Boncresa denosumab-mobz 60 mg/mL Injection, Solution, 1 syringe
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the RANK Ligand Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Denosumab works by blocking a protein in your body that signals bone-dissolving cells to break down bone. By slowing that process, it helps your bones stay denser and stronger — wh...
- What exactly does this injection do, and why do I need it?
- You only need the injection once every 6 months — so just two visits a year. Between those visits, the most important thing you can do is take your calcium and vitamin D every sing...
- How often do I have to come in for the shot, and what do I need to do between visits?
Patient education
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Boncresa 60 mg/mLthis 70121-2702-01 | Amneal | 1 syringe | — | — | FDA listed | — |
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⏳ Availability & biosimilar status
18 interchangeables are FDA-licensed for this reference biologic — see the list below. (Biologics have no small-molecule generics.)
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Dec 19, 2037 |
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🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 70121-2702-01 You're viewing this | 1 SYRINGE in 1 CARTON (70121-2702-1) / 1 mL in 1 SYRINGE | 2025-12-23 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 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 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 Boncresa in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Boncresa 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 denosumab products administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported. (5.1) The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia.
(5.1) Prior to initiating Boncresa in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Boncresa in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD. (2.2) , (5.1)
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Boncresa 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)
1.1Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture Boncresa 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 [see Clinical Studies (14.1) ] .
1.2Treatment to Increase Bone Mass in Men with Osteoporosis Boncresa 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 [see Clinical Studies (14.2) ] .
1.3Treatment of Glucocorticoid-Induced Osteoporosis Boncresa 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 [see Clinical Studies (14.3) ] .
1.4Treatment of Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer Boncresa 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 [see Clinical Studies (14.4) ] .
1.5Treatment of Bone Loss in Women Receiving Adjuvant Aromatase Inhibitor Therapy for Breast Cancer Boncresa is indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer [see Clinical Studies (14.5) ] .
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Pregnancy must be ruled out prior to administration of Boncresa. (2.1) Before initiating Boncresa in patients with advanced chronic kidney disease, including dialysis patients, evaluate for the presence of chronic kidney disease mineral and bone disorder with intact parathyroid hormone, serum calcium, 25(OH) vitamin D, and 1,25(OH) 2 vitamin D. (2.2 , 5.1 , 8.6) Boncresa should be administered by a healthcare provider.
(2.3) Administer 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. (2.3) Instruct patients to take calcium 1000 mg daily and at least 400 IU vitamin D daily. (2.3)
2.1Pregnancy Testing Prior to Initiation of Boncresa Pregnancy must be ruled out prior to administration of Boncresa. Perform pregnancy testing in all females of reproductive potential prior to administration of Boncresa. Based on findings in animals, denosumab products can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1 , 8.3) ] .
2.2Laboratory Testing in Patients with Advanced Chronic Kidney Disease Prior to Initiation of Boncresa In patients with advanced chronic kidney disease [i.e., estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 ], including dialysis-dependent patients, evaluate for the presence of chronic kidney disease mineral and bone disorder (CKD-MBD) with intact parathyroid hormone (iPTH), serum calcium, 25(OH) vitamin D, and 1,25 (OH) 2 vitamin D prior to decisions regarding Boncresa treatment. Consider also assessing bone turnover status (serum markers of bone turnover or bone biopsy) to evaluate the underlying bone disease that may be present [see Warnings and Precautions (5.1) ] .
2.3Recommended Dosage Boncresa should be administered by a healthcare provider. The recommended dose of Boncresa is 60 mg administered as a single subcutaneous injection once every 6 months. Administer Boncresa via subcutaneous injection in the upper arm, the upper thigh, or the abdomen.
All patients should receive calcium 1000 mg daily and at least 400 IU vitamin D daily [see Warnings and Precautions (5.1) ] . If a dose of Boncresa is missed, administer the injection as soon as the patient is available. Thereafter, schedule injections every 6 months from the date of the last injection.
2.4Preparation and Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Boncresais a clear, colorless to pale yellow solution. Do not use if the solution is discolored or cloudy or if the solution contains visible particles or foreign particulate matter.
Prior to administration, Boncresamay be removed from the refrigerator and brought to room temperature up to 25°C (77°F) by standing in the original container. This generally takes 15 to 30 minutes. Do not warm Boncresain any other way [see How Supplied/Storage and Handling (16) ] .
Instructions for Administration of Boncresa Prefilled Syringe with Needle Safety Guard IMPORTANT: In order to minimize accidental needlesticks, the Boncresasingle-dose prefilled syringe has a transparent safety guard, which is automatically activated after the injection. DO NOT attempt to activate the transparent safety guard before injection. Step 1: Remove Gray Needle Cap Step 2: Administer Subcutaneous Injection Choose an injection site.
The recommended injection sites for Boncresa include: the upper arm OR the upper thigh OR the abdomen. Insert needle and inject all the liquid subcutaneously into pinched skin. Do not administer into muscle or blood vessels.
Slowly push the plunger all the way down until all the liquid is injected and the transparent safety guard is automatically activated. Step 3: Release Plunger and Remove the Syringe From Skin Release your thumb upwards from the plunger. This will allow the needle to move automatically up into the transparent safety guard.
Then lift the syringe…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 60 mg/mL clear, colorless to pale yellow solution in a single-dose prefilled syringe. Injection: 60 mg/mL solution in a single-dose prefilled syringe (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Boncresa is contraindicated in: Patients with hypocalcemia: Pre-existing hypocalcemia must be corrected prior to initiating therapy with Boncresa [see Warnings and Precautions (5.1) ] . 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 Boncresa [see Use in Specific Populations (8.1) ] .
Patients with hypersensitivity to denosumab products: Boncresa 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 denosumab products (4 , 5.3)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Same Active Ingredient: Patients receiving Boncresa 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) Hypocalcemia: Pre-existing hypocalcemia must be corrected before initiating Boncresa. 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) Osteonecrosis of the jaw: Has been reported with denosumab products. 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 Boncresa discontinuation. Patients should be transitioned to another antiresorptive agent if Boncresa 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 signs or symptoms of infection, including cellulitis. (5.7) Dermatologic reactions: Dermatitis, rashes, and eczema have been reported.
Consider discontinuing Boncresa if severe symptoms develop. (5.8) Severe bone, joint, muscle pain may occur. Discontinue use if severe symptoms develop.
(5.9) Suppression of bone turnover: Significant suppression has been demonstrated. Monitor for consequences of bone over-suppression. (5.10)
5.1Severe Hypocalcemia and Mineral Metabolism Changes Denosumab products can cause severe hypocalcemia and fatal cases have been reported. Pre-existing hypocalcemia must be corrected prior to initiating therapy with Boncresa. Adequately supplement all patients with calcium and vitamin D [see Dosage and Administration (2.1) , Contraindications (4) , and Adverse Reactions (6.1) ].
In patients without advanced chronic kidney disease who are predisposed to hypocalcemia and disturbances of mineral metabolism (e.g., history of hypoparathyroidism, thyroid surgery, parathyroid surgery, malabsorption syndromes, excision of small intestine, treatment with other calcium-lowering drugs), assess serum calcium and mineral levels (phosphorus and magnesium) 10 to14 days after Boncresa 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 [i.e., eGFR <30 mL/min/1.73 m 2 ] including dialysis-dependent patients are at greater risk for severe hypocalcemia following denosumab products administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported. The presence of underlying chronic kidney disease-mineral bone disorder (CKD-MBD, renal osteodystrophy) markedly increases the risk of hypocalcemia.
Concomitant use of calcimimetic drugs may also worsen hypocalcemia risk. To minimize the risk of hypocalcemia in patients with advanced chronic kidney disease, evaluate for the presence of chronic kidney disease mineral and bone disorder with intact parathyroid hormone (iPTH), serum calcium, 25(OH) vitamin D, and 1,25(OH) 2 vitamin D prior to decisions regarding Boncresa treatment. Consider also assessing bone turnover status (serum markers of bone turnover or bone biopsy) to evaluate the underlying bone disease that may be present.
Monitor serum calcium weekly for the first month after Boncresa administration and monthly thereafter. Instruct all 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 c…
🤒 Adverse Reactions ▾
6 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 Treatment Discontinuation [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 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. The most common adverse reactions leading to discontinuation of denosumab products in patients with postmenopausal osteoporosis are back pain and constipation. Postmenopausal osteoporosis: Most common adverse reactions (> 5% and more common than placebo) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis.
Pancreatitis has been reported in clinical trials. (6.1) Male osteoporosis: Most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis. (6.1) Glucocorticoid-induced osteoporosis: Most common adverse reactions (> 3% and more common than active-control group) were: back pain, hypertension, bronchitis, and headache.
(6.1) Bone loss due to hormone ablation for cancer: Most common adverse reactions (≥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals LLC at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. Treatment of Postmenopausal Women with Osteoporosis The safety of denosumab in the treatment of postmenopausal osteoporosis was assessed in a 3-year, randomized, double-blind, placebo-controlled, multinational study of 7808 postmenopausal women aged 60 to 91 years.
A total of 3876 women were exposed to placebo and 3886 women were exposed to denosumab administered subcutaneously once every 6 months as a single 60 mg dose. All women were instructed to take at least 1000 mg of calcium and 400 IU of vitamin D supplementation per day. The incidence of all-cause mortality was 2.3% (n = 90) in the placebo group and 1.8% (n = 70) in the denosumab group.
The incidence of nonfatal serious adverse events was 24.2% in the placebo group and 25.0% in the denosumab group. The percentage of patients who withdrew from the study due to adverse events was 2.1% and 2.4% for the placebo and denosumab groups, respectively. The most common adverse reactions reported with denosumab in patients with postmenopausal osteoporosis are back pain, pain in extremity, musc…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnant women and females of reproductive potential: Denosumab products may cause fetal harm when administered to pregnant women. Advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of Boncresa. (8.1 , 8.3) Pediatric patients: Boncresa is not approved for use in pediatric patients.
(8.4) Renal impairment: No dose adjustment is necessary in patients with renal impairment. 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. The presence of underlying chronic kidney disease-mineral bone disorder markedly increases the risk of hypocalcemia.
(5.1 , 8.6) *Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of BONCRESA has been demonstrated for the condition(s) of use (e.g., indication(s), dosing regimen(s), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information.
8.1Pregnancy Risk Summary Boncresa 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. In utero denosumab exposure from cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 50-fold higher than the recommended human dose based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality, and absent lymph nodes, abnormal bone growth, and decreased neonatal growth [see Data] .
Data Animal Data The effects of denosumab on prenatal development have been studied in both cynomolgus monkeys and genetically engineered mice in which RANK ligand (RANKL) expression was turned off by gene removal (a “knockout mouse”). In cynomolgus monkeys dosed subcutaneously with denosumab throughout pregnancy starting at gestational day 20 and at a pharmacologically active dose 50-fold higher than the recommended human dose based on body weight, there was increased fetal loss during gestation, stillbirths, and postnatal mortality.
Other findings in offspring included absence of axillary, inguinal, mandibular, and mesenteric lymph nodes; abnormal bone growth, reduced bone strength, reduced hematopoiesis, dental dysplasia, and tooth malalignment; and decreased neonatal growth. At birth out to 1 month of age, infants had measurable blood levels of denosumab (22% to 621% of maternal levels). Following a recovery period from birth out to 6 months of age, the effects on bone quality and strength returned to normal; there were no adverse effects on tooth eruption, though dental dysplasia was still apparent; axillary and inguinal lymph nodes remained absent, while mandibular and mesenteric lymph nodes were present, though small; and minimal to moderate mineralization in multiple tissues was seen in one recovery animal.
There was no evidence of maternal harm prior to labor; adverse maternal effects occurred infrequently during labor. Maternal mammary gland development was normal. There was no fetal NOAEL (no observable adverse effect level) established for this study because only one dose of 50 mg/kg was evaluated.
Mammary gland histopathology at 6 months of age was normal in female offspring exposed to denosumab in utero ; however, development and lactation have not been fully evaluated. In RANKL knockout mice, absence of RANKL (the target of denosumab) also caused fetal lymph node agenesis and led to postnatal impairment of dentition and bone growth. Pregnant RANKL knockout mice showed altered maturation of the maternal mammary gland, leading to impaired lactation [se…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Boncresa 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. In utero denosumab exposure from cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 50-fold higher than the recommended human dose based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality, and absent lymph nodes, abnormal bone growth, and decreased neonatal growth [see Data] .
Data Animal Data The effects of denosumab on prenatal development have been studied in both cynomolgus monkeys and genetically engineered mice in which RANK ligand (RANKL) expression was turned off by gene removal (a “knockout mouse”). In cynomolgus monkeys dosed subcutaneously with denosumab throughout pregnancy starting at gestational day 20 and at a pharmacologically active dose 50-fold higher than the recommended human dose based on body weight, there was increased fetal loss during gestation, stillbirths, and postnatal mortality.
Other findings in offspring included absence of axillary, inguinal, mandibular, and mesenteric lymph nodes; abnormal bone growth, reduced bone strength, reduced hematopoiesis, dental dysplasia, and tooth malalignment; and decreased neonatal growth. At birth out to 1 month of age, infants had measurable blood levels of denosumab (22% to 621% of maternal levels). Following a recovery period from birth out to 6 months of age, the effects on bone quality and strength returned to normal; there were no adverse effects on tooth eruption, though dental dysplasia was still apparent; axillary and inguinal lymph nodes remained absent, while mandibular and mesenteric lymph nodes were present, though small; and minimal to moderate mineralization in multiple tissues was seen in one recovery animal.
There was no evidence of maternal harm prior to labor; adverse maternal effects occurred infrequently during labor. Maternal mammary gland development was normal. There was no fetal NOAEL (no observable adverse effect level) established for this study because only one dose of 50 mg/kg was evaluated.
Mammary gland histopathology at 6 months of age was normal in female offspring exposed to denosumab in utero ; however, development and lactation have not been fully evaluated. In RANKL knockout mice, absence of RANKL (the target of denosumab) also caused fetal lymph node agenesis and led to postnatal impairment of dentition and bone growth. Pregnant RANKL knockout mice showed altered maturation of the maternal mammary gland, leading to impaired lactation [see Use in Specific Populations (8.2) and Nonclinical Toxicology (13.2) ] .
The no effect dose for denosumab products-induced teratogenicity is unknown. However, a C max of 22.9 ng/mL was identified in cynomolgus monkeys as a level in which no biologic effects (NOEL) of denosumab were observed (no inhibition of RANKL) [see Clinical Pharmacology (12.3) ] .
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of Boncresa have not been established in pediatric patients In one multicenter, open-label study with denosumab conducted in 153 pediatric patients with osteogenesis imperfecta, aged 2 to 17 years, evaluating fracture risk reduction, efficacy was not demonstrated. Hypercalcemia has been reported in pediatric patients with osteogenesis imperfecta treated with denosumab products. Some cases required hospitalization and were complicated by acute renal injury [see Warnings and Precautions (5.11) ] .
Clinical studies in pediatric patients with osteogenesis imperfecta were terminated early due to the occurrence of life-threatening events and hospitalizations due to hypercalcemia. Safety and effectiveness were not demonstrated for the treatment of glucocorticoid-induced osteoporosis in one multicenter, randomized, double-blind, placebo-controlled, parallel-group study conducted in 24 pediatric patients with glucocorticoid-induced osteoporosis, aged 5 to 17 years, evaluating change from baseline in lumbar spine BMD Z-score.
Based on results from animal studies, denosumab may negatively affect long-bone growth and dentition in pediatric patients below the age of 4 years. Juvenile Animal Toxicity Data Treatment with denosumab products may impair long-bone growth in children with open growth plates and may inhibit eruption of dentition. In neonatal rats, inhibition of RANKL (the target of denosumab therapy) with a construct of osteoprotegerin bound to Fc (OPG-Fc) at doses ≤ 10 mg/kg was associated with inhibition of bone growth and tooth eruption.
Adolescent primates treated with denosumab at doses 10 and 50 times (10 and 50 mg/kg dose) higher than the recommended human dose of 60 mg administered every 6 months, based on body weight (mg/kg), had abnormal growth plates, considered to be consistent with the pharmacological activity of denosumab [see Nonclinical Toxicology (13.2) ] . Cynomolgus monkeys exposed in utero to denosumab exhibited bone abnormalities, an absence of axillary, inguinal, mandibular, and mesenteric lymph nodes, reduced hematopoiesis, tooth malalignment, and decreased neonatal growth.
Some bone abnormalities recovered once exposure was ceased following birth; however, axillary and inguinal lymph nodes remained absent 6 months post-birth [see Use in Specific Populations (8.1) ] .
🧓 Geriatric Use ▾
8.5Geriatric Use Of the total number of patients in clinical studies of denosumab, 9943 patients (76%) were ≥ 65 years old, while 3576 (27%) were ≥ 75 years old. Of the patients in the osteoporosis study in men, 133 patients (55%) were ≥ 65 years old, while 39 patients (16%) were ≥ 75 years old. Of the patients in the glucocorticoid-induced osteoporosis study, 355 patients (47%) were ≥ 65 years old, while 132 patients (17%) were ≥ 75 years old.
No overall differences in safety or efficacy were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Denosumab productsbinds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption. Denosumab productsprevent RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone.
12.2Pharmacodynamics In clinical studies, treatment with 60 mg of denosumab resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days, with maximal reductions occurring by 1 month. CTX levels were below the limit of assay quantitation (0.049 ng/mL) in 39% to 68% of patients 1 to 3 months after dosing of denosumab. At the end of each dosing interval, CTX reductions were partially attenuated from a maximal reduction of ≥ 87% to ≥ 45% (range: 45% to 80%), as serum denosumab levels diminished, reflecting the reversibility of the effects of denosumab on bone remodeling.
These effects were sustained with continued treatment. Upon reinitiation, the degree of inhibition of CTX by denosumab was similar to that observed in patients initiating denosumab treatment. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e., osteocalcin and procollagen type 1 N-terminal peptide [P1NP]) were observed starting 1 month after the first dose of denosumab.
After discontinuation of denosumab therapy, markers of bone resorption increased to levels 40% to 60% above pretreatment values but returned to baseline levels within 12 months.
12.3Pharmacokinetics In a study conducted in healthy male and female volunteers (n = 73, age range: 18 to 64 years) following a single subcutaneously administered denosumab dose of 60 mg, the mean area-under-the-concentration-time curve up to 16 weeks (AUC 0-16 weeks ) of denosumab was 316 mcg⋅day/mL (standard deviation [SD] = 101 mcg⋅day/mL). The mean maximum denosumab concentration (C max ) was 6.75 mcg/mL (SD = 1.89 mcg/mL). No accumulation or change in denosumab pharmacokinetics with time is observed with multiple dosing of 60 mg subcutaneously administered once every 6 months.
Absorption Following subcutaneous administration, the median time to maximum denosumab concentration (T max ) was 10 days (range: 3 to 21 days). Distribution The mean volume of distribution for denosumab was
5.2 L (SD =
1.7L). Elimination Serum denosumab concentrations declined over a period of 4 to 5 months with a mean half-life of 25.4 days (SD = 8.5 days; n = 46). A population pharmacokinetic analysis was performed to evaluate the effects of demographic characteristics.
This analysis showed no notable differences in pharmacokinetics with age (in postmenopausal women), race, or body weight (36 to 140 kg). Seminal Fluid Pharmacokinetic Study Serum and seminal fluid concentrations of denosumab were measured in 12 healthy male volunteers (age range: 43 to 65 years). After a single 60 mg subcutaneous administration of denosumab, the mean (± SD) C max values in the serum and seminal fluid samples were 6170 (± 2070) and 100 (± 81.9) ng/mL, respectively, resulting in a maximum seminal fluid concentration of approximately 2% of serum levels.
The median (range) T max values in the serum and seminal fluid samples were 8.0 (7.9 to 21) and 21 (8.0 to 49) days, respectively. Among the subjects, the highest denosumab concentration in seminal fluid was 301 ng/mL at 22 days post-dose. On the first day of measurement (10 days post-dose), nine of eleven subjects had quantifiable concentrations in semen.
On the last day of measurement (106 days post-dose), five subjects still had quantifiable concentrations of denosumab in seminal fluid, with a mean (± SD) se…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Denosumab productsbinds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption. Denosumab productsprevent RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED How Supplied Boncresa(denosumab-mobz) injection is a clear, colorless to pale yellow solution supplied in a single-dose prefilled syringe with needle safety guard. The prefilled syringe is not made with natural rubber latex. 60 mg/mL in a single-dose prefilled syringe 1 per carton NDC 70121-2702-1 Storage and Handling Store Boncresa refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.
Do not freeze. Prior to administration, Boncresamay be allowed to reach room temperature up to 25°C (77°F) in the original container. Once removed from the refrigerator, Boncresa must not be exposed to temperatures above 25°C (77°F) and must be used within 14 days.
Discard Boncresa if not used within the 14 days. Do not use Boncresa after the expiry date printed on the label. Protect Boncresa from direct light and heat.
Avoid vigorous shaking of Boncresa.
📋 Description ▾
11 DESCRIPTION Denosumab-mobz is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL (receptor activator of nuclear factor kappa-B ligand). Denosumab-mobz has an approximate molecular weight of 147 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells. Boncresa(denosumab-mobz) injection is a sterile, preservative-free, clear, colorless to pale yellow solution for subcutaneous use.
Each single-dose prefilled syringe contains 1 mL solution of 60 mg denosumab-mobz (60 mg/mL solution), glacial acetic acid (1 mg), polysorbate 20 (0.1 mg), sorbitol (46 mg), Water for Injection (USP), and sodium hydroxide to adjust the pH to 5.2.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION 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 Boncresa [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 Boncresa 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 Boncresa, they should not receive other denosumab products concomitantly [see Warnings and Precautions (5.2) ] . Hypersensitivity Advise patients to seek prompt medical attention if signs or symptoms of hypersensitivity reactions occur. Advise patients who have had signs or symptoms of systemic hypersensitivity reactions that they should not receive denosumab products [see Warnings and Precautions (5.3) and Contraindications (4) ] .
Osteonecrosis of the Jaw Advise patients to maintain good oral hygiene during treatment with Boncresa and to inform their dentist prior to dental procedures that they are receiving Boncresa. Patients should inform their physician or dentist if they experience persistent pain and/or slow healing of the mouth or jaw after dental surgery [see Warnings and Precautions (5.4) ] . Atypical Subtrochanteric and Diaphyseal Femoral Fractures Advise patients to report new or unusual thigh, hip, or groin pain [see Warnings and Precautions (5.5) ] .
Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation Advise patients not to interrupt Boncresa therapy without talking to their physician [see Warnings and Precautions (5.6) ] . Serious Infections Advise patients to seek prompt medical attention if they develop signs or symptoms of infections, including cellulitis [see Warnings and Precautions (5.7) ] . Dermatologic Adverse Reactions Advise patients to seek prompt medical attention if they develop signs or symptoms of dermatological reactions (such as dermatitis, rashes, and eczema) [see Warnings and Precautions (5.8) ] .
Musculoskeletal Pain Inform patients that severe bone, joint, and/or muscle pain have been reported in patients taking denosumab products. Patients should report severe symptoms if they develop [see Warnings and Precautions (5.9) ] . Pregnancy/Nursing Counsel females of reproductive potential to use effective contraceptive measure to prevent pregnancy during treatment and for at least 5 months after the last dose of Boncresa.
Advise the patient to contact their physician immediately if pregnancy does occur during these times. Advise patients not to take Boncresa while pregnant or breastfeeding. If a patient wishes to start breastfeeding after treatment, advise her to discuss the appropriate timing with her physician [see Contraindications (4) and Use in Specific Populations (8.1) ] .
Schedule of Administration Advise patients that if a dose of Boncresa is missed, the injection should be administered as soon as convenient. Thereafter, schedule injections every 6 months from the date of the last injection. Boncresa ® (denosumab) Manufactured by: Amneal Pharmaceuticals LLC Piscataway, NJ 08854 Product of Spain US License No.
2241
💬 Medication Guide ▾
Medication Guide Boncresa ® (bon kree' sah) (denosumab-mobz) Injection, for subcutaneous use What is the most important information I should know about Boncresa? If you receive Boncresa, you should not receive other denosumab products at the same time. Boncresa can cause serious side effects including: Increased risk of severe low calcium levels in your blood (hypocalcemia).
Boncresa may lower the calcium levels in your blood. If you have low blood calcium before you start receiving Boncresa, it may get worse during treatment. Your low blood calcium must be treated before you receive Boncresa.
Talk to your doctor before starting Boncresa. Your doctor may prescribe calcium and vitamin D to help prevent low calcium levels in your blood while you take Boncresa. 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), Boncresa 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 chronic kidney disease-mineral bone disorder (CKD-MBD) may increase your risk for severe low calcium levels in blood. Before you start Boncresa and during treatment, your doctor may need to do certain blood tests to check for CKD-MBD.
Most people with low blood calcium levels do not have symptoms, but some people may have symptoms. Call your doctor right away if you have symptoms of low blood calcium such as: spasms, twitches, or cramps in your muscles numbness or tingling in your fingers, toes, or around your mouth Serious allergic reactions. Serious allergic reactions have happened in people who take denosumab products.
Call your doctor or go to your nearest emergency room right away if you have any symptoms of a serious allergic reaction. Symptoms of a serious allergic reaction may include: low blood pressure (hypotension) rash trouble breathing itching throat tightness hives swelling of your face, lips, or tongue Severe jaw bone problems (osteonecrosis). Severe jaw bone problems may happen when you take Boncresa.
Your doctor should examine your mouth before you start Boncresa. Your doctor may tell you to see your dentist before you start Boncresa. It is important for you to practice good mouth care during treatment with Boncresa.
Ask your doctor or dentist about good mouth care if you have any questions. Unusual thigh bone fractures. Some people have developed unusual fractures in their thigh bone.
Symptoms of a fracture include new or unusual pain in your hip, groin, or thigh. Increased risk of broken bones, including broken bones in the spine, after stopping, skipping or delaying Boncresa. Talk with your doctor before starting Boncresa treatment.
After your treatment with Boncresa is stopped, or if you skip or delay taking a dose, your risk for breaking bones, including bones in your spine, is increased. Your risk for having more than 1 broken bone in your spine is increased if you have already had a broken bone in your spine. Do not stop, skip or delay taking Boncresa without first talking with your doctor.
If your Boncresa treatment is stopped, talk to your doctor about other medicine that you can take. Serious infections. Serious infections in your skin, lower stomach area (abdomen), bladder, or ear may happen if you take Boncresa.
Inflammation of the inner lining of the heart (endocarditis) due to an infection also may happen more often in people who take Boncresa. You may need to go to the hospital for treatment if you develop an infection. Boncresa is a medicine that may affect the ability of your body to fight infections.
People who have a weakened immune system or take medicines that affect the immune system may have an increased risk for developing serious infections. Call your doctor right away if you have any of the following symptoms of infection: fever or chills skin that looks red or swollen and is hot…