Peringatan Keamanan

Adverse events occurred more frequently with higher doses, 800 mg once daily when compared to a lower dose of 200 mg once daily. In the 200 mg group, frequent adverse events (occurring in ?2% of patients) included: elevated creatine phosphokinase (6%), increased lipase (5%), muscle spasms (3%), asthenia (3%), and hypertension (3%). In the 800 mg group, frequent adverse events included: elevated creatine phosphokinase (13%), increased lipase (5%), weight loss (5%), muscle spasms (5%), decreased appetite (4%), rhabdomyolysis (3%), nausea (3%), hypertension (3%), increased alanine aminotransferase (3%), increased aspartate aminotransferase (3%), fatigue (2%), syncope (2%), anaemia (2%), dehydration (2%), hyperkalaemia (2%) and myalgia (2%). Rhabdomyolysis cases reported by investigators were not confirmed by the adjudication committee on muscle toxicity or the independent safety review. (2)

Sonidegib

DB09143

small molecule approved investigational

Deskripsi

Sonidegib is a Hedgehog signaling pathway inhibitor (via smoothened antagonism) developed as an anticancer agent by Novartis. It was FDA approved in 2015 for the treatment of basal cell carcinoma.

Struktur Molekul 2D

Berat 485.507
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Half-life ~ 28 days (2)
Volume Distribusi Estimated volume of distribution = 9166 L (2)
Klirens (Clearance) -

Absorpsi

Sonidegib is rapidly absorbed in the fasted state with peak concentrations occurring 2-4 hours after administration. (2) However, the total absorption of Sonidegib is low (roughly 6-7%). (1)

Metabolisme

Sonidegib is primarily metabolized via oxidation and amide hydrolysis. (1) The enzyme responsible for the majority of metabolism is the cytochrome P450 (CYP) 3A4 enzyme. (2)

Rute Eliminasi

Around 70% of Sonidegib is eliminated in the feces, while 30% is eliminated in the urine. (2)

Interaksi Makanan

3 Data
  • 1. Exercise caution with grapefruit products. Grapefruit inhibits the CYP3A metabolism of sonidegib, which may increase its serum concentration.
  • 2. Exercise caution with St. John's Wort. This herb induces the CYP3A metabolism of sonidegib, which may reduce its serum concentration.
  • 3. Take on an empty stomach. Take sonidegib at least 1 hour before or 2 hours after eating.

Interaksi Obat

477 Data
Modafinil The metabolism of Sonidegib can be increased when combined with Modafinil.
Armodafinil The metabolism of Sonidegib can be increased when combined with Armodafinil.
Fluvoxamine The metabolism of Sonidegib can be decreased when combined with Fluvoxamine.
Voriconazole The metabolism of Sonidegib can be decreased when combined with Voriconazole.
Fluconazole The metabolism of Sonidegib can be decreased when combined with Fluconazole.
Erythromycin The metabolism of Sonidegib can be decreased when combined with Erythromycin.
Ziprasidone The metabolism of Sonidegib can be decreased when combined with Ziprasidone.
Isradipine The metabolism of Sonidegib can be decreased when combined with Isradipine.
Diltiazem The metabolism of Sonidegib can be decreased when combined with Diltiazem.
Haloperidol The metabolism of Sonidegib can be decreased when combined with Haloperidol.
Nicardipine The metabolism of Sonidegib can be decreased when combined with Nicardipine.
Verapamil The metabolism of Sonidegib can be decreased when combined with Verapamil.
Isoniazid The metabolism of Sonidegib can be decreased when combined with Isoniazid.
Primaquine The metabolism of Sonidegib can be decreased when combined with Primaquine.
Miconazole The metabolism of Sonidegib can be decreased when combined with Miconazole.
Danazol The metabolism of Sonidegib can be decreased when combined with Danazol.
Fusidic acid The metabolism of Sonidegib can be decreased when combined with Fusidic acid.
Zimelidine The metabolism of Sonidegib can be decreased when combined with Zimelidine.
Milnacipran The metabolism of Sonidegib can be decreased when combined with Milnacipran.
Simeprevir The metabolism of Sonidegib can be decreased when combined with Simeprevir.
Desvenlafaxine The metabolism of Sonidegib can be decreased when combined with Desvenlafaxine.
Nilvadipine The metabolism of Sonidegib can be decreased when combined with Nilvadipine.
Seproxetine The metabolism of Sonidegib can be decreased when combined with Seproxetine.
Crizotinib The metabolism of Sonidegib can be decreased when combined with Crizotinib.
Linagliptin The metabolism of Sonidegib can be decreased when combined with Linagliptin.
Indalpine The metabolism of Sonidegib can be decreased when combined with Indalpine.
Netupitant The metabolism of Sonidegib can be decreased when combined with Netupitant.
Barnidipine The metabolism of Sonidegib can be decreased when combined with Barnidipine.
Benidipine The metabolism of Sonidegib can be decreased when combined with Benidipine.
Venetoclax The metabolism of Sonidegib can be decreased when combined with Venetoclax.
Fosnetupitant The metabolism of Sonidegib can be decreased when combined with Fosnetupitant.
Clozapine The metabolism of Sonidegib can be decreased when combined with Clozapine.
Isavuconazonium The metabolism of Sonidegib can be decreased when combined with Isavuconazonium.
Cyclosporine The metabolism of Sonidegib can be decreased when combined with Cyclosporine.
Aprepitant The metabolism of Sonidegib can be decreased when combined with Aprepitant.
Dronedarone The metabolism of Sonidegib can be decreased when combined with Dronedarone.
Isavuconazole The metabolism of Sonidegib can be decreased when combined with Isavuconazole.
Ciprofloxacin The metabolism of Sonidegib can be decreased when combined with Ciprofloxacin.
Berotralstat The metabolism of Sonidegib can be decreased when combined with Berotralstat.
Metreleptin The metabolism of Sonidegib can be increased when combined with Metreleptin.
Pitolisant The serum concentration of Sonidegib can be decreased when it is combined with Pitolisant.
Bexarotene The metabolism of Sonidegib can be increased when combined with Bexarotene.
Bosentan The metabolism of Sonidegib can be increased when combined with Bosentan.
Nafcillin The metabolism of Sonidegib can be increased when combined with Nafcillin.
Etravirine The metabolism of Sonidegib can be increased when combined with Etravirine.
Avasimibe The metabolism of Sonidegib can be increased when combined with Avasimibe.
Echinacea The metabolism of Sonidegib can be increased when combined with Echinacea.
Dexamethasone acetate The metabolism of Sonidegib can be increased when combined with Dexamethasone acetate.
Topiramate The metabolism of Sonidegib can be increased when combined with Topiramate.
Rifabutin The metabolism of Sonidegib can be increased when combined with Rifabutin.
Warfarin The metabolism of Sonidegib can be increased when combined with Warfarin.
Felbamate The metabolism of Sonidegib can be increased when combined with Felbamate.
Genistein The metabolism of Sonidegib can be increased when combined with Genistein.
Oritavancin The metabolism of Sonidegib can be increased when combined with Oritavancin.
Rufinamide The metabolism of Sonidegib can be increased when combined with Rufinamide.
Glycerol phenylbutyrate The metabolism of Sonidegib can be increased when combined with Glycerol phenylbutyrate.
Eslicarbazepine acetate The metabolism of Sonidegib can be increased when combined with Eslicarbazepine acetate.
Lesinurad The metabolism of Sonidegib can be increased when combined with Lesinurad.
Asunaprevir The metabolism of Sonidegib can be increased when combined with Asunaprevir.
Sarilumab The metabolism of Sonidegib can be increased when combined with Sarilumab.
Esketamine The metabolism of Sonidegib can be increased when combined with Esketamine.
Alpelisib The metabolism of Sonidegib can be increased when combined with Alpelisib.
Calcitriol The metabolism of Sonidegib can be increased when combined with Calcitriol.
Vitamin E The metabolism of Sonidegib can be increased when combined with Vitamin E.
Flunisolide The metabolism of Sonidegib can be increased when combined with Flunisolide.
Troglitazone The metabolism of Sonidegib can be increased when combined with Troglitazone.
Butalbital The metabolism of Sonidegib can be increased when combined with Butalbital.
Flucloxacillin The metabolism of Sonidegib can be increased when combined with Flucloxacillin.
Acetaminophen The metabolism of Sonidegib can be increased when combined with Acetaminophen.
Clobazam The metabolism of Sonidegib can be increased when combined with Clobazam.
Aminoglutethimide The metabolism of Sonidegib can be increased when combined with Aminoglutethimide.
Beclomethasone dipropionate The metabolism of Sonidegib can be increased when combined with Beclomethasone dipropionate.
Griseofulvin The metabolism of Sonidegib can be increased when combined with Griseofulvin.
Secobarbital The metabolism of Sonidegib can be increased when combined with Secobarbital.
Cerivastatin The metabolism of Sonidegib can be increased when combined with Cerivastatin.
Betamethasone The metabolism of Sonidegib can be increased when combined with Betamethasone.
Quinine The metabolism of Sonidegib can be increased when combined with Quinine.
Chlorpromazine The metabolism of Sonidegib can be increased when combined with Chlorpromazine.
Dicloxacillin The metabolism of Sonidegib can be increased when combined with Dicloxacillin.
Cyclophosphamide The metabolism of Sonidegib can be increased when combined with Cyclophosphamide.
Rofecoxib The metabolism of Sonidegib can be increased when combined with Rofecoxib.
Vinblastine The metabolism of Sonidegib can be increased when combined with Vinblastine.
Fluocinolone acetonide The metabolism of Sonidegib can be increased when combined with Fluocinolone acetonide.
Medroxyprogesterone acetate The metabolism of Sonidegib can be increased when combined with Medroxyprogesterone acetate.
Triamcinolone The metabolism of Sonidegib can be increased when combined with Triamcinolone.
Testosterone The metabolism of Sonidegib can be increased when combined with Testosterone.
Clofibrate The metabolism of Sonidegib can be increased when combined with Clofibrate.
Tamoxifen The metabolism of Sonidegib can be increased when combined with Tamoxifen.
Hydrocortisone The metabolism of Sonidegib can be increased when combined with Hydrocortisone.
Hydrocortamate The metabolism of Sonidegib can be increased when combined with Hydrocortamate.
Oxcarbazepine The metabolism of Sonidegib can be increased when combined with Oxcarbazepine.
Phenylbutazone The metabolism of Sonidegib can be increased when combined with Phenylbutazone.
Mifepristone The metabolism of Sonidegib can be increased when combined with Mifepristone.
Methylphenobarbital The metabolism of Sonidegib can be increased when combined with Methylphenobarbital.
Terbinafine The metabolism of Sonidegib can be increased when combined with Terbinafine.
Prednisolone The metabolism of Sonidegib can be increased when combined with Prednisolone.
Ethanol The metabolism of Sonidegib can be increased when combined with Ethanol.
Norgestimate The metabolism of Sonidegib can be increased when combined with Norgestimate.
Methylprednisolone The metabolism of Sonidegib can be increased when combined with Methylprednisolone.
Metyrapone The metabolism of Sonidegib can be increased when combined with Metyrapone.

Target Protein

Protein smoothened SMO

Referensi & Sumber

Artikel (PubMed)
  • PMID: 24817600
    Zollinger M, Lozac'h F, Hurh E, Emotte C, Bauly H, Swart P: Absorption, distribution, metabolism, and excretion (ADME) of (1)(4)C-sonidegib (LDE225) in healthy volunteers. Cancer Chemother Pharmacol. 2014 Jul;74(1):63-75. doi: 10.1007/s00280-014-2468-y. Epub 2014 May 10.
  • PMID: 26323341
    Burness CB: Sonidegib: First Global Approval. Drugs. 2015 Sep;75(13):1559-66. doi: 10.1007/s40265-015-0458-y.

Contoh Produk & Brand

Produk: 5 • International brands: 0
Produk
  • Odomzo
    Capsule • 200 mg/1 • Oral • US • Approved
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  • Odomzo
    Capsule • 200 mg • Oral • Canada • Approved
  • Odomzo
    Capsule • 200 mg • Oral • EU • Approved
  • Odomzo
    Capsule • 200 mg • Oral • EU • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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