Peringatan Keamanan

Toxicity information regarding vismodegib is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as severe cutaneous adverse reactions and musculoskeletal adverse reactions. Symptomatic and supportive measures are recommended. Patients treated with vismodegib have an increased risk of embryo-fetal death and significant birth defects. Common adverse event include muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia.L45803

Based on the results of in vitro and in vivo studies, vismodegib is not mutagenic. No evidence of carcinogenicity was found in mice and rats given vismodegib. A 26-week rat fertility study found that at doses of 100 mg/kg/day, vismodegib has no effects on male reproductive organs or fertility. In female rats, the administration of vismodegib was associated with decreased implantations, increased percent preimplantation loss, and decreased numbers of dams with viable embryos.L45803

Vismodegib

DB08828

small molecule approved investigational

Deskripsi

Vismodegib is an orally active small molecule that inhibits the hedgehog signaling pathway by binding to and inhibiting the transmembrane protein smoothened homologue (SMO).A258613,A258618,L45803 It was discovered by high-throughput screening of a library of small-molecule compounds and subsequent optimization through medicinal chemistry.A7369 Since it targets the hedgehog signaling pathway, vismodegib has anti-tumor activity in basal-cell carcinoma. The Hedgehog signaling pathway plays an important role in the development of organs and tissues during embryogenesis. Afterwards, it is silenced in all cells and tissues, except for hair, skin and stem cells. However, dysregulated or aberrant Hedgehog signaling has been associated with basal cell carcinoma pathogenesis.A258608,L45803 In January 2012, vismodegib was approved by the FDA for the treatment of adult basal cell carcinoma. In July 2013, it was approved by the EMA, and since then, it has been approved by several other countries.A7370,A258618,L45803

Struktur Molekul 2D

Berat 421.297
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 vismodegib after a single dose is 12 days, and after continuous daily dosing is 4 days.[L45803]
Volume Distribusi The volume of distribution of vismodegib ranges between 16.4 and 26.6 L.[L45803]
Klirens (Clearance) -

Absorpsi

Vismodegib appears to have a nonlinear pharmacokinetic profile following daily oral dosing, and steady state is achieved within 7 days. A dose increase from 150 mg to 540 mg (1 to 3.6 times the recommended dose) does not lead to an increase in steady-state plasma concentrations. With a once-daily dose of 150 mg, the average plasma concentration of vismodegib at steady state is approximately 23 µM. The absolute bioavailability of a single dose of vismodegib is 31.8%. Absorption is saturable and is not affected by food.L45803

Metabolisme

Vismodegib is mainly metabolized by CYP2C9 and CYP3A4 in the liver; however, more than 98% of total systemic vismodegib is not metabolized. Metabolic pathways of vismodegib in humans include oxidation, glucuronidation, and pyridine ring cleavage. The two most abundant oxidative metabolites recovered in feces are produced in vitro by recombinant CYP2C9 and CYP3A4/5.L45803

Rute Eliminasi

Vismodegib is excreted mostly unchanged. Vismodegib and its metabolites are mainly eliminated through feces. Approximately 82% and 4.4% of the administered dose are recovered in feces and urine, respectively.L45803

Interaksi Makanan

1 Data
  • 1. Take with or without food. Food does not affect absorption. The Cmax and AUC of vismodegib at steady state are not affected by food.

Interaksi Obat

137 Data
Imatinib Vismodegib may decrease the excretion rate of Imatinib which could result in a higher serum level.
Dabrafenib Vismodegib may decrease the excretion rate of Dabrafenib which could result in a higher serum level.
Folic acid Vismodegib may decrease the excretion rate of Folic acid which could result in a higher serum level.
Pravastatin Vismodegib may decrease the excretion rate of Pravastatin which could result in a higher serum level.
Conjugated estrogens Vismodegib may decrease the excretion rate of Conjugated estrogens which could result in a higher serum level.
Allopurinol Vismodegib may decrease the excretion rate of Allopurinol which could result in a higher serum level.
Cerivastatin Vismodegib may decrease the excretion rate of Cerivastatin which could result in a higher serum level.
Zidovudine Vismodegib may decrease the excretion rate of Zidovudine which could result in a higher serum level.
Oxaliplatin Vismodegib may decrease the excretion rate of Oxaliplatin which could result in a higher serum level.
Methotrexate Vismodegib may decrease the excretion rate of Methotrexate which could result in a higher serum level.
Clofarabine Vismodegib may decrease the excretion rate of Clofarabine which could result in a higher serum level.
Sumatriptan Vismodegib may decrease the excretion rate of Sumatriptan which could result in a higher serum level.
Mycophenolate mofetil Vismodegib may decrease the excretion rate of Mycophenolate mofetil which could result in a higher serum level.
Nitrofurantoin Vismodegib may decrease the excretion rate of Nitrofurantoin which could result in a higher serum level.
Lamivudine Vismodegib may decrease the excretion rate of Lamivudine which could result in a higher serum level.
Riluzole Vismodegib may decrease the excretion rate of Riluzole which could result in a higher serum level.
Irinotecan Vismodegib may decrease the excretion rate of Irinotecan which could result in a higher serum level.
Sulfasalazine Vismodegib may decrease the excretion rate of Sulfasalazine which could result in a higher serum level.
Ezetimibe Vismodegib may decrease the excretion rate of Ezetimibe which could result in a higher serum level.
Topotecan Vismodegib may decrease the excretion rate of Topotecan which could result in a higher serum level.
Tegaserod Vismodegib may decrease the excretion rate of Tegaserod which could result in a higher serum level.
Leflunomide Vismodegib may decrease the excretion rate of Leflunomide which could result in a higher serum level.
Rosuvastatin Vismodegib may decrease the excretion rate of Rosuvastatin which could result in a higher serum level.
Alvocidib Vismodegib may decrease the excretion rate of Alvocidib which could result in a higher serum level.
Camptothecin Vismodegib may decrease the excretion rate of Camptothecin which could result in a higher serum level.
Simeprevir Vismodegib may decrease the excretion rate of Simeprevir which could result in a higher serum level.
Apixaban Vismodegib may decrease the excretion rate of Apixaban which could result in a higher serum level.
Teriflunomide Vismodegib may decrease the excretion rate of Teriflunomide which could result in a higher serum level.
Dolutegravir Vismodegib may decrease the excretion rate of Dolutegravir which could result in a higher serum level.
Riociguat Vismodegib may decrease the excretion rate of Riociguat which could result in a higher serum level.
Sofosbuvir Vismodegib may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
Palbociclib Vismodegib may decrease the excretion rate of Palbociclib which could result in a higher serum level.
Lenvatinib Vismodegib may decrease the excretion rate of Lenvatinib which could result in a higher serum level.
Fimasartan Vismodegib may decrease the excretion rate of Fimasartan which could result in a higher serum level.
Ombitasvir Vismodegib may decrease the excretion rate of Ombitasvir which could result in a higher serum level.
Osimertinib Vismodegib may decrease the excretion rate of Osimertinib which could result in a higher serum level.
Talazoparib The serum concentration of Talazoparib can be increased when it is combined with Vismodegib.
Revefenacin Vismodegib may decrease the excretion rate of Revefenacin which could result in a higher serum level.
Delafloxacin Vismodegib may decrease the excretion rate of Delafloxacin which could result in a higher serum level.
Duvelisib Vismodegib may decrease the excretion rate of Duvelisib which could result in a higher serum level.
Glasdegib Vismodegib may decrease the excretion rate of Glasdegib which could result in a higher serum level.
Copanlisib Vismodegib may decrease the excretion rate of Copanlisib which could result in a higher serum level.
Darolutamide Vismodegib may decrease the excretion rate of Darolutamide which could result in a higher serum level.
Tazemetostat Vismodegib may decrease the excretion rate of Tazemetostat which could result in a higher serum level.
Vemurafenib Vismodegib may decrease the excretion rate of Vemurafenib which could result in a higher serum level.
Gefitinib Vismodegib may decrease the excretion rate of Gefitinib which could result in a higher serum level.
Prazosin Vismodegib may decrease the excretion rate of Prazosin which could result in a higher serum level.
Raloxifene Vismodegib may decrease the excretion rate of Raloxifene which could result in a higher serum level.
Vincristine Vismodegib may decrease the excretion rate of Vincristine which could result in a higher serum level.
Ivermectin Vismodegib may decrease the excretion rate of Ivermectin which could result in a higher serum level.
Testosterone Vismodegib may decrease the excretion rate of Testosterone which could result in a higher serum level.
Daunorubicin Vismodegib may decrease the excretion rate of Daunorubicin which could result in a higher serum level.
Etoposide Vismodegib may decrease the excretion rate of Etoposide which could result in a higher serum level.
Dactinomycin Vismodegib may decrease the excretion rate of Dactinomycin which could result in a higher serum level.
Doxorubicin Vismodegib may decrease the excretion rate of Doxorubicin which could result in a higher serum level.
Glyburide Vismodegib may decrease the excretion rate of Glyburide which could result in a higher serum level.
Mitoxantrone Vismodegib may decrease the excretion rate of Mitoxantrone which could result in a higher serum level.
Dasatinib Vismodegib may decrease the excretion rate of Dasatinib which could result in a higher serum level.
Rivaroxaban Vismodegib may decrease the excretion rate of Rivaroxaban which could result in a higher serum level.
Afatinib Vismodegib may decrease the excretion rate of Afatinib which could result in a higher serum level.
Idelalisib Vismodegib may decrease the excretion rate of Idelalisib which could result in a higher serum level.
Tenofovir alafenamide The serum concentration of Tenofovir alafenamide can be increased when it is combined with Vismodegib.
Venetoclax Vismodegib may decrease the excretion rate of Venetoclax which could result in a higher serum level.
Velpatasvir Vismodegib may decrease the excretion rate of Velpatasvir which could result in a higher serum level.
Abemaciclib Vismodegib may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
Voxilaprevir Vismodegib may decrease the excretion rate of Voxilaprevir which could result in a higher serum level.
Rucaparib Vismodegib may decrease the excretion rate of Rucaparib which could result in a higher serum level.
Lusutrombopag Vismodegib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Pibrentasvir Vismodegib may decrease the excretion rate of Pibrentasvir which could result in a higher serum level.
Glecaprevir Vismodegib may decrease the excretion rate of Glecaprevir which could result in a higher serum level.
Testosterone cypionate Vismodegib may decrease the excretion rate of Testosterone cypionate which could result in a higher serum level.
Testosterone enanthate Vismodegib may decrease the excretion rate of Testosterone enanthate which could result in a higher serum level.
Selumetinib Vismodegib may decrease the excretion rate of Selumetinib which could result in a higher serum level.
Pralatrexate Vismodegib may decrease the excretion rate of Pralatrexate which could result in a higher serum level.
Ripretinib Vismodegib may decrease the excretion rate of Ripretinib which could result in a higher serum level.
Fostemsavir Vismodegib may decrease the excretion rate of Fostemsavir which could result in a higher serum level.
Pralsetinib Vismodegib may decrease the excretion rate of Pralsetinib which could result in a higher serum level.
Celecoxib Vismodegib may decrease the excretion rate of Celecoxib which could result in a higher serum level.
Donepezil Vismodegib may decrease the excretion rate of Donepezil which could result in a higher serum level.
Pazopanib Vismodegib may decrease the excretion rate of Pazopanib which could result in a higher serum level.
Ponatinib Vismodegib may decrease the excretion rate of Ponatinib which could result in a higher serum level.
Brigatinib Vismodegib may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Trilaciclib Vismodegib may decrease the excretion rate of Trilaciclib which could result in a higher serum level.
Teniposide Vismodegib may decrease the excretion rate of Teniposide which could result in a higher serum level.
Fluorouracil Vismodegib may decrease the excretion rate of Fluorouracil which could result in a higher serum level.
Meloxicam The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Meloxicam.
Diphenhydramine The risk or severity of methemoglobinemia can be increased when Vismodegib is combined with Diphenhydramine.
Dacomitinib Vismodegib may decrease the excretion rate of Dacomitinib which could result in a higher serum level.
Tamoxifen Vismodegib may decrease the excretion rate of Tamoxifen which could result in a higher serum level.
Enasidenib Vismodegib may decrease the excretion rate of Enasidenib which could result in a higher serum level.
Alpelisib The serum concentration of Alpelisib can be increased when it is combined with Vismodegib.
Ubrogepant The serum concentration of Ubrogepant can be increased when it is combined with Vismodegib.
Rimegepant The serum concentration of Rimegepant can be increased when it is combined with Vismodegib.
Ritonavir Vismodegib may decrease the excretion rate of Ritonavir which could result in a higher serum level.
Ozanimod Vismodegib may decrease the excretion rate of Ozanimod which could result in a higher serum level.
Tucatinib Vismodegib may decrease the excretion rate of Tucatinib which could result in a higher serum level.
Berotralstat The serum concentration of Berotralstat can be increased when it is combined with Vismodegib.
Nilotinib Vismodegib may decrease the excretion rate of Nilotinib which could result in a higher serum level.
Darbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Vismodegib.
Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Vismodegib.

Target Protein

Protein smoothened SMO

Referensi & Sumber

Synthesis reference: Gunzner-Toste, JL., et al. (2020). Pyridyl inhibitors of hedgehog signalling (U.S. Patent No. 2020/0010420 A1 ). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/72/c1/79/c08582c18507d5/US20200010420A1.pdf
Artikel (PubMed)
  • PMID: 19726763
    Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JR, Mackey HM, Lum BL, Darbonne WC, Marsters JC Jr, de Sauvage FJ, Low JA: Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. 2009 Sep 17;361(12):1164-72. doi: 10.1056/NEJMoa0905360. Epub 2009 Sep 2.
  • PMID: 23662017
    Sandhiya S, Melvin G, Kumar SS, Dkhar SA: The dawn of hedgehog inhibitors: Vismodegib. J Pharmacol Pharmacother. 2013 Jan;4(1):4-7. doi: 10.4103/0976-500X.107628.
  • PMID: 24350028
    Aditya S, Rattan A: Vismodegib: A smoothened inhibitor for the treatment of advanced basal cell carcinoma. Indian Dermatol Online J. 2013 Oct;4(4):365-8. doi: 10.4103/2229-5178.120685.
  • PMID: 28523596
    Abou-Alfa GK, Lewis LD, LoRusso P, Maitland M, Chandra P, Cheeti S, Colburn D, Williams S, Simmons B, Graham RA: Pharmacokinetics and safety of vismodegib in patients with advanced solid malignancies and hepatic impairment. Cancer Chemother Pharmacol. 2017 Jul;80(1):29-36. doi: 10.1007/s00280-017-3315-8. Epub 2017 May 18.
  • PMID: 24941979
    Dessinioti C, Plaka M, Stratigos AJ: Vismodegib for the treatment of basal cell carcinoma: results and implications of the ERIVANCE BCC trial. Future Oncol. 2014 May;10(6):927-36. doi: 10.2217/fon.14.50.

Contoh Produk & Brand

Produk: 3 • International brands: 1
Produk
  • Erivedge
    Capsule • 150 mg • Oral • EU • Approved
  • Erivedge
    Capsule • 150 mg/1 • Oral • US • Approved
  • Erivedge
    Capsule • 150 mg • Oral • Canada • Approved
International Brands
  • Erivedge — Genentech

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