Denosumab is approved by the FDA for the treatment of osteoporosis in postmenopausal women at high risk of fracture and to increase bone mass in men with osteoporosis at high risk of fracture. The medicine is also approved to increase bone mass in men receiving androgen deprivation therapy for prostate cancer who are at high risk of fracture and to increase bone mass in women at high risk for fracture receiving aromatase inhibitor therapy for breast cancer.
U.S. Food and Drug Administration (FDA) has approved the use of Prolia®(denosumab) for the treatment of glucocorticoid-induced osteoporosis (GIOP) in men and women at high risk of fracture, 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. This approval is based on data from a Phase 3 study which showed patients on glucocorticoid therapy who received Prolia had greater gains in bone mineral density (BMD) compared to those who received active comparator (risedronate).
Denosumab is a RANK ligand (RANKL) inhibitor/human monoclonal antibody. A healthcare professional gives denosumab by injection every six months. Denosumab increases bone density and reduces the incidence of spine and non-spine fractures, including hip fractures.
Side Effects
Denosumab may lower the calcium levels in the blood. If blood calcium levels are low before receiving denosumab, the low calcium level must be corrected before giving the medicine or it will get worse. Patients need to have a blood test after each dose to confirm that blood calcium level is not abnormally low. Signs of low calcium levels include spasms, twitches or cramps in the muscles; or numbness and tingling in the fingers, toes or around the mouth. If any of these symptoms are seen while on this medicine, patients should contact their healthcare provider. Most patients with low calcium levels, however, do not show these signs.
People who have weak immune systems or take other medicines that affect the immune system may have an increased chance of having serious infections with denosumab. Even patients who have no immune system problems may be at higher risk of certain infections such as those of the skin. Patients should contact their healthcare provider right away if signs of infection occur. These signs may include fever, chills, red and swollen skin, skin that is hot or sore to the touch, severe pains in the abdomen, or pain or burning when passing urine or passing urine more frequently and in small amounts.
Denosumab may also cause skin rashes. Call your healthcare provider if you notice any abnormal skin-related symptoms. Any groin or thigh discomfort or pain should be reported to your healthcare provider as well as any unhealed dental lesions. Patients should practice good dental care during treatment and should have an examination of the mouth by a doctor or dentist before starting the medicine.
Prolia® REMS
A REMS (Risk Evaluation and Mitigation Strategy) is a program required by the Food and Drug Administration to manage known or potential serious risks associated with a drug product.
The purpose of the Prolia® REMS is to inform healthcare providers and patients about the following serious risk of:
- Severe Hypocalcemia in Patients with Advanced Kidney Disease
The Prolia® REMS program materials are designed to inform healthcare providers and patients about this risk with Prolia®. The Prolia® REMS program materials include a REMS Letter for Healthcare Providers and a Patient Guide. It is important that you discuss with each patient the information included in the Patient Guide.
Materials for Healthcare Providers
REMS Letter for Healthcare Providers
Patient Guide
Prescribing Information
Materials for Patients
CONEXXENCE (denosumab-bnht) REMS
CONEXXENCE (denosumab-bnht) is biosimilar to PROLIA® (denosumab).
The CONEXXENCE REMS (Risk Evaluation and Mitigation Strategy) is a safety program required by the Food and Drug Administration.
Severe Hypocalcemia in Patients with Advanced Kidney Disease
Patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m2), including dialysis-dependent patients, are at greater risk of severe hypocalcemia following CONEXXENCE administration.
- Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported.
- To minimize the risk of hypocalcemia in patients with advanced chronic kidney disease (CKD):
- Evaluate for the presence of chronic kidney disease-mineral 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 assessing bone turnover status (serum markers of bone turnover or bone biopsy) to evaluate the underlying bone disease that may be present.
- Monitor serum calcium weekly for the first month after CONEXXENCE administration and monthly thereafter.
- Coordinate care with healthcare providers with expertise in CKD-MBD for patients with advanced chronic kidney disease.
Role of the Healthcare Provider
- Provide each patient with a copy of the Patient Guide.
- Review information in the Patient Guide with each patient, including the serious risk of CONEXXENCE and the symptoms of severe hypocalcemia.
- Advise each patient to seek prompt medical attention if they have signs or symptoms of severe hypocalcemia.
This letter does not contain the complete safety profile for CONEXXENCE. Please review the Prescribing Information enclosed. All CONEXXENCE REMS materials are also available at www.conexxencerems.com.
Reporting Adverse Events
To report Adverse Reactions with CONEXXENCE, please call Fresenius Kabi USA, LLC Vigilance at 1-800-551-7176, or report the event at FDA MedWatch.