Patients with severe renal impairment (creatinine clearance < 30 ml/min) or receiving dialysis are at greater risk of developing hypocalcaemia. Regular monitoring of calcium levels is especially important in these patients.[SmPC, p. 4]
OSTEONECROSIS OF THE JAW (ONJ)
ONJ has been reported commonly in patients receiving XGEVA®. 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 preventative dentistry and an individual benefit-risk assessment is recommended prior to treatment with XGEVA®.[SmPC, p. 4]
The following risk factors should be considered when evaluating a patient’s risk of developing ONJ:[SmPC, p. 4]
- Potency of the medicinal product that inhibits bone resorption (higher risk for highly potent compounds), route of administration (higher risk for parenteral administration), and cumulative dose of bone resorption therapy.
- Cancer, comorbid conditions (e.g. anaemia, coagulopathies, infection), and smoking.
- Concomitant therapies, including corticosteroids, chemotherapy, angiogenesis inhibitors, and radiotherapy to head and neck.
- Poor oral hygiene, periodontal disease, poorly fitting dentures, pre-existing dental disease, and invasive dental procedures e.g. tooth extractions.
All patients on XGEVA® should be encouraged to maintain good oral hygiene, receive routine dental checkups, and immediately report oral symptoms such as dental mobility, pain or swelling or non-healing of sores or discharge during treatment. While being treated with XGEVA®, invasive dental procedures should be performed only after careful consideration and be avoided in close proximity to XGEVA® administration. [SmPC, p. 4]
The management plan of the patients who develop ONJ should be setup 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.[SmPC, p. 4]
ATYPICAL FRACTURES OF THE FEMUR
Atypical femoral fractures have been reported in patients receiving XGEVA®. 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 XGEVA® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Patients presenting with such symptoms should be evaluated for incomplete femoral fracture. [SmPC, p. 5]
PATIENTS WITH GROWING SKELETONS
XGEVA® is not recommended in patients with growing skeletons. Clinically significant hypercalcaemia has been reported in XGEVA®-treated patients with growing skeletons weeks to months following treatment discontinuation.[SmPC, p. 5]