Peringatan Keamanan

LD50 information for tivozanib is not readily available in the literature, however the European Medicines Agency (EMA) assessment report indicates the oral maximum tolerated dose (MTD) in mice was 524 mg/kg; doses ? 750 mg/kg led to severe and lethal effects. In rats, the oral MTD was to 276 mg/kg; at doses ? 369 mg/kg, severe effects and death occurred.L32549

In tivozanib monotherapy studies, two patients received overdoses of tivozanib. One volunteer with a prior history of hypertension experienced aggravated uncontrolled hypertension that resulted in death after taking 3 doses of 1340 microgram tivozanib in one day (total of 4020 micrograms). A second patient patient ingested two doses of 1340 microgram tivozanib in one day (total of 2680 micrograms), and experienced no adverse effects. Carefully control blood pressure before starting tivozanib; regularly monitor blood pressure during treatment. In the case of a confirmed or suspected overdose, discontinue tivozanib, monitor the patient closely, and provide supportive treatment as necessary. No antidote exists for an overdose with tivozanib.L17180

Tivozanib

DB11800

small molecule approved investigational

Deskripsi

Renal cell carcinoma (RCC) is responsible for 3% of cancer casesA231314 and is one of the 10 most common cancers in adults. The average age of diagnosis is between age 65 to 74.L32529 Tivozanib, also known as FOTIVDA, is a kinase inhibitor developed to treat adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) after prior failed systemic therapies. It was approved on March 10, 2021 by the FDA. Marketed by Aveo Oncology, tivozanib is a promising therapy for individuals with RCC who have not been treated successfully with other therapies.L32524

Struktur Molekul 2D

Berat 454.863
Wujud solid

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 tivozanib is about 111 hours according to prescribing information.[L32524] Information from clinical studies reveals a half-life of 4-5 days.[A231339,L32554]
Volume Distribusi Tivozanib has an apparent volume of distribution (V/F) of 123 L.[L32524]
Klirens (Clearance) The apparent clearance (CL/F) of tivozanib is approximately 0.75 L/h.[L32524]

Absorpsi

The median Tmax of tivozanib is 10 hours, however, can range from 3 to 24 hours.L32524 A pharmacokinetic study in 8 healthy subjects revealed a Cmax and AUC for radiolabeled tivozanib of 12.1 ± 5.67 ng/mL and 1084 ± 417.0 ng·h/mL, respectively.A231339 Steady-state tivozanib concentrations are achieved at concentrations 6-7 times higher the normal dose.L32554

Metabolisme

Tivozanib is primarily metabolized by CYP3A4.A231344,L17180 After oral ingestion of a radiolabeled 1.34 mg dose of tivozanib in healthy volunteers, unchanged tivozanib accounted for 90% of the radioactive drug detected in serum.L32524

Rute Eliminasi

Tivozanib is primarily excreted in the feces. After oral ingestion of a radiolabeled 1.34 mg dose of tivozanib in healthy volunteers, 79% of the administered dose was found in the feces (with 26% unchanged) and 12% was found in the urine solely as metabolites.A231339,L32524

Interaksi Makanan

1 Data
  • 1. Take with or without food.

Interaksi Obat

477 Data
Ranolazine The serum concentration of Tivozanib can be increased when it is combined with Ranolazine.
Propacetamol The serum concentration of Propacetamol can be increased when it is combined with Tivozanib.
Folic acid Tivozanib may decrease the excretion rate of Folic acid which could result in a higher serum level.
Pravastatin Tivozanib may decrease the excretion rate of Pravastatin which could result in a higher serum level.
Conjugated estrogens Tivozanib may decrease the excretion rate of Conjugated estrogens which could result in a higher serum level.
Gefitinib Tivozanib may decrease the excretion rate of Gefitinib which could result in a higher serum level.
Sorafenib The serum concentration of Tivozanib can be increased when it is combined with Sorafenib.
Allopurinol Tivozanib may decrease the excretion rate of Allopurinol which could result in a higher serum level.
Teniposide Tivozanib may decrease the excretion rate of Teniposide which could result in a higher serum level.
Prazosin Tivozanib may decrease the excretion rate of Prazosin which could result in a higher serum level.
Raloxifene Tivozanib may decrease the excretion rate of Raloxifene which could result in a higher serum level.
Celecoxib Tivozanib may decrease the excretion rate of Celecoxib which could result in a higher serum level.
Zidovudine Tivozanib may decrease the excretion rate of Zidovudine which could result in a higher serum level.
Ritonavir Tivozanib may decrease the excretion rate of Ritonavir which could result in a higher serum level.
Oxaliplatin Tivozanib may decrease the excretion rate of Oxaliplatin which could result in a higher serum level.
Vincristine Tivozanib may decrease the excretion rate of Vincristine which could result in a higher serum level.
Fluorouracil Tivozanib may decrease the excretion rate of Fluorouracil which could result in a higher serum level.
Methotrexate Tivozanib may decrease the excretion rate of Methotrexate which could result in a higher serum level.
Ivermectin Tivozanib may decrease the excretion rate of Ivermectin which could result in a higher serum level.
Imatinib Tivozanib may decrease the excretion rate of Imatinib which could result in a higher serum level.
Clofarabine Tivozanib may decrease the excretion rate of Clofarabine which could result in a higher serum level.
Sumatriptan Tivozanib may decrease the excretion rate of Sumatriptan which could result in a higher serum level.
Mycophenolate mofetil Tivozanib may decrease the excretion rate of Mycophenolate mofetil which could result in a higher serum level.
Daunorubicin Tivozanib may decrease the excretion rate of Daunorubicin which could result in a higher serum level.
Nitrofurantoin Tivozanib may decrease the excretion rate of Nitrofurantoin which could result in a higher serum level.
Lamivudine Tivozanib may decrease the excretion rate of Lamivudine which could result in a higher serum level.
Riluzole Tivozanib may decrease the excretion rate of Riluzole which could result in a higher serum level.
Irinotecan Tivozanib may decrease the excretion rate of Irinotecan which could result in a higher serum level.
Sulfasalazine Tivozanib may decrease the excretion rate of Sulfasalazine which could result in a higher serum level.
Donepezil Tivozanib may decrease the excretion rate of Donepezil which could result in a higher serum level.
Dactinomycin Tivozanib may decrease the excretion rate of Dactinomycin which could result in a higher serum level.
Ezetimibe Tivozanib may decrease the excretion rate of Ezetimibe which could result in a higher serum level.
Doxorubicin Tivozanib may decrease the excretion rate of Doxorubicin which could result in a higher serum level.
Glyburide Tivozanib may decrease the excretion rate of Glyburide which could result in a higher serum level.
Topotecan Tivozanib may decrease the excretion rate of Topotecan which could result in a higher serum level.
Tegaserod Tivozanib may decrease the excretion rate of Tegaserod which could result in a higher serum level.
Leflunomide Tivozanib may decrease the excretion rate of Leflunomide which could result in a higher serum level.
Rosuvastatin Tivozanib may decrease the excretion rate of Rosuvastatin which could result in a higher serum level.
Mitoxantrone Tivozanib may decrease the excretion rate of Mitoxantrone which could result in a higher serum level.
Dasatinib Tivozanib may decrease the excretion rate of Dasatinib which could result in a higher serum level.
Alvocidib Tivozanib may decrease the excretion rate of Alvocidib which could result in a higher serum level.
Camptothecin Tivozanib may decrease the excretion rate of Camptothecin which could result in a higher serum level.
Nilotinib Tivozanib may decrease the excretion rate of Nilotinib which could result in a higher serum level.
Rivaroxaban Tivozanib may decrease the excretion rate of Rivaroxaban which could result in a higher serum level.
Simeprevir Tivozanib may decrease the excretion rate of Simeprevir which could result in a higher serum level.
Pazopanib Tivozanib may decrease the excretion rate of Pazopanib which could result in a higher serum level.
Apixaban Tivozanib may decrease the excretion rate of Apixaban which could result in a higher serum level.
Pralatrexate Tivozanib may decrease the excretion rate of Pralatrexate which could result in a higher serum level.
Teriflunomide Tivozanib may decrease the excretion rate of Teriflunomide which could result in a higher serum level.
Ponatinib Tivozanib may decrease the excretion rate of Ponatinib which could result in a higher serum level.
Afatinib Tivozanib may decrease the excretion rate of Afatinib which could result in a higher serum level.
Dolutegravir Tivozanib may decrease the excretion rate of Dolutegravir which could result in a higher serum level.
Riociguat Tivozanib may decrease the excretion rate of Riociguat which could result in a higher serum level.
Sofosbuvir Tivozanib may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
Idelalisib Tivozanib may decrease the excretion rate of Idelalisib which could result in a higher serum level.
Palbociclib Tivozanib may decrease the excretion rate of Palbociclib which could result in a higher serum level.
Lenvatinib Tivozanib may decrease the excretion rate of Lenvatinib which could result in a higher serum level.
Fimasartan Tivozanib may decrease the excretion rate of Fimasartan which could result in a higher serum level.
Ombitasvir Tivozanib may decrease the excretion rate of Ombitasvir which could result in a higher serum level.
Tenofovir alafenamide The serum concentration of Tenofovir alafenamide can be increased when it is combined with Tivozanib.
Osimertinib Tivozanib may decrease the excretion rate of Osimertinib which could result in a higher serum level.
Venetoclax Tivozanib may decrease the excretion rate of Venetoclax which could result in a higher serum level.
Velpatasvir Tivozanib may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Selumetinib Tivozanib may decrease the excretion rate of Selumetinib which could result in a higher serum level.
Talazoparib The serum concentration of Talazoparib can be increased when it is combined with Tivozanib.
Fostemsavir Tivozanib may decrease the excretion rate of Fostemsavir which could result in a higher serum level.
Revefenacin Tivozanib may decrease the excretion rate of Revefenacin which could result in a higher serum level.
Duvelisib Tivozanib may decrease the excretion rate of Duvelisib which could result in a higher serum level.
Dacomitinib Tivozanib may decrease the excretion rate of Dacomitinib which could result in a higher serum level.
Glasdegib Tivozanib may decrease the excretion rate of Glasdegib which could result in a higher serum level.
Abemaciclib Tivozanib may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
Voxilaprevir Tivozanib may decrease the excretion rate of Voxilaprevir which could result in a higher serum level.
Rucaparib Tivozanib may decrease the excretion rate of Rucaparib which could result in a higher serum level.
Copanlisib Tivozanib may decrease the excretion rate of Copanlisib which could result in a higher serum level.
Tazemetostat Tivozanib may decrease the excretion rate of Tazemetostat which could result in a higher serum level.
Darolutamide Tivozanib may decrease the excretion rate of Darolutamide which could result in a higher serum level.
Lusutrombopag Tivozanib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Pibrentasvir Tivozanib may decrease the excretion rate of Pibrentasvir which could result in a higher serum level.
Glecaprevir Tivozanib may decrease the excretion rate of Glecaprevir which could result in a higher serum level.
Ripretinib Tivozanib may decrease the excretion rate of Ripretinib which could result in a higher serum level.
Trilaciclib Tivozanib may decrease the excretion rate of Trilaciclib which could result in a higher serum level.
Cyclosporine The serum concentration of Tivozanib can be increased when it is combined with Cyclosporine.
Fluconazole The serum concentration of Tivozanib can be increased when it is combined with Fluconazole.
Erythromycin The serum concentration of Tivozanib can be increased when it is combined with Erythromycin.
Sildenafil The serum concentration of Tivozanib can be increased when it is combined with Sildenafil.
Reserpine The serum concentration of Tivozanib can be increased when it is combined with Reserpine.
Mefloquine The serum concentration of Tivozanib can be increased when it is combined with Mefloquine.
Sapropterin The serum concentration of Tivozanib can be increased when it is combined with Sapropterin.
Loxapine The serum concentration of Tivozanib can be increased when it is combined with Loxapine.
Toremifene The serum concentration of Tivozanib can be increased when it is combined with Toremifene.
Simvastatin The serum concentration of Tivozanib can be increased when it is combined with Simvastatin.
Verapamil The serum concentration of Tivozanib can be increased when it is combined with Verapamil.
Clofazimine The serum concentration of Tivozanib can be increased when it is combined with Clofazimine.
Vardenafil The serum concentration of Tivozanib can be increased when it is combined with Vardenafil.
Tacrolimus The serum concentration of Tivozanib can be increased when it is combined with Tacrolimus.
Conivaptan The serum concentration of Tivozanib can be increased when it is combined with Conivaptan.
Quinidine The serum concentration of Tivozanib can be increased when it is combined with Quinidine.
Zonisamide The serum concentration of Tivozanib can be increased when it is combined with Zonisamide.
Tipranavir The serum concentration of Tivozanib can be increased when it is combined with Tipranavir.
Ketoconazole The serum concentration of Tivozanib can be increased when it is combined with Ketoconazole.

Target Protein

Vascular endothelial growth factor receptor 1 FLT1
Vascular endothelial growth factor receptor 2 KDR
Vascular endothelial growth factor receptor 3 FLT4
Mast/stem cell growth factor receptor Kit KIT
Platelet-derived growth factor receptor beta PDGFRB
Receptor-type tyrosine-protein kinase FLT3 FLT3
Platelet-derived growth factor receptor alpha PDGFRA
Protein-tyrosine kinase 6 PTK6
Angiopoietin-1 receptor TEK
Fibroblast growth factor receptor 1 FGFR1
Hepatocyte growth factor receptor MET

Referensi & Sumber

Synthesis reference: Liu, M. X., Hu, L. X., Wang, X. W., & Zhu, H. D. (2011). Synthesis of Anti-Cancer Targeted Therapies Drug Tivozanib. Advanced Materials Research, 396–398, 1490–1492. https://doi.org/10.4028/www.scientific.net/amr.396-398.1490
Artikel (PubMed)
  • PMID: 22112490
    Cairns P: Renal cell carcinoma. Cancer Biomark. 2010;9(1-6):461-73. doi: 10.3233/CBM-2011-0176.
  • PMID: 33552876
    Pallagani L, Choudhary GR, Himanshu P, Madduri VKS, Singh M, Gupta P, Shrivastava N, Baid G, Meenakshi R, Aasma N, Pareek P, Sanjeev M: Epidemiology and Clinicopathological Profile of Renal Cell Carcinoma: A Review from Tertiary Care Referral Centre. J Kidney Cancer VHL. 2021 Jan 20;8(1):1-6. doi: 10.15586/jkcvhl.2021.154. eCollection 2021.
  • PMID: 27121337
    Cotreau MM, Hale CL, Jacobson L, Oelke CS, Strahs AL, Kochan RG, Sanga M, Slichenmyer W, Vargo DL: Absorption, Metabolism, and Excretion of (14) C-Tivozanib, a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Healthy Male Participants: A Phase I, Open-Label, Mass-Balance Study. Clin Pharmacol Drug Dev. 2012 Jul;1(3):102-9. doi: 10.1177/2160763X12447303.
  • PMID: 32234426
    Wang J, Bruin MAC, Gan C, Lebre MC, Rosing H, Beijnen JH, Schinkel AH: Brain accumulation of tivozanib is restricted by ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) in mice. Int J Pharm. 2020 May 15;581:119277. doi: 10.1016/j.ijpharm.2020.119277. Epub 2020 Mar 28.
  • PMID: 27128461
    Cotreau MM, Massmanian L, Strahs AL, Slichenmyer W, Vargo DL: The effect of food on the pharmacokinetics of tivozanib hydrochloride. Clin Pharmacol Drug Dev. 2014 Mar;3(2):158-62. doi: 10.1002/cpdd.76. Epub 2013 Oct 30.
  • PMID: 28971328
    Kim ES: Tivozanib: First Global Approval. Drugs. 2017 Nov;77(17):1917-1923. doi: 10.1007/s40265-017-0825-y.
  • PMID: 32692256
    Jacob A, Shook J, Hutson TE: Tivozanib, a highly potent and selective inhibitor of VEGF receptor tyrosine kinases, for the treatment of metastatic renal cell carcinoma. Future Oncol. 2020 Oct;16(28):2147-2164. doi: 10.2217/fon-2020-0443. Epub 2020 Jul 21.

Contoh Produk & Brand

Produk: 4 • International brands: 1
Produk
  • Fotivda
    Capsule • 890 ?g • Oral • EU • Approved
  • Fotivda
    Capsule • 1340 ?g • Oral • EU • Approved
  • Fotivda
    Capsule • 0.89 mg/1 • Oral • US • Approved
  • Fotivda
    Capsule • 1.34 mg/1 • Oral • US • Approved
International Brands
  • Fotivda — AVEO Oncology

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