amiodarone hydrochloride
(a mee o' da rone)
Cordarone, Pacerone

Pregnancy Category D

Drug classes
Antiarrhythmic
Adrenergic blocker (not used as sympatholytic agent)

Therapeutic actions
Type III antiarrhythmic: acts directly on cardiac cell membrane; prolongs repolarization and refractory period; increases ventricular fibrillation threshold; acts on peripheral smooth muscle to decrease peripheral resistance

Indications
· Only for treatment of the following documented life-threatening recurrent ventricular arrhythmias that do not respond to other antiarrhythmics or when alternative agents are not tolerated: recurrent ventricular fibrillation, recurrent hemodynamically unstable ventricular tachycardia. Serious and even fatal toxicity has been reported with this drug; use alternative agents first; very closely monitor patient receiving this drug.
· Unlabeled uses: treatment of refractory sustained or paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia; treatment of symptomatic atrial flutter.

Contraindications and cautions
· Contraindicated with hypersensitivity to amiodarone, sinus node dysfunction, heart block, severe bradycardia, hypokalemia, lactation.
· Use cautiously with thyroid dysfunction, pregnancy.

Available forms
Tablets--200, 400 mg; injection--50 mg/mL

Dosages
Careful patient assessment and evaluation with continual monitoring of cardiac response are necessary for titrating the dosage. Therapy should begin in the hospital with continual monitoring and emergency equipment on standby. The following is a guide to usual dosage.
ADULTS
PO
· Loading dose: 800–1,600 mg/day PO in divided doses, for 1–3 wk; reduce dose to 600–800 mg/day in divided doses for 1 mo; if rhythm is stable, reduce dose to 400 mg/day in one to two divided doses for maintenance dose. Adjust to the lowest possible dose to limit side effects.
IV
1,000 mg IV over 24 hr--150 mg loading dose over 10 min, followed by 360 mg over 6 hr at rate of 1 mg/min; maintenance infusion: 540 mg at 0.5 mg/min over 18 hr. May be continued up to 96 hr or until rhythm is stable. Switch to oral form as soon as possible.
PEDIATRIC PATIENTS
Safety and efficacy not established.

Pharmacokinetics
Route
Onset
Peak
Duration
Oral
2–3 days
3–7 hr
6–8 hr
IV
Immediate
20 min
Infusion


Metabolism: Hepatic; T1/2: 10 days, then 40–55 days
Distribution: Crosses placenta; passes into breast milk
Excretion: Bile and feces

IV facts
Preparation: Do not use PVC container. Dilute 150 mg in 100 mL D5W for rapid loading dose (1.5 mg/mL). Dilute 900 mg in 500 mL D5W for slow infusions (1.8 mg/mL). Store at room temperature and use within 24 hr.
Infusion: Infuse loading dose over 10 min. Immediately follow with slow infusion of 1 mg/min or 33.3 mL/hr. Maintenance infusion of 0.5 mg/min or 16.6 mL/hr can be continued up to 96 hr. Use of an infusion pump is advised.
Incompatibilities: Do not mix with aminophylline, cefamandole, cefazolin, meclocillin, heparin, sodium bicarbonate; do not mix in solution with other drugs.

Adverse effects
· CNS: Malaise, fatigue, dizziness, tremors, ataxia, paresthesias, lack of coordination
· CV: Cardiac arrhythmias, congestive heart failure, cardiac arrest, hypotension
· EENT: Corneal microdeposits (photophobia, dry eyes, halos, blurred vision); ophthalmic abnormalities including permanent blindness
· Endocrine: Hypothyroidism or hyperthyroidism
· GI: Nausea, vomiting, anorexia, constipation, abnormal liver function tests, liver toxicity
· Respiratory: Pulmonary toxicity--pneumonitis, infiltrates (shortness of breath, cough, rales, wheezes)
· Other: Photosensitivity, angioedema

Interactions
Drug-drug
· Increased digitalis toxicity with digoxin
· Increased quinidine toxicity with quinidine
· Increased procainamide toxicity with procainamide
· Increased flecainide toxicity with amiodarone
· Increased phenytoin toxicity with phenytoin, ethotoin, mephenytoin
· Increased bleeding tendencies with warfarin
· Potential sinus arrest and heart block with beta-blockers, calcium channel-blockers
Drug-lab test
· Increased T3 levels, increased serum reverse T3 levels

Nursing considerations
CLINICAL ALERT!
Name confusion has occurred with amrinone (name has now been changed to inamrinone, but confusion may still occur); use caution.

Assessment
· History: Hypersensitivity to amiodarone, sinus node dysfunction, heart block, severe bradycardia, hypokalemia, lactation, thyroid dysfunction, pregnancy
· Physical: Skin color, lesions; reflexes, gait, eye exam; P, BP, auscultation, continuous ECG monitoring; R, adventitious sounds, baseline chest x-ray; liver evaluation; liver function tests, serum electrolytes, T4, and T3

Interventions
· Monitor cardiac rhythm continuously.
· Monitor for an extended period when dosage adjustments are made.
· Monitor for safe and effective serum levels (0.5–2.5 mcg/mL).
· Doses of digoxin, quinidine, procainamide, phenytoin, and warfarin may need to be reduced one-third to one-half when amiodarone is started.
· Give drug with meals to decrease GI problems.
· Arrange for ophthalmologic exams; reevaluate at any sign of optic neuropathy.
· Arrange for periodic chest x-ray to evaluate pulmonary status (every 3–6 mo).
· Arrange for regular periodic blood tests for liver enzymes, thyroid hormone levels.

Teaching points
· Drug dosage will be changed in relation to response of arrhythmias; you will need to be hospitalized during initiation of drug therapy; you will be closely monitored when dosage is changed.
· These side effects may occur: changes in vision (halos, dry eyes, sensitivity to light; wear sunglasses, monitor light exposure); nausea, vomiting, loss of appetite (take with meals; small, frequent meals may help); sensitivity to the sun (use a sunscreen or protective clothing when outdoors); constipation (a laxative may be ordered); tremors, twitching, dizziness, loss of coordination (do not drive, operate dangerous machinery, or undertake tasks that require coordination until drug effects stabilize and your body adjusts to it).
· Have regular medical follow-up, monitoring of cardiac rhythm, chest x-ray, eye exam, blood tests.
· Report unusual bleeding or bruising; fever, chills; intolerance to heat or cold; shortness of breath, difficulty breathing, cough; swelling of ankles or fingers; palpitations; difficulty with vision.

Adverse effects in Italic are most common; those in Bold are life-threatening.