Peringatan Keamanan

The most common adverse events that occurred in lenvatinib recipients were hypertension (67.8 vs. 9.2 % in the placebo group), diarrhea (59.4 vs. 8.4 %), fatigue or asthenia (59.0 vs. 27.5 %), decreased appetite (50.2 vs. 11.5 %), decreased bodyweight (46.4 vs. 9.2 %), nausea (41.0 vs. 13.7 %), stomatitis (35.6 vs. 3.8 %), palmar-plantar erythrodysethesia syndrome (31.8 vs. 8.0 %) and proteinuria (31.0 vs. 1.5 %). Adverse events that occurred in clinical trials and for which there is a warning/precaution in US manufacturer’s pre- scribing information were hypertension, cardiac dysfunction (decreased left or right ventricular function, cardiac failure or pulmonary edema), arterial thromboembolic events, hepatotoxicity, proteinuria, renal failure and impairment, gastrointestinal perforation and fistula formation, QT interval prolongation, hypocalcaemia, reversible posterior leucoencephalopathy syndrome, haemorrhagic events, and impairment of thyroid stimulating hormone (TSH) suppression. Based on the mechanism of action of lenvatinib and results from animal reproduction studies, which showed embryotoxicity, foetotoxicity and teratogenicity at lenvatinib doses below the recommended dose in humans, females of reproductive potential should be advised to use effective contraception during treatment and for at least 2 weeks following completion of therapy.

Lenvatinib

DB09078

small molecule approved investigational

Deskripsi

Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFR?), KIT, and RET. These receptor tyrosine kinases (RTKs) located in the cell membrane play a central role in the activation of signal transduction pathways involved in the normal regulation of cellular processes, such as cell proliferation, migration, apoptosis and differentiation, and in pathogenic angiogenesis, lymphogenesis, tumour growth and cancer progression. In particular, VEGF has been identified as a crucial regulator of both physiologic and pathologic angiogenesis and increased expression of VEGF is associated with a poor prognosis in many types of cancers.

Lenvatinib is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer. Most patients with thyroid cancer have a very good prognosis with treatment (98% 5 year survival rate) involving surgery and hormone therapy. However, for patients with RAI-refractory thyroid cancer, treatment options are limited and the prognosis is poor, leading to a push for the development of more targeted therapies such as lenvatinib.

Struktur Molekul 2D

Berat 426.86
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal elimination half­life of lenvatinib is approximately 28 hours.
Volume Distribusi -
Klirens (Clearance) -

Absorpsi

Time to peak plasma concentration occurred from 1 to 4 hours post­dose. Administration with food did not affect the extent of absorption, but decreased the rate of absorption and delayed the median Tmax from 2 hours to 4 hours.

Metabolisme

Lenvatinib is metabolized by CYP3A and aldehyde oxidase.

Rute Eliminasi

Following administration of a radiolabeled dose, approximately 64% and 25% of the radiolabel were eliminated in the feces and urine, respectively.

Interaksi Makanan

3 Data
  • 1. Avoid hypertensive herbs (e.g. bayberry, blue cohosh, cayenne, ephedra, and licorice). Lenvatinib may cause hypertension as an adverse effect; therefore, there may be additive blood pressure elevation when using hypertensive herbs.
  • 2. Take at the same time every day.
  • 3. Take with or without food.

Interaksi Obat

795 Data
Ivabradine Ivabradine may increase the QTc-prolonging activities of Lenvatinib.
Glycochenodeoxycholic Acid Lenvatinib may decrease the excretion rate of Glycochenodeoxycholic Acid which could result in a higher serum level.
Pravastatin Lenvatinib may decrease the excretion rate of Pravastatin which could result in a higher serum level.
Fluvoxamine Lenvatinib may decrease the excretion rate of Fluvoxamine which could result in a higher serum level.
Glimepiride Lenvatinib may decrease the excretion rate of Glimepiride which could result in a higher serum level.
Diethylstilbestrol Lenvatinib may decrease the excretion rate of Diethylstilbestrol which could result in a higher serum level.
Isradipine Lenvatinib may decrease the excretion rate of Isradipine which could result in a higher serum level.
Flucloxacillin Lenvatinib may decrease the excretion rate of Flucloxacillin which could result in a higher serum level.
Indomethacin Lenvatinib may decrease the excretion rate of Indomethacin which could result in a higher serum level.
Atenolol Lenvatinib may decrease the excretion rate of Atenolol which could result in a higher serum level.
Rosiglitazone Lenvatinib may decrease the excretion rate of Rosiglitazone which could result in a higher serum level.
Cerivastatin Lenvatinib may decrease the excretion rate of Cerivastatin which could result in a higher serum level.
Loratadine Lenvatinib may decrease the excretion rate of Loratadine which could result in a higher serum level.
Atropine Lenvatinib may decrease the excretion rate of Atropine which could result in a higher serum level.
Diclofenac Lenvatinib may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Nicardipine Lenvatinib may decrease the excretion rate of Nicardipine which could result in a higher serum level.
Fluorescein Lenvatinib may decrease the excretion rate of Fluorescein which could result in a higher serum level.
Nitrofurantoin Lenvatinib may decrease the excretion rate of Nitrofurantoin which could result in a higher serum level.
Naproxen Lenvatinib may decrease the excretion rate of Naproxen which could result in a higher serum level.
Disulfiram Lenvatinib may decrease the excretion rate of Disulfiram which could result in a higher serum level.
Cefaclor Lenvatinib may decrease the excretion rate of Cefaclor which could result in a higher serum level.
Tinidazole Lenvatinib may decrease the excretion rate of Tinidazole which could result in a higher serum level.
Repaglinide Lenvatinib may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Telmisartan Lenvatinib may decrease the excretion rate of Telmisartan which could result in a higher serum level.
Ezetimibe Lenvatinib may decrease the excretion rate of Ezetimibe which could result in a higher serum level.
Dipyridamole Lenvatinib may decrease the excretion rate of Dipyridamole which could result in a higher serum level.
Sulfamethoxazole Lenvatinib may decrease the excretion rate of Sulfamethoxazole which could result in a higher serum level.
Fenofibrate Lenvatinib may decrease the excretion rate of Fenofibrate which could result in a higher serum level.
Nitrendipine Lenvatinib may decrease the excretion rate of Nitrendipine which could result in a higher serum level.
Glipizide Lenvatinib may decrease the excretion rate of Glipizide which could result in a higher serum level.
Rosuvastatin Lenvatinib may decrease the excretion rate of Rosuvastatin which could result in a higher serum level.
Nifedipine Lenvatinib may decrease the excretion rate of Nifedipine which could result in a higher serum level.
Sulfinpyrazone Lenvatinib may decrease the excretion rate of Sulfinpyrazone which could result in a higher serum level.
Ofloxacin Lenvatinib may decrease the excretion rate of Ofloxacin which could result in a higher serum level.
Taurocholic acid Lenvatinib may decrease the excretion rate of Taurocholic acid which could result in a higher serum level.
Prasterone sulfate Lenvatinib may decrease the excretion rate of Prasterone sulfate which could result in a higher serum level.
Indocyanine green acid form Lenvatinib may decrease the excretion rate of Indocyanine green acid form which could result in a higher serum level.
Benzbromarone Lenvatinib may decrease the excretion rate of Benzbromarone which could result in a higher serum level.
Pilsicainide Lenvatinib may decrease the excretion rate of Pilsicainide which could result in a higher serum level.
Dihydroergocristine Lenvatinib may decrease the excretion rate of Dihydroergocristine which could result in a higher serum level.
Glycyrrhizic acid Lenvatinib may decrease the excretion rate of Glycyrrhizic acid which could result in a higher serum level.
Budesonide Lenvatinib may decrease the excretion rate of Budesonide which could result in a higher serum level.
Indinavir Lenvatinib may decrease the excretion rate of Indinavir which could result in a higher serum level.
Felodipine Lenvatinib may decrease the excretion rate of Felodipine which could result in a higher serum level.
Belantamab mafodotin Lenvatinib may decrease the excretion rate of Belantamab mafodotin which could result in a higher serum level.
Atorvastatin Lenvatinib may decrease the excretion rate of Atorvastatin which could result in a higher serum level.
Efavirenz Lenvatinib may decrease the excretion rate of Efavirenz which could result in a higher serum level.
Nefazodone Lenvatinib may decrease the excretion rate of Nefazodone which could result in a higher serum level.
Ranolazine The serum concentration of Lenvatinib can be increased when it is combined with Ranolazine.
Acetaminophen The serum concentration of Acetaminophen can be increased when it is combined with Lenvatinib.
Propacetamol The serum concentration of Propacetamol can be increased when it is combined with Lenvatinib.
Succinic acid The excretion of Succinic acid can be decreased when combined with Lenvatinib.
Citrulline The excretion of Citrulline can be decreased when combined with Lenvatinib.
Oseltamivir The excretion of Oseltamivir can be decreased when combined with Lenvatinib.
Cefotiam The excretion of Cefotiam can be decreased when combined with Lenvatinib.
Piperacillin The excretion of Piperacillin can be decreased when combined with Lenvatinib.
Aminohippuric acid The excretion of Aminohippuric acid can be decreased when combined with Lenvatinib.
Trifluridine The excretion of Trifluridine can be decreased when combined with Lenvatinib.
Allopurinol The excretion of Allopurinol can be decreased when combined with Lenvatinib.
Cefdinir The excretion of Cefdinir can be decreased when combined with Lenvatinib.
Cephalexin The excretion of Cephalexin can be decreased when combined with Lenvatinib.
Valaciclovir The excretion of Valaciclovir can be decreased when combined with Lenvatinib.
Levocarnitine The excretion of Levocarnitine can be decreased when combined with Lenvatinib.
Leucovorin The excretion of Leucovorin can be decreased when combined with Lenvatinib.
Quinapril The excretion of Quinapril can be decreased when combined with Lenvatinib.
Bumetanide The excretion of Bumetanide can be decreased when combined with Lenvatinib.
Dinoprostone The excretion of Dinoprostone can be decreased when combined with Lenvatinib.
Benzylpenicillin The excretion of Benzylpenicillin can be decreased when combined with Lenvatinib.
Cefazolin The excretion of Cefazolin can be decreased when combined with Lenvatinib.
Ceftizoxime The excretion of Ceftizoxime can be decreased when combined with Lenvatinib.
Cefacetrile The excretion of Cefacetrile can be decreased when combined with Lenvatinib.
Ceftibuten The excretion of Ceftibuten can be decreased when combined with Lenvatinib.
Tazobactam The excretion of Tazobactam can be decreased when combined with Lenvatinib.
Cyclic adenosine monophosphate The excretion of Cyclic adenosine monophosphate can be decreased when combined with Lenvatinib.
Glutaric Acid The excretion of Glutaric Acid can be decreased when combined with Lenvatinib.
Oxalic Acid The excretion of Oxalic Acid can be decreased when combined with Lenvatinib.
Doripenem The excretion of Doripenem can be decreased when combined with Lenvatinib.
Saxagliptin The excretion of Saxagliptin can be decreased when combined with Lenvatinib.
Ellagic acid The excretion of Ellagic acid can be decreased when combined with Lenvatinib.
Cefaloridine The excretion of Cefaloridine can be decreased when combined with Lenvatinib.
Avibactam The excretion of Avibactam can be decreased when combined with Lenvatinib.
Silibinin The excretion of Silibinin can be decreased when combined with Lenvatinib.
Relebactam The excretion of Relebactam can be decreased when combined with Lenvatinib.
Hydrocortisone The excretion of Hydrocortisone can be decreased when combined with Lenvatinib.
Tetracycline The excretion of Tetracycline can be decreased when combined with Lenvatinib.
Ranitidine The excretion of Ranitidine can be decreased when combined with Lenvatinib.
Captopril The excretion of Captopril can be decreased when combined with Lenvatinib.
Dexamethasone The excretion of Dexamethasone can be decreased when combined with Lenvatinib.
Tenofovir alafenamide The excretion of Tenofovir alafenamide can be decreased when combined with Lenvatinib.
Tenofovir disoproxil The excretion of Tenofovir disoproxil can be decreased when combined with Lenvatinib.
Cimetidine The excretion of Cimetidine can be decreased when combined with Lenvatinib.
Oxytetracycline The excretion of Oxytetracycline can be decreased when combined with Lenvatinib.
Polythiazide The excretion of Polythiazide can be decreased when combined with Lenvatinib.
Prednisolone phosphate The excretion of Prednisolone phosphate can be decreased when combined with Lenvatinib.
Conjugated estrogens The excretion of Conjugated estrogens can be decreased when combined with Lenvatinib.
Methotrexate The excretion of Methotrexate can be decreased when combined with Lenvatinib.
Zidovudine The excretion of Zidovudine can be decreased when combined with Lenvatinib.
Acyclovir The excretion of Acyclovir can be decreased when combined with Lenvatinib.
Dexamethasone acetate The excretion of Dexamethasone acetate can be decreased when combined with Lenvatinib.
Acamprosate The excretion of Acamprosate can be decreased when combined with Lenvatinib.

Target Protein

Vascular endothelial growth factor receptor 1 FLT1
Vascular endothelial growth factor receptor 2 KDR
Vascular endothelial growth factor receptor 3 FLT4
Fibroblast growth factor receptor 1 FGFR1
Fibroblast growth factor receptor 2 FGFR2
Fibroblast growth factor receptor 3 FGFR3
Fibroblast growth factor receptor 4 FGFR4
Platelet-derived growth factor receptor alpha PDGFRA
Proto-oncogene tyrosine-protein kinase receptor Ret RET
Mast/stem cell growth factor receptor Kit KIT

Referensi & Sumber

Artikel (PubMed)
  • PMID: 17943726
    Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M: E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer. 2008 Feb 1;122(3):664-71.
  • PMID: 21781317
    Glen H, Mason S, Patel H, Macleod K, Brunton VG: E7080, a multi-targeted tyrosine kinase inhibitor suppresses tumor cell migration and invasion. BMC Cancer. 2011 Jul 22;11:309. doi: 10.1186/1471-2407-11-309.
  • PMID: 25795101
    Scott LJ: Lenvatinib: first global approval. Drugs. 2015 Apr;75(5):553-60. doi: 10.1007/s40265-015-0383-0.
  • PMID: 25707627
    Killock D: Neuroendocrine cancer: SELECT-lenvatinib in thyroid cancer. Nat Rev Clin Oncol. 2015 Apr;12(4):189. doi: 10.1038/nrclinonc.2015.30. Epub 2015 Feb 24.

Contoh Produk & Brand

Produk: 31 • International brands: 0
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