Peringatan Keamanan

In an acute toxicity study, the oral LD50 in rat was >2,000 mg/kg.L8687

In oral studies, dronedarone showed a limited potential for toxicity in humans in acute overdose situations.L8684 However, it is recommended that the patient's cardiac rhythm and blood pressure is monitored in the event of overdose. Symptomatic and supportive treatments should be initiated.L8699

Dronedarone

DB04855

small molecule approved

Deskripsi

Dronedarone is a Class III antiarrhythmic drug that works to restore the normal sinus rhythm in patients with paroxysmal or persistent atrial fibrillation. Atrial fibrillation is a common sustained arrhythmia where the treatment primarily focuses on stroke prevention and symptom management. It is managed by rate control, rhythm control, prevention of thromboembolic events, and treatment of the underlying disease.A34604 Similar to amiodarone, dronedarone is a multichannel blocker that works to control rhythm and rate in atrial fibrillation.A186071 It meets criteria of all four Vaughan Williams antiarrhythmic drug classes by blocking sodium, potassium, and calcium ion channels and inhibiting ?-adrenergic receptors.A34604,L8699

Dronedarone is a related benzofuran compound to amiodarone but its chemical structure lacks iodine moieties which are associated with amiodarone-induced thyroid problems.A34604,T28 Additionally, the methyl sulfonyl group in its structure renders dronedarone to be more lipophilic with a shorter half-life than amiodarone.A34604 This ultimately leads to reduced tissue accumulation of the drug and decreased risk for organ toxicities, such as thyroid and pulmonary toxicities.T28 Commonly marketed as Multaq®, dronedarone was approved by the FDA in July 2009 and Health Canada in August 2009. A safety concern for the risk of drug-induced hepatocellular injury has been issued following marketing of dronedarone.L8800

Struktur Molekul 2D

Berat 556.756
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The elimination half life ranges from 13 to 19 hours.[L8699]
Volume Distribusi The volume of distribution at steady-state ranges from 1200 to 1400 L following intravenous administration.[L8699]
Klirens (Clearance) Following intravenous administration, the clearance ranged from 130 to 150 L/h.[L8699]

Absorpsi

Dronedarone is well absorbed after oral administration (>70%).A34604 It displays low systemic bioavailability due to extensive first-pass metabolism. The absolute bioavailability of dronedarone without and with a high-fat meal is 4% and 15%, respectively. The peak plasma concentrations of dronedarone and its main circulating N-debutyl metabolite are reached within 3 to 6 hours after administration with food. Following repeated administration of 400 mg dronedarone twice daily, the steady-state was reached within 4 to 8 days of initial treatment. The steady-state Cmax and systemic exposure to the N-debutyl metabolite are similar to that of the parent compound.L8699

Metabolisme

Dronedarone predominantly undergoes CYP3A-mediated hepatic metabolism. Initial metabolism of dronedarone involves N-debutylation to form the N-debutyl-dronedarone, which retains 1/10 to 1/3 of pharmacological activity of the parent compound.L8699 N-debutyl-dronedarone can be further metabolized to phenol-dronedarone via O-dealkylation and propanoic acid-dronedarone via oxidative deamination. Dronedarone can also be metabolized by CYP2D6 to form benzofuran-hydroxyl-dronedarone. Other detectable metabolites include C-dealkyl-dronedarone and dibutylamine-hydroxyl-dronedarone, along with other minor downstream metabolites with undetermined chemical structures.A186110

Rute Eliminasi

Following oral administration, about 84% of the labeled dose is excreted in feces and 6% is excreted in urine, mainly as metabolites. Unchanged parent compound and the N-debutyl metabolite accounted for less than 15% of the total radioactivity in the plasma.L8699

Interaksi Makanan

3 Data
  • 1. Avoid grapefruit products. Co-administration with grapefruit may increase drug concentrations by 3-fold.
  • 2. Avoid St. John's Wort. This herb induces CYP3A4 and may increase the serum concentration of dronedarone.
  • 3. Take with food. Food, especially high-fat food, increases drug absorption.

Interaksi Obat

1682 Data
Afatinib The serum concentration of Afatinib can be increased when it is combined with Dronedarone.
Modafinil The metabolism of Dronedarone can be increased when combined with Modafinil.
Armodafinil The metabolism of Dronedarone can be increased when combined with Armodafinil.
Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Dronedarone.
Brentuximab vedotin The serum concentration of Brentuximab vedotin can be increased when it is combined with Dronedarone.
Cyclosporine The serum concentration of Dronedarone can be increased when it is combined with Cyclosporine.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Dronedarone.
Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Dronedarone.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Dronedarone.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Dronedarone.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Dronedarone.
Silodosin The excretion of Silodosin can be decreased when combined with Dronedarone.
Topotecan The serum concentration of Topotecan can be increased when it is combined with Dronedarone.
Ceritinib Dronedarone may increase the bradycardic activities of Ceritinib.
Valsartan Dronedarone may decrease the antihypertensive activities of Valsartan.
Ramipril Dronedarone may decrease the antihypertensive activities of Ramipril.
Remikiren Dronedarone may decrease the antihypertensive activities of Remikiren.
Torasemide Dronedarone may decrease the antihypertensive activities of Torasemide.
Guanadrel Dronedarone may decrease the antihypertensive activities of Guanadrel.
Olmesartan Dronedarone may decrease the antihypertensive activities of Olmesartan.
Chlorthalidone Dronedarone may decrease the antihypertensive activities of Chlorthalidone.
Nitroprusside Dronedarone may decrease the antihypertensive activities of Nitroprusside.
Minoxidil Dronedarone may decrease the antihypertensive activities of Minoxidil.
Fosinopril Dronedarone may decrease the antihypertensive activities of Fosinopril.
Trandolapril Dronedarone may decrease the antihypertensive activities of Trandolapril.
Metolazone Dronedarone may decrease the antihypertensive activities of Metolazone.
Benazepril Dronedarone may decrease the antihypertensive activities of Benazepril.
Cyclothiazide Dronedarone may decrease the antihypertensive activities of Cyclothiazide.
Candoxatril Dronedarone may decrease the antihypertensive activities of Candoxatril.
Mecamylamine Dronedarone may decrease the antihypertensive activities of Mecamylamine.
Lisinopril Dronedarone may decrease the antihypertensive activities of Lisinopril.
Nitroglycerin Dronedarone may decrease the antihypertensive activities of Nitroglycerin.
Metyrosine Dronedarone may decrease the antihypertensive activities of Metyrosine.
Hydroflumethiazide Dronedarone may decrease the antihypertensive activities of Hydroflumethiazide.
Cryptenamine Dronedarone may decrease the antihypertensive activities of Cryptenamine.
Perindopril Dronedarone may decrease the antihypertensive activities of Perindopril.
Candesartan cilexetil Dronedarone may decrease the antihypertensive activities of Candesartan cilexetil.
Fenoldopam Dronedarone may decrease the antihypertensive activities of Fenoldopam.
Eprosartan Dronedarone may decrease the antihypertensive activities of Eprosartan.
Chlorothiazide Dronedarone may decrease the antihypertensive activities of Chlorothiazide.
Telmisartan Dronedarone may decrease the antihypertensive activities of Telmisartan.
Trichlormethiazide Dronedarone may decrease the antihypertensive activities of Trichlormethiazide.
Deserpidine Dronedarone may decrease the antihypertensive activities of Deserpidine.
Pentolinium Dronedarone may decrease the antihypertensive activities of Pentolinium.
Trimethaphan Dronedarone may decrease the antihypertensive activities of Trimethaphan.
Diazoxide Dronedarone may decrease the antihypertensive activities of Diazoxide.
Epoprostenol Dronedarone may decrease the antihypertensive activities of Epoprostenol.
Cilazapril Dronedarone may decrease the antihypertensive activities of Cilazapril.
Saprisartan Dronedarone may decrease the antihypertensive activities of Saprisartan.
Spirapril Dronedarone may decrease the antihypertensive activities of Spirapril.
Tienilic acid Dronedarone may decrease the antihypertensive activities of Tienilic acid.
Diethylnorspermine Dronedarone may decrease the antihypertensive activities of Diethylnorspermine.
Temocapril Dronedarone may decrease the antihypertensive activities of Temocapril.
Hexamethonium Dronedarone may decrease the antihypertensive activities of Hexamethonium.
Rauwolfia serpentina root Dronedarone may decrease the antihypertensive activities of Rauwolfia serpentina root.
Enalaprilat Dronedarone may decrease the antihypertensive activities of Enalaprilat.
Angiotensin 1-7 Dronedarone may decrease the antihypertensive activities of Angiotensin 1-7.
Imidapril Dronedarone may decrease the antihypertensive activities of Imidapril.
BQ-123 Dronedarone may decrease the antihypertensive activities of BQ-123.
Dihydralazine Dronedarone may decrease the antihypertensive activities of Dihydralazine.
Zofenopril Dronedarone may decrease the antihypertensive activities of Zofenopril.
Guanoxan Dronedarone may decrease the antihypertensive activities of Guanoxan.
Delapril Dronedarone may decrease the antihypertensive activities of Delapril.
Vincamine Dronedarone may decrease the antihypertensive activities of Vincamine.
Linsidomine Dronedarone may decrease the antihypertensive activities of Linsidomine.
Guanoxabenz Dronedarone may decrease the antihypertensive activities of Guanoxabenz.
Tolonidine Dronedarone may decrease the antihypertensive activities of Tolonidine.
Endralazine Dronedarone may decrease the antihypertensive activities of Endralazine.
Cadralazine Dronedarone may decrease the antihypertensive activities of Cadralazine.
Cyclopenthiazide Dronedarone may decrease the antihypertensive activities of Cyclopenthiazide.
Bietaserpine Dronedarone may decrease the antihypertensive activities of Bietaserpine.
Guanazodine Dronedarone may decrease the antihypertensive activities of Guanazodine.
Methoserpidine Dronedarone may decrease the antihypertensive activities of Methoserpidine.
Guanoclor Dronedarone may decrease the antihypertensive activities of Guanoclor.
Muzolimine Dronedarone may decrease the antihypertensive activities of Muzolimine.
Xipamide Dronedarone may decrease the antihypertensive activities of Xipamide.
Candesartan Dronedarone may decrease the antihypertensive activities of Candesartan.
Tocopherylquinone Dronedarone may decrease the antihypertensive activities of Tocopherylquinone.
Benazeprilat Dronedarone may decrease the antihypertensive activities of Benazeprilat.
Ramiprilat Dronedarone may decrease the antihypertensive activities of Ramiprilat.
Perindoprilat Dronedarone may decrease the antihypertensive activities of Perindoprilat.
Quinaprilat Dronedarone may decrease the antihypertensive activities of Quinaprilat.
Furosemide Dronedarone may decrease the antihypertensive activities of Furosemide.
Enalapril Dronedarone may decrease the antihypertensive activities of Enalapril.
Guanethidine Dronedarone may decrease the antihypertensive activities of Guanethidine.
Buthiazide Dronedarone may decrease the antihypertensive activities of Buthiazide.
Azilsartan medoxomil Dronedarone may decrease the antihypertensive activities of Azilsartan medoxomil.
Esmolol Dronedarone may increase the bradycardic activities of Esmolol.
Betaxolol Dronedarone may increase the bradycardic activities of Betaxolol.
Metoprolol Dronedarone may increase the bradycardic activities of Metoprolol.
Atenolol Dronedarone may increase the bradycardic activities of Atenolol.
Propranolol Dronedarone may increase the bradycardic activities of Propranolol.
Labetalol Dronedarone may increase the bradycardic activities of Labetalol.
Alprenolol Dronedarone may increase the bradycardic activities of Alprenolol.
Pindolol Dronedarone may increase the bradycardic activities of Pindolol.
Carvedilol Dronedarone may increase the bradycardic activities of Carvedilol.
Acebutolol Dronedarone may increase the bradycardic activities of Acebutolol.
Nadolol Dronedarone may increase the bradycardic activities of Nadolol.
Bevantolol Dronedarone may increase the bradycardic activities of Bevantolol.
Practolol Dronedarone may increase the bradycardic activities of Practolol.

Target Protein

Alpha-1A adrenergic receptor ADRA1A
Potassium voltage-gated channel subfamily A member 5 KCNA5
Alpha-1B adrenergic receptor ADRA1B
Alpha-1D adrenergic receptor ADRA1D
Alpha-2A adrenergic receptor ADRA2A
Alpha-2B adrenergic receptor ADRA2B
Alpha-2C adrenergic receptor ADRA2C
Voltage-gated inwardly rectifying potassium channel KCNH2 KCNH2
Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C
Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D
Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F
Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S
Voltage-dependent L-type calcium channel subunit beta-1 CACNB1
Voltage-dependent L-type calcium channel subunit beta-2 CACNB2
Voltage-dependent L-type calcium channel subunit beta-3 CACNB3
Voltage-dependent L-type calcium channel subunit beta-4 CACNB4
Potassium channel subfamily K member 2 KCNK2
Sodium channel protein type 5 subunit alpha SCN5A
G protein-activated inward rectifier potassium channel 1 KCNJ3
Potassium voltage-gated channel subfamily KQT member 1 KCNQ1
Inward rectifier potassium channel KCNJ12
Sodium/calcium exchanger 1 SLC8A1
A-type voltage-gated potassium channel KCND3 KCND3
Beta-1 adrenergic receptor ADRB1
Thyroid hormone receptor alpha THRA

Referensi & Sumber

Synthesis reference: Arie Gutman, Gennadi Nisnevich, Lev Yudovitch, "Process for the preparation of dronedarone." U.S. Patent US20050049302, issued March 03, 2005.
Artikel (PubMed)
  • PMID: 21267357
    Schweizer PA, Becker R, Katus HA, Thomas D: Dronedarone: current evidence for its safety and efficacy in the management of atrial fibrillation. Drug Des Devel Ther. 2011 Jan 6;5:27-39. doi: 10.2147/DDDT.S10315.
  • PMID: 19688104
    Patel PD, Bhuriya R, Patel DD, Arora BL, Singh PP, Arora RR: Dronedarone for atrial fibrillation: a new therapeutic agent. Vasc Health Risk Manag. 2009;5:635-42. doi: 10.2147/vhrm.s6185. Epub 2009 Aug 6.
  • PMID: 23997577
    Heijman J, Heusch G, Dobrev D: Pleiotropic effects of antiarrhythmic agents: dronedarone in the treatment of atrial fibrillation. Clin Med Insights Cardiol. 2013 Aug 11;7:127-40. doi: 10.4137/CMC.S8445. eCollection 2013.
  • PMID: 18565860
    Kober L, Torp-Pedersen C, McMurray JJ, Gotzsche O, Levy S, Crijns H, Amlie J, Carlsen J: Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008 Jun 19;358(25):2678-87. doi: 10.1056/NEJMoa0800456.
  • PMID: 25505590
    Klieber S, Arabeyre-Fabre C, Moliner P, Marti E, Mandray M, Ngo R, Ollier C, Brun P, Fabre G: Identification of metabolic pathways and enzyme systems involved in the in vitro human hepatic metabolism of dronedarone, a potent new oral antiarrhythmic drug. Pharmacol Res Perspect. 2014 Jun;2(3):e00044. doi: 10.1002/prp2.44. Epub 2014 Apr 22.
  • PMID: 30019205
    Rahm AK, Lugenbiel P, Schweizer PA, Katus HA, Thomas D: Role of ion channels in heart failure and channelopathies. Biophys Rev. 2018 Aug;10(4):1097-1106. doi: 10.1007/s12551-018-0442-3. Epub 2018 Jul 17.
  • PMID: 12538616
    Van Beeren HC, Jong WM, Kaptein E, Visser TJ, Bakker O, Wiersinga WM: Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-alpha1: in vitro and in vivo evidence. Endocrinology. 2003 Feb;144(2):552-8. doi: 10.1210/en.2002-220604.
Textbook
  • ISBN: 978-0-7020-3471-8
    21. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 257). Edinburgh: Elsevier/Churchill Livingstone.

Contoh Produk & Brand

Produk: 9 • International brands: 0
Produk
  • Asn-dronedarone
    Tablet • 400 mg • Oral • Canada • Approved
  • Multaq
    Tablet, film coated • 400 mg/1 • Oral • US • Approved
  • Multaq
    Tablet, film coated • 400 mg/1 • Oral • US • Approved
  • Multaq
    Tablet, film coated • 400 mg/1 • Oral • US • Approved
  • Multaq
    Tablet • 400 mg • Oral • Canada • Approved
  • Multaq
    Tablet, film coated • 400 mg • Oral • EU • Approved
  • Multaq
    Tablet, film coated • 400 mg • Oral • EU • Approved
  • Multaq
    Tablet, film coated • 400 mg • Oral • EU • Approved
Menampilkan 8 dari 9 produk.

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