Denosis 120 Subcutaneous Injection

Denosis 120 Subcutaneous Injection is used for: Treatment of postmenopausal women with osteoporosis at high risk for fracture Treatment to increase bone mass in men with osteoporosis at high risk for fracture Treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

Subcutaneous Osteoporosis 60 mg SC every 6 months Supplement with calcium 1000 mg/day and vitamin D 400 IU/day Aromatase Inhibitor-Induced Bone Loss Women with breast cancer: 60 mg SC every 6 months Androgen Deprivation-Induced Bone Loss Men with prostate cancer: 60 mg SC every 6 months Denosumab 120mg Subcutaneous Skeletal-Related Events Prevention of skeletal-related events (SREs; eg, bone fractures and pain) in patients with bone metastases from solid tumors 120 mg (1.7 mL) SC every 4 weeks Giant Cell Tumor Treatment of adults and skeletally mature adolescents with giant cell tumor of bone in whom surgical resection is impossible or is likely to result in severe morbidity 120 mg SC every 4 weeks with an additional 120 mg on days 8 and 15 during the first month of therapy Hypercalcemia of Malignancy Indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy 120 mg SC q4wk Give 2 additional 120 mg doses during the first month of therapy on Days 8 and 15

Renal Impairment: Based on the available safety and efficacy data in the elderly, no dosage adjustment is required in patients with renal impairment. Patients with severe renal impairment [creatinine clearance (CrCl) <30 mL/min] or receiving dialysis are at greater risk of developing hypocalcemia. Adequate intake of calcium and vitamin D is important in patients with severe renal impairment or receiving dialysis.

SC Preparation Visually inspect for particulate matter and discoloration prior to administration Solution should appear clear, colorless-to-pale yellow solution that may contain trace amounts of translucent to white proteinaceous particles Discard if discolored or cloudy, or if the solution contains many particles or foreign particulate matter Before administering, remove from refrigerator bring to room temperature (up to 25ºC/77ºF); generally takes 15-30 minutes; do not warm in any other way To minimize accidental needlesticks, single-dose prefilled syringe has a green safety guard; manually activate safety guard after injection is given; DO NOT slide green safety guard forward over needle before administering; it will lock in place and prevent injection SC Administration SC administration only Must be administered by healthcare professional Use a 27-gauge needle to withdraw and inject the entire contents of the vial; do not reenter the vial Do not administer intradermally, IM, or IV Administer SC in upper arm, upper thigh, or abdomen Administer calcium and vitamin D as needed to treat or prevent hypocalcemia Avoid vigorous shaking of vial/syringe Discard vial after single-dose or entry

Clinically significant hypersensitivity to denosumab or to any of the components. Hypocalcemia.

Patients with advanced chronic kidney disease are at greater risk of severe hypocalcemia following Denosumab administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported. The presence of chronic kidney disease-mineral bone disorder (CKDMBD) markedly increases the risk of hypocalcemia. Prior to initiating Denosumab in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Denosumab in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD. Hypersensitivity including anaphylactic reactions may occur. Discontinue permanently if a clinically significant reaction occurs. Hypocalcemia: Pre-existing hypocalcemia must be corrected before initiating Denosumab. May worsen, especially in patients with renal impairment. Adequately supplement all patients with calcium and vitamin D. Concomitant use of calcimimetic drugs may also worsen hypocalcemia risk. Evaluate for presence of chronic kidney disease mineral-bone disorder. Monitor serum calcium. Osteonecrosis of the jaw: Has been reported with Denosumab Monitor for symptoms. Atypical femoral fractures: Have been reported. Evaluate patients with thigh or groin pain to rule out a femoral fracture. Multiple vertebral fractures have been reported following Denosumab discontinuation. Patients should be transitioned to another antiresorptive agent if Denosumab is discontinued. Serious infections including skin infections: May occur, including those leading to hospitalization. Advise patients to seek prompt medical attention if they develop signs or symptoms of infection, including cellulitis. Dermatologic reactions: Dermatitis, rashes, and eczema have been reported. Consider discontinuing Denosumab if severe symptoms develop. Severe bone, joint, muscle pain may occur. Discontinue use if severe symptoms develop. Suppression of bone turnover: Significant suppression has been demonstrated. Monitor for the consequences of bone over-suppression. MONITORING PARAMETERS Correct hypocalcaemia and vitamin D deficiency before starting. Monitor plasmacalcium concentration during therapy.

Pregnancy Contraindicated Based on findings in animals and its mechanism of action, denosumab can cause fetal harm when administered to a pregnant woman In utero exposure in cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 50-fold higher than the recommended human dose based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality, and absent lymph nodes, abnormal bone growth, and decreased neonatal growth Present at low concentrations (~2% of serum exposure) in seminal fluid of male subjects receiving therapy; following vaginal intercourse, maximum amount of denosumab delivered to a female partner would result in exposures ~11,000 times lower than the prescribed 60 mg subcutaneous dose; male condom use not necessary as it is unlikely that a female partner or fetus would be exposed to pharmacologically relevant concentrations of denosumab via seminal fluid Contraception Females: Advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of denosumab Males: Denosumab was present at low concentrations (~2% of serum exposure) in the seminal fluid of male subjects; condom use would not be necessary as it is unlikely that a female partner or fetus would be exposed to pharmacologically relevant concentrations of denosumab via seminal fluid Lactation There is no information regarding presence of denosumab in human milk, effects on breastfed infant, or effects on milk production;

Increased risk of serious infections w/ immunosuppressive agents. Denosumab did not affect the pharmacokinetics of midazolam, a drug metabolised by cytochrome P450 3A4 (CYP3A4). Incompatibilities: Denosumab must not be mixed with other medicinal products. Contraindicated (0) Serious (10) axicabtagene ciloleucel brexucabtagene autoleucel ciltacabtagene autoleucel etrasimod idecabtagene vicleucel influenza virus vaccine quadrivalent, adjuvanted influenza virus vaccine trivalent, adjuvanted lisocabtagene maraleucel palifermin tisagenlecleucel

Side effects of Denosumab : >10% Back pain (34.7%),Extremity pain (11.7%) 1-10% Musculoskeletal pain (7.6%),Hypercholesterolemia (7.2%),Cystitis (5.9%),Upper respiratory tract infection (4.9%),New malignancies (4.8%, compared with 4.3% in placebo group),Sciatica (4.6%),Nonfatal serious infection (4%),Bone pain (3.7%),Anemia (3.3%),Upper abdominal pain (3.3%),Rash (2.5%),Flatulence (2.2%),Osteonecrosis of jaw (2.2%),Pruritus (2.2%),Hypocalcemia (1.7%) <1% Serious infection of abdomen resulting in hospitalization (0.9%),Serious infection of urinary tract resulting in hospitalization (0.7%),Serious infection resulting in death (0.2%),Pancreatitis (0.2%),Serious infection of ear resulting in hospitalization (0.1%)

Denosumab is a human monoclonal antibody (IgG2) that targets and binds with high affinity and specificity to receptor activator of nuclear factor kappa-B ligand (RANKL) preventing RANKL from activating its only receptor, RANK, on the surface of osteoclasts and their precursors, independent of bone surface. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function and survival. Denosumab therefore reduces bone resorption and increases bone mass and strength in both cortical and trabecular bone.

Denosis 120 120 mg/1.7 ml Subcutaneous Injection manufactured by Incepta Pharmaceuticals Ltd.. Its generic name is Denosumab. Denosis 120 is availble in Bangladesh. Farmaco BD drug index information on Denosis 120 Subcutaneous Injection is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.