{ "query": "denosumab", "ingredient": "denosumab", "slug": "denosumab", "rxcui": "993449", "brands": [ "Prolia", "Xgeva" ], "names": [ "denosumab" ], "classes": [], "alternatives": [], "label": { "route_mode": "SUBCUTANEOUS", "route_counts": { "SUBCUTANEOUS": 19 }, "boxed_warning": "WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE Patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m 2 ), including dialysis-dependent patients, are at greater risk of severe hypocalcemia following Prolia 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 Prolia in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Prolia 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) ]. 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 Prolia administration. Severe hypocalcemia resulting ...", "indications_and_usage": "Prolia is a RANK ligand (RANKL) inhibitor indicated for treatment: of postmenopausal women with osteoporosis at high risk for fracture ( 1.1 ) to increase bone mass in men with osteoporosis at high risk for fracture ( 1.2 ) of glucocorticoid-induced osteoporosis in men and women at high risk for fracture ( 1.3 ) to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer ( 1.4 ) to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer ( 1.5 ) 1.1 Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture Prolia 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, Prolia reduces the incidence of vertebral, nonvertebral, and hip fractures [see Clinical Studies (14.1) ] . 1.2 Treatment to Increase Bone Mass in Men with Osteoporosis Prolia is indicated for treatment to increase ...", "contraindications": "Prolia is contraindicated in: Patients with hypocalcemia: Pre-existing hypocalcemia must be corrected prior to initiating therapy with Prolia [see Warnings and Precautions (5.1) ] . Pregnant women: Prolia 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 Prolia [see Use in Specific Populations (8.1) ] . Patients with hypersensitivity to Prolia: Prolia is contraindicated in patients with a history of systemic hypersensitivity to any component of the product. Reactions have included anaphylaxis, facial swelling, and urticaria [see Warnings and Precautions (5.3) and Adverse Reactions (6.2) ] . Hypocalcemia ( 4 , 5.1 ) Pregnancy ( 4 , 8.1 ) Known hypersensitivity to Prolia ( 4 , 5.3 )", "warnings_and_cautions": "Hypocalcemia: Pre-existing hypocalcemia must be corrected before initiating Prolia. May worsen, especially in patients with renal impairment. Adequately supplement all patients with calcium and vitamin D. Concomitant use of calcimimetic drugs may also worsen hypocalcemia risk. Evaluate for presence of chronic kidney disease mineral-bone disorder. Monitor serum calcium. ( 5.1 ) Same Active Ingredient: Patients receiving Prolia should not receive other denosumab products concomitantly. ( 5.2 ) Hypersensitivity including anaphylactic reactions may occur. Discontinue permanently if a clinically significant reaction occurs. ( 5.3 ) Osteonecrosis of the jaw: Has been reported with Prolia. Monitor for symptoms. ( 5.4 ) Atypical femoral fractures: Have been reported. Evaluate patients with thigh or groin pain to rule out a femoral fracture. ( 5.5 ) Multiple vertebral fractures have been reported following Prolia discontinuation. Patients should be transitioned to another antiresorptive agent if Prolia is discontinued. ( 5.6 ) Serious infections including skin infections: May occur, including those leading to hospitalization. Advise patients to seek prompt medical attention if they develop ...", "warnings": "", "adverse_reactions": "The following serious adverse reactions are discussed below and also elsewhere in the labeling: Severe Hypocalcemia and Mineral Metabolism Changes [see Warnings and Precautions (5.1) ] Hypersensitivity [see Warnings and Precautions (5.3) ] Osteonecrosis of the Jaw [see Warnings and Precautions (5.4) ] Atypical Subtrochanteric and Diaphyseal Femoral Fractures [see Warnings and Precautions (5.5) ] Multiple Vertebral Fractures (MVF) Following Discontinuation of Prolia Treatment [see Warnings and Precautions (5.6) ] Serious Infections [see Warnings and Precautions (5.7) ] Dermatologic Adverse Reactions [see Warnings and Precautions (5.8) ] The most common adverse reactions reported with Prolia in patients with postmenopausal osteoporosis are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. The most common adverse reactions reported with Prolia in men with osteoporosis are back pain, arthralgia, and nasopharyngitis. The most common adverse reactions reported with Prolia in patients with glucocorticoid-induced osteoporosis are back pain, hypertension, bronchitis, and headache. The most common (per patient incidence \u2265 10%) adverse reactions reported ...", "drug_abuse_and_dependence": "", "controlled_substance": "", "recent_major_changes": "Warnings and Precautions ( 5.2 ) 06/2026", "information_for_patients": "Advise the patient to read the FDA-approved patient labeling (Medication Guide). Hypocalcemia Advise the patient to adequately supplement with calcium and vitamin D and instruct them on the importance of maintaining serum calcium levels while receiving Prolia [see Warnings and Precautions (5.1) and Use in Specific Populations (8.6) ] . Advise patients to seek prompt medical attention if they develop signs or symptoms of hypocalcemia. Severe Hypocalcemia in Patients with Advanced Chronic Kidney Disease Advise patients with advanced chronic kidney disease, including those who are dialysis-dependent, about the symptoms of hypocalcemia and the importance of maintaining serum calcium levels with adequate calcium and activated vitamin D supplementation. Advise these patients to have their serum calcium measured weekly for the first month after Prolia administration and monthly thereafter [see Dosage and Administration (2.2) , Warnings and Precautions (5.1) and Use in Specific Populations (8.6) ] . Drug Products with Same Active Ingredient Advise patients that if they receive Prolia, they should not receive other denosumab products concomitantly [see Warnings and Precautions (5.2) ] . Hyp...", "spl_medguide": "This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 05/2025 Medication Guide Prolia \u00ae (PR\u00d3-lee-a) (denosumab) Injection, for subcutaneous use What is the most important information I should know about Prolia? If you receive Prolia, you should not receive other denosumab products at the same time. Prolia can cause serious side effects including: Increased risk of severe low calcium levels in your blood (hypocalcemia). Prolia may lower the calcium levels in your blood. If you have low blood calcium before you start receiving Prolia, it may get worse during treatment. Your low blood calcium must be treated before you receive Prolia. Talk to your doctor before starting Prolia. Your doctor may prescribe calcium and vitamin D to help prevent low calcium levels in your blood while you take Prolia. Take calcium and vitamin D as your doctor tells you to. If you have advanced chronic kidney disease (may or may not be on kidney dialysis), Prolia may increase your risk for severe low calcium levels in your blood, which could result in hospitalization, life-threatening events and death. A mineral and bone disorder associated with kidney disease called chro...", "clinical_studies": "14.1 Treatment of Postmenopausal Women with Osteoporosis The efficacy and safety of Prolia in the treatment of postmenopausal osteoporosis was demonstrated in a 3-year, randomized, double-blind, placebo-controlled trial. Enrolled women had a baseline BMD T-score between -2.5 and -4.0 at either the lumbar spine or total hip. Women with other diseases (such as rheumatoid arthritis, osteogenesis imperfecta, and Paget's disease) or on therapies that affect bone were excluded from this study. The 7808 enrolled women were aged 60 to 91 years with a mean age of 72 years. Overall, the mean baseline lumbar spine BMD T-score was -2.8, and 23% of women had a vertebral fracture at baseline. Women were randomized to receive subcutaneous injections of either placebo (N = 3906) or Prolia 60 mg (N = 3902) once every 6 months. All women received at least 1000 mg calcium and 400 IU vitamin D supplementation daily. The primary efficacy variable was the incidence of new morphometric (radiologically-diagnosed) vertebral fractures at 3 years. Vertebral fractures were diagnosed based on lateral spine radiographs (T4-L4) using a semiquantitative scoring method. Secondary efficacy variables included the in...", "brand_name": "Prolia", "manufacturer": "Amgen, Inc", "application_number": "BLA125320", "pharm_class_epc": [ "RANK Ligand Inhibitor [EPC]" ], "route": [ "SUBCUTANEOUS" ], "effective_time": "20260626", "set_id": "49e5afe9-a0c7-40c4-af9f-f287a80c5c88", "has_boxed_warning": true, "controlled": false, "mentions_rems": false }, "faers": { "total": 186449, "serious": 102387, "death": 23492, "hospitalization": 29764, "primary_suspect": 186300, "top_reactions": [ [ "Off Label Use", 36758 ], [ "Death", 18372 ], [ "Osteonecrosis Of Jaw", 8960 ], [ "Arthralgia", 7681 ], [ "Fatigue", 7152 ], [ "Pain", 5915 ], [ "Back Pain", 5753 ], [ "Pain In Extremity", 5727 ], [ "Diarrhoea", 5046 ], [ "Nausea", 4960 ], [ "Fall", 4839 ], [ "Product Storage Error", 3674 ], [ "Rash", 3603 ], [ "Asthenia", 3592 ], [ "Myalgia", 3562 ] ], "by_year": { "2019": 12119, "2020": 10954, "2021": 10426, "2022": 9809, "2023": 10668, "2024": 9312, "2025": 7941, "2026": 4651 }, "by_year_primary": { "2019": 12118, "2020": 10953, "2021": 10402, "2022": 9771, "2023": 10645, "2024": 9298, "2025": 7910, "2026": 4635 } }, "faers_base": { "total": 20692304, "serious_share": 0.5742697381596559, "death_share": 0.09102355155810585 }, "recalls": [ { "class": "Class II", "date": "20250421", "reason": "CGMP Deviations; potential temperature excursions due to transit delays", "firm": "Mckesson Medical-Surgical Inc. Corporate Office", "status": "Ongoing" }, { "class": "Class II", "date": "20130917", "reason": "Presence of Particulate Matter: Visible cellulose fibers were observed in a small number of prefilled syringes during a routine quality examination.", "firm": "Amgen, Inc.", "status": "Terminated" } ], "recall_total": 2, "drugsfda": { "applications": 1, "nda": 0, "anda": 0, "first_approval": "20100601", "rems": true, "rems_last": "20240409", "labeling_supplements": 0, "labeling_recent": 0, "sponsors": [ "AMGEN" ], "unapproved": false, "first_approval_fmt": "06/01/2010" }, "trials": { "total": 337, "completed": 188, "terminated": 35, "with_results": 115, "industry": 177, "phase3": 82, "results_share": 0.6117021276595744, "terminated_share": 0.10385756676557864 }, "pubmed": { "rct": 276, "meta": 123, "recent_rct": 106, "cochrane": [] }, "payments": { "year": "2024", "usd": 133803.16, "records": 767, "by_name": [ [ "Prolia", 112295.37 ], [ "Xgeva", 21507.79 ] ], "names_checked": [ "denosumab", "Prolia", "Xgeva" ], "source": "bulk-index" }, "partd": { "year": "2024", "claims": 468512, "beneficiaries": 288460, "spend": 827665924.3, "by_brand": [ { "brand": "Prolia", "claims": 450858, "per_claim": 1711.9304929, "is_generic": false }, { "brand": "Xgeva", "claims": 17654, "per_claim": 3162.363551, "is_generic": false } ], "per_claim": 1766.5842588877124 }, "mdl": [ { "number": "3138", "title": "Denosumab Patent Litigation", "judge": "O'Hearn, Christine P.", "court": "NJ", "docket": "1:25-md-3138", "actions": "", "matched": "denosumab" } ], "dsc": [ { "date": "20240119", "title": "FDA adds Boxed Warning for increased risk of severe hypocalcemia in patients with advanced chronic kidney disease taking osteoporosis medicine Prolia (denosumab)", "url": "https://www.fda.gov/drugs/drug-safety-communications/fda-adds-boxed-warning-increased-risk-severe-hypocalcemia-patients-advanced-chronic-kidney-disease", "kind": "drug", "matched": "denosumab" } ], "settlements": [], "prescrire": { "section": "Haematology", "names": [ "denosumab" ], "reason": "Denosumab 60 mg has very modest efficacy in the prevention of osteoporotic fractures and no efficacy for \u201cbone loss\u201d during prostate cancer ( e). This monoclonal antibody carries a disproportionate risk of adverse effects, including back, muscle and bone pain, multiple fractures after its discontinuation, osteonecrosis, immune dysfunction, and serious infections (including endocarditis) due to its immunosuppressive effects (Prescrire Int n\u00b0 117 , 130, 168, 198).", "edition": "2026", "qualifier": "denosumab 60 mg", "qualified": true, "matched": "denosumab" }, "eml": { "listed": false, "status": "", "name": "", "matched": null, "stewardship": [] }, "exposure": { "years": [ "2024", "2025", "2026" ], "reports_recent": 21843, "fills": 468512, "per_million": 46622.07157981012, "ratio": 16.83745669851493, "median": 2768.949753790441 }, "scores": { "safety": { "score": 32, "letter": "F", "why": [ "Carries an FDA boxed warning, the strongest warning the FDA issues (-30)", "FDA issued 1 Drug Safety Communication(s) naming this drug since 2010, most recently 2024 (-8)", "Prescrire lists one form only (denosumab 60 mg) as a drug to avoid; shown for context, no score effect", "46,622 FDA reports naming it as the suspect drug per million Medicare fills, 16.8x the median drug on this site (-15)", "Subject to a REMS safety program: FDA requires special controls to use it (-10)", "Death share in reports is near or below the FAERS average (1.4x)", "Off-label use is among the five most-reported items: widely used beyond its approved evidence (-5)" ], "weight": 0.35 }, "evidence": { "score": 78, "letter": "B", "why": [ "276 randomized trials and 123 systematic reviews/meta-analyses indexed in PubMed", "No Cochrane review found (-5)" ], "weight": 0.25 }, "regulatory": { "score": 82, "letter": "B", "why": [ "Recalls since 2016: 0 Class I, 1 Class II, 0 Class III (-3)", "REMS program in force (-10)", "Label lists recent major changes to warnings or indications (-5)" ], "weight": 0.15 }, "conflict": { "score": 45, "letter": "F", "why": [ "Pharma paid doctors $133,803 tied to this drug last year (-15)", "Named in 1 active federal multidistrict litigation(s) (-40)" ], "weight": 0.15 }, "options": { "score": 40, "letter": "F", "why": [ "No generic version approved: brand-only pricing (-30)", "No same-class alternatives found: little leverage to switch (-30)" ], "weight": 0.1 } }, "total": 54, "grade": "D", "questions": [ "In 2024 the FDA issued a safety communication about this drug (FDA adds Boxed Warning for increased risk of severe hypocalcemia in patients with advanced chronic kidney dise). Does that risk apply to me?", "An independent reviewer (Prescrire) lists this as a drug to avoid because the harms outweigh the benefits versus alternatives. What is your view on that?", "This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?", "This drug has a REMS safety program. What monitoring does that require from us?", "The most-reported problems in FDA's adverse event data are death, osteonecrosis of jaw, arthralgia. How would we recognize and handle those?", "Off-label use is among the most-reported items for this drug. Is my use on-label, and if not, what evidence supports it?", "There is no generic. Is there an older generic in the same class that works as well for my situation?", "This drug is in active federal litigation. What is the claim, and does it affect my risk?", "What result are we expecting, by when, and what is the plan if it does not happen?", "If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)" ] }