Common use of CLINICAL INFORMATION Clause in Contracts

CLINICAL INFORMATION. i. Prescribed indications For the treatment of osteoporosis in men and postmenopausal women at increased risk of fractures, and for the treatment of bone loss associated with hormone ablation in men with prostate cancer. Not relevant to this section Alendronic acid remains the first line treatment for osteoporosis in accordance with NICE guidance. Approximately 25% of patients cannot be treated with alendronic acid because of side effects, inability to comply with dosing instructions or malabsorption leading to inefficacy. Risedronate should also be tried if appropriate before Denosumab is considered. Denosumab provides another option for those patients also unable to take risedronate and has been recommended by NICE in this context. The guidance is available at ▇▇▇▇://▇▇▇▇▇▇▇▇.▇▇▇▇.▇▇▇.▇▇/TA204. ii. Therapeutic summary Denosumab 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. iii. Dose & Route of administration 60mg administered as a single subcutaneous injection once every 6 months into the thigh, abdomen or back of arm. Patients must be calcium and vitamin D replete and in most cases advice will be given to provide supplementation with calcium and vitamin D (daily dosage: calcium 1g and colecalciferol 800 units). No dosage adjustment is required in patients with renal impairment. iv. Duration of treatment Contact specialist after 5 years of treatment to determine if treatment should continue. There is a risk of rebound fractures, especially vertebral fractures, with the cessation of treatment. Bone mineral density is also likely to return back to prior to commencing denosumab. v. Adverse effects Common (≥ 1/100 to < 1/10): urinary tract infection, upper respiratory tract infection, sciatica, abdominal discomfort, constipation, rash and pain in extremity. Uncommon (≥ 1/1000 to < 1/100): diverticulitis, cellulitis, ear infection. Skin infections requiring hospitalisations Rare (≥ 1/10,000 to < 1/1,000): atypical femur fracture, osteonecrosis of the jaw (ONJ), hypocalcaemia (< 1.88 mmols/l), The above details are not a complete list and the current BNF and the SPC should be consulted. vi. Monitoring Requirements Prior to initiation of therapy 1) Vitamin D deficiency and hypocalcaemia must be corrected before initiation of therapy. 2) A dental examination should be considered prior to treatment with Denosumab in patients with concomitant risk factors (refer to SPC)

CLINICAL INFORMATION. i. Prescribed indications For the treatment of osteoporosis in men and postmenopausal women at increased risk of fractures, and for the treatment of bone loss associated with hormone ablation in men with prostate cancer. Not relevant to this section Alendronic acid remains the first line treatment for osteoporosis in accordance with NICE guidance. Approximately 25% of patients cannot be treated with alendronic acid because of side effects, inability to comply with dosing instructions or malabsorption leading to inefficacy. Risedronate should also be tried if appropriate before Denosumab is considered. Denosumab provides another option for those patients also unable to take risedronate and has been recommended by NICE in this context. The guidance is available at ▇▇▇▇://▇▇▇▇▇▇▇▇.▇▇▇▇.▇▇▇.▇▇/TA204. ii. Therapeutic summary Denosumab 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. iii. Dose & Route of administration 60mg administered as a single subcutaneous injection once every 6 months into the thigh, abdomen or back of arm. Patients must be calcium and vitamin D replete and in most cases advice will be given to provide supplementation with calcium and vitamin D (daily dosage: calcium 1g and colecalciferol 800 units). No dosage adjustment is required in patients with renal impairment. iv. Duration of treatment Contact specialist after 5 years of treatment to determine if treatment should continue. There is a risk of rebound fractures, especially vertebral fractures, with the cessation of treatment. Bone mineral density is also likely to return back to prior to commencing denosumab. v. Adverse effects Common (≥ 1/100 to < 1/10): urinary tract infection, upper respiratory tract infection, sciatica, abdominal discomfort, constipation, rash and pain in extremity. Uncommon (≥ 1/1000 to < 1/100): diverticulitis, cellulitis, ear infection. Skin infections requiring hospitalisations Rare (≥ 1/10,000 to < 1/1,000): atypical femur fracture, osteonecrosis of the jaw (ONJ), hypocalcaemia (< 1.88 mmols/l), The above details are not a complete list and the current BNF and the SPC should be consulted. vi. Monitoring Requirements Prior to initiation of therapy 1) Vitamin D deficiency and hypocalcaemia must be corrected before initiation of therapy. 2) A dental examination should be considered prior to treatment with Denosumab in patients with concomitant risk factors (refer to SPC)) Subsequent monitoring 1) Monitoring of calcium levels prior to each injection is recommended ensuring that the adjusted calcium is not less than 2.20mmol/L and the vitamin D level is >50nmol/l prior to the injection 2) Patients receiving denosumab may develop skin infections (predominantly cellulitis) leading to hospitalisation and thus should be advised to seek prompt medical attention if they develop signs or symptoms of cellulitis.