Peringatan Keamanan

Most common adverse reactions (?20%) are diarrhea, rash/dermatitis, acneiform, stomatitis, paronychia, dry skin, decreased appetite, pruritus FDA Label.

Conversely, overdose in 2 healthy adolescents involving the ingestion of 360 mg each of afatinib (as part of a mixed drug ingestion) was associated with adverse events of nausea, vomiting, asthenia, dizziness, headache, abdominal pain and elevated amylase (< 1.5 times ULN) L2937. Both individuals recovered from these adverse events L2937.

Afatinib

DB08916

small molecule approved

Deskripsi

Afatinib is a 4-anilinoquinazoline tyrosine kinase inhibitor in the form of a dimaleate salt available as Boehringer Ingelheim's brand name Gilotrif FDA Label. For oral use, afatinib tablets are a first-line (initial) treatment for patients with metastatic non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test L2939. Gilotrif (afatinib) is the first FDA-approved oncology product from Boehringer Ingelheim L2939.

Struktur Molekul 2D

Berat 485.938
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Afatinib is eliminated with an effective half-life of approximately 37 hours [L2937]. Thus, steady-state plasma concentrations of afatinib were achieved within 8 days of multiple dosing of afatinib resulting in an accumulation of 2.77-fold (AUC0-?) and 2.11-fold (Cmax) [L2937]. In patients treated with afatinib for more than 6 months, a terminal half-life of 344 h was estimated [L2937].
Volume Distribusi The volume of distribution of afatinib recorded in healthy male volunteers is documented as 4500 L [A33298]. Such a high volume of distribution in plasma suggests a potentially high tissue distribution [A33298].
Klirens (Clearance) The apparent total body clearance of afatinib as recorded in healthy male volunteers is documented as being a high geometric mean of 1530 mL/min [A33298].

Absorpsi

Following oral administration, time to peak plasma concentration (Tmax) is 2 to 5 hours FDA Label. Maximum concentration (Cmax) and area under the concentration-time curve from time zero to infinity (AUC0-?) values increased slightly more than dose proportional in the range of 20 to 50 mg FDA Label. The geometric mean relative bioavailability of 20 mg tablets was 92% as compared to an oral solution FDA Label. Additionally, systemic exposure to afatinib is decreased by 50% (Cmax) and 39% (AUC0-?), when administered with a high-fat meal compared to administration in the fasted state L2937. Based on population pharmacokinetic data derived from clinical trials in various tumor types, an average decrease of 26% in AUCss was observed when food was consumed within 3 hours before or 1 hour after taking afatinib L2937.

Metabolisme

Enzyme-catalyzed metabolic reactions play a negligible role for afatinib in vivo L2937. Covalent adducts to proteins were the major circulating metabolites of afatinib L2937.

Rute Eliminasi

In humans, excretion of afatinib is primarily via the feces L2937. Following administration of an oral solution of 15 mg afatinib, 85.4% of the dose was recovered in the feces and 4.3% in urine L2937. The parent compound afatinib accounted for 88% of the recovered dose L2937.

Farmakogenomik

3 Varian
EGFR (rs121913444)

The presence of this polymorphism in EGFR is associated with a higher response rate to afatinib.

EGFR (rs121434568)

The presence of this polymorphism in EGFR is associated with a higher response rate to afatinib.

EGFR (rs28929495)

The presence of this polymorphism in EGFR is associated with a higher response rate to afatinib.

Interaksi Makanan

1 Data
  • 1. Take separate from meals. Take at least one hour before or two hours after a meal.

Interaksi Obat

407 Data
Fluconazole The serum concentration of Afatinib can be increased when it is combined with Fluconazole.
Erythromycin The serum concentration of Afatinib can be increased when it is combined with Erythromycin.
Sildenafil The serum concentration of Afatinib can be increased when it is combined with Sildenafil.
Reserpine The serum concentration of Afatinib can be increased when it is combined with Reserpine.
Sorafenib The serum concentration of Afatinib can be increased when it is combined with Sorafenib.
Loxapine The serum concentration of Afatinib can be increased when it is combined with Loxapine.
Quinine The serum concentration of Afatinib can be increased when it is combined with Quinine.
Ritonavir The serum concentration of Afatinib can be increased when it is combined with Ritonavir.
Toremifene The serum concentration of Afatinib can be increased when it is combined with Toremifene.
Simvastatin The serum concentration of Afatinib can be increased when it is combined with Simvastatin.
Verapamil The serum concentration of Afatinib can be increased when it is combined with Verapamil.
Tamoxifen The serum concentration of Afatinib can be increased when it is combined with Tamoxifen.
Mifepristone The serum concentration of Afatinib can be increased when it is combined with Mifepristone.
Vardenafil The serum concentration of Afatinib can be increased when it is combined with Vardenafil.
Tacrolimus The serum concentration of Afatinib can be increased when it is combined with Tacrolimus.
Conivaptan The serum concentration of Afatinib can be increased when it is combined with Conivaptan.
Quinidine The serum concentration of Afatinib can be increased when it is combined with Quinidine.
Zonisamide The serum concentration of Afatinib can be increased when it is combined with Zonisamide.
Tipranavir The serum concentration of Afatinib can be increased when it is combined with Tipranavir.
Ketoconazole The serum concentration of Afatinib can be increased when it is combined with Ketoconazole.
Amiodarone The serum concentration of Afatinib can be increased when it is combined with Amiodarone.
Carvedilol The serum concentration of Afatinib can be increased when it is combined with Carvedilol.
Itraconazole The serum concentration of Afatinib can be increased when it is combined with Itraconazole.
Propafenone The serum concentration of Afatinib can be increased when it is combined with Propafenone.
Clarithromycin The serum concentration of Afatinib can be increased when it is combined with Clarithromycin.
Saquinavir The serum concentration of Afatinib can be increased when it is combined with Saquinavir.
Lapatinib The serum concentration of Afatinib can be increased when it is combined with Lapatinib.
Paliperidone The serum concentration of Afatinib can be increased when it is combined with Paliperidone.
Mibefradil The serum concentration of Afatinib can be increased when it is combined with Mibefradil.
Lopinavir The serum concentration of Afatinib can be increased when it is combined with Lopinavir.
Biricodar The serum concentration of Afatinib can be increased when it is combined with Biricodar.
Dronedarone The serum concentration of Afatinib can be increased when it is combined with Dronedarone.
Nilotinib The serum concentration of Afatinib can be increased when it is combined with Nilotinib.
Elacridar The serum concentration of Afatinib can be increased when it is combined with Elacridar.
Flibanserin The serum concentration of Afatinib can be increased when it is combined with Flibanserin.
Vandetanib The serum concentration of Afatinib can be increased when it is combined with Vandetanib.
Telaprevir The serum concentration of Afatinib can be increased when it is combined with Telaprevir.
Zosuquidar The serum concentration of Afatinib can be increased when it is combined with Zosuquidar.
Tariquidar The serum concentration of Afatinib can be increased when it is combined with Tariquidar.
Temsirolimus The serum concentration of Afatinib can be increased when it is combined with Temsirolimus.
Simeprevir The serum concentration of Afatinib can be increased when it is combined with Simeprevir.
Isavuconazonium The serum concentration of Afatinib can be increased when it is combined with Isavuconazonium.
Brefeldin A The serum concentration of Afatinib can be increased when it is combined with Brefeldin A.
Ticagrelor The serum concentration of Afatinib can be increased when it is combined with Ticagrelor.
Ivacaftor The serum concentration of Afatinib can be increased when it is combined with Ivacaftor.
Lomitapide The serum concentration of Afatinib can be increased when it is combined with Lomitapide.
Crizotinib The serum concentration of Afatinib can be increased when it is combined with Crizotinib.
Linagliptin The serum concentration of Afatinib can be increased when it is combined with Linagliptin.
Mirabegron The serum concentration of Afatinib can be increased when it is combined with Mirabegron.
Regorafenib The serum concentration of Afatinib can be increased when it is combined with Regorafenib.
Ponatinib The serum concentration of Afatinib can be increased when it is combined with Ponatinib.
Canagliflozin The serum concentration of Afatinib can be increased when it is combined with Canagliflozin.
Vorapaxar The serum concentration of Afatinib can be increased when it is combined with Vorapaxar.
Suvorexant The serum concentration of Afatinib can be increased when it is combined with Suvorexant.
Netupitant The serum concentration of Afatinib can be increased when it is combined with Netupitant.
Cobicistat The serum concentration of Afatinib can be increased when it is combined with Cobicistat.
Palbociclib The serum concentration of Afatinib can be increased when it is combined with Palbociclib.
Daclatasvir The serum concentration of Afatinib can be increased when it is combined with Daclatasvir.
Niguldipine The serum concentration of Afatinib can be increased when it is combined with Niguldipine.
Lumacaftor The serum concentration of Afatinib can be increased when it is combined with Lumacaftor.
Rolapitant The serum concentration of Afatinib can be increased when it is combined with Rolapitant.
Venetoclax The serum concentration of Afatinib can be increased when it is combined with Venetoclax.
Asunaprevir The serum concentration of Afatinib can be increased when it is combined with Asunaprevir.
Velpatasvir The serum concentration of Afatinib can be increased when it is combined with Velpatasvir.
Neratinib The serum concentration of Afatinib can be increased when it is combined with Neratinib.
Valspodar The serum concentration of Afatinib can be increased when it is combined with Valspodar.
Dacomitinib The serum concentration of Afatinib can be increased when it is combined with Dacomitinib.
Glasdegib The serum concentration of Afatinib can be increased when it is combined with Glasdegib.
Voxilaprevir The serum concentration of Afatinib can be increased when it is combined with Voxilaprevir.
Sarecycline The serum concentration of Afatinib can be increased when it is combined with Sarecycline.
Rucaparib Afatinib may decrease the excretion rate of Rucaparib which could result in a higher serum level.
Laniquidar The serum concentration of Afatinib can be increased when it is combined with Laniquidar.
Enasidenib The serum concentration of Afatinib can be increased when it is combined with Enasidenib.
Pibrentasvir The serum concentration of Afatinib can be increased when it is combined with Pibrentasvir.
Glecaprevir The serum concentration of Afatinib can be increased when it is combined with Glecaprevir.
Dexniguldipine The serum concentration of Afatinib can be increased when it is combined with Dexniguldipine.
ONT-093 The serum concentration of Afatinib can be increased when it is combined with ONT-093.
Isavuconazole The serum concentration of Afatinib can be increased when it is combined with Isavuconazole.
Carfilzomib The serum concentration of Afatinib can be increased when it is combined with Carfilzomib.
Elagolix The serum concentration of Afatinib can be increased when it is combined with Elagolix.
Entrectinib The serum concentration of Afatinib can be increased when it is combined with Entrectinib.
Fedratinib The serum concentration of Afatinib can be increased when it is combined with Fedratinib.
Istradefylline The serum concentration of Afatinib can be increased when it is combined with Istradefylline.
Cyclosporine The serum concentration of Afatinib can be increased when it is combined with Cyclosporine.
Norgestimate The serum concentration of Afatinib can be increased when it is combined with Norgestimate.
Eliglustat The serum concentration of Afatinib can be increased when it is combined with Eliglustat.
Favipiravir The serum concentration of Afatinib can be increased when it is combined with Favipiravir.
Methylene blue The serum concentration of Afatinib can be increased when it is combined with Methylene blue.
Ripretinib The serum concentration of Afatinib can be increased when it is combined with Ripretinib.
Lonafarnib The serum concentration of Afatinib can be increased when it is combined with Lonafarnib.
Clofazimine The serum concentration of Afatinib can be increased when it is combined with Clofazimine.
Arsenic trioxide The serum concentration of Afatinib can be increased when it is combined with Arsenic trioxide.
Mefloquine The serum concentration of Afatinib can be increased when it is combined with Mefloquine.
Cethromycin The serum concentration of Afatinib can be increased when it is combined with Cethromycin.
Ixabepilone The serum concentration of Afatinib can be increased when it is combined with Ixabepilone.
Voclosporin The serum concentration of Afatinib can be increased when it is combined with Voclosporin.
Umbralisib The serum concentration of Afatinib can be increased when it is combined with Umbralisib.
Diosmin The serum concentration of Afatinib can be increased when it is combined with Diosmin.
Sapropterin The serum concentration of Afatinib can be increased when it is combined with Sapropterin.
Levoketoconazole The serum concentration of Afatinib can be increased when it is combined with Levoketoconazole.

Target Protein

Epidermal growth factor receptor EGFR
Receptor tyrosine-protein kinase erbB-2 ERBB2
Receptor tyrosine-protein kinase erbB-4 ERBB4

Referensi & Sumber

Artikel (PubMed)
  • PMID: 27470518
    Wind S, Schnell D, Ebner T, Freiwald M, Stopfer P: Clinical Pharmacokinetics and Pharmacodynamics of Afatinib. Clin Pharmacokinet. 2017 Mar;56(3):235-250. doi: 10.1007/s40262-016-0440-1.
  • PMID: 22200729
    Stopfer P, Marzin K, Narjes H, Gansser D, Shahidi M, Uttereuther-Fischer M, Ebner T: Afatinib pharmacokinetics and metabolism after oral administration to healthy male volunteers. Cancer Chemother Pharmacol. 2012 Apr;69(4):1051-61. doi: 10.1007/s00280-011-1803-9. Epub 2011 Dec 27.

Contoh Produk & Brand

Produk: 27 • International brands: 0
Produk
  • Gilotrif
    Tablet, film coated • 20 mg/1 • Oral • US • Approved
  • Gilotrif
    Tablet, film coated • 30 mg/1 • Oral • US • Approved
  • Gilotrif
    Tablet, film coated • 40 mg/1 • Oral • US • Approved
  • Giotrif
    Tablet, film coated • 20 mg • Oral • EU • Approved
  • Giotrif
    Tablet, film coated • 20 mg • Oral • EU • Approved
  • Giotrif
    Tablet, film coated • 20 mg • Oral • EU • Approved
  • Giotrif
    Tablet, film coated • 30 mg • Oral • EU • Approved
  • Giotrif
    Tablet, film coated • 30 mg • Oral • EU • Approved
Menampilkan 8 dari 27 produk.

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