amiodarone

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/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

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Cardiogenic shock;
Severe sinus node dysfunction;
2nd- and 3rd-degree AV block;
Bradycardia (unless a pacemaker is in place);
Hypersensitivity to amiodarone or iodine;
Lactation: Lactation.

Use Cautiously in:

Thyroid disorders;
Corneal refractive laser surgery;
Severe pulmonary or liver disease;
OB: Should only be used during pregnancy when arrhythmias are refractory to other treatments or when other treatments are contraindicated;
Pedi: Safety and effectiveness not established in children;
Geri: Appears on Beers list. Avoid use as first-line therapy for rhythm control in atrial fibrillation in older adults unless HF or significant left ventricular hypertrophy present.

Adv. Reactions/Side Effects ⬆ ⬇

CV: bradycardia, hypotension, HF, QT interval prolongation, WORSENING OF ARRHYTHMIAS

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

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

Endo: hypothyroidism, hyperthyroidism

GI: anorexia, constipation, nausea, vomiting, ↑liver enzymes, abdominal pain, abnormal sense of taste

GU: ↓libido, epididymitis

Neuro: ataxia, dizziness, fatigue, involuntary movement, malaise, paresthesia, peripheral neuropathy, poor coordination, tremor, confusional states, disorientation, hallucinations, headache, insomnia

Resp: ACUTE RESPIRATORY DISTRESS SYNDROME, PULMONARY FIBROSIS

Interactions ⬆ ⬇

Drug-drug:

↑risk of QT interval prolongation with fluoroquinolones, macrolides, and azole antifungals (undertake concurrent use with caution).
↑levels of digoxin (↓ dose of digoxin by 50%).
↑levels of class I antiarrhythmics (quinidine, mexiletine, lidocaine, or flecainide—↓ doses of other drugs by 30–50%).
↑levels of cyclosporine, dextromethorphan, methotrexate, phenytoin, carvedilol, and theophylline.
Phenytoin↓ amiodarone levels.
↑activity of warfarin (↓ dose of warfarin by 33–50%).
↑risk of bradyarrhythmias, sinus arrest, or AV heart block with beta blockers, verapamil, diltiazem, digoxin, ivabradine, or clonidine.
↑risk of bradycardia when used with sofosbuvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, or sofosbuvir/velpatasvir/voxilaprevir; concurrent use not recommended.
Cholestyramine may ↓ amiodarone levels.
Cimetidine and ritonavir↑ amiodarone levels.
Risk of myocardial depression is ↑ by volatile anesthetics.
↑risk 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; may ↓ levels and effectiveness. Avoid concurrent use.

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 wk, then ↓ 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 ↑. 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, then ↓ 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 wk, then ↓ to 2.5 mg/kg/day (200 mg/1.72 m²/day) or lowest effective maintenance dose.

Availability ⬆ ⬇

(Generic available)

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)
Solution for injection: 50 mg/mL
Tablets: 100 mg; 200 mg; 400 mg

Assessment ⬆ ⬇

Monitor ECG continuously during IV therapy or initiation of oral therapy. Monitor heart rate and rhythm throughout therapy; PR prolongation, slight QRS widening, and T-wave amplitude reduction with T-wave widening and bifurcation may occur. QT prolongation may be associated with worsening of arrhythmias; monitor 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 pacing and defibrillation threshold in patients with pacemakers and implanted defibrillators at beginning and periodically during therapy.
- 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 during therapy. Report dyspnea, tachypnea, or rales/crackles promptly. Bilateral, diffuse pulmonary infiltrates are seen on chest x-ray.
- Monitor BP frequently. Hypotension usually occurs during first several hrs 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 mo 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 every 6 mo during therapy. Drug 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 ↑ in ANA titer concentrations.
- Monitor serum potassium, calcium, and magnesium prior to starting and periodically during therapy. Hypokalemia, hypocalcemia, and/or hypomagnesemia may ↓ effectiveness or cause additional arrhythmias; correct levels before beginning therapy. Monitor closely when converting from IV to oral therapy, especially in geriatric patients.

Implementation ⬆ ⬇

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 clinicians experienced in treating life-threatening arrhythmias.
Do not confuse amiodarone with amantadine.
PO: May be administered with meals and in divided doses if GI intolerance occurs or if daily dose exceeds 1000 mg.

IV Administration:

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.
Intermittent Infusion: Diluent: Dilute 150 mg of amiodarone in 100 mL of D5W. Infusion stable for 2 hr in PVC bag, or use pre-mixed bags.Concentration: 1.5 mg/mL.
Diluent: Dilute 900 mg (18 mL) of amiodarone in 500 mL of D5W. Infusion stable for 24 hr in glass or polyolefin bottle.Concentration: 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.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take amiodarone as directed. If a dose is missed, do not take at all. Consult health care professional if more than two doses are missed. Advise patient to read the Medication Guide prior to first dose and with each Rx refill in case of changes.
Advise patient to avoid drinking grapefruit juice during therapy.
Inform patient that side effects may not appear until several days, weeks, or yr after initiation of therapy and may persist for several mo 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 mo after therapy. If photosensitivity occurs, dose 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 mo. Notify health care professional if this occurs.
Instruct male patients to notify health care professional if signs and symptoms of epididymitis (pain and swelling in scrotum) occur. May require reduction in dose.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
Instruct patient to notify health care professional of medication regimen before treatment or surgery.
Advise patient to notify health care professional if signs and symptoms of thyroid dysfunction occur.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception and to avoid breastfeeding during therapy. May cause neonatal bradycardia, QT prolongation, periodic ventricular extrasystoles; neonatal hypothyroidism (with or without goiter) detected antenatally or in the newborn and reported even after a few days of exposure; neonatal hyperthyroxinemia; neurodevelopmental abnormalities independent of thyroid function, including speech delay and difficulties with written language and arithmetic, delayed motor development, and ataxia; jerk nystagmus with synchronous head titubation; fetal growth retardation; and premature birth. Advise patient to notify health care professional if pregnancy is planned or suspected.
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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇