QuickView for Amiodarone (compound)

Summary
General Info

PubChem

PubChem Compound 2157

Name:	Amiodarone
PubChem Compound ID:	2157
Description:	An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance.
Molecular formula:	C₂₅H₂₉I₂NO₃
Molecular weight:	645.312 g/mol
Synonyms:	NINDS_000079; 2-Butyl-3-(4'-beta-N-diethylaminoethoxy-3',5'-diiodobenzoyl)benzofuran; Ketone, 2-butyl-3-benzofuranyl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl; 1951-25-3; (2-Butyl-3-benzofuranyl)(4-(2-(diethylamino)ethoxy)-3,5-diidophenyl)methanone; Amiodarone; CHEBI:2663; AIDS-114337; nchembio732-comp1; 2-Butyl-3-(3,5-diiodo-4-(beta-diethylaminoethoxy)benzoyl)benzofuran. show more » NINDS_000079; 2-Butyl-3-(4'-beta-N-diethylaminoethoxy-3',5'-diiodobenzoyl)benzofuran; Ketone, 2-butyl-3-benzofuranyl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl; 1951-25-3; (2-Butyl-3-benzofuranyl)(4-(2-(diethylamino)ethoxy)-3,5-diidophenyl)methanone; Amiodarone; CHEBI:2663; AIDS-114337; nchembio732-comp1; 2-Butyl-3-(3,5-diiodo-4-(beta-diethylaminoethoxy)benzoyl)benzofuran; KBio3_001800; KBio2_003309; Prestwick1_000409; Prestwick0_000409; Bio1_000026; KBio1_000079; Spectrum3_001050; Amiodarone (USAN); EINECS 217-772-1; KBioSS_000294; Amjodaronum; Amiodaronum [INN-Latin]; BRN 1271711; Spectrum2_001813; KBio2_002862; L 3428; KBio3_000587; KBio3_000588; CAS-19774-82-4; Amiodarona; NCI60_041885; SPBio_001825; AIDS114337; SPBio_002277; Spectrum4_001190; C06823; Lopac-A-8423; KBioGR_001859; 2-Butyl-3-benzofuranyl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketone; CBiol_001740; 19774-82-4; Spectrum_000261; Cordarone; Amiodarona [INN-Spanish]; KBioGR_000294; D02910; 51087 N HCl; KBio2_000294; Ketone, 2-butyl-3-benzofuranyl 4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl, hydrochloride; Uro-Septra; 2-Butyl-3-benzofuranyl p-((2-diethylamino)ethoxy)-m,m-diiodophenyl ketone; (2-butyl-1-benzofuran-3-yl){4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl}methanone; Bio2_000774; Cordarone (TN); 2-Butyl-3-(3,5-diiodo-4-(2-diethylaminoethoxy)benzoyl)benzofuran; Methanone, (2-butyl-3-benzofuranyl)(4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl)-; Methanone, (2-butyl-3-benzofuranyl) [4-[2-(diethylamino)ethoxy]-3, 5-diiodophenyl]-, hydrochloride; 2-n-Butyl-3',5'-diiodo-4'-N-diethylaminoethoxy-3-benzoylbenzofuran; Amiodarone [USAN:BAN:INN]; DivK1c_000079; KBio2_005877; Bio1_000515; NSC85442; KBio2_000741; Bio1_001004; 5-18-02-00353 (Beilstein Handbook Reference); Methanone, (2-butyl-3-benzofuranyl)[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]-; NCGC00015096-02; Methanone, (2-butyl-3-benzofuranyl)[4-[2-(diethylamino)ethoxy]-3, 5-diiodophenyl]-, hydrochloride; KBio2_005430; NCGC00015096-01; KBioSS_000741; Bio2_000294; Amiodarone hydrochloride show less «

DrugBank

Identification

Name:	Amiodarone
Name (isomeric):	DB01118
Drug Type:	small molecule
Description:	An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance.
Synonyms:	Amiodarona [INN-Spanish]; Amiodarone Base; Amiodaronum [INN-Latin]; Amiodarone HCL; Amiodarone Hydrochloride
Brand:	Aratac, Labaz, Amio-Aqueous IV, Aminodarone, Cordarone Intravenous, Cordarone, Amiodarons, pms-Amiodarone, Pacerone, Arycor
Category:	Vasodilator Agents, Enzyme Inhibitors, Anti-Arrhythmia Agents
CAS number:	1951-25-3

Pharmacology

Indication:	Intravenously, for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia in patients refractory to other therapy. Orally, for the treatment of life-threatening recurrent ventricular arrhythmias such as recurrent ventricular fibrillation and recurrent hemodynamically unstable ventricular tachycardia.
Pharmacology:	Amiodarone belongs to a class of drugs called Vaughan-Williams Class III antiarrhythmic agents. It is used in the treatment of a wide range of cardiac tachyarhthmias, including both ventricular and supraventricular (atrial) arrhythmias. After intravenous administration in man, amiodarone relaxes vascular smooth muscle, reduces peripheral vascular r... show more » Amiodarone belongs to a class of drugs called Vaughan-Williams Class III antiarrhythmic agents. It is used in the treatment of a wide range of cardiac tachyarhthmias, including both ventricular and supraventricular (atrial) arrhythmias. After intravenous administration in man, amiodarone relaxes vascular smooth muscle, reduces peripheral vascular resistance (afterload), and slightly increases cardiac index. Amiodarone prolongs phase 3 of the cardiac action potential. It has numerous other effects however, including actions that are similar to those of antiarrhythmic classes Ia, II, and IV. Amiodarone shows beta blocker-like and calcium channel blocker-like actions on the SA and AV nodes, increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects. show less «
Mechanism of Action:	The antiarrhythmic effect of amiodarone may be due to at least two major actions. It prolongs the myocardial cell-action potential (phase 3) duration and refractory period and acts as a noncompetitive a- and b-adrenergic inhibitor.
Absorption:	Slow and variable (about 20 to 55% of an oral dose is absorbed).
Protein binding:	>96%
Biotransformation:	Amiodarone is extensively metabolized in the liver via CYP2C8 (under 1% unchanged in urine), and can effect the metabolism of numerous other drugs. The major metabolite of amiodarone is desethylamiodarone (DEA), which also has antiarrhythmic properties. The metabolism of amiodarone is inhibited by grapefruit juice, leading to elevated serum levels of amiodarone.
Route of elimination:	Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion and there is negligible excretion of amiodarone or DEA in urine.
Half Life:	58 days (range 15-142 days)
Clearance:	90-158 mL/h/kg [Healthy with a single dose IV (5 mg/kg over 15 min)] 100 mL/h/kg [Normal subjects > 65 yrs] 150 mL/h/kg [younger subjects] 220 and 440 mL/h/kg [patients with VT and VF]
Toxicity:	Intravenous, mouse: LD₅₀ = 178 mg/kg. Some side effects have a significant mortality rate: specifically, hepatitis, exacerbation of asthma and congestive failure, and pneumonitis.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Grapefruit and grapefruit juice should be avoided throughout treatment.

Grapefruit can significantly increase serum levels of this product.

Take without regard to meals.

Drug interaction:

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Erythromycin	Increased risk of cardiotoxicity and arrhythmias
Tipranavir	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Amiodarone. Concomitant therapy is contraindicated.
Levofloxacin	Increased risk of cardiotoxicity and arrhythmias
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Erythromycin	Increased risk of cardiotoxicity and arrhythmias
Tipranavir	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Amiodarone. Concomitant therapy is contraindicated.
Levofloxacin	Increased risk of cardiotoxicity and arrhythmias
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias
Colesevelam	Bile Acid Sequestrants may decrease the bioavailability of Amiodarone. Consider alternative antilipemic agent. The risk of subtherapeutic amiodarone serum concentrations when such is being used for the treatment of malignant arrhythmias can be very large. The effect (ie, reduced risk) of separating doses of these agents is unknown. Amiodarone should be administered at least 1 hour before or 4 hours after colesevelam.1 Similar dosing with other agents seems warranted.
Cyclosporine	Amiodarone may increase the therapeutic and adverse effects of cyclosporine.
Digoxin	Amiodarone may increase the effect of digoxin.
Fosamprenavir	The protease inhibitor, fosamprenavir, may increase the effect and toxicity of amiodarone.
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Topotecan	The p-glycoprotein inhibitor, Amiodarone, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Tizanidine	Amiodarone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Rifampin	Rifampin decreases the effect of amiodarone
Acenocoumarol	Amiodarone may increase the anticoagulant effect of acenocoumarol.
Dabigatran etexilate	Amiodarone may increase the serum concentration of dabigatran etexilate, resulting in increased risk of bleeding. Consider modifying therapy.
Ranolazine	Possible additive effect on QT prolongation
Simvastatin	Increased risk of rhabdomyolysis
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
Clarithromycin	Increased risk of cardiotoxicity and arrhythmias
Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Atomoxetine	The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Mephenytoin	Increases the effect of hydantoin
Quinidine barbiturate	Increases the effect of qiunidine
Amprenavir	The protease inhibitor, amprenavir, may increase the effect and toxicity of amiodarone.
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Moxifloxacin	Increased risk of cardiotoxicity and arrhythmias
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Quinidine	Amiodarone may increase the effect of quinidine.
Trazodone	The CYP3A4 inhibitor, Amiodarone, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Amiodarone is initiated, discontinued or dose changed.
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Gatifloxacin	Increased risk of cardiotoxicity and arrhythmias
Tolterodine	Amiodarone may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Tramadol	Amiodarone may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Amiodarone may decrease the effect of Tramadol by decreasing active metabolite production.
Procainamide	Amiodarone may increase serum levels and toxicity of procainamide.
Warfarin	Amiodarone may increase the anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if amiodarone is initiated, discontinued or dose changed.
Tamsulosin	Amiodarone, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Amiodarone is initiated, discontinued, or dose changed.
Atazanavir	Increased risk of cardiotoxicity and arrhythmias.
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Verapamil	Additive bradycardic effects may occur. One case report of sinus arrest has been reported. Monitor for changes in the therapeutic effect and signs of Verapamil toxicity if Amiodarone is initiated, discontinued or dose changed.
Tamoxifen	Amiodarone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Flecainide	Amiodarone may increase the effect and toxicity of flecainide
Mesoridazine	Increased risk of cardiotoxicity and arrhythmias
Nelfinavir	Nelfinavir may increase the effect and toxicity of amiodarone.
Dicumarol	Amiodarone may increase the anticoagulant effect of dicumarol.
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Iohexol	Increased risk of cardiotoxicity and arrhythmias
Fentanyl	Possible bradycardia, hypotension
Ritonavir	Ritonavir increases the effect and toxicity of amiodarone
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Telithromycin	Telithromycin may reduce clearance of Amiodarone. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Amiodarone if Telithromycin is initiated, discontinued or dose changed.
Phenytoin	Amiodarone may increase the therapeutic and adverse effects of phenytoin.
Indinavir	Indinavir increases the effect and toxicity of amiodarone
Fosphenytoin	Amiodarone may increase the effect of fosphenytoin.
Saquinavir	The protease inhibitor, saquinavir, may increase the effect and toxicity of amiodarone.
Voriconazole	Additive QTc prolongation may occur. Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of amiodarone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of amiodarone if voriconazole is initiated, discontinued or dose changed.
Trimipramine	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Diltiazem	Increased risk of cardiotoxicity and arrhythmias
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Anisindione	Amiodarone may increase the anticoagulant effect of anisindione.
Vardenafil	Increased risk of cardiotoxicity and arrhythmias
Ethotoin	Increases the effect of hydantoin
Dihydroquinidine barbiturate	Increases the effect of quinidine

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Targets

Potassium voltage-gated channel subfamily H member 2

Beta-1 adrenergic receptor

Voltage-dependent T-type calcium channel subunit alpha-1H

Voltage-dependent calcium channel subunit alpha-2/delta-2

Enzymes

Transporters

Multidrug resistance protein 1