Peringatan Keamanan

The most common adverse reactions (?20%) are asthenia/fatigue, HFSR, diarrhea, decreased appetite/food intake, hypertension, mucositis, dysphonia, and infection, pain (not otherwise specified), decreased weight, gastrointestinal and abdominal pain, rash, fever, and nausea

Regorafenib

DB08896

small molecule approved

Deskripsi

Regorafenib is an orally-administered inhibitor of multiple kinases. It is used for the treatment of metastatic colorectal cancer, advanced gastrointestinal stromal tumours, and hepatocellular carcinoma. FDA approved on September 27, 2012. Approved use of Regorafenib was expanded to treat Hepatocellular Carcinoma in April 2017.

Struktur Molekul 2D

Berat 482.815
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Regorafenib, 160 mg oral dose = 28 hours (14 - 58 hours); M2 metabolite, 160 mg oral dose = 25 hours (14-32 hours); M5 metabolite, 160 mg oral dose = 51 hours (32-72 hours);
Volume Distribusi Regorafenib undergoes enterohepatic circulation with multiple plasma concentration peaks observed across the 24-hour dosing interval.
Klirens (Clearance) -

Absorpsi

Cmax = 2.5 ?g/mL; Tmax = 4 hours; AUC = 70.4 ?g*h/mL; Cmax, steady-state = 3.9 ?g/mL; AUC, steady-state = 58.3 ?g*h/mL; The mean relative bioavailability of tablets compared to an oral solution is 69% to 83%.

Metabolisme

Regorafenib is metabolized by CYP3A4 and UGT1A9. The main circulating metabolites of regorafenib measured at steady-state in human plasma are M-2 (N-oxide) and M-5 (N-oxide and N-desmethyl), both of them having similar in vitro pharmacological activity and steady-state concentrations as regorafenib. M-2 and M-5 are highly protein bound (99.8% and 99.95%, respectively). Regorafenib is an inhibitor of P-glycoprotein FDA Label, while its active metabolites M-2 (N-oxide) and M-5 (N-oxide and N-desmethyl) are substrates of P-glycoprotein A36336.

Rute Eliminasi

Approximately 71% of a radiolabeled dose was excreted in feces (47% as parent compound, 24% as metabolites) and 19% of the dose was excreted in urine (17% as glucuronides) within 12 days after administration of a radiolabeled oral solution at a dose of 120 mg.

Interaksi Makanan

4 Data
  • 1. Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum levels of regorafenib.
  • 2. Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce serum levels of regorafenib.
  • 3. Take after a meal. Should be taken following a low-fat meal containing less than 600 calories and less than 30% fat.
  • 4. Take at the same time every day.

Interaksi Obat

971 Data
Afatinib The serum concentration of Afatinib can be increased when it is combined with Regorafenib.
Modafinil The metabolism of Regorafenib can be increased when combined with Modafinil.
Armodafinil The metabolism of Regorafenib can be increased when combined with Armodafinil.
Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Regorafenib.
Brentuximab vedotin The serum concentration of Brentuximab vedotin can be increased when it is combined with Regorafenib.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Regorafenib.
Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Regorafenib.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Regorafenib.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Regorafenib.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Regorafenib.
Ranolazine The serum concentration of Ranolazine can be increased when it is combined with Regorafenib.
Silodosin The excretion of Silodosin can be decreased when combined with Regorafenib.
Topotecan The serum concentration of Topotecan can be increased when it is combined with Regorafenib.
Ceritinib Regorafenib may increase the bradycardic activities of Ceritinib.
Ivabradine Regorafenib may increase the bradycardic activities of Ivabradine.
Ruxolitinib Ruxolitinib may increase the bradycardic activities of Regorafenib.
Esmolol Regorafenib may increase the bradycardic activities of Esmolol.
Betaxolol Regorafenib may increase the bradycardic activities of Betaxolol.
Metoprolol Regorafenib may increase the bradycardic activities of Metoprolol.
Atenolol Regorafenib may increase the bradycardic activities of Atenolol.
Timolol Regorafenib may increase the bradycardic activities of Timolol.
Sotalol Regorafenib may increase the bradycardic activities of Sotalol.
Propranolol Regorafenib may increase the bradycardic activities of Propranolol.
Labetalol Regorafenib may increase the bradycardic activities of Labetalol.
Bisoprolol Regorafenib may increase the bradycardic activities of Bisoprolol.
Alprenolol Regorafenib may increase the bradycardic activities of Alprenolol.
Pindolol Regorafenib may increase the bradycardic activities of Pindolol.
Carvedilol Regorafenib may increase the bradycardic activities of Carvedilol.
Propafenone Regorafenib may increase the bradycardic activities of Propafenone.
Acebutolol Regorafenib may increase the bradycardic activities of Acebutolol.
Nadolol Regorafenib may increase the bradycardic activities of Nadolol.
Bevantolol Regorafenib may increase the bradycardic activities of Bevantolol.
Practolol Regorafenib may increase the bradycardic activities of Practolol.
Penbutolol Regorafenib may increase the bradycardic activities of Penbutolol.
Oxprenolol Regorafenib may increase the bradycardic activities of Oxprenolol.
Dexpropranolol Regorafenib may increase the bradycardic activities of Dexpropranolol.
Celiprolol Regorafenib may increase the bradycardic activities of Celiprolol.
Nebivolol Regorafenib may increase the bradycardic activities of Nebivolol.
Bufuralol Regorafenib may increase the bradycardic activities of Bufuralol.
Bopindolol Regorafenib may increase the bradycardic activities of Bopindolol.
Bupranolol Regorafenib may increase the bradycardic activities of Bupranolol.
Indenolol Regorafenib may increase the bradycardic activities of Indenolol.
Arotinolol Regorafenib may increase the bradycardic activities of Arotinolol.
Levobetaxolol Regorafenib may increase the bradycardic activities of Levobetaxolol.
Talinolol Regorafenib may increase the bradycardic activities of Talinolol.
Anisodamine Regorafenib may increase the bradycardic activities of Anisodamine.
Bucindolol Regorafenib may increase the bradycardic activities of Bucindolol.
Esatenolol Regorafenib may increase the bradycardic activities of Esatenolol.
Cloranolol Regorafenib may increase the bradycardic activities of Cloranolol.
Mepindolol Regorafenib may increase the bradycardic activities of Mepindolol.
Epanolol Regorafenib may increase the bradycardic activities of Epanolol.
Tertatolol Regorafenib may increase the bradycardic activities of Tertatolol.
Landiolol Regorafenib may increase the bradycardic activities of Landiolol.
Eliglustat The metabolism of Eliglustat can be decreased when combined with Regorafenib.
Ibrutinib The metabolism of Ibrutinib can be decreased when combined with Regorafenib.
Everolimus The serum concentration of Everolimus can be increased when it is combined with Regorafenib.
Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Regorafenib.
Cilostazol The metabolism of Cilostazol can be decreased when combined with Regorafenib.
Colchicine The serum concentration of Colchicine can be increased when it is combined with Regorafenib.
Fentanyl Fentanyl may increase the bradycardic activities of Regorafenib.
Iloperidone The metabolism of Iloperidone can be decreased when combined with Regorafenib.
Retapamulin The metabolism of Retapamulin can be decreased when combined with Regorafenib.
Tofacitinib The metabolism of Tofacitinib can be decreased when combined with Regorafenib.
Vardenafil The metabolism of Vardenafil can be decreased when combined with Regorafenib.
Eszopiclone The metabolism of Eszopiclone can be decreased when combined with Regorafenib.
Zopiclone The metabolism of Zopiclone can be decreased when combined with Regorafenib.
Irinotecan The risk or severity of neutropenia can be increased when Regorafenib is combined with Irinotecan.
Lovastatin The metabolism of Lovastatin can be decreased when combined with Regorafenib.
Metreleptin The metabolism of Regorafenib can be increased when combined with Metreleptin.
Alfuzosin The metabolism of Alfuzosin can be decreased when combined with Regorafenib.
Alprazolam The metabolism of Alprazolam can be decreased when combined with Regorafenib.
Warfarin The serum concentration of Warfarin can be increased when it is combined with Regorafenib.
Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Regorafenib.
(R)-warfarin The serum concentration of (R)-warfarin can be increased when it is combined with Regorafenib.
R,S-Warfarin alcohol The serum concentration of R,S-Warfarin alcohol can be increased when it is combined with Regorafenib.
S,R-Warfarin alcohol The serum concentration of S,R-Warfarin alcohol can be increased when it is combined with Regorafenib.
(S)-Warfarin The serum concentration of (S)-Warfarin can be increased when it is combined with Regorafenib.
Midazolam The serum concentration of Midazolam can be increased when it is combined with Regorafenib.
Tacrolimus The serum concentration of Tacrolimus can be increased when it is combined with Regorafenib.
Crizotinib The metabolism of Regorafenib can be decreased when combined with Crizotinib.
Atorvastatin The metabolism of Atorvastatin can be decreased when combined with Regorafenib.
Vincristine The excretion of Vincristine can be decreased when combined with Regorafenib.
Doxorubicin The serum concentration of Doxorubicin can be increased when it is combined with Regorafenib.
Midodrine Midodrine may increase the bradycardic activities of Regorafenib.
Bendroflumethiazide Bendroflumethiazide may increase the bradycardic activities of Regorafenib.
Dexmedetomidine Dexmedetomidine may increase the bradycardic activities of Regorafenib.
Magnesium sulfate Magnesium sulfate may increase the bradycardic activities of Regorafenib.
Tizanidine Tizanidine may increase the bradycardic activities of Regorafenib.
Remifentanil Remifentanil may increase the bradycardic activities of Regorafenib.
Methyldopa Methyldopa may increase the bradycardic activities of Regorafenib.
Bretylium Bretylium may increase the bradycardic activities of Regorafenib.
Lucinactant Lucinactant may increase the bradycardic activities of Regorafenib.
Methsuximide Methsuximide may increase the bradycardic activities of Regorafenib.
Calfactant Calfactant may increase the bradycardic activities of Regorafenib.
Beractant Beractant may increase the bradycardic activities of Regorafenib.
Fingolimod Fingolimod may increase the bradycardic activities of Regorafenib.
Poractant alfa Regorafenib may increase the bradycardic activities of Poractant alfa.
Rivastigmine Rivastigmine may increase the bradycardic activities of Regorafenib.
Pregabalin Pregabalin may increase the bradycardic activities of Regorafenib.
Lercanidipine Lercanidipine may increase the bradycardic activities of Regorafenib.

Target Protein

Vascular endothelial growth factor receptor 1 FLT1
Vascular endothelial growth factor receptor 2 KDR
Vascular endothelial growth factor receptor 3 FLT4
Mast/stem cell growth factor receptor Kit KIT
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
Angiopoietin-1 receptor TEK
Discoidin domain-containing receptor 2 DDR2
High affinity nerve growth factor receptor NTRK1
Ephrin type-A receptor 2 EPHA2
RAF proto-oncogene serine/threonine-protein kinase RAF1
Serine/threonine-protein kinase B-raf BRAF
Mitogen-activated protein kinase 11 MAPK11
Tyrosine-protein kinase FRK FRK
Tyrosine-protein kinase ABL1 ABL1
Proto-oncogene tyrosine-protein kinase receptor Ret RET

Referensi & Sumber

Artikel (PubMed)
  • PMID: 26254357
    Hotta K, Ueyama J, Tatsumi Y, Tsukiyama I, Sugiura Y, Saito H, Matsuura K, Hasegawa T: Lack of Contribution of Multidrug Resistance-associated Protein and Organic Anion-transporting Polypeptide to Pharmacokinetics of Regorafenib, a Novel Multi-Kinase Inhibitor, in Rats. Anticancer Res. 2015 Sep;35(9):4681-9.

Contoh Produk & Brand

Produk: 4 • International brands: 0
Produk
  • Stivarga
    Tablet, film coated • 40 mg/1 • Oral • US • Approved
  • Stivarga
    Tablet • 40 mg • Oral • Canada • Approved
  • Stivarga
    Tablet, film coated • 40 mg • Oral • EU • Approved
  • Stivarga
    Tablet, film coated • 40 mg • Oral • EU • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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