Peringatan Keamanan

Denosumab is contraindicated for use in pregnant women because it may cause harm to a fetus. There are insufficient data with denosumab 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.L49796

In clinical trials, hypercalcemia has been reported in pediatric patients with osteogenesis imperfect treated with denosumab products, including Prolia. Some cases required hospitalization and were complicated by acute renal injury. Based on results from animal studies, denosumab may negatively affect long-bone growth and dentition in pediatric patients below the age of 4 years.L49796

The carcinogenic and genotoxic potential of denosumab has not been evaluated in long-term animal studies. Denosumab had no effect on female fertility or male reproductive organs in monkeys at doses that were 13- to 50-fold higher than the recommended human dose of 60 mg subcutaneously administered once every 6 months, based on body weight (mg/kg).L49796

Denosumab

DB06643

biotech approved

Deskripsi

Denosumab is a novel, fully human IgG2 monoclonal antibody specific to receptor activator of nuclear factor kappa-B ligand (RANKL), suppresses bone resorption via inhibiting RANK-mediated activation of osteoclasts. It is the first and currently the only RANKL inhibitor approved to prevent osteoclast-mediated bone loss.A263071 Chemically, it consists of 2 heavy and 2 light chains, with each light chain consisting of 215 amino acids and each heavy chain consisting of 448 amino acids with 4 intramolecular disulfides.A263066

Denosumab was approved by the FDA approved on June 2010 for the treatment of osteoporosis in postmenopausal women. It further received additional indication approval to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for non-metastatic prostate cancer and women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer in September 2011 and in men with osteoporosis at high risk for fracture in September 2012.A263066

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) After C<sub>max</sub>, 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).[L49796]
Volume Distribusi The central volume of distribution and volume of distribution at steady-state were calculated to be 2.49 L/66 kg and 3.5-7 L respectively.[A263056]
Klirens (Clearance) No information is available on the clearance of denosumab.

Absorpsi

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 after fasting (at least for 12 hours), the mean maximum denosumab concentration (Cmax) was 6.75 mcg/mL (standard deviation SD = 1.89 mcg/mL). The median time to maximum denosumab concentration (Tmax) was 10 days (range: 3 to 21 days). The mean area-under-the-concentration-time curve up to 16 weeks (AUC0-16 weeks) of denosumab was 316 mcg?day/mL (SD = 101 mcg?day/mL.L49796 No accumulation or change in denosumab pharmacokinetics with time was observed upon multiple dosing of 60 mg subcutaneously administered once every 6 months.L49796 Serum and seminal fluid concentrations of denosumab were measured in 12 healthy male volunteers (age range: 43-65 years). After a single 60 mg subcutaneous administration of denosumab, the mean (± SD) Cmax 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) Tmax 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 the 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) seminal fluid concentration of 21.1 (± 36.5) ng/mL across all subjects (n = 12).L49796 In patients with newly diagnosed multiple myeloma who received 120 mg every 4 weeks, denosumab concentrations appear to reach a steady state by month 6. In patients with giant cell tumor of bone, after administration of subcutaneous doses of 120 mg once every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy, mean (± standard deviation) serum trough concentrations on Day 8, 15, and one month after the first dose were 19.0 (± 24.1), 31.6 (± 27.3), 36.4 (± 20.6) mcg/mL, respectively. Steady-state was achieved in 3 months after initiation of treatment with a mean serum trough concentration of 23.4 (± 12.1) mcg/mL.L49806

Metabolisme

No information is available on the metabolism of denosumab.

Rute Eliminasi

As an antibody, denosumab is likely cleared by the reticuloendothelial system with minimal renal filtration and excretion.A263061

Interaksi Makanan

2 Data
  • 1. Administer calcium supplement. Calcium supplements should be used as necessary to prevent hypocalcemia.
  • 2. Administer vitamin supplements. Vitamin D should be administered as necessary to complement calcium in preventing hypocalcemia.

Interaksi Obat

671 Data
Etanercept The risk or severity of adverse effects can be increased when Denosumab is combined with Etanercept.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Denosumab is combined with Peginterferon alfa-2a.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Denosumab is combined with Interferon alfa-n1.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Denosumab is combined with Interferon alfa-n3.
Peginterferon alfa-2b The risk or severity of adverse effects can be increased when Denosumab is combined with Peginterferon alfa-2b.
Anakinra The risk or severity of adverse effects can be increased when Denosumab is combined with Anakinra.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Denosumab is combined with Interferon gamma-1b.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Denosumab is combined with Interferon alfa-2a.
Aldesleukin The risk or severity of adverse effects can be increased when Denosumab is combined with Aldesleukin.
Adalimumab The risk or severity of adverse effects can be increased when Denosumab is combined with Adalimumab.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Denosumab is combined with Gemtuzumab ozogamicin.
Pegaspargase The risk or severity of adverse effects can be increased when Denosumab is combined with Pegaspargase.
Infliximab The risk or severity of adverse effects can be increased when Denosumab is combined with Infliximab.
Interferon beta-1b The risk or severity of adverse effects can be increased when Denosumab is combined with Interferon beta-1b.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Denosumab is combined with Interferon alfacon-1.
Trastuzumab The risk or severity of neutropenia can be increased when Trastuzumab is combined with Denosumab.
Rituximab The risk or severity of adverse effects can be increased when Denosumab is combined with Rituximab.
Basiliximab The risk or severity of adverse effects can be increased when Denosumab is combined with Basiliximab.
Muromonab The risk or severity of adverse effects can be increased when Denosumab is combined with Muromonab.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Denosumab is combined with Ibritumomab tiuxetan.
Tositumomab The risk or severity of adverse effects can be increased when Denosumab is combined with Tositumomab.
Alemtuzumab The risk or severity of adverse effects can be increased when Denosumab is combined with Alemtuzumab.
Alefacept The risk or severity of adverse effects can be increased when Denosumab is combined with Alefacept.
Efalizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Efalizumab.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Denosumab is combined with Antithymocyte immunoglobulin (rabbit).
Interferon alfa-2b The risk or severity of adverse effects can be increased when Denosumab is combined with Interferon alfa-2b.
Natalizumab The risk or severity of immunosuppression can be increased when Denosumab is combined with Natalizumab.
Daclizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Daclizumab.
Phenylalanine The risk or severity of adverse effects can be increased when Denosumab is combined with Phenylalanine.
Flunisolide The risk or severity of adverse effects can be increased when Denosumab is combined with Flunisolide.
Bortezomib The risk or severity of adverse effects can be increased when Denosumab is combined with Bortezomib.
Cladribine The risk or severity of adverse effects can be increased when Denosumab is combined with Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Denosumab is combined with Carmustine.
Amsacrine The risk or severity of adverse effects can be increased when Denosumab is combined with Amsacrine.
Bleomycin The risk or severity of adverse effects can be increased when Denosumab is combined with Bleomycin.
Chlorambucil The risk or severity of adverse effects can be increased when Denosumab is combined with Chlorambucil.
Raltitrexed The risk or severity of adverse effects can be increased when Denosumab is combined with Raltitrexed.
Mitomycin The risk or severity of adverse effects can be increased when Denosumab is combined with Mitomycin.
Bexarotene The risk or severity of adverse effects can be increased when Denosumab is combined with Bexarotene.
Vindesine The risk or severity of adverse effects can be increased when Denosumab is combined with Vindesine.
Floxuridine The risk or severity of adverse effects can be increased when Denosumab is combined with Floxuridine.
Indomethacin The risk or severity of adverse effects can be increased when Denosumab is combined with Indomethacin.
Tioguanine The risk or severity of adverse effects can be increased when Denosumab is combined with Tioguanine.
Vinorelbine The risk or severity of adverse effects can be increased when Denosumab is combined with Vinorelbine.
Dexrazoxane The risk or severity of adverse effects can be increased when Denosumab is combined with Dexrazoxane.
Beclomethasone dipropionate The risk or severity of adverse effects can be increased when Denosumab is combined with Beclomethasone dipropionate.
Sorafenib The risk or severity of adverse effects can be increased when Denosumab is combined with Sorafenib.
Streptozocin The risk or severity of adverse effects can be increased when Denosumab is combined with Streptozocin.
Trifluridine The risk or severity of adverse effects can be increased when Denosumab is combined with Trifluridine.
Gemcitabine The risk or severity of adverse effects can be increased when Denosumab is combined with Gemcitabine.
Betamethasone The risk or severity of adverse effects can be increased when Denosumab is combined with Betamethasone.
Teniposide The risk or severity of adverse effects can be increased when Denosumab is combined with Teniposide.
Epirubicin The risk or severity of adverse effects can be increased when Denosumab is combined with Epirubicin.
Chloramphenicol The risk or severity of adverse effects can be increased when Denosumab is combined with Chloramphenicol.
Lenalidomide The risk or severity of adverse effects can be increased when Denosumab is combined with Lenalidomide.
Altretamine The risk or severity of adverse effects can be increased when Denosumab is combined with Altretamine.
Zidovudine The risk or severity of adverse effects can be increased when Denosumab is combined with Zidovudine.
Cisplatin The risk or severity of adverse effects can be increased when Denosumab is combined with Cisplatin.
Oxaliplatin The risk or severity of adverse effects can be increased when Denosumab is combined with Oxaliplatin.
Cyclophosphamide The risk or severity of adverse effects can be increased when Denosumab is combined with Cyclophosphamide.
Vincristine The risk or severity of adverse effects can be increased when Denosumab is combined with Vincristine.
Fluorouracil The risk or severity of adverse effects can be increased when Denosumab is combined with Fluorouracil.
Propylthiouracil The risk or severity of adverse effects can be increased when Denosumab is combined with Propylthiouracil.
Pentostatin The risk or severity of adverse effects can be increased when Denosumab is combined with Pentostatin.
Methotrexate The risk or severity of adverse effects can be increased when Denosumab is combined with Methotrexate.
Carbamazepine The risk or severity of adverse effects can be increased when Denosumab is combined with Carbamazepine.
Vinblastine The risk or severity of adverse effects can be increased when Denosumab is combined with Vinblastine.
Fluticasone propionate The risk or severity of adverse effects can be increased when Denosumab is combined with Fluticasone propionate.
Fluocinolone acetonide The risk or severity of adverse effects can be increased when Denosumab is combined with Fluocinolone acetonide.
Linezolid The risk or severity of adverse effects can be increased when Denosumab is combined with Linezolid.
Imatinib The risk or severity of adverse effects can be increased when Denosumab is combined with Imatinib.
Triamcinolone The risk or severity of adverse effects can be increased when Denosumab is combined with Triamcinolone.
Clofarabine The risk or severity of adverse effects can be increased when Denosumab is combined with Clofarabine.
Prednisone The risk or severity of adverse effects can be increased when Denosumab is combined with Prednisone.
Pemetrexed The risk or severity of adverse effects can be increased when Denosumab is combined with Pemetrexed.
Fludrocortisone The risk or severity of adverse effects can be increased when Denosumab is combined with Fludrocortisone.
Mycophenolate mofetil The risk or severity of adverse effects can be increased when Denosumab is combined with Mycophenolate mofetil.
Daunorubicin The risk or severity of adverse effects can be increased when Denosumab is combined with Daunorubicin.
Irinotecan The risk or severity of adverse effects can be increased when Denosumab is combined with Irinotecan.
Methimazole The risk or severity of adverse effects can be increased when Denosumab is combined with Methimazole.
Etoposide The risk or severity of adverse effects can be increased when Denosumab is combined with Etoposide.
Sulfasalazine The risk or severity of adverse effects can be increased when Denosumab is combined with Sulfasalazine.
Dacarbazine The risk or severity of adverse effects can be increased when Denosumab is combined with Dacarbazine.
Temozolomide The risk or severity of adverse effects can be increased when Denosumab is combined with Temozolomide.
Penicillamine The risk or severity of adverse effects can be increased when Denosumab is combined with Penicillamine.
Prednisolone The risk or severity of adverse effects can be increased when Denosumab is combined with Prednisolone.
Tacrolimus The risk or severity of adverse effects can be increased when Denosumab is combined with Tacrolimus.
Sirolimus The risk or severity of adverse effects can be increased when Denosumab is combined with Sirolimus.
Mechlorethamine The risk or severity of adverse effects can be increased when Denosumab is combined with Mechlorethamine.
Azacitidine The risk or severity of adverse effects can be increased when Denosumab is combined with Azacitidine.
Carboplatin The risk or severity of adverse effects can be increased when Denosumab is combined with Carboplatin.
Methylprednisolone The risk or severity of adverse effects can be increased when Denosumab is combined with Methylprednisolone.
Dactinomycin The risk or severity of adverse effects can be increased when Denosumab is combined with Dactinomycin.
Cytarabine The risk or severity of adverse effects can be increased when Denosumab is combined with Cytarabine.
Azathioprine The risk or severity of adverse effects can be increased when Denosumab is combined with Azathioprine.
Doxorubicin The risk or severity of adverse effects can be increased when Denosumab is combined with Doxorubicin.
Hydroxyurea The risk or severity of adverse effects can be increased when Denosumab is combined with Hydroxyurea.
Busulfan The risk or severity of adverse effects can be increased when Denosumab is combined with Busulfan.
Mycophenolic acid The risk or severity of adverse effects can be increased when Denosumab is combined with Mycophenolic acid.
Topotecan The risk or severity of adverse effects can be increased when Denosumab is combined with Topotecan.

Target Protein

Tumor necrosis factor ligand superfamily member 11 TNFSF11

Referensi & Sumber

Artikel (PubMed)
  • PMID: 23159111
    Malan J, Ettinger K, Naumann E, Beirne OR: The relationship of denosumab pharmacology and osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Dec;114(6):671-6. doi: 10.1016/j.oooo.2012.08.439.
  • PMID: 36841226
    Stefania S, Rotondo C, Mele A, Trotta A, Cantatore FP, Corrado A: Role of denosumab in bone erosions in rheumatoid arthritis. Postgrad Med J. 2023 Aug 22;99(1175):976-984. doi: 10.1093/postmj/qgad013.
  • PMID: 22087866
    Sutjandra L, Rodriguez RD, Doshi S, Ma M, Peterson MC, Jang GR, Chow AT, Perez-Ruixo JJ: Population pharmacokinetic meta-analysis of denosumab in healthy subjects and postmenopausal women with osteopenia or osteoporosis. Clin Pharmacokinet. 2011 Dec 1;50(12):793-807. doi: 10.2165/11594240-000000000-00000.
  • PMID: 24455656
    Narayanan P: Denosumab: A comprehensive review. South Asian J Cancer. 2013 Oct;2(4):272-7. doi: 10.4103/2278-330X.119895.
  • PMID: 25614274
    Zaheer S, LeBoff M, Lewiecki EM: Denosumab for the treatment of osteoporosis. Expert Opin Drug Metab Toxicol. 2015 Mar;11(3):461-70. doi: 10.1517/17425255.2015.1000860. Epub 2015 Jan 22.
  • PMID: 34762286
    Kendler DL, Cosman F, Stad RK, Ferrari S: Denosumab in the Treatment of Osteoporosis: 10 Years Later: A Narrative Review. Adv Ther. 2022 Jan;39(1):58-74. doi: 10.1007/s12325-021-01936-y. Epub 2021 Nov 11.

Contoh Produk & Brand

Produk: 18 • International brands: 1
Produk
  • Jubbonti
    Solution • 60 mg / mL • Subcutaneous • Canada • Approved
  • Jubbonti
    Injection, solution • 60 mg/ml • Subcutaneous • EU • Approved
  • Prolia
    Injection • 60 mg/1mL • Subcutaneous • US • Approved
  • Prolia
    Solution • 60 mg / mL • Subcutaneous • Canada • Approved
  • Prolia
    Solution • 60 mg / mL • Subcutaneous • Canada • Approved
  • Prolia
    Injection, solution • 60 mg/ml • Subcutaneous • EU • Approved
  • Prolia
    Injection, solution • 60 mg/ml • Subcutaneous • EU • Approved
  • Prolia
    Injection, solution • 60 mg/ml • Subcutaneous • EU • Approved
Menampilkan 8 dari 18 produk.
International Brands
  • Ranmark — Daiichi Sankyo

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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