Drugs Xagena
Denosumab ( Prolia ) is a human monoclonal antibody ( IgG2 ) that targets and binds with high affinity and specificity to RANKL, preventing activation of its receptor, RANK, on the surface of osteoclast precursors and osteoclasts. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function and survival, thereby decreasing bone resorption in cortical and trabecular bone.
Prolia is indicated for: a) treatment of osteoporosis in postmenopausal women at increased risk of fractures. Prolia significantly reduces the risk of vertebral, non vertebral and hip fractures; b) treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures. In men with prostate cancer receiving hormone ablation, Prolia significantly reduces the risk of vertebral fractures.
Osteonecrosis of the jaw
Osteonecrosis of the jaw ( ONJ ) has been reported in patients treated with Denosumab ( Prolia ) or bisphosphonates, another class of anti-resorptive agents. Most cases have been in cancer patients; however some have occurred in patients with osteoporosis.
Osteonecrosis of the jaw has been reported rarely in clinical studies in patients receiving Denosumab at a dose of 60 mg every 6 months for osteoporosis.
There have been reports of osteonecrosis of the jaw in clinical studies in patients with advanced cancer treated with Denosumab ( Xgeva ) at the studied dose of 120 mg administered monthly.
Known risk factors for osteonecrosis of the jaw include a diagnosis of cancer with bone lesions, concomitant therapies ( e.g., chemotherapy, antiangiogenic biologics, corticosteroids, radiotherapy to head and neck ), poor oral hygiene, dental extractions, and co-morbid disorders ( e.g., pre-existing dental disease, anaemia, coagulopathy, infection ) and previous treatment with bisphosphonates.
A dental examination with appropriate preventive dentistry should be considered prior to treatment with Denosumab in patients with concomitant risk factors. While on treatment, these patients should avoid invasive dental procedures if possible.
Good oral hygiene practices should be maintained during treatment with Denosumab. For patients who develop osteonecrosis of the jaw while on Denosumab therapy, dental surgery may exacerbate the condition. If osteonecrosis of the jaw occurs during treatment with Denosumab, use clinical judgment and guide the management plan of each patient based on individual benefit/risk evaluation.
Atypical fractures of the femur
Atypical femoral fractures have been reported in patients receiving Denosumab. Atypical femoral fractures may occur with little or no trauma in the subtrochanteric and diaphyseal regions of the femur. Specific radiographic findings characterize these events.
Atypical femoral fractures have also been reported in patients with certain comorbid 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 Denosumab 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. ( Xagena )
Source: Summary of Product Characteristics UK, 2013
XagenaMedicine_2013
