Peringatan Keamanan

Intravenous LD50 in rat was 2946 mg/kg MSDS. Oral LD50 in rat and mouse were > 4379mg/kg MSDS. Overdosage via ocular instillation is unlikely. The highest dose of orally-administered Lonsurf, trifluridine in combination with tipiracil, administered in clinical studies was 180 mg/m^2 per day. The primary anticipated complication of an overdose is bone marrow suppression. There is no known antidote for trifluridine overdose: in case of an overdose, management should include customary therapeutic and supportive medical intervention aimed at correcting the presenting clinical manifestations and preventing their possible complications F649. Based on the findings from animal studies, trifluridine may cause fetal toxicity when administered to pregnant patients F649.

Trifluridine

DB00432

small molecule approved investigational

Deskripsi

Trifluridine is a fluorinated pyrimidine nucleoside that is structurally related to idoxuridine A35271. It is an active antiviral agent in ophthalmic solutions used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus. It displays effective antiviral activity against Herpes simplex virus type 1 and 2 A35271.

The combination product of trifluridine with tipiracil marketed as Lonsurf has been approved in Japan, the United States, and the European Union for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. In the anticancer therapy, trifluridine acts as a thymidine-based nucleoside metabolic inhibitor that gets incorporated into DNA of cancer cells following cell uptake to aberrate DNA function during cell replication F649.

Struktur Molekul 2D

Berat 296.1999
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) After administration of LONSURF 35 mg/m<sup>2</sup>, the mean elimination and steady-state half-life (t<sub>1/2</sub>) of trifluridine was 1.4 hours and 2.1 hours respectively.[L47676] For the ophthalmic formulation, the half-life is significantly shorter, approximately only 12 minutes.[L47671]
Volume Distribusi Following a single dose of LONSURF (35 mg/m<sup>2</sup>) in patients with advanced solid tumours, the apparent volume of distribution (Vd/F) for trifluridine was 21 L.[L47681]
Klirens (Clearance) Following a single dose of LONSURF (35 mg/m<sup>2</sup>) in patients with advanced solid tumours, the oral clearance (CL/F) for trifluridine was 10.5 L/hr.[L47681]

Absorpsi

After oral administration of LONSURF with 14C-trifluridine, at least 57% of the administered trifluridine was absorbed. Following a single dose of LONSURF (35 mg/m2) in patients with advanced solid tumors, the mean times to peak plasma concentrations (Tmax) of trifluridine was around 2 hours.L47681 Trifluridine area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last) was approximately 3-fold higher and maximum concentration (Cmax) was approximately 2-fold higher after multiple dose administration (twice daily for 5 days a week with 2 days rest for 2 weeks followed by a 14-day rest, repeated every 4 weeks) than after single-dose administration.L47681 Following a single oral administration of LONSURF at 35 mg/m2 in patients with cancer, the mean time to peak plasma concentration (Tmax) of trifluridine was around 2 hours.L47676 For the ophthalmic formulation, systemic absorption appears to be negligible.L47671 A standardized high-fat, high-calorie meal decreased trifluridine Cmax by approximately 40% but did not change trifluridine AUC compared to those in a fasting state in patients with cancer following administration of a single dose of LONSURF 35 mg/m2.L47671 In a dose finding study (15 to 35 mg/m2 twice daily), the AUC from time 0 to 10 hours (AUC0-10) of trifluridine tended to increase more than expected based on the increase in dose.L47681

Metabolisme

Trifluridine is not metabolized by cytochrome P450 (CYP) enzymes. Trifluridine is mainly eliminated by metabolism via thymidine phosphorylase to form an inactive metabolite, 5-(trifluoromethyl) uracil (FTY). No other major metabolites were detected in plasma or urine.L47676 Other minor metabolites, such as 5-carboxy-2'-deoxyuridine found on the endothelial side of the cornea or 5-carboxyuraci, were also detected, but only at low or trace level in plasma and urine.A35307, L47681

Rute Eliminasi

After single oral administration of LONSURF (60 mg) with 14C-trifluridine, the total cumulative excretion of radioactivity was 60% of the administered dose. The majority of recovered radioactivity was eliminated into urine (55% of the dose) as FTY and trifluridine glucuronide isomers within 24 hours and the excretion into feces and expired air was <3% for both. The unchanged trifluridine was <3% of administered dose recovered in the urine and feces.L47676

Interaksi Makanan

1 Data
  • 1. Take with food.

Interaksi Obat

1167 Data
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Trifluridine.
Etanercept The risk or severity of adverse effects can be increased when Etanercept is combined with Trifluridine.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Trifluridine.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Trifluridine.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Trifluridine.
Peginterferon alfa-2b The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Trifluridine.
Anakinra The risk or severity of adverse effects can be increased when Anakinra is combined with Trifluridine.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Trifluridine.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Trifluridine.
Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Trifluridine.
Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Trifluridine.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Trifluridine.
Pegaspargase The risk or severity of adverse effects can be increased when Pegaspargase is combined with Trifluridine.
Infliximab The risk or severity of adverse effects can be increased when Infliximab is combined with Trifluridine.
Interferon beta-1b The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Trifluridine.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Trifluridine.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Trifluridine.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Trifluridine.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Trifluridine.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Trifluridine.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Trifluridine.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Trifluridine.
Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Trifluridine.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Trifluridine.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Trifluridine.
Interferon alfa-2b The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Trifluridine.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Trifluridine.
Phenylalanine The risk or severity of adverse effects can be increased when Phenylalanine is combined with Trifluridine.
Flunisolide The risk or severity of adverse effects can be increased when Flunisolide is combined with Trifluridine.
Bortezomib The risk or severity of adverse effects can be increased when Bortezomib is combined with Trifluridine.
Cladribine Trifluridine may increase the immunosuppressive activities of Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Carmustine is combined with Trifluridine.
Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Trifluridine.
Bleomycin The risk or severity of adverse effects can be increased when Bleomycin is combined with Trifluridine.
Chlorambucil The risk or severity of adverse effects can be increased when Chlorambucil is combined with Trifluridine.
Raltitrexed The risk or severity of adverse effects can be increased when Raltitrexed is combined with Trifluridine.
Mitomycin The risk or severity of adverse effects can be increased when Mitomycin is combined with Trifluridine.
Bexarotene The risk or severity of adverse effects can be increased when Bexarotene is combined with Trifluridine.
Vindesine The risk or severity of adverse effects can be increased when Vindesine is combined with Trifluridine.
Floxuridine The risk or severity of adverse effects can be increased when Floxuridine is combined with Trifluridine.
Indomethacin The risk or severity of adverse effects can be increased when Indomethacin is combined with Trifluridine.
Tioguanine The risk or severity of adverse effects can be increased when Tioguanine is combined with Trifluridine.
Vinorelbine The risk or severity of adverse effects can be increased when Vinorelbine is combined with Trifluridine.
Dexrazoxane The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Trifluridine.
Beclomethasone dipropionate The risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Trifluridine.
Sorafenib The risk or severity of adverse effects can be increased when Sorafenib is combined with Trifluridine.
Streptozocin The risk or severity of adverse effects can be increased when Streptozocin is combined with Trifluridine.
Gemcitabine The risk or severity of adverse effects can be increased when Trifluridine is combined with Gemcitabine.
Betamethasone The risk or severity of adverse effects can be increased when Trifluridine is combined with Betamethasone.
Teniposide The risk or severity of adverse effects can be increased when Trifluridine is combined with Teniposide.
Epirubicin The risk or severity of adverse effects can be increased when Trifluridine is combined with Epirubicin.
Chloramphenicol The risk or severity of adverse effects can be increased when Trifluridine is combined with Chloramphenicol.
Lenalidomide The risk or severity of adverse effects can be increased when Trifluridine is combined with Lenalidomide.
Altretamine The risk or severity of adverse effects can be increased when Trifluridine is combined with Altretamine.
Zidovudine The risk or severity of adverse effects can be increased when Trifluridine is combined with Zidovudine.
Cisplatin The risk or severity of adverse effects can be increased when Trifluridine is combined with Cisplatin.
Oxaliplatin The risk or severity of adverse effects can be increased when Trifluridine is combined with Oxaliplatin.
Cyclophosphamide The risk or severity of adverse effects can be increased when Trifluridine is combined with Cyclophosphamide.
Vincristine The risk or severity of adverse effects can be increased when Trifluridine is combined with Vincristine.
Fluorouracil The risk or severity of adverse effects can be increased when Trifluridine is combined with Fluorouracil.
Propylthiouracil The risk or severity of adverse effects can be increased when Trifluridine is combined with Propylthiouracil.
Pentostatin The risk or severity of adverse effects can be increased when Trifluridine is combined with Pentostatin.
Methotrexate The risk or severity of adverse effects can be increased when Trifluridine is combined with Methotrexate.
Carbamazepine The risk or severity of adverse effects can be increased when Trifluridine is combined with Carbamazepine.
Vinblastine The risk or severity of adverse effects can be increased when Trifluridine is combined with Vinblastine.
Fluticasone propionate The risk or severity of adverse effects can be increased when Trifluridine is combined with Fluticasone propionate.
Fluocinolone acetonide The risk or severity of adverse effects can be increased when Trifluridine is combined with Fluocinolone acetonide.
Linezolid The risk or severity of adverse effects can be increased when Trifluridine is combined with Linezolid.
Imatinib The risk or severity of adverse effects can be increased when Trifluridine is combined with Imatinib.
Triamcinolone The risk or severity of adverse effects can be increased when Trifluridine is combined with Triamcinolone.
Clofarabine The risk or severity of adverse effects can be increased when Trifluridine is combined with Clofarabine.
Prednisone The risk or severity of adverse effects can be increased when Trifluridine is combined with Prednisone.
Pemetrexed The risk or severity of adverse effects can be increased when Trifluridine is combined with Pemetrexed.
Fludrocortisone The risk or severity of adverse effects can be increased when Trifluridine is combined with Fludrocortisone.
Mycophenolate mofetil The risk or severity of adverse effects can be increased when Trifluridine is combined with Mycophenolate mofetil.
Daunorubicin The risk or severity of adverse effects can be increased when Trifluridine is combined with Daunorubicin.
Irinotecan The risk or severity of adverse effects can be increased when Trifluridine is combined with Irinotecan.
Methimazole The risk or severity of adverse effects can be increased when Trifluridine is combined with Methimazole.
Etoposide The risk or severity of adverse effects can be increased when Trifluridine is combined with Etoposide.
Sulfasalazine The risk or severity of adverse effects can be increased when Trifluridine is combined with Sulfasalazine.
Dacarbazine The risk or severity of adverse effects can be increased when Trifluridine is combined with Dacarbazine.
Temozolomide The risk or severity of adverse effects can be increased when Trifluridine is combined with Temozolomide.
Penicillamine The risk or severity of adverse effects can be increased when Trifluridine is combined with Penicillamine.
Prednisolone The risk or severity of adverse effects can be increased when Trifluridine is combined with Prednisolone.
Sirolimus The risk or severity of adverse effects can be increased when Trifluridine is combined with Sirolimus.
Mechlorethamine The risk or severity of adverse effects can be increased when Trifluridine is combined with Mechlorethamine.
Azacitidine The risk or severity of adverse effects can be increased when Trifluridine is combined with Azacitidine.
Carboplatin The risk or severity of adverse effects can be increased when Trifluridine is combined with Carboplatin.
Methylprednisolone The risk or severity of adverse effects can be increased when Trifluridine is combined with Methylprednisolone.
Dactinomycin The risk or severity of adverse effects can be increased when Trifluridine is combined with Dactinomycin.
Cytarabine The risk or severity of adverse effects can be increased when Trifluridine is combined with Cytarabine.
Azathioprine The risk or severity of adverse effects can be increased when Trifluridine is combined with Azathioprine.
Doxorubicin The risk or severity of adverse effects can be increased when Trifluridine is combined with Doxorubicin.
Hydroxyurea The risk or severity of adverse effects can be increased when Trifluridine is combined with Hydroxyurea.
Busulfan The risk or severity of adverse effects can be increased when Trifluridine is combined with Busulfan.
Mycophenolic acid The risk or severity of adverse effects can be increased when Trifluridine is combined with Mycophenolic acid.
Topotecan The risk or severity of adverse effects can be increased when Trifluridine is combined with Topotecan.
Mercaptopurine The risk or severity of adverse effects can be increased when Trifluridine is combined with Mercaptopurine.
Thalidomide The risk or severity of adverse effects can be increased when Trifluridine is combined with Thalidomide.
Melphalan The risk or severity of adverse effects can be increased when Trifluridine is combined with Melphalan.

Target Protein

Thymidylate synthase TMP1
DNA
Thymidylate synthase TYMS

Referensi & Sumber

Artikel (PubMed)
  • PMID: 6284470
    Carmine AA, Brogden RN, Heel RC, Speight TM, Avery GS: Trifluridine: a review of its antiviral activity and therapeutic use in the topical treatment of viral eye infections. Drugs. 1982 May;23(5):329-53.
  • PMID: 27568360
    Burness CB, Duggan ST: Trifluridine/Tipiracil: A Review in Metastatic Colorectal Cancer. Drugs. 2016 Sep;76(14):1393-402. doi: 10.1007/s40265-016-0633-9.
  • PMID: 29568368
    Matsuoka K, Nakagawa F, Kobunai T, Takechi T: Trifluridine/tipiracil overcomes the resistance of human gastric 5-fluorouracil-refractory cells with high thymidylate synthase expression. Oncotarget. 2018 Feb 5;9(17):13438-13450. doi: 10.18632/oncotarget.24412. eCollection 2018 Mar 2.
  • PMID: 110152
    Pavan-Langston D, Nelson DJ: Intraocular penetration of trifluridine. Am J Ophthalmol. 1979 Jun;87(6):814-8.
  • PMID: 21278209
    Altmann S, Brandt CR, Murphy CJ, Patnaikuni R, Takla T, Toomey M, Nesbit B, McIntyre K, Covert J, Dubielzig R, Leatherberry G, Adkins E, Kodihalli S: Evaluation of therapeutic interventions for vaccinia virus keratitis. J Infect Dis. 2011 Mar 1;203(5):683-90. doi: 10.1093/infdis/jiq103. Epub 2011 Jan 28.

Contoh Produk & Brand

Produk: 18 • International brands: 4
Produk
  • Apo-trifluridine Ophthalmic Solution
    Solution • 1 % • Ophthalmic • Canada • Generic • Approved
  • Lonsurf
    Tablet, film coated • - • Oral • US • Approved
  • Lonsurf
    Tablet, film coated • - • Oral • US • Approved
  • Lonsurf
    Tablet • - • Oral • Canada • Approved
  • Lonsurf
    Tablet • - • Oral • Canada • Approved
  • Lonsurf
    Tablet, film coated • - • Oral • EU • Approved
  • Lonsurf
    Tablet, film coated • - • Oral • EU • Approved
  • Lonsurf
    Tablet, film coated • - • Oral • EU • Approved
Menampilkan 8 dari 18 produk.
International Brands
  • Thilol — Pharmex
  • Triflumann — Dr. Gerhard Mann
  • Triherpine — Medivis
  • Virophta — Horus

Sekuens Gen/Protein (FASTA)

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