Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Monoisotopic mass
645.023680639
InChI
InChI=1S/C25H29I2NO3/c1-4-7-11-22-23(18-10-8-9-12-21(18)31-22)24(29)17-15-19(26)25(20(27)16-17)30-14-13-28(5-2)6-3/h8-10,12,15-16H,4-7,11,13-14H2,1-3H3
InChI Key
InChIKey=IYIKLHRQXLHMJQ-UHFFFAOYSA-N
IUPAC Name
(2-{4-[(2-butyl-1-benzofuran-3-yl)carbonyl]-2,6-diiodophenoxy}ethyl)diethylamine
Traditional IUPAC Name
amiodarone
SMILES
CCCCC1=C(C(=O)C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)C2=CC=CC=C2O1
pKa (Strongest Basic)
8.47
Refractivity
145.05 m3·mol-1
Dược Lực Học :
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.
Cơ Chế Tác Dụng :
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. [PubChem]
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.
Dược Động Học :
▧ Absorption :
Slow and variable (about 20 to 55% of an oral dose is absorbed).
▧ Protein binding :
>96%
▧ Metabolism :
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]
Độc Tính :
Intravenous, mouse: LD50 = 178 mg/kg. Some side effects have a significant mortality rate: specifically, hepatitis, exacerbation of asthma and congestive failure, and pneumonitis.
Chỉ Định :
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.
Tương Tác Thuốc :
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Acenocoumarol
Amiodarone may increase the anticoagulant effect of acenocoumarol.
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Alvimopan
Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
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Amprenavir
The protease inhibitor, amprenavir, may increase the effect and toxicity of amiodarone.
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Anisindione
Amiodarone may increase the anticoagulant effect of anisindione.
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Artemether
Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
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Atazanavir
Increased risk of cardiotoxicity and arrhythmias.
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Atomoxetine
The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
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Cisapride
Increased risk of cardiotoxicity and arrhythmias
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Clarithromycin
Increased risk of cardiotoxicity and arrhythmias
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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.
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Cyclosporine
Amiodarone may increase the therapeutic and adverse effects of cyclosporine.
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Dabigatran etexilate
Amiodarone may increase the serum concentration of dabigatran etexilate, resulting in increased risk of bleeding. Consider modifying therapy.
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Dicoumarol
Amiodarone may increase the anticoagulant effect of dicumarol.
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Digoxin
Amiodarone may increase the effect of digoxin.
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Dihydroquinidine barbiturate
Increases the effect of quinidine
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Diltiazem
Increased risk of cardiotoxicity and arrhythmias
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Eltrombopag
Affects hepatic enzyme CYP2C9/10 metabolism, increases effect/level of eltrombopag.
-
Erythromycin
Increased risk of cardiotoxicity and arrhythmias
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Ethotoin
Increases the effect of hydantoin
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Etravirine
Amiodarone, when used concomitantly with etravirine, may decrease in serum concentration. If possible, monitoring for decreased amiodarone levels is recommended.
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Etravirine
Amiodarone, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. If possible, monitoring of amiodarone levels is recommended.
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Fentanyl
Possible bradycardia, hypotension
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Fingolimod
Pharmacodynamic synergist. Contraindicated. Increased risk of bradycardia, AV block, and torsade de pointes.
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Flecainide
Amiodarone may increase the effect and toxicity of flecainide
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Fosamprenavir
The protease inhibitor, fosamprenavir, may increase the effect and toxicity of amiodarone.
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Fosphenytoin
Amiodarone may increase the effect of fosphenytoin.
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Gatifloxacin
Increased risk of cardiotoxicity and arrhythmias
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Grepafloxacin
Increased risk of cardiotoxicity and arrhythmias
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Indacaterol
Concomitant therapy with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs that prolong the QTc interval should be monitored closely. These drugs may potentiate the effect of adrenergic agonist on the cardiovascular system.
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Indinavir
Indinavir increases the effect and toxicity of amiodarone
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Iohexol
Increased risk of cardiotoxicity and arrhythmias
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Levofloxacin
Increased risk of cardiotoxicity and arrhythmias
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Lumefantrine
Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
-
Mephenytoin
Increases the effect of hydantoin
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Mesoridazine
Increased risk of cardiotoxicity and arrhythmias
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Moxifloxacin
Increased risk of cardiotoxicity and arrhythmias
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Nelfinavir
Nelfinavir may increase the effect and toxicity of amiodarone.
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Phenytoin
Amiodarone may increase the therapeutic and adverse effects of phenytoin.
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Procainamide
Amiodarone may increase serum levels and toxicity of procainamide.
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Quinidine
Amiodarone may increase the effect of quinidine.
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Quinidine barbiturate
Increases the effect of qiunidine
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Ranolazine
Possible additive effect on QT prolongation
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Rifampicin
Rifampin decreases the effect of amiodarone
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Ritonavir
Ritonavir increases the effect and toxicity of amiodarone
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Roflumilast
Increases roflumilast levels.
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Saquinavir
The protease inhibitor, saquinavir, may increase the effect and toxicity of amiodarone.
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Simvastatin
Increased risk of rhabdomyolysis
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Sparfloxacin
Increased risk of cardiotoxicity and arrhythmias
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Tacrolimus
Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
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Tamoxifen
Amiodarone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
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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.
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Telavancin
Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
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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.
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Terfenadine
Increased risk of cardiotoxicity and arrhythmias
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Thioridazine
Increased risk of cardiotoxicity and arrhythmias
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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.
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Tipranavir
Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Amiodarone. Concomitant therapy is contraindicated.
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Tizanidine
Amiodarone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
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Tolterodine
Amiodarone may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
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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.
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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.
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Tramadol
Amiodarone may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Amiodarone may decrease the effect of Tramadol by decreasing active metabolite production.
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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.
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Trimipramine
Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
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Vardenafil
Increased risk of cardiotoxicity and arrhythmias
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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.
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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.
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Vorinostat
Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
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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.
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Ziprasidone
Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
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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).
Liều Lượng & Cách Dùng :
Liquid - Intravenous
Solution - Intravenous
Tablet - Oral
Dữ Kiện Thương Mại
Nhà Sản Xuất
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Sản phẩm biệt dược : Amio-Aqueous IV
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Sản phẩm biệt dược : Aratac
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Sản phẩm biệt dược : Arycor
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Sản phẩm biệt dược : Atlansil
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Sản phẩm biệt dược : Cordarone
-
Sản phẩm biệt dược : Nexterone
-
Sản phẩm biệt dược : Pacerone
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Sản phẩm biệt dược : Tachyra
Tài Liệu Tham Khảo Thêm
National Drug Code Directory