Important Safety Information for ENOBY™ (denosumab-qbde) Injection
IMPORTANT SAFETY INFORMATION
WARNING: 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 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 ENOBY™ in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with ENOBY™ 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)].
CONTRAINDICATIONS
ENOBY™ is contraindicated in:
- Patients with hypocalcemia: Pre-existing hypocalcemia must be corrected prior to initiating therapy with ENOBY™.
- Pregnant women: Denosumab products may cause fetal harm when administered to a pregnant woman. In women of reproductive potential, pregnancy testing should be performed prior to initiating treatment with ENOBY™.
- Patients with hypersensitivity to denosumab products: ENOBYTM is contraindicated in patients with a history of systemic hypersensitivity to any component of the product. Reactions have included anaphylaxis, facial swelling, and urticaria.
WARNINGS & PRECAUTIONS
- Severe Hypocalcemia and Mineral Metabolism Changes – Denosumab products can cause severe hypocalcemia and fatal cases have been reported. Patients with advanced chronic kidney disease including dialysis-dependent patients are at greater risk for severe hypocalcemia following denosumab products administration.
- Drug Products with Same Active Ingredient – Patients receiving ENOBY™ should not receive other denosumab products concomitantly.
- Hypersensitivity – Clinically significant hypersensitivity including anaphylaxis has been reported with denosumab products. Symptoms have included hypotension, dyspnea, throat tightness, facial and upper airway edema, pruritus, and urticaria.
- Osteonecrosis of the Jaw – Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing. ONJ has been reported in patients receiving denosumab products.
- Atypical Subtrochanteric and Diaphyseal Femoral Fractures – Atypical low energy or low trauma fractures of the shaft have been reported in patients receiving denosumab products.
- Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation – Following discontinuation of denosumab treatment, fracture risk increases, including the risk of multiple vertebral fractures.
- Serious Infections – In a clinical trial of over 7,800 women with postmenopausal osteoporosis, serious infections leading to hospitalization were reported more frequently in the denosumab group than in the placebo group.
- Dermatologic Adverse Reactions – In a large clinical trial of over 7,800 women with postmenopausal osteoporosis, epidermal and dermal adverse events such as dermatitis, eczema, and rashes occurred at a significantly higher rate in the denosumab group compared to the placebo group.
- Musculoskeletal Pain – In postmarketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking denosumab products.
- Suppression of Bone Turnover – In clinical trials in women with postmenopausal osteoporosis, treatment with denosumab resulted in significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry.
- Hypercalcemia in Pediatric Patients with Osteogenesis Imperfecta – ENOBY™ 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.
ADVERSE REACTIONS
The most common adverse reactions reported with denosumab products in patients with postmenopausal osteoporosis are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis.
The most common adverse reactions reported with denosumab products in men with osteoporosis are back pain, arthralgia, and nasopharyngitis.
The most common adverse reactions reported with denosumab products in patients with glucocorticoid-induced osteoporosis are back pain, hypertension, bronchitis, and headache.
The most common (per patient incidence ≥ 10%) adverse reactions reported with denosumab products in patients with bone loss receiving androgen deprivation therapy for prostate cancer or adjuvant aromatase inhibitor therapy for breast cancer are arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials.
USE IN SPECIFIC POPULATIONS
Pregnancy: ENOBY™ is contraindicated for use in pregnant women because it may cause harm to a fetus. There are insufficient data with denosumab products use in pregnant women to inform any drug-associated risks for adverse developmental outcomes.
Females of Reproductive Potential: Advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of ENOBY™.
INDICATIONS AND USAGE
Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture
ENOBY™ 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.
Treatment to Increase Bone Mass in Men with Osteoporosis
ENOBY™ 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.
Treatment of Glucocorticoid-Induced Osteoporosis
ENOBY™ 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.
Treatment of Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer
ENOBY™ 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.
Treatment of Bone Loss in Women Receiving Adjuvant Aromatase Inhibitor Therapy for Breast Cancer
ENOBY™ is indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.
ENDING INFORMATION
Patient Counseling Information should be shared with the patient prior to administration.
For additional information, please refer to the Package Insert for full prescribing information, available on www.hikma.com.
To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800 FDA-1088 or www.fda.gov/medwatch.
Manufactured by:
Hikma Pharmaceuticals USA Inc.
2 Esterbrook Lane
Cherry Hill, NJ 08003 USA
U.S. License No. 2356
Product of Hungary