Trade Names:Cordarone- Tablets 200 mg
Trade Names:Nexterone- Injection 50 mg/mL
Trade Names:Pacerone- Tablets 100 mg- Tablets 200 mg- Tablets 300 mg- Tablets 400 mgAmiodarone Hydrochloride for Injection Sandoz Standard (Canada)Apo-Amiodarone (Canada)Gen-Amiodarone (Canada)Novo-Amiodarone (Canada)PMS-Amiodarone (Canada)ratio-Amiodarone (Canada)Sandoz Amiodarone (Canada)
Prolongs action potential, duration, and refractory period in myocardial cells; acts as noncompetitive inhibitor of alpha- and beta-adrenergic receptors.
Bioavailability is 35% to 65%; T max is 3 to 7 h. Concentrations of 1 to 2.5 mg/L are effective with acceptable toxicity. Food increases rate and extent of absorption.
Vd is about 60 L/kg.Oral/IV
Crosses the placenta; excreted in breast milk. More than 96% protein bound.IV
Rapidly distributed; serum concentrations decline to 10% of peak values within 30 to 45 min after the end of the infusion. Vd is 40 to 84 L/kg (amiodarone) and 68 to 168 L/kg (N-desethyl amiodarone [DEA]).
Metabolized by CYP3A4 to DEA (active).
Eliminated primarily by hepatic excretion into bile; some enterohepatic recirculation may occur; negligible renal excretion. Biphasic elimination with initial 50% reduction in plasma levels after 2.5 to 10 days; terminal t ½ is 26 to 107 days (mean, about 53 days) (oral) and 20 to 47 days (IV). Not dialyzable.
2 to 3 days but more commonly 1 to 3 wk.
Cl is lower and t ½ is increased; monitor closely.Severe left ventricular dysfunction
The t ½ of DEA is prolonged; monitor closely.
Treatment of life-threatening, recurrent ventricular arrhythmias (ie, ventricular fibrillation and hemodynamically unstable ventricular tachycardia) that do not respond to other antiarrhythmic agents. Use only in patients with the indicated life-threatening arrhythmias because use is accompanied by substantial toxicity.Parenteral
Initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia in patients refractory to other therapy; treatment of ventricular tachycardia and fibrillation when oral amiodarone is indicated but patient is unable to take oral medication.
Conversion of atrial fibrillation and maintenance of sinus rhythm; treatment of supraventricular tachycardia; IV amiodarone has been used to treat atrioventricular (AV) nodal reentry tachycardia.
Cardiogenic shock, severe sinus-node dysfunction, causing marked sinus bradycardia; second- or third-degree AV block; when bradycardia produces syncope, unless used with pacemaker; hypersensitivity to the drug, including iodine.Parenteral
Known hypersensitivity to the drug, including iodine; marked sinus bradycardia; second- and third-degree AV block unless functioning pacemaker is available; cardiogenic shock.
PO 800 to 1,600 mg/day for 1 to 3 wk. Reduce doses of other antiarrhythmic agents gradually. When adequate arrhythmia control is achieved, reduce dose to 600 to 800 mg/day for 1 mo.Usual maintenance dose
PO 400 mg/day.Adults
IV Recommended starting dose is approximately 1,000 mg over the first 24 h administered as follows: rapid administration of 150 mg over first 10 min (15 mg/min), followed by 360 mg over next 6 h (1 mg/min), then 540 mg over remaining 18 h (0.5 mg/min). After first 24 h, continue maintenance infusion rate of 0.5 mg/min (720 mg/24 h).IV to Oral TransitionAdults
Clinical monitoring is recommended when changing from IV to oral therapy. PO 800 to 1,600 mg amiodarone if duration of IV infusion less than 1 wk; 600 to 800 mg amiodarone if duration of IV infusion 1 to 3 wk; 400 mg amiodarone if duration of IV infusion more than 3 wk.
Store tablets at controlled room temperature (68° to 77°F for Cordarone ; 59° to 86°F for Pacerone ). Store injection at controlled room temperature (59° to 77°F). Protect from light and excessive heat.
Warfarin PT increased by 100% after 3 to 4 days; reduce dose of anticoagulant by one third to one half.Antihypertensives
Use with caution with beta blockers or calcium channel blockers because of the possible potentiation of bradycardia, sinus arrest, and AV block.Azole antifungals/fluoroquinolones/macrolides
Reports of QTc prolongation with or without torsades de pointes may occur when used concomitantly with amiodarone.Cardiac glycosides (eg, digoxin)
Digoxin levels are increased and may result in toxicity. Reduce digoxin dose by approximately 50% or discontinue.Cholestyramine
Cholestyramine increases enterohepatic elimination of amiodarone and may reduce its serum levels and t ½ .CYP3A4 inducers (eg, rifampin)
Amiodarone and the metabolite, desethylamiodarone, plasma levels may be reduced, decreasing the pharmacologic effect.CYP3A4 inhibitors (eg, cimetidine, ritonavir)
Amiodarone plasma concentrations may be elevated, increasing the pharmacologic and adverse reactions.Fentanyl
In combination with amiodarone may cause hypotension, bradycardia, and decreased cardiac output.Grapefruit juice
Amiodarone plasma concentrations may be elevated, increasing the risk of side effects. Patients taking oral amiodarone should avoid grapefruit juice.HMG-CoA reductase inhibitors (eg, simvastatin)
Simvastatin plasma levels may be elevated, increasing the risk of adverse reactions (eg, myopathy, rhabdomyolysis).Lidocaine
Lidocaine plasma concentrations may be elevated, increasing the risk of seizures.P-glycoprotein and CYP1A2, CYP2C9, CYP2D6, and CYP3A4 (eg, cyclosporine)
Plasma concentrations of drugs metabolized by these CYP enzymes or substrates of P-glycoprotein may be elevated, increasing the risk of side effects.Protease inhibitors (eg, ritonavir)
Amiodarone plasma concentrations may be elevated, increasing the pharmacologic and adverse reactions.St. John's wort
Amiodarone plasma levels may be reduced, decreasing the pharmacologic effects.Trazodone
QT interval prolongation and torsade de pointes have been reported with coadministration.
Cardiac arrhythmias, CHF, SA node dysfunction (1% to 3%); hypotension, sinus arrest (postmarketing).Parenteral
Hypotension (20%); bradycardia (6%); cardiac arrest (4%); CHF, ventricular tachycardia (2%); atrial fibrillation, nodal arrhythmia, prolonged QT interval, sinus bradycardia, ventricular fibrillation (less than 2%); asystole/cardiac arrest/electromechanical dissociation, cardiogenic shock, AV block.
Abnormal gait/ataxia, dizziness, fatigue, lack of coordination, malaise, paresthesias, tremor/abnormal involuntary movement (4% to 9%); decreased libido, headache, insomnia, sleep disturbances (1% to 3%); confusional states, delirium, disorientation, hallucinations, pseudotumor cerebri (postmarketing).
Photosensitivity/Solar dermatitis (4% to 9%); flushing (1% to 3%); erythema multiforme, exfoliative dermatitis, pruritus, skin cancer, Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis (postmarketing).Parenteral
Stevens-Johnson syndrome (less than 2%).
Visual disturbances (4% to 9%); abnormal smell sensation (1% to 3%).
Nausea, vomiting (10% to 33%); anorexia, constipation (4% to 9%); abdominal pain, abnormal salivation, abnormal taste (1% to 3%); pancreatitis (postmarketing).Parenteral
Nausea (4%); diarrhea, vomiting (less than 2%).
Acute renal failure, epididymitis, impotence, renal function impairment, renal insufficiency (postmarketing).Parenteral
Abnormal kidney function (less than 2%).
Coagulation abnormalities (1% to 3%); agranulocytosis, aplastic anemia, hemolytic anemia, neutropenia, pancytopenia, thrombocytopenia (postmarketing).
Abnormal liver function tests (4% to 9%); nonspecific hepatic disorders (1% to 3%); cholestatic hepatitis, cirrhosis, hepatitis (postmarketing).Parenteral
Liver function test abnormalities (4%); increased ALT and AST, thrombocytopenia (less than 2%).
Cellulitis, edema, erythema, necrosis, pain, pigment changes, phlebitis, skin sloughing, thrombophlebitis, venous thrombosis at injection site.
Muscle weakness, myopathy, rhabdomyolysis (postmarketing).
Pulmonary inflammation or fibrosis (4% to 9%); bronchospasm, possibly fatal respiratory disorders (including ARDS, arrest, distress, and failure), bronchiolitis obliterans organizing pneumonia, cough, dyspnea, hemoptysis, hypoxia, pleuritis, pulmonary infiltrates and mass, wheezing (postmarketing).Parenteral
Lung edema, respiratory disorder (less than 2%).
Edema, hyperthyroidism, hypothyroidism (1% to 3%); anaphylactic/anaphylactoid reaction (including shock), angioedema, fever, granuloma, SIADH, thyroid nodules/thyroid cancer (postmarketing).Parenteral
Fever (3%); shock (less than 2%).
Amiodarone is used for life-threatening arrhythmias only.
Potentially fatal pulmonary toxicities include hypersensitivity pneumonitis or interstitial/alveolar pneumonitis. Rates of clinically manifested disease are as high as 10% to 17% in some series of patients with ventricular arrhythmias given doses around 400 mg/day. Fatality rate approximates 10%.
Liver injury may occur and has been fatal in a few cases.
Proarrhythmic effects, significant heart block, or sinus bradycardia has occurred. Patients must be hospitalized during loading dose administration.
Even in patients at high risk of arrhythmic death, in whom toxicity of amiodarone is an acceptable risk, every effort should be made to utilize alternative agents first because of the major management problems posed by amiodarone that could be life-threatening in a population at risk of sudden death.
Because absorption and elimination are variable, maintenance-dose selection is difficult and dosage reduction or discontinuation of treatment is not unusual. The time at which a previously controlled life-threatening arrhythmia will recur after discontinuation or dose adjustment is unpredictable, ranging from weeks to months. Attempts to substitute other antiarrhythmic agents when amiodarone must be stopped will be made difficult by the gradually, but unpredictably, changing amiodarone body burden.
Monitor effectiveness in long-term prevention of ventricular tachycardia and ventricular fibrillation using ambulatory monitoring, programmed electrical stimulation, or a combination of these, as appropriate.Hepatic
Obtain liver enzymes before starting therapy and periodically thereafter during long-term therapy.Ophthalmic
Perform regular ophthalmic exams, including funduscopy and slit-lamp exam, during amiodarone administration.Pulmonary
Obtain baseline chest x-ray and pulmonary function tests, including diffusion capacity. Repeat chest x-ray, history, and physical exam every 3 to 6 mo thereafter.QTc prolongation
Monitor for QTc prolongation during IV infusion of amiodarone.Thyroid
Monitor thyroid function before starting therapy and periodically thereafter, especially in elderly patients and any patient with history of thyroid nodules, goiter, or other thyroid dysfunction.
Category D .
Excreted in breast milk.
Safety and efficacy not established.
Cautiously make dose selection, usually starting at the lower end of the dosing range, reflecting the greater frequency of decreased hepatic and renal function and comorbidity.
Occurs in about 10% of patients.
Has been reported in patients receiving IV amiodarone who have experienced lung injuries from trauma, shock, prolonged cardiopulmonary resuscitation, and aspiration pneumonia. Postoperative occurrences of ARDS have been reported in patients receiving oral amiodarone who have undergone cardiac or noncardiac surgery.
Benzyl alcohol, contained in IV amiodarone products as a preservative, has been associated with fatal gasping syndrome in neonates (children younger than 1 mo of age).
Occurs with IV amiodarone but is not dose related. Treat by slowing infusion rate or discontinuing IV amiodarone; insertion of temporary pacemaker may be required. Treat patients with known predisposition to bradycardia or AV block in setting where temporary pacemaker is available.
Most manufacturers of corneal refractive laser surgery devices contraindicate that procedure in patients taking amiodarone.
Correct any potassium or magnesium deficiency before starting amiodarone therapy.
Avoid grapefruit juice during amiodarone treatment because of risk of increased amiodarone plasma levels and toxicity.
Hypotension is the most common adverse reaction seen with IV amiodarone. Hypotension occurs most often during first several hours of treatment and appears to be related to rate of infusion. Monitor infusion rate closely and do not exceed recommended rates of infusion. Treat hypotensive episodes initially by slowing infusion rate; be prepared to provide additional standard therapy (eg, positive inotropic agents, vasopressor drugs, volume expansion).
Hepatic enzyme elevations occur frequently in patients on oral amiodarone, but most patients are asymptomatic. If liver enzyme increase exceeds 3 × ULN, or doubles in patient with elevated baseline, consider discontinuing amiodarone or reducing the dose. Acute, centrolobular confluent hepatocellular necrosis leading to hepatic coma, acute renal failure, and death have been associated with administration of IV amiodarone at a much higher loading dose concentration and much faster rate of infusion than recommended; monitor initial concentration of IV amiodarone and rate of infusion closely to avoid exceeding recommended doses and infusion rates. Reduce rate of administration or discontinue IV amiodarone if evidence of progressive hepatic injury noted.
Congenital goiter/hypothyroidism and hyperthyroidism have been reported in children exposed in-utero to amiodarone.
Optic neuropathy or neuritis, resulting in visual impairment (in some cases progressing to permanent blindness), has been reported. If symptoms of visual impairment appear, prompt ophthalmic examination is recommended. Appearance of optic neuropathy or neuritis calls for reevaluation of amiodarone therapy. Corneal microdeposits appear in majority of adults and may cause visual halos or blurred vision. Corneal microdeposits are reversible upon dose reduction or termination of treatment.
Rare cases of peripheral neuropathy have been reported during chronic amiodarone administration. Discontinuation of amiodarone results in slow and incomplete resolution of symptoms.
Acute-onset (days to weeks) pulmonary injury (bronchospasm, cough, dyspnea, fever, hemoptysis, hypoxia, pulmonary infiltrates and/or mass on x-ray, wheezing) has been reported. Some cases have progressed to respiratory failure and/or death. Patients with preexisting pulmonary disease have a poorer prognosis if pulmonary toxicity develops. Any new respiratory symptoms should suggest pulmonary toxicity and history, physical exam, chest X-ray, and pulmonary function tests (with diffusion capacity) should be repeated and evaluated. Reduce dose, or preferably withdraw amiodarone, if pulmonary toxicity is suspected
A blue-gray discoloration of exposed skin may occur during long-term treatment. Risk may be increased in patients with fair complexion or those with excessive sun exposure.
Patients on amiodarone and undergoing general surgery may be more sensitive to myocardial depressant and conduction effects of halogenated inhalational anesthetics. Rare occurrences of hypotension upon discontinuation of cardiopulmonary bypass during open-heart surgery in patients receiving amiodarone have been reported.
Can cause hypo- or hyperthyroidism. Arrhythmia breakthroughs may accompany amiodarone-induced hyperthyroidism.
Carefully assess potential risks and benefits of coadministering amiodarone with any drug known to prolong the QTc interval, or when treating patients with thyroid dysfunction, because of the possibility of arrhythmia breakthrough or exacerbation of arrhythmia.
Bradycardia, hypotension, life-threatening cardiac arrhythmias.
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