Rates of severe and serious adverse events were similar between both treatment groups. Multiple Vertebral Fractures (MVF) Following Discontinuation of Prolia Prolia Field Representatives are here to answer any questions you may have or to schedule a visit. Canon JR, Roudier M, Bryant R, Morony S, Stolina M, Kostenuik PJ, et al. Copyright 1996-2022 Cerner Multum, Inc. Prolia is a prescription medicine used to treat osteoporosis in women after menopause who are at high risk for fracture or cannot use another osteoporosis medicine or other osteoporosis medicines did not work well. June 1, 2010. Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: Coinci-dence or causal association. It is not known whether this time period of accelerated bone turnover is associated with an increase in fracture risk. prescriber prior to initiation of Prolia. Contraindications Denosumab 120 mg (for cancer indications) should not be used in patients with severe, untreated hypocalcaemia. Greenspan S, Bone H, Ettinger M, et al. Learn Bone H, Chapurlat R, Brandi M, et al. High risk of fracture is defined as in patients with a history of systemic hypersensitivity to any component of the product. Liberman U, Weiss S, Broll J, et al. Continue reading, Low blood pressure is not a common side effect of Xgeva; however, it may occur in people who are allergic to Xgeva alongside other allergy symptoms such as facial and throat swelling and tightness, shortness of breath, and a rash. Xgeva (denosumab) injection, for subcutaneous use . Most Common : Fatigue/weakness, decreased level of phosphate and calcium in blood, nausea, diarrhea, headache and cough. Prolia is contraindicated in patients with a history of systemic hypersensitivity to any component of the product. Safety profiles overall are similar to placebo, with no new safety concerns in extension trials, though a theoretical increased risk of infection exists with RANKL inhibition. Adult Indications and Dosage FDA-Labeled Indications and Dosage (Adult) Recommended Dosage. Contraindications: Prolia is contraindicated in patients with Bone Joint J. Efficacy and safety of denosumab in postmenopausal women with osteopenia or osteoporosis: a systematic review and a meta-analysis. Of note, the placebo group also showed a decrease of 46% at 12 hours, which was expected due to the diurnal variation of urinary NTX. Clipboard, Search History, and several other advanced features are temporarily unavailable. In the trial by Fizazi et al., which compared zoledronic acid to denosumab in prostate cancer, 1,901 patients meeting the eligibility criteria were randomized one to one to either denosumab 120 mg subcutaneous injection or to IV injection of zoledronic acid 4 mg adjusted for creatinine clearance. Roodman GD. You may need to have a dental exam before you begin treatment with Prolia. ODonnell S, Cranney A, Wells G, et al. Papers of special note have been highlighted as either of interest () or of considerable interest () to readers. The second phase 2 study evaluated the effect of denosumab treatment in patients with advanced cancer and bone metastases or multiple myeloma with bone disease who had previously been treated with IV bisphosphonates (n = 111) yet still had elevated concentrations of urinary N-telopeptide normalized to urinary creatinine (uNTx/Cr) (50 nmol/mmol). There are numerous ongoing Phase III trials investigating denosumab use in osteoporosis, including denosumab use for prevention of post-teriparatide bone loss ({"type":"clinical-trial","attrs":{"text":"NCT02166437","term_id":"NCT02166437"}}NCT02166437), denosumab use in glucocorticoid-induced osteoporosis ({"type":"clinical-trial","attrs":{"text":"NCT01465568","term_id":"NCT01465568"}}NCT01465568), denosumab compared with zoledronic acid in women with postmenopausal osteoporosis ({"type":"clinical-trial","attrs":{"text":"NCT01732770","term_id":"NCT01732770"}}NCT01732770), and investigations for use in thalassemia-induced osteoporosis [45] (clinicaltrials.gov). Treatment of postmenopausal women with osteoporosis at high risk for fracture; Treatment to increase bone mass in men with osteoporosis at high risk of fracture; Suppression of bone resorption by binding to RANK ligand, preventing its binding to RANK and decreasing osteoclast formation, activity, and survival, Route of administrationChemical structure, Subcutaneous every 6 months(C6404 H9912 N1724 O2004 S50) consists of 2 heavy and 2 light chains; each light chain consists of 215 amino acids and each heavy chain consists of 448 amino acids with 4 intramolecular disulfides. Extensive dental surgery to treat ONJ Consider discontinuing about navigating our updated article layout. Serious infections may occur during treatment with Prolia. Introduction Side effects and potential harms Careers. Take the medicine XGEVA (denosumab) Have low blood calcium Cannot take daily calcium and vitamin D Had parathyroid or thyroid surgery (glands located in your neck) Have been told you have trouble absorbing minerals in your stomach or intestines (malabsorption syndrome) Have kidney problems or are on kidney dialysis Black D, Cummings S, Karpf D, et al. She serves on the Board of Trustees of the National Osteoporosis Foundation (no monetary remuneration). It was found that a 60 mg fixed dose of denosumab given every 6 months provided similar RANKL inhibition as using weight-based dosing. Significant differences between denosumab treatment and placebo were seen with skin-related conditions in the parent FREEDOM trial (3% denosumab vs 1.7% placebo), with cellulitis as a serious adverse event (AE) more common with denosumab (12 subjects denosumab vs one subject placebo). Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. It is an antibody to RANK-Ligand, the factor made by osteoblasts that is necessary for the formation of mature osteoclasts. [36], HALT Breast Cancer (HALT-BC) trial included 252 hormone receptor positive breast cancer patients on aromatase inhibitor therapy in adjuvant clinical setting. CONTRAINDICATIONS: Hypersensitivity to the active substance or product ingredients Hypocalcemia Pregnancy (Prolia) Safety and efficacy of Prolia have not been established in patients younger than 18 years. Ann Pharmacother. FDA-approved indications include prevention of skeletal-related events (e.g., bone pain and fractures) secondary to multiple myeloma or bone metastases from solid tumors, giant cell tumor of the bone, hypercalcemia of malignancy, osteoporosis in postmenopausal women with osteoporosis at high risk for fracture as well as men with osteoporosis at high risk of fracture, glucocorticoid-induced osteoporosis, and bone loss. Prior vertebral fracture was a predictor of multiple vertebral fractures after Prolia discontinuation. The https:// ensures that you are connecting to the [15] It has been shown that metastatic prostate cancer cells in bone (and not at other sites) express both RANKL and its antagonist OPG. -----INDICATIONS AND USAGE-----Xgeva is a RANK ligand (RANKL) inhibitor indicated for: Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. Denosumab binds to RANKL, preventing RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. At 12 months, LS BMD increased more in the combination group (9.1%, [SD 3.9]) than in the teriparatide (6.2% [4.6], p = 0.0139) or denosumab (5.5% [3.3], p = 0.0005) groups, as did total-hip BMD (combination, 4.9% [2.9]; teriparatide, 0.7% [2.7], p < 0.0001; denosumab 2.5% [2.6], p = 0.0011). In More. Gonzalez-Suarez E, Jacob AP, Jones J, Miller R, Roudier-Meyer MP, Erwert R, et al. Of note, rates of opportunistic infections were similar between denosumab and placebo groups. In some cases, health care professionals may use the trade names Prolia or Xgeva when referring to the generic drug name denosumab. Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: efficacy and safety results from a randomized open-label study. However, an earlier meta-analysis of three Phase II and III studies [49] showed a relative risk of infectious serious AE of 4.45 (95% CI 1.15 17.14, p = 0.03) at 24 months of therapy (n = 17 infectious serious AE in combined denosumab arms, n = two infectious serious AE in combined placebo arms). The (>5% and more common than placebo) in men with osteoporosis are back pain, arthralgia, As with all therapeutic proteins, there is Get emergency medical help if you have signs of an allergic reaction: hives, itching, rash; difficult breathing, feeling light-headed; swelling of your face, lips, tongue, or throat. The initial U.S. FDA approval for denosumab was in June 2010 for the indication of treatment of osteoporosis in post-menopausal women at high risk for fracture. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Boyce BF, Hughes DE, Wright KR, Xing L, Dai A. Padhi D, Jang G, Stouch B, et al. In women of reproductive potential, pregnancy testing should be performed Same Active Ingredient: Prolia contains the same active ingredient Suppression of Bone Turnover: In clinical trials in women with postmenopausal 5. Monoclonal antibodies are made to target and destroy only certain cells in the body. Pre-existing hypocalcemia must be corrected prior to initiating Furthermore, when treatment is started, adherence is often poor [8]. Narrative [corrected] review: Bisphosphonates and osteonecrosis of the jaws. [8] Additional data suggest that RANKL also may play a role in primary tumorigenesis and metastasis. Studies in prevention of skeletal-related events in multiple myeloma have yielded less favorable results, though data is limited [51]. You are now leaving ProliaHCP.com. At 12 months, denosumab showed a significantly greater BMD increase at the total hip compared to alendronate (3.5% denosumab, 2.6% alendronate, p < 0.0001), with treatment difference of 0.6% at femoral neck, and 1.1% at LS. management plan of each patient. [44] On the other hand, in the FREEDOM study (which was analyzed in the above meta-analysis), there was no clear relationship between overall infections and exposure to denosumab. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. [30] These data suggest that denosumab treatment may further suppress markers of bone resorption even in patients who were previously treated with IV bisphosphonates. Eight cases of SSH were reported including symptoms of seizure and/or tetany; seven of eight of these patients had chronic kidney disease, a known risk factor for hypocalcemia. Interruption of Prolia Xgeva is used for prevention of skeletal-related events due to bone metastases . Geller M, Wagman R, Ho P, et al. ONJ is a form of avascular necrosis where there is persistence of exposed, necrotic bone in the oral cavity for more than 8 weeks, and where there is no history of local evidence of malignancy or radiation exposure in the affected region. Prolia Dosage Guide - Drugs.com. The Hormone Ablation Bone Loss Trial (HALT) was an RCT of denosumab use in men undergoing androgen-deprivation therapy for non-metastatic, hormone-sensitive prostate cancer resulting in FDA approval for use for that indication (Table 1) [39]. Rates of adverse events and serious adverse events were similar in both groups, except for ONJ and hypocalcemia. All patients should receive calcium 1000 mg daily and at least 400 IU vitamin D daily [see . Patients received denosumab 120 mg or zoledronic acid 4 mg every 4 weeks. The clinical sequelae from bone metastases, termed skeletal-related events (SREs), are among the most frequent and debilitating complications in patients with advanced cancer. The 120 mg dose of denosumab administered subcutaneously (SC) once every 4 weeks (Q4W) was the minimal dose that maintained maximal suppression of bone turnover over the entire dosing interval in a high proportion of patients. Denosumab should be administered by a healthcare professional. Coleman RE. Serious Infections: In a clinical trial (N=7808) in women with postmenopausal Cessation of denosumab results in an increase of BTMs back to, and transiently above, baseline levels. Monitor patients for these Another major safety concern is infection risk, given RANKL inhibition of non-skeletal immune cells, causing a theoretical immune suppression. Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal. 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