Prolia Special Precautions

Drug Products with Same Active Ingredient: Denosumab (Prolia) contains the same active ingredient (denosumab) found in denosumab (Xgeva). Patients receiving denosumab (Prolia) should not receive denosumab (Xgeva).
Hypersensitivity: Clinically significant hypersensitivity including anaphylaxis has been reported with denosumab (Prolia). Symptoms have 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 denosumab (Prolia) [see Contraindications and Postmarketing Experience under Adverse Reactions].
Hypocalcemia and Mineral Metabolism: Hypocalcemia may be exacerbated by the use of denosumab (Prolia). Pre-existing hypocalcemia must be corrected prior to initiating therapy with denosumab (Prolia). In patients predisposed to hypocalcemia and disturbances of mineral metabolism (e.g. history of hypoparathyroidism, thyroid surgery, parathyroid surgery, malabsorption syndromes, excision of small intestine, severe renal impairment [creatinine clearance < 30 mL/min] or receiving dialysis), clinical monitoring of calcium and mineral levels (phosphorus and magnesium) is highly recommended within 14 days of denosumab (Prolia) 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.
Hypocalcemia following denosumab (Prolia) administration is a significant risk in patients with severe renal impairment [creatinine clearance < 30 mL/min] or receiving dialysis. These patients may also develop marked elevations of serum parathyroid hormone (PTH). Instruct all patients with severe renal impairment, including those receiving dialysis, about the symptoms of hypocalcemia and the importance of maintaining calcium levels with adequate calcium and vitamin D supplementation.
Adequately supplement all patients with calcium and vitamin D [see Information Essential to Safe Dosing or Administration under Dosage & Administration, Contraindications, and Clinical Trials Experience under Adverse Reactions].
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 [see Clinical Trials Experience under Adverse Reactions]. A routine oral exam should be performed by the prescriber prior to initiation of denosumab (Prolia) treatment. A dental examination with appropriate preventive dentistry is recommended prior to treatment with denosumab (Prolia) in patients with risk factors for ONJ such as invasive dental procedures (e.g. tooth extraction, dental implants, oral surgery), diagnosis of cancer, concomitant therapies (e.g. chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and comorbid disorders (e.g. periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, ill-fitting dentures). Good oral hygiene practices should be maintained during treatment with denosumab (Prolia). 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 (Prolia).
For patients requiring invasive dental procedures, clinical judgment of the treating physician and/or oral surgeon should guide the management plan of each patient based on individual benefit-risk assessment.
Patients who are suspected of having or who develop ONJ while on denosumab (Prolia) should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of denosumab (Prolia) therapy 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 in patients receiving denosumab (Prolia) [see Clinical Trials Experience under Adverse Reactions]. 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 denosumab (Prolia) treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patient presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of denosumab (Prolia) therapy should be considered, pending a benefit-risk assessment, on an individual basis.
Multiple Vertebral Fractures (MVF) Following Discontinuation of denosumab (Prolia) Treatment: Following discontinuation of denosumab (Prolia) treatment, fracture risk increases, including the risk of multiple vertebral fractures. Cessation of denosumab (Prolia) treatment results in markers of bone resorption increasing above pretreatment values then returning to pretreatment values 24 months after the last dose of denosumab (Prolia). In addition, bone mineral density returns to pretreatment values within 18 months after the last injection [see Postmenopausal Women with Osteoporosis as follows].
New vertebral fractures occurred as early as 7 months (on average 19 months) after the last dose of denosumab (Prolia). Prior vertebral fracture was a predictor of multiple vertebral fractures after denosumab (Prolia) discontinuation. Evaluate an individual's benefit-risk before initiating treatment with denosumab (Prolia).
If denosumab (Prolia) treatment is discontinued, consider transitioning to an alternative antiresorptive therapy [see Clinical Trials Experience under Adverse Reactions].
Serious Infections: In a clinical trial of over 7800 women with postmenopausal osteoporosis, serious infections leading to hospitalization were reported more frequently in the denosumab (Prolia) group than in the placebo group [see Clinical Trials Experience under Adverse Reactions]. Serious skin infections, as well as infections of the abdomen, urinary tract, and ear, were more frequent in patients treated with denosumab (Prolia). Endocarditis was also reported more frequently in denosumab (Prolia)-treated patients. The incidence of opportunistic infections was similar between placebo and denosumab (Prolia) groups, and the overall incidence of infections was similar between the treatment groups. 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. Consider the benefit-risk profile in such patients before treating with denosumab (Prolia). In patients who develop serious infections while on denosumab (Prolia), prescribers should assess the need for continued denosumab (Prolia®) therapy.
Dermatologic Adverse Reactions: In a large clinical trial of over 7800 women with postmenopausal osteoporosis, epidermal and dermal adverse events such as dermatitis, eczema, and rashes occurred at a significantly higher rate in the denosumab (Prolia) group compared to the placebo group. Most of these events were not specific to the injection site [see Clinical Trials Experience under Adverse Reactions]. Consider discontinuing denosumab (Prolia) if severe symptoms develop.
Musculoskeletal Pain: In postmarketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking denosumab (Prolia) [see Postmarketing Experience under Adverse Reactions]. The time to onset of symptoms varied from one day to several months after starting denosumab (Prolia). Consider discontinuing use if severe symptoms develop.
Suppression of Bone Turnover: In clinical trials in women with postmenopausal osteoporosis, treatment with denosumab (Prolia) resulted in significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry [see Postmenopausal Women with Osteoporosis as follows]. The significance of these findings and the effect of long-term treatment with denosumab (Prolia) are unknown. The long-term consequences of the degree of suppression of bone remodeling observed with denosumab (Prolia) may contribute to adverse outcomes such as osteonecrosis of the jaw, atypical fractures, and delayed fracture healing. Monitor patients for these consequences.