Peringatan Keamanan

There are no data available regarding overdosage with givinostat. In healthy subjects administered a dose of 265.8 mg (approximately 5-fold the 53.2 mg dose recommended for DMD patients weighing 60 kg or more), an increase in QTc interval 5 hours post-administration was observed, the largest mean increase being 13.6 ms.L50311

Givinostat

DB12645

small molecule approved investigational

Deskripsi

Givinostat is a small molecule histone deacetylase (HDAC) inhibitor. It has been investigated as a treatment for a variety of inflammatory diseases, like Crohn's disease and juvenile idiopathic arthritis, cancers like leukemia and lymphoma, as well as several muscular dystrophies. In the context of muscular dystrophy, inhibitors of HDAC appear to exert their therapeutic effects by targeting pathogenic processes that cause inflammation and muscle loss.L50316,A263446

Givinostat was granted FDA approval in March 2024 for the treatment of patients ?6 years of age with Duchenne muscular dystrophy (DMD).L50311,L50316 It is the first non-steroidal drug approved to treat patients with all genetic variants of DMD.L50316

Struktur Molekul 2D

Berat 421.497
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The apparent plasma elimination half-life of givinostat is approximately 6 hours.[L50311]
Volume Distribusi According to population pharmacokinetic modeling, the estimated apparent volume of distribution of the central compartment is 160 L.[A263466] The estimated apparent volume of distribution of the peripheral compartment is 483 L.[A263466]
Klirens (Clearance) According to population pharmacokinetic modeling, the estimated apparent oral clearance of givinostat is 121 L/h.[A263466] The estimated compartmental clearance of givinostat is 33.8 L/h.[A263466]

Absorpsi

The absolute bioavailability of givinostat has not been determined. The Tmax of givinostat occurs approximately 2-3 hours following oral administration, and steady-state is achieved within 5 to 7 days with twice daily dosing.L50311 Systemic exposure is proportional to the administered dose across the therapeutic dose range. Administration with a high-fat meal resulted in a 40% increase in AUC, a 23% increase in Cmax, and a delay in Tmax of 2-3 hours.L50311

Metabolisme

Givinostat is extensively metabolized to several metabolites, four of which have been characterized: ITF2374, ITF2375, ITF2440, and ITF2563.L50311 These metabolites do not contribute to the efficacy of givinostat.L50311 The enzymes responsible for the metabolism of givinostat are unclear; its metabolism is not mediated by CYP450 or UGT enzymes.L50311

Rute Eliminasi

Urinary excretion of givinostat is minimal (<3%).L50311 The elimination of givinostat is likely driven by metabolism followed by renal and biliary excretion of the resulting metabolites.L50311

Interaksi Makanan

1 Data
  • 1. Take with food. Prescribing information for givinostat recommends it be administered with food twice daily.

Interaksi Obat

436 Data
Vorinostat The risk or severity of QTc prolongation can be increased when Vorinostat is combined with Givinostat.
Leuprolide The risk or severity of QTc prolongation can be increased when Leuprolide is combined with Givinostat.
Goserelin The risk or severity of QTc prolongation can be increased when Goserelin is combined with Givinostat.
Erythromycin The risk or severity of QTc prolongation can be increased when Erythromycin is combined with Givinostat.
Azithromycin The risk or severity of QTc prolongation can be increased when Azithromycin is combined with Givinostat.
Moxifloxacin The risk or severity of QTc prolongation can be increased when Moxifloxacin is combined with Givinostat.
Ranolazine The risk or severity of QTc prolongation can be increased when Ranolazine is combined with Givinostat.
Sulfisoxazole The risk or severity of QTc prolongation can be increased when Sulfisoxazole is combined with Givinostat.
Amitriptyline The risk or severity of QTc prolongation can be increased when Amitriptyline is combined with Givinostat.
Methadone The risk or severity of QTc prolongation can be increased when Methadone is combined with Givinostat.
Diltiazem The risk or severity of QTc prolongation can be increased when Diltiazem is combined with Givinostat.
Clozapine The risk or severity of QTc prolongation can be increased when Clozapine is combined with Givinostat.
Sulpiride The risk or severity of QTc prolongation can be increased when Sulpiride is combined with Givinostat.
Nimodipine The risk or severity of QTc prolongation can be increased when Nimodipine is combined with Givinostat.
Promazine The risk or severity of QTc prolongation can be increased when Promazine is combined with Givinostat.
Prochlorperazine The risk or severity of QTc prolongation can be increased when Prochlorperazine is combined with Givinostat.
Droperidol The risk or severity of QTc prolongation can be increased when Droperidol is combined with Givinostat.
Imipramine The risk or severity of QTc prolongation can be increased when Imipramine is combined with Givinostat.
Chlorpromazine The risk or severity of QTc prolongation can be increased when Chlorpromazine is combined with Givinostat.
Oxaliplatin The risk or severity of QTc prolongation can be increased when Oxaliplatin is combined with Givinostat.
Ciprofloxacin The risk or severity of QTc prolongation can be increased when Ciprofloxacin is combined with Givinostat.
Fluorouracil The risk or severity of QTc prolongation can be increased when Fluorouracil is combined with Givinostat.
Perflutren The risk or severity of QTc prolongation can be increased when Perflutren is combined with Givinostat.
Cinnarizine The risk or severity of QTc prolongation can be increased when Cinnarizine is combined with Givinostat.
Atropine The risk or severity of QTc prolongation can be increased when Atropine is combined with Givinostat.
Chloroquine The risk or severity of QTc prolongation can be increased when Chloroquine is combined with Givinostat.
Efavirenz The risk or severity of QTc prolongation can be increased when Efavirenz is combined with Givinostat.
Adenosine The risk or severity of QTc prolongation can be increased when Adenosine is combined with Givinostat.
Pentamidine The risk or severity of QTc prolongation can be increased when Pentamidine is combined with Givinostat.
Gadobenic acid The risk or severity of QTc prolongation can be increased when Gadobenic acid is combined with Givinostat.
Carbinoxamine The risk or severity of QTc prolongation can be increased when Carbinoxamine is combined with Givinostat.
Dolasetron The risk or severity of QTc prolongation can be increased when Dolasetron is combined with Givinostat.
Roxithromycin The risk or severity of QTc prolongation can be increased when Roxithromycin is combined with Givinostat.
Nalidixic acid The risk or severity of QTc prolongation can be increased when Nalidixic acid is combined with Givinostat.
Cinoxacin The risk or severity of QTc prolongation can be increased when Cinoxacin is combined with Givinostat.
Loperamide The risk or severity of QTc prolongation can be increased when Loperamide is combined with Givinostat.
Granisetron The risk or severity of QTc prolongation can be increased when Granisetron is combined with Givinostat.
Ondansetron The risk or severity of QTc prolongation can be increased when Ondansetron is combined with Givinostat.
Levosimendan The risk or severity of QTc prolongation can be increased when Levosimendan is combined with Givinostat.
Mesoridazine The risk or severity of QTc prolongation can be increased when Mesoridazine is combined with Givinostat.
Desloratadine The risk or severity of QTc prolongation can be increased when Desloratadine is combined with Givinostat.
Telithromycin The risk or severity of QTc prolongation can be increased when Telithromycin is combined with Givinostat.
Lomefloxacin The risk or severity of QTc prolongation can be increased when Lomefloxacin is combined with Givinostat.
Dimenhydrinate The risk or severity of QTc prolongation can be increased when Dimenhydrinate is combined with Givinostat.
Primaquine The risk or severity of QTc prolongation can be increased when Primaquine is combined with Givinostat.
Papaverine The risk or severity of QTc prolongation can be increased when Papaverine is combined with Givinostat.
Chlorpheniramine The risk or severity of QTc prolongation can be increased when Chlorpheniramine is combined with Givinostat.
Nifedipine The risk or severity of QTc prolongation can be increased when Nifedipine is combined with Givinostat.
Levofloxacin The risk or severity of QTc prolongation can be increased when Levofloxacin is combined with Givinostat.
Gemifloxacin The risk or severity of QTc prolongation can be increased when Gemifloxacin is combined with Givinostat.
Ofloxacin The risk or severity of QTc prolongation can be increased when Ofloxacin is combined with Givinostat.
Propafenone The risk or severity of QTc prolongation can be increased when Propafenone is combined with Givinostat.
Flecainide The risk or severity of QTc prolongation can be increased when Flecainide is combined with Givinostat.
Clarithromycin The risk or severity of QTc prolongation can be increased when Clarithromycin is combined with Givinostat.
Levacetylmethadol The risk or severity of QTc prolongation can be increased when Levacetylmethadol is combined with Givinostat.
Saquinavir The risk or severity of QTc prolongation can be increased when Saquinavir is combined with Givinostat.
Clomipramine The risk or severity of QTc prolongation can be increased when Clomipramine is combined with Givinostat.
Mibefradil The risk or severity of QTc prolongation can be increased when Mibefradil is combined with Givinostat.
Probucol The risk or severity of QTc prolongation can be increased when Probucol is combined with Givinostat.
Aceprometazine The risk or severity of QTc prolongation can be increased when Aceprometazine is combined with Givinostat.
Terlipressin The risk or severity of QTc prolongation can be increased when Terlipressin is combined with Givinostat.
Prenylamine The risk or severity of QTc prolongation can be increased when Prenylamine is combined with Givinostat.
Fluspirilene The risk or severity of QTc prolongation can be increased when Fluspirilene is combined with Givinostat.
Lofexidine The risk or severity of QTc prolongation can be increased when Lofexidine is combined with Givinostat.
Azimilide The risk or severity of QTc prolongation can be increased when Azimilide is combined with Givinostat.
Pracinostat The risk or severity of QTc prolongation can be increased when Pracinostat is combined with Givinostat.
Technetium Tc-99m ciprofloxacin The risk or severity of QTc prolongation can be increased when Technetium Tc-99m ciprofloxacin is combined with Givinostat.
Garenoxacin The risk or severity of QTc prolongation can be increased when Garenoxacin is combined with Givinostat.
Tedisamil The risk or severity of QTc prolongation can be increased when Tedisamil is combined with Givinostat.
Tucidinostat The risk or severity of QTc prolongation can be increased when Tucidinostat is combined with Givinostat.
Telavancin The risk or severity of QTc prolongation can be increased when Telavancin is combined with Givinostat.
Pazopanib The risk or severity of QTc prolongation can be increased when Pazopanib is combined with Givinostat.
Nemonoxacin The risk or severity of QTc prolongation can be increased when Nemonoxacin is combined with Givinostat.
Panobinostat The risk or severity of QTc prolongation can be increased when Panobinostat is combined with Givinostat.
Nilvadipine The risk or severity of QTc prolongation can be increased when Nilvadipine is combined with Givinostat.
Antazoline The risk or severity of QTc prolongation can be increased when Antazoline is combined with Givinostat.
Crizotinib The risk or severity of QTc prolongation can be increased when Crizotinib is combined with Givinostat.
Bedaquiline The risk or severity of QTc prolongation can be increased when Bedaquiline is combined with Givinostat.
Fendiline The risk or severity of QTc prolongation can be increased when Fendiline is combined with Givinostat.
Eperisone The risk or severity of QTc prolongation can be increased when Eperisone is combined with Givinostat.
Butriptyline The risk or severity of QTc prolongation can be increased when Butriptyline is combined with Givinostat.
Ceritinib The risk or severity of QTc prolongation can be increased when Ceritinib is combined with Givinostat.
Lenvatinib The risk or severity of QTc prolongation can be increased when Lenvatinib is combined with Givinostat.
Melperone The risk or severity of QTc prolongation can be increased when Melperone is combined with Givinostat.
Benidipine The risk or severity of QTc prolongation can be increased when Benidipine is combined with Givinostat.
Dexchlorpheniramine maleate The risk or severity of QTc prolongation can be increased when Dexchlorpheniramine maleate is combined with Givinostat.
Amifampridine The risk or severity of QTc prolongation can be increased when Amifampridine is combined with Givinostat.
Mocetinostat The risk or severity of QTc prolongation can be increased when Mocetinostat is combined with Givinostat.
Entinostat The risk or severity of QTc prolongation can be increased when Entinostat is combined with Givinostat.
Gilteritinib The risk or severity of QTc prolongation can be increased when Gilteritinib is combined with Givinostat.
CUDC-101 The risk or severity of QTc prolongation can be increased when CUDC-101 is combined with Givinostat.
Simendan The risk or severity of QTc prolongation can be increased when Simendan is combined with Givinostat.
Ricolinostat The risk or severity of QTc prolongation can be increased when Ricolinostat is combined with Givinostat.
Mizolastine The risk or severity of QTc prolongation can be increased when Mizolastine is combined with Givinostat.
Abexinostat The risk or severity of QTc prolongation can be increased when Abexinostat is combined with Givinostat.
Oxatomide The risk or severity of QTc prolongation can be increased when Oxatomide is combined with Givinostat.
Sitafloxacin The risk or severity of QTc prolongation can be increased when Sitafloxacin is combined with Givinostat.
Sultopride The risk or severity of QTc prolongation can be increased when Sultopride is combined with Givinostat.
Otilonium The risk or severity of QTc prolongation can be increased when Otilonium is combined with Givinostat.
Nizofenone The risk or severity of QTc prolongation can be increased when Nizofenone is combined with Givinostat.

Target Protein

Histone deacetylase HDAC1
Tyrosine-protein kinase JAK2 JAK2
Histone deacetylase 1 HDAC1

Referensi & Sumber

Artikel (PubMed)
  • PMID: 36901738
    Sandona M, Cavioli G, Renzini A, Cedola A, Gigli G, Coletti D, McKinsey TA, Moresi V, Saccone V: Histone Deacetylases: Molecular Mechanisms and Therapeutic Implications for Muscular Dystrophies. Int J Mol Sci. 2023 Feb 21;24(5):4306. doi: 10.3390/ijms24054306.
  • PMID: 37306105
    Fiorentini F, Germani M, Del Bene F, Pellizzoni C, Cazzaniga S, Rocchetti M, Bettica P: Population pharmacokinetic-pharmacodynamic analysis of givinostat. Expert Opin Drug Metab Toxicol. 2023 Apr;19(4):229-238. doi: 10.1080/17425255.2023.2219839. Epub 2023 Jun 12.

Contoh Produk & Brand

Produk: 1 • International brands: 0
Produk
  • Duvyzat
    Suspension • 8.86 mg/1mL • Oral • US • Approved

Sekuens Gen/Protein (FASTA)

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