone metastases, may occur following discontinuation of treatment with XGEVA, particularly in patients with risk factors such as osteoporosis or prior fractures.
Advise patients not to interrupt XGEVA therapy without their physician's advice. When XGEVA treatment is discontinued, evaluate the individual patient's risk for vertebral fractures.
Others: XGEVA contains the same active ingredient as found in Prolia (denosumab). Patients being treated with XGEVA should not be treated concomitantly with other denosumab-containing medicinal products (for osteoporosis indications).
Patients being treated with XGEVA should not be treated concomitantly with bisphosphonates.
Warnings for excipients: This medicinal product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicinal product.
This medicinal product contains less than 1 mmol sodium (23 mg) per 120 mg, i.e. essentially 'sodium-free'.
Effects on ability to drive and use machines: XGEVA has no or negligible influence on the ability to drive and use machines.