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.
- The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia.
- Prior to initiating OSVYRTI in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with OSVYRTI in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD.
Contraindications: OSVYRTI is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating OSVYRTI. OSVYRTI is contraindicated in women who are pregnant and may cause fetal harm. In women of reproductive potential, pregnancy testing should be performed prior to initiating treatment. OSVYRTI is contraindicated in patients with hypersensitivity to denosumab products. Reactions have included anaphylaxis, facial swelling and urticaria.
Severe Hypocalcemia and Mineral Metabolism Changes: Pre-existing hypocalcemia must be corrected prior to initiating therapy; severe hypocalcemia and fatal cases have been reported with denosumab products. Adequately supplement all patients with calcium and vitamin D.
In patients without advanced CKD who are predisposed to hypocalcemia and disturbances of mineral metabolism, assess serum calcium and mineral levels (phosphorus and magnesium) 10 to 14 days after OSVYRTI injection. In some postmarketing cases, hypocalcemia persisted for weeks or months and required frequent monitoring and intravenous and/or oral calcium replacement, with or without vitamin D.
Patients with Advanced Chronic Kidney Disease
Patients with advanced chronic kidney disease (eGFR <30 mL/min/1.73 m²), including dialysis-dependent patients, are at high risk for severe hypocalcemia after denosumab products administration, which can lead to hospitalization, life-threatening events, or death. CDK-MBD and concomitant calcimimetic use further increase risk.
Assess for mineral bone disorder before OSVYRTI treatment, monitor serum calcium weekly for the first month, then monthly, and educate patients on hypocalcemia symptoms and the need for adequate calcium and activated vitamin D supplementation.
Same Active Ingredient: Patients receiving OSVYRTI should not receive other denosumab products concomitantly.
Hypersensitivity: Clinically significant hypersensitivity including anaphylaxis has been reported with denosumab products. Symptoms included hypotension, dyspnea, throat tightness, facial and upper airway edema, pruritus and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of OSVYRTI.
Osteonecrosis of the Jaw (ONJ): ONJ, which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing and has been reported in patients receiving denosumab products. An oral exam should be performed prior to initiation of OSVYRTI. Concomitant administration of drugs associated with ONJ may increase the risk of developing ONJ. The risk of ONJ may increase with duration of exposure to denosumab products.
For patients requiring invasive dental procedures, clinical judgment should guide the management plan based on individual benefit-risk assessment.
Patients suspected of having or who develop ONJ should receive care by a dentist or an oral surgeon. Extensive dental surgery to treat ONJ may exacerbate the condition.
Discontinuation of OSVYRTI should be considered based on individual benefit-risk assessment.
Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Atypical low-energy, or low trauma fractures of the shaft have been reported with denosumab products. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with antiresorptive agents.
Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral, and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture.
During OSVYRTI treatment, advise patients to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be evaluated to rule out an incomplete femur fracture. Patients presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of OSVYRTI therapy should be considered, pending a risk/benefit assessment, on an individual basis.
Multiple Vertebral Fractures Following Discontinuation of Treatment: Following discontinuation of denosumab treatment, fracture risk increases, including the risk of multiple vertebral fractures.
New vertebral fractures occurred as early as 7 months (on average 19 months) after the last dose of denosumab. Prior vertebral fracture was a predictor of multiple vertebral fractures after denosumab discontinuation. Evaluate an individual’s benefit/risk before initiating treatment with OSVYRTI. If OSVYRTI treatment is discontinued, patients should be transitioned to an alternative antiresorptive therapy.
Serious Infections: Serious infections leading to hospitalization were reported more frequently in patients taking denosumab. Serious skin infections, and infections of the abdomen, urinary tract and ear were more frequent in patients treated with denosumab.
Endocarditis was also reported more frequently in denosumab-treated patients. Advise patients to seek prompt medical attention if they develop signs or symptoms of severe infection, including cellulitis.
Patients on concomitant immunosuppressant agents or with impaired immune systems may be at increased risk for serious infections. In patients who develop serious infections while on OSVYRTI, prescribers should assess the need for continued therapy.
Dermatologic Adverse Reactions: Epidermal and dermal adverse events such as dermatitis, eczema and rashes occurred at a significantly higher rate in patients taking denosumab. Most of these events were not specific to the injection site. Consider discontinuing OSVYRTI if severe symptoms develop.
Musculoskeletal Pain: Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported with denosumab products. Consider discontinuing OSVYRTI use if severe symptoms develop.
Suppression of Bone Turnover: Treatment with denosumab resulted in significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry. The significance and effect of long-term treatment with denosumab products are unknown. Monitor patients for the consequences, including ONJ, atypical fractures, and delayed fracture healing.
Hypercalcemia in Pediatric Patients with Osteogenesis Imperfecta: OSVYRTI is not approved for use in pediatric patients. Hypercalcemia has been reported in pediatric patients with osteogenesis imperfecta treated with denosumab products. Some cases required hospitalization.
Most Common Adverse Reactions:
- Postmenopausal osteoporosis: Greater than 5% and more common than placebo: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials.
- Male osteoporosis: Greater than 5% and more common than placebo: back pain, arthralgia, and nasopharyngitis.
- Glucocorticoid-induced osteoporosis: Greater than 3% and more common than active-control group were: back pain, hypertension, bronchitis, and headache.
- Bone loss due to hormone ablation for cancer: Greater than or equal to 10% and more common than placebo: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials.
INDICATIONS
OSVYRTI is a RANK ligand (RANKL) inhibitor indicated for treatment:
- of postmenopausal women with osteoporosis at high risk for fracture
- to increase bone mass in men with osteoporosis at high risk for fracture
- of glucocorticoid-induced osteoporosis in men and women at high risk for fracture
- to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
- to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer
To report SUSPECTED ADVERSE REACTIONS, contact Accord BioPharma Inc at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
OSVYRTI (denosumab-desu) injection is supplied in a 60 mg/mL single-dose prefilled syringe.
Click here for full Prescribing Information, including Boxed Warning.
PROLIA® (denosumab) is a registered trademark of Amgen Inc.
