Peringatan Keamanan

Experience with nintedanib overdose is limited, but patients who inadvertently received higher-than-intended doses during initial trials experienced adverse effects consistent with the known safety profile of nintedanib, for example elevated liver enzymes and significant gastrointestinal effects.L8453,L8459

There are no specific guidelines for the treatment of nintedanib overdose - in this case, therapy should be interrupted and general supportive measures employed as indicated.L8453,L8459

Nintedanib

DB09079

small molecule approved

Deskripsi

Nintedanib is a small molecule kinase inhibitor used in the treatment of pulmonary fibrosis, systemic sclerosis-associated interstitial lung disease, and non-small cell lung cancer (NSCLC).L8453,L8459 It was first approved for use in the United States in 2014.L8453 Within the spectrum of idiopathic pulmonary fibrosis treatment options, nintedanib is currently one of only two disease-modifying therapies available and indicated for the condition (the other being Pirfenidone) and as such is used as a first-line treatment following diagnosis to slow down the progressive loss of lung function.A185237 As a chemotherapeutic agent for NSCLC, nintedanib, in combination with Docetaxel, is reserved for patients who have tried and failed first-line chemotherapeutic options.L8459

Struktur Molekul 2D

Berat 539.6248
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal elimination half-life of nintedanib is approximately 10-15 hours.[L8459,A185123] In patients with idiopathic pulmonary fibrosis, the effective half-life of nintedanib has been estimated to be approximately 9.5 hours.[L8453,A185123]
Volume Distribusi Nintedanib appears to follow biphasic disposition kinetics - the observed volume of distribution following intravenous administration is 1050 L[L8453,L8459], indicating extensive distribution into peripheral tissues. In rats, nintedanib was shown to rapidly and homogeneously distribute into peripheral tissues with the exception of the CNS, suggestive of an inability of nintedanib to cross the blood-brain barrier.[A185123]
Klirens (Clearance) Nintedanib is has a high total plasma clearance of approximately 1390 mL/min and a renal clearance of 20 mL/min.[L8453]

Absorpsi

The absolute bioavailability of nintedanib is low at approximately 4.7%, likely owing to substantial first-pass metabolism and the effects of p-glycoprotein (P-gp) transporters.L8453,L8459,A185123 Tmax following oral administration is reached after approximately 2 hours in fasted patients and approximately 4 hours in fed patients, regardless of the food consumed.L8453,L8459 Administration of nintedanib following a high-fat, high-calorie meal resulted in an increase in Cmax by approximately 15% and an increase in AUC by approximately 20%.A185123 Age, body weight, and smoking status have been found to alter exposure to nintedanib, but these effects are not significant enough to warrant dose alterations.L8453,A185123

Metabolisme

Nintedanib is predominantly metabolized via hydrolytic cleavage by esterases to its principle metabolite, BIBF 1202, which then undergoes glucuronidation via UGT enzymes in the intestines and liver (specifically UGT 1A1, UGT 1A7, UGT 1A8, and UGT 1A10) to form BIBF 1202 glucuronide.L8453,L8459,A185123 The CYP450 enzyme system plays a minor role in nintedanib metabolism, with CYP3A4 believed to be the main contributor - the major CYP-dependent metabolite of nintedanib, a demethylated metabolite termed BIBF 1053, could not be detected in plasma during pharmacokinetic studies and was found only in small quantities in the feces (approximately 4% of total dose).A185123 CYP-dependent metabolism of nintedanib accounts for roughly 5% of total drug metabolism, as opposed to 25% for esterase cleavage.L8453,L8459 Other minor metabolites, M7 and M8, are found in very small quantities in the urine (0.03% and 0.01%, respectively), though their origin and relevance is currently unclear.A185123

Rute Eliminasi

Nintedanib is eliminated primarily via fecal and biliary excretion, with 93.4% of radio labelled nintedanib found in feces within 120 hours following administration.L8453,L8459,A185123 Renal clearance accounts for a small portion of nintedanib's elimination, approximately 0.65% of the total dose, and excretion of unchanged nintedanib 48 hours after oral and intravenous doses was 0.05% and 1.4%, respectively.L8453,L8459,A185123

Interaksi Makanan

1 Data
  • 1. Take with food. Co-administration with food improves absorption.

Interaksi Obat

752 Data
Ranolazine The serum concentration of Nintedanib can be increased when it is combined with Ranolazine.
Phenytoin The metabolism of Nintedanib can be increased when combined with Phenytoin.
Fosphenytoin The metabolism of Nintedanib can be increased when combined with Fosphenytoin.
Acetaminophen The serum concentration of Acetaminophen can be increased when it is combined with Nintedanib.
Propacetamol The serum concentration of Propacetamol can be increased when it is combined with Nintedanib.
Desogestrel The metabolism of Nintedanib can be increased when combined with Desogestrel.
Zidovudine The metabolism of Nintedanib can be increased when combined with Zidovudine.
Lamotrigine The metabolism of Nintedanib can be increased when combined with Lamotrigine.
Ethinylestradiol The metabolism of Nintedanib can be increased when combined with Ethinylestradiol.
Testosterone propionate The metabolism of Nintedanib can be increased when combined with Testosterone propionate.
Pirfenidone The risk or severity of adverse effects can be increased when Pirfenidone is combined with Nintedanib.
Lumacaftor The serum concentration of Nintedanib can be decreased when it is combined with Lumacaftor.
Bexarotene The metabolism of Nintedanib can be increased when combined with Bexarotene.
Bosentan The metabolism of Nintedanib can be increased when combined with Bosentan.
Nafcillin The metabolism of Nintedanib can be increased when combined with Nafcillin.
Modafinil The metabolism of Nintedanib can be increased when combined with Modafinil.
Etravirine The metabolism of Nintedanib can be increased when combined with Etravirine.
Avasimibe The metabolism of Nintedanib can be increased when combined with Avasimibe.
Echinacea The metabolism of Nintedanib can be increased when combined with Echinacea.
Dexamethasone acetate The metabolism of Nintedanib can be increased when combined with Dexamethasone acetate.
Vemurafenib The serum concentration of Nintedanib can be increased when it is combined with Vemurafenib.
Apalutamide The serum concentration of Nintedanib can be decreased when it is combined with Apalutamide.
Pitolisant The serum concentration of Nintedanib can be decreased when it is combined with Pitolisant.
Isavuconazole The serum concentration of Nintedanib can be increased when it is combined with Isavuconazole.
Isavuconazonium The serum concentration of Nintedanib can be increased when it is combined with Isavuconazonium.
Fluconazole The metabolism of Nintedanib can be decreased when combined with Fluconazole.
Erythromycin The serum concentration of Nintedanib can be increased when it is combined with Erythromycin.
Reserpine The serum concentration of Nintedanib can be increased when it is combined with Reserpine.
Loxapine The serum concentration of Nintedanib can be increased when it is combined with Loxapine.
Quinine The serum concentration of Nintedanib can be increased when it is combined with Quinine.
Toremifene The serum concentration of Nintedanib can be increased when it is combined with Toremifene.
Verapamil The metabolism of Nintedanib can be decreased when combined with Verapamil.
Mifepristone The serum concentration of Nintedanib can be increased when it is combined with Mifepristone.
Zonisamide The serum concentration of Nintedanib can be increased when it is combined with Zonisamide.
Carvedilol The serum concentration of Nintedanib can be increased when it is combined with Carvedilol.
Propafenone The serum concentration of Nintedanib can be increased when it is combined with Propafenone.
Lapatinib The serum concentration of Nintedanib can be increased when it is combined with Lapatinib.
Paliperidone The serum concentration of Nintedanib can be increased when it is combined with Paliperidone.
Mibefradil The serum concentration of Nintedanib can be increased when it is combined with Mibefradil.
Biricodar The serum concentration of Nintedanib can be increased when it is combined with Biricodar.
Elacridar The serum concentration of Nintedanib can be increased when it is combined with Elacridar.
Flibanserin The serum concentration of Nintedanib can be increased when it is combined with Flibanserin.
Zosuquidar The serum concentration of Nintedanib can be increased when it is combined with Zosuquidar.
Tariquidar The serum concentration of Nintedanib can be increased when it is combined with Tariquidar.
Simeprevir The metabolism of Nintedanib can be decreased when combined with Simeprevir.
Brefeldin A The serum concentration of Nintedanib can be increased when it is combined with Brefeldin A.
Ivacaftor The serum concentration of Nintedanib can be increased when it is combined with Ivacaftor.
Linagliptin The metabolism of Nintedanib can be decreased when combined with Linagliptin.
Canagliflozin The serum concentration of Nintedanib can be increased when it is combined with Canagliflozin.
Afatinib The serum concentration of Nintedanib can be increased when it is combined with Afatinib.
Ledipasvir The serum concentration of Nintedanib can be increased when it is combined with Ledipasvir.
Suvorexant The serum concentration of Nintedanib can be increased when it is combined with Suvorexant.
Netupitant The metabolism of Nintedanib can be decreased when combined with Netupitant.
Daclatasvir The serum concentration of Nintedanib can be increased when it is combined with Daclatasvir.
Niguldipine The serum concentration of Nintedanib can be increased when it is combined with Niguldipine.
Rolapitant The serum concentration of Nintedanib can be increased when it is combined with Rolapitant.
Asunaprevir The serum concentration of Nintedanib can be increased when it is combined with Asunaprevir.
Velpatasvir The serum concentration of Nintedanib can be increased when it is combined with Velpatasvir.
Valspodar The serum concentration of Nintedanib can be increased when it is combined with Valspodar.
Glasdegib The serum concentration of Nintedanib can be increased when it is combined with Glasdegib.
Voxilaprevir The serum concentration of Nintedanib can be increased when it is combined with Voxilaprevir.
Sarecycline The serum concentration of Nintedanib can be increased when it is combined with Sarecycline.
Rucaparib The metabolism of Nintedanib can be decreased when combined with Rucaparib.
Laniquidar The serum concentration of Nintedanib can be increased when it is combined with Laniquidar.
Pibrentasvir The serum concentration of Nintedanib can be increased when it is combined with Pibrentasvir.
Glecaprevir The serum concentration of Nintedanib can be increased when it is combined with Glecaprevir.
Dexniguldipine The serum concentration of Nintedanib can be increased when it is combined with Dexniguldipine.
ONT-093 The serum concentration of Nintedanib can be increased when it is combined with ONT-093.
Fedratinib The serum concentration of Nintedanib can be increased when it is combined with Fedratinib.
Istradefylline The serum concentration of Nintedanib can be increased when it is combined with Istradefylline.
Sildenafil The serum concentration of Nintedanib can be increased when it is combined with Sildenafil.
Simvastatin The serum concentration of Nintedanib can be increased when it is combined with Simvastatin.
Vardenafil The serum concentration of Nintedanib can be increased when it is combined with Vardenafil.
Carfilzomib The serum concentration of Nintedanib can be increased when it is combined with Carfilzomib.
Favipiravir The serum concentration of Nintedanib can be increased when it is combined with Favipiravir.
Methylene blue The serum concentration of Nintedanib can be increased when it is combined with Methylene blue.
Ripretinib The serum concentration of Nintedanib can be increased when it is combined with Ripretinib.
Pralsetinib The serum concentration of Nintedanib can be increased when it is combined with Pralsetinib.
Arsenic trioxide The serum concentration of Nintedanib can be increased when it is combined with Arsenic trioxide.
Mefloquine The serum concentration of Nintedanib can be increased when it is combined with Mefloquine.
Voclosporin The serum concentration of Nintedanib can be increased when it is combined with Voclosporin.
Eliglustat The serum concentration of Nintedanib can be increased when it is combined with Eliglustat.
Umbralisib The serum concentration of Nintedanib can be increased when it is combined with Umbralisib.
Diosmin The serum concentration of Nintedanib can be increased when it is combined with Diosmin.
Sapropterin The serum concentration of Nintedanib can be increased when it is combined with Sapropterin.
Levoketoconazole The metabolism of Nintedanib can be decreased when combined with Levoketoconazole.
Capmatinib The serum concentration of Nintedanib can be increased when it is combined with Capmatinib.
Belumosudil The serum concentration of Nintedanib can be increased when it is combined with Belumosudil.
Metreleptin The metabolism of Nintedanib can be increased when combined with Metreleptin.
Gemfibrozil The metabolism of Nintedanib can be decreased when combined with Gemfibrozil.
Flunitrazepam The metabolism of Nintedanib can be decreased when combined with Flunitrazepam.
Adenine The metabolism of Nintedanib can be decreased when combined with Adenine.
Flurbiprofen The metabolism of Nintedanib can be decreased when combined with Flurbiprofen.
Eltrombopag The metabolism of Nintedanib can be decreased when combined with Eltrombopag.
Sodium aurothiomalate The metabolism of Nintedanib can be decreased when combined with Sodium aurothiomalate.
Silibinin The metabolism of Nintedanib can be decreased when combined with Silibinin.
Propofol The metabolism of Nintedanib can be decreased when combined with Propofol.
Amitriptyline The metabolism of Nintedanib can be decreased when combined with Amitriptyline.
Indomethacin The metabolism of Nintedanib can be decreased when combined with Indomethacin.
Rifabutin The metabolism of Nintedanib can be increased when combined with Rifabutin.

Target Protein

Vascular endothelial growth factor receptor 1 FLT1
Vascular endothelial growth factor receptor 2 KDR
Vascular endothelial growth factor receptor 3 FLT4
Platelet-derived growth factor receptor alpha PDGFRA
Platelet-derived growth factor receptor beta PDGFRB
Fibroblast growth factor receptor 1 FGFR1
Fibroblast growth factor receptor 2 FGFR2
Fibroblast growth factor receptor 3 FGFR3
Receptor-type tyrosine-protein kinase FLT3 FLT3
Tyrosine-protein kinase Lck LCK
Tyrosine-protein kinase Lyn LYN
Proto-oncogene tyrosine-protein kinase Src SRC

Referensi & Sumber

Synthesis reference: Gerald J. Roth, Armin Heckel, Florian Colbatzky, Sandra Handschuh, Jörg Kley, Thorsten Lehmann-Lintz, Ralf Lotz, Ulrike Tontsch-Grunt, Rainer Walter, and Frank Hilberg Journal of Medicinal Chemistry 2009 52 (14), 4466-4480 DOI: 10.1021/jm900431g
Artikel (PubMed)
  • PMID: 26063212
    Keating GM: Nintedanib: A Review of Its Use in Patients with Idiopathic Pulmonary Fibrosis. Drugs. 2015 Jul;75(10):1131-40. doi: 10.1007/s40265-015-0418-6.
  • PMID: 18559524
    Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82. doi: 10.1158/0008-5472.CAN-07-6307.
  • PMID: 25862013
    Mazzei ME, Richeldi L, Collard HR: Nintedanib in the treatment of idiopathic pulmonary fibrosis. Ther Adv Respir Dis. 2015 Jun;9(3):121-9. doi: 10.1177/1753465815579365. Epub 2015 Apr 10.
  • PMID: 21204634
    Stopfer P, Rathgen K, Bischoff D, Ludtke S, Marzin K, Kaiser R, Wagner K, Ebner T: Pharmacokinetics and metabolism of BIBF 1120 after oral dosing to healthy male volunteers. Xenobiotica. 2011 Apr;41(4):297-311. doi: 10.3109/00498254.2010.545452. Epub 2011 Jan 4.
  • PMID: 31016670
    Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C: Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib. Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0.
  • PMID: 28365056
    Richeldi L, Collard HR, Jones MG: Idiopathic pulmonary fibrosis. Lancet. 2017 May 13;389(10082):1941-1952. doi: 10.1016/S0140-6736(17)30866-8. Epub 2017 Mar 30.
  • PMID: 28598023
    Li LF, Kao KC, Liu YY, Lin CW, Chen NH, Lee CS, Wang CW, Yang CT: Nintedanib reduces ventilation-augmented bleomycin-induced epithelial-mesenchymal transition and lung fibrosis through suppression of the Src pathway. J Cell Mol Med. 2017 Nov;21(11):2937-2949. doi: 10.1111/jcmm.13206. Epub 2017 Jun 9.

Contoh Produk & Brand

Produk: 27 • International brands: 1
Produk
  • Auro-nintedanib
    Capsule • 150 mg • Oral • Canada • Generic • Approved
  • Auro-nintedanib
    Capsule • 100 mg • Oral • Canada • Generic • Approved
  • Eugia-nintedanib
    Capsule • 100 mg • Oral • Canada • Approved
  • Eugia-nintedanib
    Capsule • 150 mg • Oral • Canada • Approved
  • Jamp Nintedanib
    Capsule • 150 mg • Oral • Canada • Generic • Approved
  • Nintedanib Accord
    Capsule • 100 mg • Oral • EU • Approved
  • Nintedanib Accord
    Capsule • 100 mg • Oral • EU • Approved
  • Nintedanib Accord
    Capsule • 100 mg • Oral • EU • Approved
Menampilkan 8 dari 27 produk.
International Brands
  • Vargatef — Boehringer-Ingelheim

Sekuens Gen/Protein (FASTA)

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