amiodarone, Nexterone, Pacerone

 Indications

Life-threatening ventricular arrhythmias unresponsive

to less toxic agents. Unlabeled Use: 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 (VF)/pulseless

ventricular tachycardia (VT) 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 Effects:

Suppression of arrhythmias.

Pharmacokinetics

Absorption: Slowly and variably absorbed from the

GI tract (35–65%). IV administration results in complete

bioavailability.

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 mo)

3–7 hr wk–mos

IV 2 hr 3–7 hr unknown

Contraindications/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: May cause fetal harm (cardiac, thyroid,

neurodevelopmental, neurological, and growth

adverse effects); Lactation: Enters breast milk and can

cause harm to the neonate; avoid breast feeding; Pedi:

Safety not established; products containing benzyl alcohol

should not be used in neonates.

Use Cautiously in: History of HF; Thyroid disorders;

Corneal refractive laser surgery; Severe pulmonary

or liver disease; Geri: Initiate therapy at the low

end of the dosing range due tophepatic, 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: HF,

WORSENING OF ARRHYTHMIAS, QT INTERVAL PROLONGATION,

bradycardia, hypotension. GI: anorexia, constipation,

nausea, vomiting, abdominal pain, abnormal

sense of taste,qliver enzymes. GU:plibido, epididymitis.

Derm: TOXIC EPIDERMAL NECROLYSIS (rare), photosensitivity,

blue discoloration. Endo: hypothyroidism,

hyperthyroidism. Neuro: ataxia, involuntary movement,

paresthesia, peripheral neuropathy, poor coordination,

tremor.

Interactions

Drug-Drug:qrisk of QT prolongation with fluoroquinolones,

macrolides, and azole antifungals

(undertake concurrent use with caution).qlevels of digoxin (pdose of digoxin by 50%).qlevels of class

I antiarrhythmics (quinidine, mexiletine, lidocaine,

or flecainide—pdoses of other drugs by 30–

50%).qlevels of cyclosporine, dextromethorphan,

methotrexate, phenytoin, carvedilol, and theophylline.

Phenytoinpamiodarone levels.qactivity of

warfarin (pdose of warfarin by 33–50%).qrisk of

bradyarrhythmias, sinus arrest, or AV heart block with

beta blockers, verapamil, diltiazem, digoxin, ivabradine,

or clonidine.qrisk of bradycardia when

used with ledipasvir/sofosbuvir or with sofosbuvir

with simeprevir. Cholestyramine maypamiodarone

levels. Cimetidine and ritonavirqamiodarone levels.

Risk of myocardial depression isqby volatile anesthetics.

qrisk of myopathy with lovastatin and simvastatin

(do not exceed 40 mg/day of lovastatin or 20

mg/day of simvastatin).

Drug-Natural Products: St. John’s wort induces

enzymes that metabolize amiodarone; mayplevels and

effectiveness. Avoid concurrent use.

Drug-Food: Grapefruit juice inhibits enzymes in

the GI tract that metabolize amiodarone resulting inq

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, thenpto 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 beq. 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 VF/VT—

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 VF/VT—5 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, thenpto

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) A

for 10 days or until response or side effects occur, then

5 mg/kg/day (400 mg/1.72 m2/day) for several weeks,

thenpto 2.5 mg/kg/day (200 mg/1.72 m2/day) or lowest

effective maintenance dose.

Availability (generic available)

Tablets: 100 mg, 200 mg, 400 mg. Injection: 50 mg/

mL. Premixed infusion (Nexterone): 150 mg/100

mL D5W (does not contain polysorbate 80 or benzyl alcohol),

360 mg/200 mL D5W (does not contain polysorbate

80 or benzyl alcohol).