Denosumab

bone density conservation agents, monoclonal antibodies

Thuốc Gốc

Biotech

CAS: 615258-40-7

ATC: M05BX04

CTHH: C₆₄₀₄H₉₉₁₂N₁₇₂₄O₂₀₀₄S₅₀

PTK: 144.7 kDa

Denosumab is a novel, fully human IgG2 monoclonal antibody specific to receptor activator of nuclear factor kappa-B ligand (RANKL), suppresses bone resorption markers in patients with a variety of metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Chemically, it consists of 2 heavy and 2 light chains. Each light chain consists of 215 amino acids. Each heavy chain consists of 448 amino acids with 4 intramolecular disulfides. FDA approved on June 1, 2010.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₆₄₀₄H₉₉₁₂N₁₇₂₄O₂₀₀₄S₅₀

Phân tử khối

144.7 kDa

Dược Lực Học : In clinical studies, treatment with 60 mg of Prolia resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days. 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 [PlNP]) were observed starting 1 month after the first dose of Prolia.

Cơ Chế Tác Dụng : Denosumab is a novel, fully human IgG2 monoclonal antibody specific to receptor activator of nuclear factor kappa-B ligand (RANKL), suppresses bone resorption markers in patients with a variety of metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Chemically, it consists of 2 heavy and 2 light chains. Each light chain consists of 215 amino acids. Each heavy chain consists of 448 amino acids with 4 intramolecular disulfides. FDA approved on June 1, 2010. Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Denosumab prevents 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.

Dược Động Học :

▧ Absorption :
When 60 mg of denosumab was subcutaneously administered to healthy subjects after fasting for 12 hours, the pharmacokinetic parameters are as follows: Cmax = 6.75 mcg/mL; Tmax= 10 days (range of 3 to 21 days); AUC (0-16 weeks) = 316 mcg•day/mL. Denosumab does not accumulate following multiple doses once every 6 months. The pharmacokinetics of denosumab were not affected by the formation of antibodies.
▧ Half Life :
25.4 days

Độc Tính : In patients with postmenopausal osteoporosis, the 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. In male patients with osteoporosis, the most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis. In patients experiencing bone loss due to hormone ablation for cancer, the 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

Chỉ Định : Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. It reduces the incidence of vertebral, nonvertebral, and hip fractures. Prolia is also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. It can also be used in men with osteoporosis at high risk for fracture or in men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

Tương Tác Thuốc :

Abatacept Monitor therapy due to enhanced effects of immunosuppressants and the risk of serious infections.
Antithymocyte globulin Monitor therapy because of the enhanced immunosuppressive effect and increased risk of infections.
Belatacept Montinor therapy due to enhanced adverse effects of immunosuppressants and the risk of infections.
Belimumab Belimumab increases the immunosupressive effect. Interaction is significant so monitor closely.
Etanercept Monitor therapy as there may be an enhanced immunosuppressive effect.
Gemtuzumab ozogamicin Monitor therapy due to enhanced adverse effects of immunosuppressants including the risk of infections.
Glatiramer Acetate Monitor therapy due to enhanced immunosuppressive effects and the risk of infections.
Ibritumomab Monitor therapy for enhanced immunosuppressive effects and increased risk of infections.
Infliximab Therapy should be monitored when combination is initiated as there may be an increase in serious infections.
Obinutuzumab Monitor therapy due to increased risk of infections due to adverse effects of immunosuppressants.
Omalizumab Monitor therapy due to increased risk of infections consequent to increased adverse effects of immunosuppressants.
Pegaspargase Monitor therapy due to increased immunosuppressive effect and risk of infections.
Pralatrexate Increased immunosuppresive effects and risk of infection. Monitor for adverse effects .
Rilonacept Use caution with patients on concomitant immunosuppressants or those with compromised immune systems; increased risk of serious infection.
Tofacitinib Denosumab, when used in combination with tofacitinib, may increase tofaciitinib toxicity and worsen side effects. It may specifically increase the risk of serious infection. It is recommended to monitor therapy.

Liều Lượng & Cách Dùng : Solution - Subcutaneous - 60 mg/mL; 120 mg/1.7 mL

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty : Amgen

Sản phẩm biệt dược : Prolia
Công ty : Daiichi Sankyo

Sản phẩm biệt dược : Ranmark
Công ty : Amgen

Sản phẩm biệt dược : Xgeva

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB06643

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D03684

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/55513-710-01

PharmGKB

http://www.pharmgkb.org/drug/PA166048634

Wikipedia

http://en.wikipedia.org/wiki/Denosumab

RxList

http://www.rxlist.com/prolia-drug.htm

Drugs.com

http://www.drugs.com/ppa/denosumab.html

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