Peringatan Keamanan

There are no data regarding overdosage of tepotinib. Symptoms of overdose are likely to be consistent with tepotinib's adverse effect profile and may therefore involve significant gastrointestinal symptoms, musculoskeletal pain, and laboratory abnormalities.L31443 Treatment of overdose should involve symptomatic and supportive measures. In the event of overdose, dialysis is unlikely to be of benefit given the high degree of plasma protein binding exhibited by tepotinib.

Tepotinib

DB15133

small molecule approved investigational

Deskripsi

Tepotinib is a MET tyrosine kinase inhibitor intended to treat a variety of MET-overexpressing solid tumors.A228058 It was originally developed in partnership between EMD Serono and the University of Texas M.D. Anderson Cancer Center in 2009 and has since been investigated in the treatment of neuroblastoma,A228053 gastric cancers,A228033 non-small cell lung cancer, and hepatocellular carcinoma.A228058 MET is a desirable target in the treatment of certain solid tumors as it appears to play a critical role, both directly and indirectly, in the growth and proliferation of tumors in which it is overexpressed and/or mutated.

Tepotinib was first approved in Japan in March 2020 for the treatment of non-small cell lung cancers (NSCLC) with MET alterations, and was subsequently granted accelerated approval by the US FDA in February 2021, under the brand name Tepmetko, for the treatment of adult patients with metastatic NSCLC and MET exon 14 skipping alterations.L31443,L31473 It is the first oral MET-targeted tyrosine kinase inhibitor to allow for once-daily dosing,L31473 an advantage that may aid in easing the pill burden often associated with chemotherapeutic regimens. In February 2022, tepotinib was approved for use in Europe.L42200

Struktur Molekul 2D

Berat 492.583
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Following oral administration, the half-life of tepotinib is approximately 32 hours.[L31443]
Volume Distribusi The mean apparent volume of distribution is 1,038L.[L31443]
Klirens (Clearance) The apparent clearance of tepotinib is 23.8 L/h.[L31443]

Absorpsi

The absolute bioavailability of tepotinib following oral administration is approximately 72%.L31443,A228038 At the recommended dosage of 450mg once daily, the median Tmax is 8 hours and the mean steady-state Cmax and AUC0-24h were 1,291 ng/mL and 27,438 ng·h/mL, respectively.L31443 Co-administration with a high-fat, high-calorie meal increases the AUC and Cmax of tepotinib by approximately 1.6-fold and 2-fold, respectively.L31443

Metabolisme

Tepotinib is metabolized primarily by CYP3A4 and CYP2C8,L31443 with some apparent contribution by unspecified UGT enzymes.A228038 The metabolite M506 is the major circulating metabolite, comprising approximately 40.4% of observed drug material in plasma,L31443 while the M668 glucuronide metabolite has been observed in plasma at much lower quantities (~4% of an orally administered dose).A228038 A total of 10 phase I and phase II metabolites have been detected following tepotinib administration, most of which are excreted in the feces.A228038

Rute Eliminasi

Following oral administration, approximately 85% of the given dose is excreted in the feces with the remainder excreted in the urine.L31443 Unchanged parent drug accounts for roughly half of the dose excreted in the feces,L31443,A228038 with the remainder comprising the demethylated M478 metabolite, a glucuronide metabolite, the racemic M506 metabolite, and some minor oxidative metabolites.A228038 Unchanged parent drug also accounts for roughly half of the dose excreted in the urine, with the remainder comprising a glucuronide metabolite and a pair of N-oxide diastereomer metabolites.A228038

Interaksi Makanan

1 Data
  • 1. Take with food. Co-administration with a meal improves the absorption of tepotinib.

Interaksi Obat

584 Data
Colchicine The serum concentration of Colchicine can be increased when it is combined with Tepotinib.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Tepotinib.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Tepotinib.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Tepotinib.
Silodosin The excretion of Silodosin can be decreased when combined with Tepotinib.
Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Tepotinib.
Acetaminophen The serum concentration of Acetaminophen can be increased when it is combined with Tepotinib.
Propacetamol The metabolism of Propacetamol can be decreased when combined with Tepotinib.
Doxorubicin The serum concentration of Doxorubicin can be increased when it is combined with Tepotinib.
Betrixaban The serum concentration of Betrixaban can be increased when it is combined with Tepotinib.
Pitolisant The serum concentration of Tepotinib can be decreased when it is combined with Pitolisant.
Folic acid Tepotinib may decrease the excretion rate of Folic acid which could result in a higher serum level.
Conjugated estrogens Tepotinib may decrease the excretion rate of Conjugated estrogens which could result in a higher serum level.
Gefitinib Tepotinib may decrease the excretion rate of Gefitinib which could result in a higher serum level.
Allopurinol Tepotinib may decrease the excretion rate of Allopurinol which could result in a higher serum level.
Cerivastatin Tepotinib may decrease the excretion rate of Cerivastatin which could result in a higher serum level.
Teniposide Tepotinib may decrease the excretion rate of Teniposide which could result in a higher serum level.
Prazosin Tepotinib may decrease the excretion rate of Prazosin which could result in a higher serum level.
Raloxifene Tepotinib may decrease the excretion rate of Raloxifene which could result in a higher serum level.
Celecoxib The metabolism of Celecoxib can be decreased when combined with Tepotinib.
Zidovudine The metabolism of Zidovudine can be decreased when combined with Tepotinib.
Oxaliplatin Tepotinib may decrease the excretion rate of Oxaliplatin which could result in a higher serum level.
Fluorouracil Tepotinib may decrease the excretion rate of Fluorouracil which could result in a higher serum level.
Methotrexate Tepotinib may decrease the excretion rate of Methotrexate which could result in a higher serum level.
Ivermectin Tepotinib may decrease the excretion rate of Ivermectin which could result in a higher serum level.
Imatinib The metabolism of Imatinib can be decreased when combined with Tepotinib.
Testosterone The metabolism of Testosterone can be decreased when combined with Tepotinib.
Clofarabine Tepotinib may decrease the excretion rate of Clofarabine which could result in a higher serum level.
Sumatriptan Tepotinib may decrease the excretion rate of Sumatriptan which could result in a higher serum level.
Mycophenolate mofetil Tepotinib may decrease the excretion rate of Mycophenolate mofetil which could result in a higher serum level.
Daunorubicin Tepotinib may decrease the excretion rate of Daunorubicin which could result in a higher serum level.
Nitrofurantoin Tepotinib may decrease the excretion rate of Nitrofurantoin which could result in a higher serum level.
Lamivudine Tepotinib may decrease the excretion rate of Lamivudine which could result in a higher serum level.
Riluzole Tepotinib may decrease the excretion rate of Riluzole which could result in a higher serum level.
Irinotecan Tepotinib may decrease the excretion rate of Irinotecan which could result in a higher serum level.
Sulfasalazine Tepotinib may decrease the excretion rate of Sulfasalazine which could result in a higher serum level.
Donepezil The metabolism of Donepezil can be decreased when combined with Tepotinib.
Ezetimibe Tepotinib may decrease the excretion rate of Ezetimibe which could result in a higher serum level.
Glyburide The metabolism of Glyburide can be decreased when combined with Tepotinib.
Leflunomide The metabolism of Leflunomide can be decreased when combined with Tepotinib.
Rosuvastatin The metabolism of Rosuvastatin can be decreased when combined with Tepotinib.
Mitoxantrone Tepotinib may decrease the excretion rate of Mitoxantrone which could result in a higher serum level.
Alvocidib Tepotinib may decrease the excretion rate of Alvocidib which could result in a higher serum level.
Camptothecin Tepotinib may decrease the excretion rate of Camptothecin which could result in a higher serum level.
Pralatrexate Tepotinib may decrease the excretion rate of Pralatrexate which could result in a higher serum level.
Teriflunomide Tepotinib may decrease the excretion rate of Teriflunomide which could result in a higher serum level.
Riociguat The serum concentration of Riociguat can be increased when it is combined with Tepotinib.
Fimasartan Tepotinib may decrease the excretion rate of Fimasartan which could result in a higher serum level.
Tenofovir alafenamide The serum concentration of Tenofovir alafenamide can be increased when it is combined with Tepotinib.
Delafloxacin Tepotinib may decrease the excretion rate of Delafloxacin which could result in a higher serum level.
Brigatinib Tepotinib may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Testosterone cypionate The metabolism of Testosterone cypionate can be decreased when combined with Tepotinib.
Testosterone enanthate The metabolism of Testosterone enanthate can be decreased when combined with Tepotinib.
Dabigatran etexilate The serum concentration of Dabigatran etexilate can be increased when it is combined with Tepotinib.
Metreleptin The metabolism of Tepotinib can be increased when combined with Metreleptin.
Salmon calcitonin The therapeutic efficacy of Salmon calcitonin can be decreased when used in combination with Tepotinib.
Thyrotropin alfa The therapeutic efficacy of Thyrotropin alfa can be decreased when used in combination with Tepotinib.
Follitropin The therapeutic efficacy of Follitropin can be decreased when used in combination with Tepotinib.
Liothyronine The therapeutic efficacy of Liothyronine can be decreased when used in combination with Tepotinib.
Carbimazole The therapeutic efficacy of Carbimazole can be decreased when used in combination with Tepotinib.
Levothyroxine The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Tepotinib.
Propylthiouracil The therapeutic efficacy of Propylthiouracil can be decreased when used in combination with Tepotinib.
Liotrix The therapeutic efficacy of Liotrix can be decreased when used in combination with Tepotinib.
3,5-Diiodotyrosine The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Tepotinib.
Tiratricol The therapeutic efficacy of Tiratricol can be decreased when used in combination with Tepotinib.
Parathyroid hormone The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Tepotinib.
Teriparatide The therapeutic efficacy of Teriparatide can be decreased when used in combination with Tepotinib.
Potassium Iodide The therapeutic efficacy of Potassium Iodide can be decreased when used in combination with Tepotinib.
Dibromotyrosine The therapeutic efficacy of Dibromotyrosine can be decreased when used in combination with Tepotinib.
Thyroid, porcine The therapeutic efficacy of Thyroid, porcine can be decreased when used in combination with Tepotinib.
Potassium perchlorate The therapeutic efficacy of Potassium perchlorate can be decreased when used in combination with Tepotinib.
Protirelin The therapeutic efficacy of Protirelin can be decreased when used in combination with Tepotinib.
3,5-diiodothyropropionic acid The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Tepotinib.
Methylthiouracil The therapeutic efficacy of Methylthiouracil can be decreased when used in combination with Tepotinib.
Elcatonin The therapeutic efficacy of Elcatonin can be decreased when used in combination with Tepotinib.
Benzylthiouracil The therapeutic efficacy of Benzylthiouracil can be decreased when used in combination with Tepotinib.
Thyrotropin The therapeutic efficacy of Thyrotropin can be decreased when used in combination with Tepotinib.
Metildigoxin Tepotinib may decrease the excretion rate of Metildigoxin which could result in a higher serum level.
Acetyldigoxin Tepotinib may decrease the excretion rate of Acetyldigoxin which could result in a higher serum level.
Alpelisib The serum concentration of Alpelisib can be increased when it is combined with Tepotinib.
Lefamulin Tepotinib may decrease the excretion rate of Lefamulin which could result in a higher serum level.
Cenobamate The serum concentration of Tepotinib can be decreased when it is combined with Cenobamate.
Ubrogepant The serum concentration of Ubrogepant can be increased when it is combined with Tepotinib.
Rimegepant The serum concentration of Rimegepant can be increased when it is combined with Tepotinib.
Ozanimod Tepotinib may decrease the excretion rate of Ozanimod which could result in a higher serum level.
Haloperidol The serum concentration of Haloperidol can be increased when it is combined with Tepotinib.
Tucatinib The serum concentration of Tepotinib can be increased when it is combined with Tucatinib.
Abametapir The serum concentration of Tepotinib can be increased when it is combined with Abametapir.
Satralizumab The serum concentration of Tepotinib can be decreased when it is combined with Satralizumab.
Berotralstat The serum concentration of Berotralstat can be increased when it is combined with Tepotinib.
Relugolix The serum concentration of Relugolix can be increased when it is combined with Tepotinib.
Afatinib The serum concentration of Tepotinib can be increased when it is combined with Afatinib.
Ledipasvir The serum concentration of Tepotinib can be increased when it is combined with Ledipasvir.
Ranolazine The serum concentration of Tepotinib can be increased when it is combined with Ranolazine.
Everolimus The serum concentration of Tepotinib can be increased when it is combined with Everolimus.
Lumacaftor The serum concentration of Tepotinib can be increased when it is combined with Lumacaftor.
Vemurafenib The serum concentration of Tepotinib can be increased when it is combined with Vemurafenib.
Isavuconazonium The serum concentration of Tepotinib can be increased when it is combined with Isavuconazonium.
Isavuconazole The serum concentration of Tepotinib can be increased when it is combined with Isavuconazole.
Cyclosporine The serum concentration of Tepotinib can be increased when it is combined with Cyclosporine.

Target Protein

Hepatocyte growth factor receptor MET
Nischarin NISCH
Melatonin receptor type 1B MTNR1B

Referensi & Sumber

Artikel (PubMed)
  • PMID: 33126762
    Abdelhameed AS, Attwa MW, Kadi AA: Identification of Iminium Intermediates Generation in the Metabolism of Tepotinib Using LC-MS/MS: In Silico and Practical Approaches to Bioactivation Pathway Elucidation. Molecules. 2020 Oct 28;25(21). pii: molecules25215004. doi: 10.3390/molecules25215004.
  • PMID: 32825724
    Sohn SH, Sul HJ, Kim B, Kim BJ, Kim HS, Zang DY: Tepotinib Inhibits the Epithelial-Mesenchymal Transition and Tumor Growth of Gastric Cancers by Increasing GSK3beta, E-Cadherin, and Mucin 5AC and 6 Levels. Int J Mol Sci. 2020 Aug 21;21(17). pii: ijms21176027. doi: 10.3390/ijms21176027.
  • PMID: 32221754
    Johne A, Scheible H, Becker A, van Lier JJ, Wolna P, Meyring M: Open-label, single-center, phase I trial to investigate the mass balance and absolute bioavailability of the highly selective oral MET inhibitor tepotinib in healthy volunteers. Invest New Drugs. 2020 Oct;38(5):1507-1519. doi: 10.1007/s10637-020-00926-1. Epub 2020 Mar 27.
  • PMID: 31078601
    Wu ZX, Teng QX, Cai CY, Wang JQ, Lei ZN, Yang Y, Fan YF, Zhang JY, Li J, Chen ZS: Tepotinib reverses ABCB1-mediated multidrug resistance in cancer cells. Biochem Pharmacol. 2019 Aug;166:120-127. doi: 10.1016/j.bcp.2019.05.015. Epub 2019 May 9.
  • PMID: 24832869
    Scorsone K, Zhang L, Woodfield SE, Hicks J, Zage PE: The novel kinase inhibitor EMD1214063 is effective against neuroblastoma. Invest New Drugs. 2014 Oct;32(5):815-24. doi: 10.1007/s10637-014-0107-4. Epub 2014 May 16.
  • PMID: 32361823
    Markham A: Tepotinib: First Approval. Drugs. 2020 Jun;80(8):829-833. doi: 10.1007/s40265-020-01317-9.

Contoh Produk & Brand

Produk: 3 • International brands: 1
Produk
  • Tepmetko
    Tablet • 225 mg/1 • Oral • US • Approved
  • Tepmetko
    Tablet • 225 mg • Oral • Canada • Approved
  • Tepmetko
    Tablet, film coated • 225 mg • Oral • EU • Approved
International Brands
  • Tepmetko — EMD Serono

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