General MedicationsSUBCUTANEOUSBlack Box

Prolia

DENOSUMAB

Standard Dose

2 DOSAGE AND ADMINISTRATION Pregnancy must be ruled out prior to administration of Prolia. ( 2.1 ) Before initiating Prolia in patients with advanced chronic kidney disease, including dialysis patients, evaluate for the presence of chronic kidney disease mineral and bone disorder with intact parathyroid hormone, serum calcium, 25(OH) vitamin D, and 1,25(OH) 2 vitamin D. ( 2.2 , 5.1 , 8.6 ) Prolia should be administered by a healthcare provider. ( 2.3 ) Administer 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. ( 2.3 ) Instruct patients to take calcium 1000 mg daily and at least 400 IU vitamin D daily. ( 2.3 ) 2.1 Pregnancy Testing Prior to Initiation of Prolia Pregnancy must be ruled out prior to administration of Prolia. Perform pregnancy testing in all females of reproductive potential prior to administration of Prolia. Based on findings in animals, Prolia can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1 , 8.3) ] . 2.2 Laboratory Testing in Patients with Advanced Chronic Kidney Disease Prior to Initiation of Prolia In patients with advanced chronic kidney disease [i.e., estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m 2 ], including dialysis-dependent patients, evaluate for the presence of chronic kidney disease mineral and bone disorder (CKD-MBD) with intact parathyroid hormone (iPTH), serum calcium, 25(OH) vitamin D, and 1,25 (OH) 2 vitamin D prior to decisions regarding Prolia treatment. Consider also assessing bone turnover status (serum markers of bone turnover or bone biopsy) to evaluate the underlying bone disease that may be present [see Warnings and Precautions (5.1) ] . 2.3 Recommended Dosage Prolia should be administered by a healthcare provider. The recommended dose of Prolia is 60 mg administered as a single subcutaneous injection once every 6 months. Administer Prolia via subcutaneous injection in the upper arm, the upper thigh, or the abdomen. All patients should receive calcium 1000 mg daily and at least 400 IU vitamin D daily [see Warnings and Precautions (5.1) ] . If a dose of Prolia is missed, administer the injection as soon as the patient is available. Thereafter, schedule injections every 6 months from the date of the last injection. 2.4 Preparation and Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Prolia is a clear, colorless to pale yellow solution that may contain trace amounts of translucent to white proteinaceous particles. Do not use if the solution is discolored or cloudy or if the solution contains many particles or foreign particulate matter. Prior to administration, Prolia may be removed from the refrigerator and brought to room temperature up to 25°C (77°F) by standing in the original container. This generally takes 15 to 30 minutes. Do not warm Prolia in any other way [see How Supplied/Storage and Handling (16) ] . Instructions for Administration of Prolia Prefilled Syringe with Needle Safety Guard IMPORTANT: In order to minimize accidental needlesticks, the Prolia single-dose prefilled syringe will have a green safety guard; manually activate the safety guard after the injection is given. DO NOT slide the green safety guard forward over the needle before administering the injection; it will lock in place and prevent injection. Activate the green safety guard (slide over the needle) after the injection. Step 1: Remove Gray Needle Cap Remove needle cap. Step 2: Administer Subcutaneous Injection Choose an injection site. The recommended injection sites for Prolia include: the upper arm OR the upper thigh OR the abdomen. Insert needle and inject all the liquid subcutaneously. Do not administer into muscle or blood vessel. DO NOT put gray needle cap back on needle. Step 3: Immediately Slide Green Safety Guard Over Needle With the needle pointing away from you. Hold the prefilled syringe by the clear finger grip with one hand. Then, with the other hand, grasp the green safety guard by its base and gently slide it towards the needle until the green safety guard locks securely in place and/or you hear a "click". DO NOT grip the green safety guard too firmly - it will move easily if you hold and slide it gently. Hold clear finger grip. Gently slide green safety guard over needle and lock securely in place. Do not grip green safety guard too firmly when sliding over needle. Immediately dispose of the syringe and needle cap in the nearest sharps container. DO NOT put the needle cap back on the used syringe. Image Image Image Image Image Image Image

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE Prolia is a RANK ligand (RANKL) inhibitor indicated for treatment: of postmenopausal women with osteoporosis at high risk for fracture ( 1.1 ) to increase bone mass in men with osteoporosis at high risk for fracture ( 1.2 ) of glucocorticoid-induced osteoporosis in men and women at high risk for fracture ( 1.3 ) to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer ( 1.4 ) to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer ( 1.5 ) 1.1 Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.

Summary

In postmenopausal women with osteoporosis, Prolia reduces the incidence of vertebral, nonvertebral, and hip fractures [see Clinical Studies (14.1) ] . 1.2 Treatment to Increase Bone Mass in Men with Osteoporosis Prolia is indicated for treatment to increase bone mass in men with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy [see Clinical Studies (14.2) ] . 1.3 Treatment of Glucocorticoid-Induced Osteoporosis Prolia is indicated for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk of fracture who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and expected to remain on glucocorticoids for at least 6 months.

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE Prolia is a RANK ligand (RANKL) inhibitor indicated for treatment: of postmenopausal women with osteoporosis at high risk for fracture ( 1.1 ) to increase bone mass in men with osteoporosis at high risk for fracture ( 1.2 ) of glucocorticoid-induced osteoporosis in men and women at high risk for fracture ( 1.3 ) to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer ( 1.4 ) to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer ( 1.5 ) 1.1 Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, Prolia reduces the incidence of vertebral, nonvertebral, and hip fractures [see Clinical Studies (14.1) ] . 1.2 Treatment to Increase Bone Mass in Men with Osteoporosis Prolia is indicated for treatment to increase bone mass in men with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy [see Clinical Studies (14.2) ] . 1.3 Treatment of Glucocorticoid-Induced Osteoporosis Prolia is indicated for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk of fracture who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and expected to remain on glucocorticoids for at least 6 months. High risk of fracture is defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy [see Clinical Studies (14.3) ] . 1.4 Treatment of Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer Prolia is indicated as a treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy (ADT) for nonmetastatic prostate cancer. In these patients Prolia also reduced the incidence of vertebral fractures [see Clinical Studies (14.4) ] . 1.5 Treatment of Bone Loss in Women Receiving Adjuvant Aromatase Inhibitor Therapy for Breast Cancer Prolia is indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer [see Clinical Studies (14.5) ] . Dosage and administration 2 DOSAGE AND ADMINISTRATION Pregnancy must be ruled out prior to administration of Prolia. ( 2.1 ) Before initiating Prolia in patients with advanced chronic kidney disease, including dialysis patients, evaluate for the presence of chronic kidney disease mineral and bone disorder with intact parathyroid hormone, serum calcium, 25(OH) vitamin D, and 1,25(OH) 2 vitamin D. ( 2.2 , 5.1 , 8.6 ) Prolia should be administered by a healthcare provider. ( 2.3 ) Administer 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. ( 2.3 ) Instruct patients to take calcium 1000 mg daily and at least 400 IU vitamin D daily. ( 2.3 ) 2.1 Pregnancy Testing Prior to Initiation of Prolia Pregnancy must be ruled out prior to administration of Prolia. Perform pregnancy testing in all females of reproductive potential prior to administration of Prolia. Based on findings in animals, Prolia can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1 , 8.3) ] . 2.2 Laboratory Testing in Patients with Advanced Chronic Kidney Disease Prior to Initiation of Prolia In patients with advanced chronic kidney disease [i.e., estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m 2 ], including dialysis-dependent patients, evaluate for the presence of chronic kidney disease mineral and bone disorder (CKD-MBD) with intact parathyroid hormone (iPTH), serum calcium, 25(OH) vitamin D, and 1,25 (OH) 2 vitamin D prior to decisions regarding Prolia treatment. Consider also assessing bone turnover status (serum markers of bone turnover or bone biopsy) to evaluate the underlying bone disease that may be present [see Warnings and Precautions (5.1) ] . 2.3 Recommended Dosage Prolia should be administered by a healthcare provider. The recommended dose of Prolia is 60 mg administered as a single subcutaneous injection once every 6 months. Administer Prolia via subcutaneous injection in the upper arm, the upper thigh, or the abdomen. All patients should receive calcium 1000 mg daily and at least 400 IU vitamin D daily [see Warnings and Precautions (5.1) ] . If a dose of Prolia is missed, administer the injection as soon as the patient is

Boxed Warning

WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE Patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m 2 ), including dialysis-dependent patients, are at greater risk of severe hypocalcemia following Prolia administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported [see Warnings and Precautions (5.1) ] . The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia in these patients [see Warnings and Precautions (5.1) ] . Prior to initiating Prolia in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Prolia in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ]. WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE See full prescribing information for complete boxed warning. Patients with advanced chronic kidney disease are at greater risk of severe hypocalcemia following Prolia administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported. ( 5.1 ) The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia. ( 5.1 ) Prior to initiating Prolia in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Prolia in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD. ( 2.2 , 5.1 )

Monitoring

• 5 WARNINGS AND PRECAUTIONS Hypocalcemia: Pre-existing hypocalcemia must be corrected before initiating Prolia.
• 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.

Interaction Notes

• Review official label interaction section.