General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation
am-ee-OH-da-rone

Trade Name(s)

• Cordarone

• Pacerone

Pregnancy Category
Category D

Ther. class.
antiarrhythmics
(class III)

Indications

Life-threatening ventricular arrhythmias unresponsive to less toxic agents

Unlabelled Use(s):

• PO: Management of supraventricular tachyarrhythmias

• IV: As part of the Advanced Cardiac Life Support (ACLS) and Pediatric Advanced Life Support (PALS) guidelines for the management of ventricular fibrillation/pulseless ventricular tachycardia after cardiopulmonary resuscitation and defibrillation have failed; also for other life-threatening tachyarrhythmias

Action

• Prolongs action potential and refractory period

• Inhibits adrenergic stimulation

• Slows the sinus rate, increases PR and QT intervals, and decreases peripheral vascular resistance (vasodilation)

Therapeutic Effect(s):
Suppression of arrhythmias

Pharmacokinetics

Absorption: IV administration results in complete bioavailability. Slowly and variably absorbed from the GI tract (35–65%)

Distribution: Distributed to and accumulates slowly in body tissues. Reaches high levels in fat, muscle, liver, lungs, and spleen. Crosses the placenta and enters breast milk

Protein Binding: 96% bound to plasma proteins

Metabolism and Excretion: Metabolized by the liver, excreted into bile. Minimal renal excretion. One metabolite has antiarrhythmic activity

Half-life: 13–107 days

TIME/ACTION PROFILE (suppression of ventricular arrhythmias)

ROUTE	ONSET	PEAK	DURATION
PO	2–3 days (up to 2–3 mos)	3–7 hr	wks–mos
IV	2 hr	3–7 hr	unknown

Contraindication/Precautions

Contraindicated in:

• Patients with cardiogenic shock

• Severe sinus node dysfunction

• 2nd- and 3rd-degree AV block

• Bradycardia (has caused syncope unless a pacemaker is in place)

• Hypersensitivity to amiodarone or iodine

• OB: Can cause fetal hypo- or hyperthyroidism

• Lactation: Enters breast milk and can cause harm to the neonate; use an alternative to breast milk

• Pedi: Safety not established; products containing benzyl alcohol should not be used in neonates

Use Cautiously in:

• History of CHF

• Thyroid disorders

• Corneal refractive laser surgery

• Severe pulmonary or liver disease

• Geri: Appears on Beers list. Potential to affect QT interval and cause torsades de pointes. Initiate therapy at the low end of the dosing range due to decreased hepatic, renal, or cardiac function; comorbid disease; or other drug therapy

Adverse Reactions/Side Effects

CNS: confusional states, disorientation, hallucinations, dizziness, fatigue, malaise, headache, insomnia.

EENT: corneal microdeposits, abnormal sense of smell, dry eyes, optic neuritis, optic neuropathy, photophobia.

Resp: ADULT RESPIRATORY DISTRESS SYNDROME (ARDS), PULMONARY FIBROSIS, PULMONARY TOXICITY.

CV: CHF, WORSENING OF ARRHYTHMIAS, bradycardia, hypotension.

GI: LIVER FUNCTION ABNORMALITIES, anorexia, constipation, nausea, vomiting, abdominal pain, abnormal sense of taste.

GU: decreased libido, epididymitis.

Derm: TOXIC EPIDERMAL NECROLYSIS (RARE), photosensitivity, blue discoloration.

Endo: hypothyroidism, hyperthyroidism.

Neuro: ataxia, involuntary movement, paresthesia, peripheral neuropathy, poor coordination, tremor.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• Increased risk of QT prolongations with fluoroquinolones, macrolides, and azole antifungals (undertake concurrent use with caution)

• blood levels and may lead to toxicity from digoxin ( dose of digoxin by 50%)

• blood levels and may lead to toxicity from other class I antiarrhythmics (quinidine, procainamide, mexiletine, lidocaine, or flecainide — doses of other drugs by 30–50%)

• blood levels of cyclosporine, dextromethorphan, methotrexate, phenytoin, and theophylline

• Phenytoin amiodarone blood levels

• activity of warfarin ( dose of warfarin by 33–50%)

• risk of bradyarrhythmias, sinus arrest, or AV heart block with beta blockers or calcium channel blockers

• Cholestyramine may amiodarone blood levels

• Cimetidine and ritonavir amiodarone blood levels

• Risk of myocardial depression is by volatile anesthetics

Drug-Natural Products
St. John's wort induces enzymes that metabolize amiodarone; may levels and effectiveness. Avoid concurrent use

Drug-Food
Grapefruit juice inhibits enzymes in the GI tract that metabolize amiodarone resulting in levels and risk of toxicity; avoid concurrent use

Route/Dosage

Ventricular Arrhythmias

• PO (Adults): 800–1600 mg/day in 1–2 doses for 1–3 wk, then 600–800 mg/day in 1–2 doses for 1 mo, then 400 mg/day maintenance dose.

• PO (Children): 10 mg/kg/day (800 mg/1.72 m²/day) for 10 days or until response or adverse reaction occurs, then 5 mg/kg/day (400 mg/1.72 m²/day) for several weeks, then decreased to 2.5 mg/kg/day (200 mg/1.72 m²/day) or lowest effective maintenance dose.

• IV (Adults): 150 mg over 10 min, followed by 360 mg over the next 6 hr and then 540 mg over the next 18 hr. Continue infusion at 0.5 mg/min until oral therapy is initiated. If arrhythmia recurs, a small loading infusion of 150 mg over 10 min should be given; in addition, the rate of the maintenance infusion may be increased.
Conversion to initial oral therapy—If duration of IV infusion was <1 wk, oral dose should be 800–1600 mg/day; if IV infusion was 1–3 wk, oral dose should be 600–800 mg/day; if IV infusion was >3 wk, oral dose should be 400 mg/day.
ACLS guidelines for pulseless VFib/VTach—300 mg IV push, may repeat once after 3–5 min with 150 mg IV push (maximum cumulative dose 2.2 g/24 hr; unlabeled).

• IV, Intraosseous (Children and infants):
PALS guidelines for pulseless VFib/VTach5 mg/kg as a bolus;
perfusion tachycardia—5 mg/kg loading dose over 20–60 min (maximum of 15 mg/kg/day; unlabeled).

Supraventricular Tachycardia

• PO (Adults): 600–800 mg/day for 1 wk or until desired response occurs or side effects develop, then decrease to 400 mg/day for 3 wk, then maintenance dose of 200–400 mg/day.

• PO (Children): 10 mg/kg/day (800 mg/1.72 m²/day) for 10 days or until response or side effects occur, then 5 mg/kg/day (400 mg/1.72 m²/day) for several weeks, then decreased to 2.5 mg/kg/day (200 mg/1.72 m²/day) or lowest effective maintenance dose.

Availability

• Tablets: 200 mg, 400 mg

» Cost: 200 mg $235.39/60.

• Injection: 50 mg/ml in 3-, 9-, and 18-ml vials

» Cost: 50 mg $1057.13/10 ampules.

Assessment

• Monitor ECG continuously during IV therapy or initiation of oral therapy. Monitor heart rate and rhythm throughout therapy; PR prolongation, slight QRS widening, T-wave amplitude reduction with T-wave widening and bifurcation, and U waves may occur. QT prolongation may be associated with worsening of arrhythmias and should be monitored closely during IV therapy. Report bradycardia or increase in arrhythmias promptly; patients receiving IV therapy may require slowing rate, discontinuing infusion, or inserting a temporary pacemaker

» Assess for signs of pulmonary toxicity (rales/crackles, decreased breath sounds, pleuritic friction rub, fatigue, dyspnea, cough, wheezing, pleuritic pain, fever, hemoptysis, hypoxia). Chest x-ray and pulmonary function tests are recommended before therapy. Monitor chest x-ray every 3–6 mo during therapy to detect diffuse interstitial changes or alveolar infiltrates. Bronchoscopy or gallium radionuclide scan may also be used for diagnosis. Usually reversible after withdrawal, but fatalities have occurred

IV

• Assess for signs and symptoms of ARDS throughout therapy. Report dyspnea, tachypnea, or rales/crackles promptly. Bilateral, diffuse pulmonary infiltrates are seen on chest x-ray

» Monitor blood pressure frequently. Hypotension usually occurs during first several hours of therapy and is related to rate of infusion. If hypotension occurs, slow rate

PO

• Assess for neurotoxicity (ataxia, proximal muscle weakness, tingling or numbness in fingers or toes, uncontrolled movements, tremors); common during initial therapy, but may occur within 1 wk to several months of initiation of therapy and may persist for more than 1 yr after withdrawal. Dose reduction is recommended. Assist patient during ambulation to prevent falls.

• Ophthalmic exams should be performed before and regularly during therapy and whenever visual changes (photophobia, halos around lights, decreased acuity) occur. May cause permanent loss of vision

• Assess for signs of thyroid dysfunction, especially during initial therapy. Lethargy; weight gain; edema of the hands, feet, and periorbital region; and cool, pale skin suggest hypothyroidism and may require decrease in dose or discontinuation of therapy and thyroid supplementation. Tachycardia; weight loss; nervousness; sensitivity to heat; insomnia; and warm, flushed, moist skin suggest hyperthyroidism and may require discontinuation of therapy and treatment with antithyroid agents

Lab Test Considerations

• Monitor liver and thyroid functions before and periodically throughout therapyDrug effects persist long after discontinuation. Thyroid function abnormalities are common, but clinical thyroid dysfunction is uncommon

» Monitor AST, ALT, and alkaline phosphatase at regular intervals during therapy, especially in patients receiving high maintenance dose. If liver function studies are 3 times normal or double in patients with elevated baseline levels or if hepatomegaly occurs, dose should be reduced

» May cause asymptomatic elevations in ANA titer concentrations

Potential Nursing Diagnoses

• Decreased cardiac output (Indications)

• Impaired gas exchange (Side Effects)

Implementation

• High Alert: IV vasoactive medications are inherently dangerous; fatalities have occurred from medication errors involving amiodarone. Before administering, have second practitioner check original order, dose calculations and infusion pump settings. Patients should be hospitalized and monitored closely during IV therapy and initiation of oral therapy. IV therapy should be administered only by physicians experienced in treating life-threatening arrhythmias. Do not confuse amiodarone with inamrinone, formerly called amrinone

• Hypokalemia and hypomagnesemia may decrease effectiveness or cause additional arrhythmias; correct before therapy

» Monitor closely when converting from IV to oral therapy, especially in geriatric patients

• PO: May be administered with meals and in divided doses if GI intolerance occurs or if daily dose exceeds 1000 mg

IV Adminstration:

• IV:
Administer via volumetric pump; drop size may be reduced, causing altered dosing with drop counter infusion sets
Administer through an in-line filter
Infusions exceeding 2 hr must be administered in glass or polyolefin bottles to prevent adsorption. However, polyvinyl chloride (PVC) tubing must be used during administration because concentrations and infusion rate recommendations have been based on PVC tubing

• Direct IV:
Diluent: Administer undiluted. May also be diluted in 20–30 ml of D5W or 0.9% NaCl.
Concentration: 50 mg/ml

• Rate:
Administer IV push

• Intermittent Infusion:
Diluent: Dilute 150 mg of amiodarone in 100 ml of D5W. Infusion stable for 2 hr in PVC bag.
Concentration: 1.5 mg/ml

• Rate:
Infuse over 10 min. Do not administer IV push

• Continuous Infusion:
Diluent: Dilute 900 mg (18 ml) of amiodarone in 500 ml of D5W. Infusion stable for 24 hr in glass or polyolefin bottle.
Concentration: Solution above: 1.8 mg/ml. Concentration may range from 1–6 mg/ml (concentrations > 2 mg/ml must be administered via central venous catheter)

• Rate:
Infuse at a rate of 1 mg/min for the first 6 hr, then decrease infusion rate to 0.5 mg/min and continue until oral therapy initiated

• Y-Site Compatibility:

» amikacin

» amphotericin B

» atracurium

» atropine

» bumetanide

» calcium chloride

» calcium gluconate

» caspofungin

» ceftizoxime

» ceftriaxone

» cefuroxime

» ciprofloxacin

» clindamycin

» daptomycin

» dexmedetomidine

» diltiazem

» dobutamine

» dopamine

» doxycycline

» epinephrine

» eptifibatide

» erythromycin lactobionate

» esmolol

» famotidine

» fenoldopam

» fentanyl

» fluconazole

» gentamicin

» granisetron

» insulin

» isoproterenol

» labetalol

» lepirudin

» lidocaine

» linezolid

» lorazepam

» methylprednisolone

» metronidazole

» midazolam

» milrinone

» morphine

» nesiritide

» nitroglycerin

» norepinephrine

» palonosetron

» penicillin G potassium

» phenylephrine

» potassium chloride

» procainamide

» quinupristin/dalfopristin

» rifampin

» tacrolimus

» tirofiban

» tobramycin

» vancomycin

» vasopressin

» vecuronium

» voriconazole

• Y-Site Incompatibility:

» aminophylline

» bivalirudin

» ceftazidime

» digoxin

» ertapenem

» heparin

» imipenem-cilastatin

» levofloxacin

» micafungin

» piperacillin/tazobactam

» potassium phosphates

» sodium bicarbonate

• Additive Incompatibility:

» aminophylline

» heparin

» sodium bicarbonate

Patient/Family Teaching

• Instruct patient to take amiodarone as directed. Patient should read the Medication Guide prior to first dose and with each Rx refill. If a dose is missed, do not take at all. Consult health care professional if more than two doses are missed

• Advise patient to avoid drinking grapefruit juice during therapy

• Inform patient that side effects may not appear until several days, weeks, or years after initiation of therapy and may persist for several months after withdrawal

• Teach patients to monitor pulse daily and report abnormalities

• Advise patients that photosensitivity reactions may occur through window glass, thin clothing, and sunscreens. Protective clothing and sunblock are recommended during and for 4 months after therapy. If photosensitivity occurs, dosage reduction may be useful

• Inform patients that bluish discoloration of the face, neck, and arms is a possible side effect of this drug after prolonged use. This is usually reversible and will fade over several months. Notify health care professional if this occurs

• Instruct male patients to notify health care professional if signs of epididymitis (pain and swelling in scrotum) occur. May require reduction in dose

• Instruct patient to notify health care professional of medication regimen before treatment or surgery

• Emphasize the importance of follow-up exams, including chest x-ray and pulmonary function tests every 3–6 mo and ophthalmic exams after 6 mo of therapy, and then annually

Evaluation/Desired Outcomes

Cessation of life-threatening ventricular arrhythmias. Adverse effects may take up to 4 months to resolve

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