General MedicationsSUBCUTANEOUSBlack Box

CONEXXENCE

DENOSUMAB

Standard Dose

2 DOSAGE AND ADMINISTRATION Pregnancy must be ruled out prior to administration of Conexxence. ( 2.1 ) Before initiating Conexxence 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 ) Conexxence 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 Conexxence Pregnancy must be ruled out prior to administration of Conexxence. Perform pregnancy testing in all females of reproductive potential prior to administration of Conexxence. Based on findings in animals, denosumab products 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 Conexxence 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 Conexxence 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 Conexxence should be administered by a healthcare provider. The recommended dose of Conexxence is 60 mg administered as a single subcutaneous injection once every 6 months. Administer Conexxence 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 Conexxence 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. Conexxence is a clear, colorless to pale yellow solution that is free from visible particles. Do not use if the solution is discolored or cloudy or if the solution contains particles or foreign particulate matter. Prior to administration, Conexxence 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 Conexxence in any other way [see How Supplied/Storage and Handling ( 16 )]. Do not shake the prefilled syringe. Instructions for Administration of Conexxence Prefilled Syringe with Needle Safety Guard IMPORTANT: In order to minimize accidental needlesticks, the Conexxence single-dose prefilled syringe has an automatic clear needle safety guard. Conexxence prefilled syringe (Before & After Use) . See figure below. Step 1: Remove Needle Cap (see Figure A ) Do not hold the prefilled syringe by the plunger rod. Do not twist or bend the needle cap. Figure A Step 2: Administer Subcutaneous Injection Choose an injection site. The recommended injection sites for Conexxence include (see Figure B ): upper thigh abdomen upper arm Figure B Do not administer into muscle or blood vessel. Pinch the skin and insert the needle at a 45 to 90-degree angle. Push the plunger with a slow and constant pressure until you cannot press further and have injected all the liquid subcutaneously (see Figure C ). You may hear or feel a “click”. Figure C Step 3. Release Plunger Keeping the prefilled syringe at the injection site, slowly release the plunger and lift syringe off the skin. The clear needle guard will automatically cover the needle (see Figure D ). Do not recap the needle. Immediately dispose of the used prefilled syringe into a sharps disposal container. Figure D Figure Figure A Figure B Figure C Figure D

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE Conexxence 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 Conexxence 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, denosumab 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 Conexxence 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 Conexxence 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 Conexxence 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 Conexxence 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, denosumab 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 Conexxence 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 Conexxence 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 Conexxence 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 denosumab 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 Conexxence 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 Conexxence. ( 2.1 ) Before initiating Conexxence 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 ) Conexxence 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 Conexxence Pregnancy must be ruled out prior to administration of Conexxence. Perform pregnancy testing in all females of reproductive potential prior to administration of Conexxence. Based on findings in animals, denosumab products 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 Conexxence 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 Conexxence 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 Conexxence should be administered by a healthcare provider. The recommended dose of Conexxence is 60 mg administered as a single subcutaneous injection once every 6 months. Administer Conexxence 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

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 denosumab products 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 Conexxence in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Conexxence 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 denosumab products 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 Conexxence in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Conexxence 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 Conexxence.
• 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.