Peringatan Keamanan

Bevacizumab toxicities are distinct from the effects of cytotoxic agents used in chemotherapy, and are normally linked to impaired VEGF function.A192960,A192963 Common toxicities associated with bevacizumab include hypertension, gastrointestinal perforation, arterial thromboembolism, reversible posterior leukoencephalopathy syndrome (RPLS), venous thromboembolism, proteinuria, bleeding/hemorrhage, and wound-healing complications.A192960

Bevacizumab

DB00112

biotech approved investigational

Deskripsi

There is a great deal of evidence indicating that vascular endothelial growth factor (VEGF) is important for the survival and proliferation of cancer cells.A192939,A192837,A192891,A193275 VEGF plays an important role in angiogenesis, lymphangiogenesis, and tumor growth, which are all factors that contribute to its attractiveness as a therapeutic target for anti-cancer therapies.A192834,A192888,A192837,A192891,A192894

In 2004, bevacizumab (Avastin) gained FDA approval for specific types of cancer, and became the first antiangiogenic agent introduced to the market.A193272,A193275 It is a humanized monoclonal IgG antibody, and inhibits angiogenesis by binding and neutralizing VEGF-A.A192888,A192939 Bevacizumab is generally indicated for use in combination with different chemotherapy regimens which are specific to the type, severity, and stage of cancer.L12648 Bevacizumab was approved by Health Canada on March 24, 2010 and by the European Commission on April 21, 2021.L45793,L43130 There are several biosimilars of bevacizumab, such as bevacizumab-awwb, bevacizumab-maly, bevacizumab-adcd, and bevacizumab-tnjn.

Interestingly, researchers have identified higher VEGF expression in patients with COVID-19, which may contribute to lung pathologies including acute respiratory syndrome (ARDS) and acute lung injury (ALI).L12699 As such, bevacizumab is being investigated for the treatment of lung complications associated with severe cases of COVID-19.L12699

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) The half-life of bevacizumab is estimated to be 20 days (range of 11-50 days).[L12648,A192921]
Volume Distribusi The volume of distribution of bevacizumab is approximately 3.29 L and 2.39 L for the average male and female, respectively.[A192939]
Klirens (Clearance) The clearance (CL) of bevacizumab is approximately 0.207 L/day.[A192939] The CL of bevacizumab can increase or decrease by 30% in patients who weigh >114 kg or <49 kg respectively.[A192939] Males tend to clear bevacizumab at a faster rate than females (26% faster on average).[A192939] Other factors including alkaline phosphatase (ALP), serum aspartate aminotransferase (AST), serum albumin, and tumor burden may cause the CL to fluctuate.[A192939]

Absorpsi

Monoclonal antibodies (mAbs) are large in size, do not readily cross cell membranes, and are unable to withstand proteolysis in the gastrointestinal tract.A40006,A192981,A19126 Given these characteristics, mAbs are poorly absorbed via the oral route and are instead administered intravenously, intramuscularly or subcutaneously.A40006,A19126 In a single dose (1mg/kg) pharmacokinetic study assessing the bioequivalence of bevacizumab and TAB008 (a biosimilar product), the pharmacokinetic parameters of Avastin (bevacizumab) were as followsA192975: Geometric mean Cmax = 17.38 ug/mL Geometric mean AUCinf = 5,358 ugxh/mL Geometric mean Tmax = 2.50 hrs

Metabolisme

There are several pathways through which monoclonal antibodies (mAbs) may be cleared.A192948 Non-specific clearance of mAbs refers to target independent pinocytosis, and proteolysis of the protein into small amino acids and peptides in the reticuloendothelial system (RES) and the liver.A192948,A40006 Target-mediated clearance is a result of specific interactions between the mAb and its target antigen.A192948 Once bound, the antibody-antigen complex may be cleared via lysosomal degradation.A192948,A40006 Additionally, the production of anti-drug antibodies (ADA), which are a result of an immunogenic response to mAb-based treatment, can form complexes with mAb’s and may impact the rate of mAb clearance.A192948

Rute Eliminasi

Due to their size, monoclonal antibodies are not renally eliminated under normal physiological conditions.A40006 Catabolism or excretion are the primary processes of elimination.A40006

Interaksi Obat

475 Data
Sorafenib The risk or severity of adverse effects can be increased when Bevacizumab is combined with Sorafenib.
Sunitinib The risk or severity of adverse effects can be increased when Sunitinib is combined with Bevacizumab.
Diethylstilbestrol Diethylstilbestrol may increase the thrombogenic activities of Bevacizumab.
Chlorotrianisene Chlorotrianisene may increase the thrombogenic activities of Bevacizumab.
Conjugated estrogens Conjugated estrogens may increase the thrombogenic activities of Bevacizumab.
Estrone Estrone may increase the thrombogenic activities of Bevacizumab.
Estradiol Estradiol may increase the thrombogenic activities of Bevacizumab.
Dienestrol Dienestrol may increase the thrombogenic activities of Bevacizumab.
Ethinylestradiol Ethinylestradiol may increase the thrombogenic activities of Bevacizumab.
Mestranol Mestranol may increase the thrombogenic activities of Bevacizumab.
Estriol Estriol may increase the thrombogenic activities of Bevacizumab.
Estrone sulfate Estrone sulfate may increase the thrombogenic activities of Bevacizumab.
Quinestrol Quinestrol may increase the thrombogenic activities of Bevacizumab.
Hexestrol Hexestrol may increase the thrombogenic activities of Bevacizumab.
Tibolone Tibolone may increase the thrombogenic activities of Bevacizumab.
Synthetic Conjugated Estrogens, A Synthetic Conjugated Estrogens, A may increase the thrombogenic activities of Bevacizumab.
Synthetic Conjugated Estrogens, B Synthetic Conjugated Estrogens, B may increase the thrombogenic activities of Bevacizumab.
Polyestradiol phosphate Polyestradiol phosphate may increase the thrombogenic activities of Bevacizumab.
Esterified estrogens Esterified estrogens may increase the thrombogenic activities of Bevacizumab.
Zeranol Zeranol may increase the thrombogenic activities of Bevacizumab.
Equol Equol may increase the thrombogenic activities of Bevacizumab.
Promestriene Promestriene may increase the thrombogenic activities of Bevacizumab.
Methallenestril Methallenestril may increase the thrombogenic activities of Bevacizumab.
Epimestrol Epimestrol may increase the thrombogenic activities of Bevacizumab.
Moxestrol Moxestrol may increase the thrombogenic activities of Bevacizumab.
Estradiol acetate Estradiol acetate may increase the thrombogenic activities of Bevacizumab.
Estradiol benzoate Estradiol benzoate may increase the thrombogenic activities of Bevacizumab.
Estradiol cypionate Estradiol cypionate may increase the thrombogenic activities of Bevacizumab.
Estradiol valerate Estradiol valerate may increase the thrombogenic activities of Bevacizumab.
Biochanin A Biochanin A may increase the thrombogenic activities of Bevacizumab.
Formononetin Formononetin may increase the thrombogenic activities of Bevacizumab.
Estetrol Estetrol may increase the thrombogenic activities of Bevacizumab.
Pamidronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Bevacizumab is combined with Pamidronic acid.
Zoledronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Bevacizumab is combined with Zoledronic acid.
Alendronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Bevacizumab is combined with Alendronic acid.
Ibandronate The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Bevacizumab is combined with Ibandronate.
Clodronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Bevacizumab is combined with Clodronic acid.
Risedronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Bevacizumab is combined with Risedronic acid.
Etidronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Bevacizumab is combined with Etidronic acid.
Tiludronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Bevacizumab is combined with Tiludronic acid.
Incadronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Bevacizumab is combined with Incadronic acid.
Digoxin Digoxin may decrease the cardiotoxic activities of Bevacizumab.
Acetyldigitoxin Acetyldigitoxin may decrease the cardiotoxic activities of Bevacizumab.
Deslanoside Deslanoside may decrease the cardiotoxic activities of Bevacizumab.
Ouabain Ouabain may decrease the cardiotoxic activities of Bevacizumab.
Digitoxin Digitoxin may decrease the cardiotoxic activities of Bevacizumab.
Oleandrin Oleandrin may decrease the cardiotoxic activities of Bevacizumab.
Cymarin Cymarin may decrease the cardiotoxic activities of Bevacizumab.
Proscillaridin Proscillaridin may decrease the cardiotoxic activities of Bevacizumab.
Metildigoxin Metildigoxin may decrease the cardiotoxic activities of Bevacizumab.
Lanatoside C Lanatoside C may decrease the cardiotoxic activities of Bevacizumab.
Gitoformate Gitoformate may decrease the cardiotoxic activities of Bevacizumab.
Acetyldigoxin Acetyldigoxin may decrease the cardiotoxic activities of Bevacizumab.
Peruvoside Peruvoside may decrease the cardiotoxic activities of Bevacizumab.
Tamoxifen The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Tamoxifen.
Anastrozole The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Anastrozole.
Aldoxorubicin The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Aldoxorubicin.
Paclitaxel trevatide The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Paclitaxel trevatide.
Paclitaxel poliglumex The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Paclitaxel poliglumex.
Pertuzumab The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Pertuzumab.
Peginterferon alfa-2a The risk or severity of cardiotoxicity can be increased when Peginterferon alfa-2a is combined with Bevacizumab.
Trastuzumab The risk or severity of cardiotoxicity can be increased when Trastuzumab is combined with Bevacizumab.
Bortezomib The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Bortezomib.
Cladribine The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Cladribine.
Carmustine The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Carmustine.
Amsacrine The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Amsacrine.
Bleomycin The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Bleomycin.
Mitomycin The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Mitomycin.
Vindesine The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Vindesine.
Vinorelbine The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Vinorelbine.
Teniposide The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Teniposide.
Epirubicin The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Epirubicin.
Cisplatin The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Cisplatin.
Cyclophosphamide The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Cyclophosphamide.
Vincristine The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Vincristine.
Fluorouracil The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Fluorouracil.
Pentostatin The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Pentostatin.
Methotrexate The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Methotrexate.
Vinblastine The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Vinblastine.
Imatinib The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Imatinib.
Daunorubicin The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Daunorubicin.
Tretinoin The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Tretinoin.
Etoposide The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Etoposide.
Mechlorethamine The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Mechlorethamine.
Doxorubicin The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Doxorubicin.
Busulfan The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Busulfan.
Thalidomide The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Thalidomide.
Fludarabine The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Fludarabine.
Capecitabine The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Capecitabine.
Arsenic trioxide The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Arsenic trioxide.
Idarubicin The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Idarubicin.
Ifosfamide The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Ifosfamide.
Mitoxantrone The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Mitoxantrone.
Paclitaxel The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Paclitaxel.
Docetaxel The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Docetaxel.
Cabazitaxel The risk or severity of cardiotoxicity can be increased when Bevacizumab is combined with Cabazitaxel.
Cetuximab The risk or severity of adverse effects can be increased when Cetuximab is combined with Bevacizumab.
Human immunoglobulin G The risk or severity of adverse effects can be increased when Human immunoglobulin G is combined with Bevacizumab.
Omalizumab The risk or severity of adverse effects can be increased when Omalizumab is combined with Bevacizumab.
Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Bevacizumab.

Target Protein

Vascular endothelial growth factor A, long form VEGFA
Complement C1q subcomponent subunit A C1QA
Complement C1q subcomponent subunit B C1QB
Complement C1q subcomponent subunit C C1QC
Low affinity immunoglobulin gamma Fc region receptor III-A FCGR3A
High affinity immunoglobulin gamma Fc receptor I FCGR1A
Low affinity immunoglobulin gamma Fc region receptor II-a FCGR2A
Low affinity immunoglobulin gamma Fc region receptor II-b FCGR2B
Low affinity immunoglobulin gamma Fc region receptor II-c FCGR2C

Referensi & Sumber

Artikel (PubMed)
  • PMID: 17409907
    Velcheti V, Viswanathan A, Govindan R: The proportion of patients with metastatic non-small cell lung cancer potentially eligible for treatment with bevacizumab: a single institutional survey. J Thorac Oncol. 2006 Jun;1(5):501.
  • PMID: 28801849
    Rosen LS, Jacobs IA, Burkes RL: Bevacizumab in Colorectal Cancer: Current Role in Treatment and the Potential of Biosimilars. Target Oncol. 2017 Oct;12(5):599-610. doi: 10.1007/s11523-017-0518-1.
  • PMID: 27329360
    Han K, Peyret T, Marchand M, Quartino A, Gosselin NH, Girish S, Allison DE, Jin J: Population pharmacokinetics of bevacizumab in cancer patients with external validation. Cancer Chemother Pharmacol. 2016 Aug;78(2):341-51. doi: 10.1007/s00280-016-3079-6. Epub 2016 Jun 21.
  • PMID: 29798953
    Apsangikar PD, Chaudhry SR, Naik MM, Deoghare SB, Joseph J: Comparative pharmacokinetics, efficacy, and safety of bevacizumab biosimilar to reference bevacizumab in patients with metastatic colorectal cancer. Indian J Cancer. 2017 Jul-Sep;54(3):535-538. doi: 10.4103/ijc.IJC39417.
  • PMID: 30030240
    Karaman S, Leppanen VM, Alitalo K: Vascular endothelial growth factor signaling in development and disease. Development. 2018 Jul 20;145(14). pii: 145/14/dev151019. doi: 10.1242/dev.151019.
  • PMID: 11970755
    Verheul HM, Pinedo HM: The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis and early clinical development of VEGF-receptor kinase inhibitors. Clin Breast Cancer. 2000 Sep;1 Suppl 1:S80-4. doi: 10.3816/cbc.2000.s.015.
  • PMID: 23419196
    Stacker SA, Achen MG: The VEGF signaling pathway in cancer: the road ahead. Chin J Cancer. 2013 Jun;32(6):297-302. doi: 10.5732/cjc.012.10319. Epub 2013 Feb 19.
  • PMID: 28056756
    Siveen KS, Prabhu K, Krishnankutty R, Kuttikrishnan S, Tsakou M, Alali FQ, Dermime S, Mohammad RM, Uddin S: Vascular Endothelial Growth Factor (VEGF) Signaling in Tumour Vascularization: Potential and Challenges. Curr Vasc Pharmacol. 2017;15(4):339-351. doi: 10.2174/1570161115666170105124038.
Menampilkan 8 dari 24 artikel.

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