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Amiodarone Hydrochloride

Pronunciation

Class: Class III Antiarrhythmics
VA Class: CV300
Chemical Name: (2-Butyl-3-benzafuranyl)[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]-methanone hydrochloride
Molecular Formula: C25H29I2NO3•HCl
CAS Number: 19774-82-4
Brands: Cordarone, Pacerone

Introduction

Class III antiarrhythmic agent;1 2 4 5 8 12 17 18 21 24 25 26 28 31 38 355 also exhibits activity in each of the 4 Vaughn-Williams antiarrhythmic classes, including some class I (membrane-stabilizing) antiarrhythmic action.5 7 8 21 25 32 35 44 46 355 364

Uses for Amiodarone Hydrochloride

Ventricular Arrhythmias

Treatment to suppress or prevent the recurrence of documented life-threatening ventricular arrhythmias (e.g., recurrent VF; recurrent, hemodynamically unstable VT) that do not respond to documented adequate dosages of other currently available antiarrhythmic agents or when alternative antiarrhythmic agents are not tolerated.1 3 355 364

Used during cardiac arrest for treatment of refractory (i.e., unresponsive to CPR, defibrillation, and a vasopressor [e.g., epinephrine]) VF or pulseless VT.500 501 Considered the preferred antiarrhythmic drug for this use in current ACLS guidelines in adults; lidocaine may be used as an alternative.500 501 In pediatric patients, current evidence supports use of either amiodarone or lidocaine.502

Also may be used for treatment of wide-complex tachycardias during periarrest period; included in current ACLS guidelines for both adult and pediatric tachycardia.500 501 503

Treatment of sustained monomorphic VT not associated with angina, pulmonary edema, or hypotension,364 442 or hemodynamically stable monomorphic VT.501

Treatment of polymorphic (irregular) VT associated with myocardial ischemia in the absence of QT interval prolongation.501

Has been used for primary prevention of sustained VT (i.e., VT lasting >30 seconds and/or associated with hemodynamic compromise),364 VF, or sudden cardiac death in patients with nonsustained ventricular arrhythmia following MI.344 368 370 384 394

Has been used in a limited number of patients for life-threatening ventricular arrhythmias associated with post-infarction aneurysm or with chronic myocarditis induced by Chagas’ disease.26 72 172

Supraventricular Tachyarrhythmias

Used for suppression and prevention of various supraventricular tachycardias (SVTs).3 4 5 9 10 12 25 26 27 35 62 66 71 72 92 109 110 111 113 116 119 120 122 125 126 402 501 701

Because of higher risk of toxicity and proarrhythmic effects, antiarrhythmic agents generally reserved for patients who do not respond to or cannot be treated with AV nodal blocking agents (β-adrenergic blocking agents, diltiazem, verapamil).501 700

Some experts state amiodarone may be useful when ventricular rate control is needed but AV nodal blocking agents are contraindicated (e.g., patients with preexcited atrial arrhythmias associated with an accessory pathway).501 701

May be effective for conversion of atrial fibrillation to normal sinus rhythm (i.e., rhythm control); however, other antiarrhythmic agents (e.g., flecainide, dofetilide, propafenone, ibutilide) are preferred.701

Used to maintain sinus rhythm in patients with atrial fibrillation or flutter.4 5 9 10 12 25 26 27 35 62 66 71 72 92 109 110 111 113 116 119 120 122 700 701

Termination of paroxysmal supraventricular tachycardia (PSVT), including atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT) (e.g., Wolff-Parkinson-White syndrome); generally reserved for use when other therapies are ineffective or contraindicated.9 38 48 501 700 Avoid IV use in patients with Wolff-Parkinson-White syndrome who have preexcited atrial fibrillation; may accelerate ventricular rate and potentially cause life-threatening ventricular arrhythmias.701

Also used for long-term prevention of PSVT,4 5 8 9 25 26 27 28 29 37 39 41 47 48 66 71 72 109 110 112 113 122 128 318 including those refractory to other antiarrhythmic agents.5 26 27 39 66 71 110 113 122 128 318

Has been used in the treatment of atrial tachycardia.700

Has been effective in the prevention of supraventricular arrhythmias associated with bradycardia-tachycardia syndrome.4 9 25 110 129 130 131

Angina

Has been used in treatment of chronic stable angina pectoris and Prinzmetal variant angina; because of potential toxicity, generally not considered a first-line agent but may have beneficial antianginal effect in patients receiving the drug for the management of arrhythmias.17 50 133 134 229

Hypertrophic Cardiomyopathy

Has been used in the management of ventricular and supraventricular arrhythmias associated with hypertrophic cardiomyopathy.25 258 259 278 292

Amiodarone Hydrochloride Dosage and Administration

General

  • Administer lowest effective dosage to minimize the risk and occurrence of adverse effects.1

  • Adjust dosage carefully according to individual requirements and response and the general condition and cardiovascular status of the patient.1 355 Adjustment of maintenance dosage is difficult due to variable absorption and elimination of amiodarone; dosage reduction or temporary withdrawal or discontinuance of the drug may be required.1 284

  • When dosage adjustment is necessary, close monitoring for an extended period of time is recommended.1 355

  • Clinical and ECG monitoring of cardiac function, including appropriate ambulatory ECG monitoring (e.g., Holter monitoring) and/or programmed electrical stimulation (PES), as appropriate, is recommended.1

  • Monitor plasma amiodarone concentrations if patient does not respond or experiences unexpectedly severe toxicity.1 2 3 5 25 35 62 63 64 70 71 75 81

  • When initiating therapy in patients receiving other antiarrhythmic agents, attempt to gradually discontinue the other antiarrhythmic agents.1 (See Antiarrhythmic Agents under Interactions.)

Administration

Administer orally or by IV infusion.1 3 9 10 25 35 355

Also has been administered via intraosseous (IO) injection during cardiac resuscitation.501

Oral Administration

Usually administered once daily.1 3 Administer in divided doses (e.g., twice daily) with meals when dosages ≥1 g daily are administered (e.g., during the loading-dose phase of therapy) or when intolerable adverse GI effects occur.1 3

Administer in a consistent manner relative to food intake.1

Administration of a loading-dose phase of therapy is required for the management of life-threatening ventricular arrhythmias;1 2 3 5 23 25 35 42 59 64 68 72 73 administer oral loading dose in hospital setting and monitor closely until risk of recurrent VT or VF has abated.1 35

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

IV therapy may be used for acute antiarrhythmic therapy until cardiac rhythm is stabilized and oral therapy can be initiated.355 IV therapy may be required for 48–96 hours, but may be administered safely for longer periods.355 Experience with IV administration of amiodarone exceeding 3 weeks is limited.355

Administer in 3-phase sequence: rapid loading phase, slow loading phase, and maintenance infusion phase.355

Dilute amiodarone hydrochloride concentrate prior to administration by IV infusion.355

Administer solutions containing an amiodarone hydrochloride concentration >2 mg/mL via central venous catheter.355

Use in-line filter.355

Amiodarone hydrochloride infusions exceeding 2 hours should be administered in 5% dextrose in glass or polyolefin containers (see Solution Compatibility under Stability).355 Manufacturer recommends using PVC tubing (used in clinical studies).355 Leaching of plasticizer diethylhexylphthalate (DEHP) from IV tubing may occur.355 (See Pediatric Use under Cautions and see Compatibility under Stability.)

Dilution

For the first rapid loading infusion or for supplemental infusions, add 3 mL of amiodarone hydrochloride concentrate to 100 mL of 5% dextrose, resulting in a final concentration of 1.5 mg/mL.355

For the slow loading infusion and maintenance infusion, add 18 mL of amiodarone hydrochloride concentrate to 500 mL of 5% dextrose, resulting in a final concentration of 1.8 mg/mL.355 For subsequent maintenance infusions, solutions containing a final amiodarone hydrochloride concentration of 1–6 mg/mL may be used.355

Rate of Administration

For treatment of ventricular arrhythmias in adults, 15 mg/minute for 10 minutes (rapid loading phase), then 1 mg/minute for 6 hours (slow loading phase), then 0.5 mg/minute (initial maintenance phase) for 18 hours;355 infuse supplemental doses of 150 mg over 10 minutes (at a rate of 15 mg/minute).355 364 Initial (rapid) loading infusion rate should not exceed 30 mg/minute.355 364 397 Monitor initial rate of infusion closely; do not exceed recommended rate.355 (See Hypotension under Cautions.)

Use volumetric infusion pump.355 Do not use drop-counter infusion sets; may result in underdosage.355

Dosage

Available as amiodarone hydrochloride; dosage expressed in terms of the salt.1 355

Pediatric Patients

Ventricular Arrhythmias
Oral

Pediatric dosage has not been established; dosage may vary considerably.201 280 281 Some clinicians have recommended loading dosages of 10–15 mg/kg daily40 242 or 600–800 mg/1.73 m2 daily9 69 189 242 for approximately 4–14 days40 69 189 242 and/or until adequate control of cardiac arrhythmias is achieved or adverse effects become prominent.40 242 Subsequently, reduce dosage to 5 mg/kg daily40 242 or 200–400 mg/1.73 m2 daily9 69 189 242 for several weeks; if possible, reduce dosage to the lowest effective level.69 189 242

Children <1 year of age may require higher oral loading and maintenance dosages than older children when dosage is calculated on the basis of body weight, but not on the basis of body surface area.280 282

Pediatric Resuscitation
IV or IO

Refractory VF or pulseless VT: 5 mg/kg as a rapid bolus.502 503 May repeat twice up to 15 mg/kg (maximum single dose of 300 mg).502 503

To minimize pediatric exposure to DEHP,408 may infuse a loading dose of 5 mg/kg given in 5 divided doses of 1 mg/kg (each dose infused over 5–10 minutes).416

Wide-complex Tachycardias in Patients Not in Cardiac Arrest
IV

5 mg/kg over 20–60 minutes (depending on urgency).503

To minimize pediatric exposure to DEHP,408 may infuse a loading dose of 5 mg/kg given in 5 divided doses of 1 mg/kg (each dose infused over 5–10 minutes).416

Supraventricular Arrhythmias
Oral

Pediatric dosage has not been established; dosage may vary considerably.201 280 281 Some clinicians have recommended loading dosages of 10–15 mg/kg daily40 242 or 600–800 mg/1.73m2 daily9 69 189 242 for approximately 4–14 days40 69 189 242 and/or until adequate control of cardiac arrhythmias is achieved or adverse effects become prominent.40 242 Subsequently, reduce dosage to 5 mg/kg daily40 242 or 200–400 mg/1.73 m2 daily9 69 189 242 for several weeks; if possible, reduce dosage to the lowest effective level.69 189 242

Children <1 year of age may require higher oral loading and maintenance dosages than older children when dosage is calculated on the basis of body weight, but not on the basis of body surface area.280 282

IV

5 mg/kg over 20–60 minutes depending on urgency.503

To minimize pediatric exposure to DEHP,408 may infuse a loading dose of 5 mg/kg given in 5 divided doses of 1 mg/kg (each dose infused over 5–10 minutes).416

Adults

Ventricular Arrhythmias
Oral
Table 1. Oral Loading and Maintenance Dosages

Loading Dose

800–1600 mg daily for 1–3 weeks or until initial therapeutic response occurs1

Dosage Adjustment

When adequate control of ventricular arrhythmias is achieved or adverse effects become prominent, decrease dosage to 600–800 mg daily for about 1 month1 3 284

Maintenance Dosage

400–600 mg daily;1 3 284 if possible, cautiously reduce dosage to 200 mg daily70 284

Consult published protocols for specific information about oral loading doses >1600 mg daily35 64 73 301 or IV loading-dose regimens 64 250 followed by oral therapy.301 If an IV loading-dose regimen is used, initiate oral therapy as soon as possible after an adequate response is obtained and gradually eliminate IV amiodarone.301

IV

Total initial dosage during first 24 hours is approximately 1000 mg.355

Table 2. IV Dosage Over First 24 Hours

Loading Phase

Initial rapid loading phase: 150 mg administered at rate of 15 mg/minute (i.e., over 10 minutes) 355 364

Followed by slow loading phase: 360 mg administered at rate of 1 mg/minute (i.e., over 6 hours)355 364 397

Maintenance Phase

First maintenance phase: 540 mg administered at rate of 0.5 mg/minute (i.e., over 18 hours)355 364 397

Table 3. IV Dosage After First 24 Hours

Maintenance Phase

0.5 mg/minute (i.e., 720 mg over 24 hours); can be administered for 2–3 weeks 355

Breakthrough Episodes of VF or Hemodynamically Unstable VT

Supplemental infusion of 150 mg administered at rate of 15 mg/minute (i.e., over 10 minutes)355

IV/Oral

When switching from IV to oral therapy, oral dosage depends on dose and duration of IV therapy, as well as bioavailability of oral drug.355 When switching from IV to oral therapy, clinical monitoring is recommended, particularly for geriatric patients.355

Assuming 720-mg/day infusion (0.5 mg/minute)

IV amiodarone not intended for maintenance treatment

Table 4. Switching to Oral Therapy Following IV Therapy355

Duration of IV Therapy

Initial Oral Daily Dosage

<1 week

800–1600 mg

1–3 weeks

600–800 mg

>3 weeks

400 mg

ACLS
IV or IO

Refractory VF or pulseless VT: 300 mg by rapid IV/IO injection; may consider an additional dose of 150 mg.500 501

Supraventricular Arrhythmias
IV

For acute treatment of SVT, 150 mg over 10 minutes.700 Follow with 1 mg/minute for 6 hours, then 0.5 mg/minute for remaining 18 hours or initiate oral dosing.700

Oral

For ongoing management of SVT, some experts recommend 400–600 mg daily (in divided doses) in adults for approximately 2–4 weeks, followed by a maintenance dosage of 100–200 mg daily.700

Consult published protocols for specific information about oral loading-dose regimens using higher dosages.

Atrial Fibrillation
IV

When used for rate control in patients with atrial fibrillation, some experts recommend an initial IV dose of 300 mg over 1 hour, followed by 10–50 mg/hr over 24 hours.701

Oral

Usual maintenance dose is 100–200 mg daily.701

Long-term Management of Recurrent Atrial Fibrillation
Oral

Initially, 10 mg/kg daily for 14 days, followed by 300 mg daily for 4 weeks, and then 200 mg daily.402

Prescribing Limits

Pediatric Patients

Ventricular Arrhythmias
IV

Maximum single dose: 300 mg,502 503 up to a total dose of 15 mg/kg.h 502 503

Adults

Ventricular Arrhythmias
IV

Mean daily doses >2.1 g are associated with an increased risk of hypotension.355

Limited experience with IV administration of amiodarone for >3 weeks.355

Special Populations

Hepatic Impairment

Dosage reduction recommended in patients with substantial hepatic impairment.35 283 284

Renal Impairment

Routine dosage reduction not required.1 35

Geriatric Patients

Select dosage with caution, usually starting at low end of dosage range, because of possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy; however, dosage requirements generally similar in geriatric and younger adults.1 355

Use caution with high dosages due to increased susceptibility to drug-induced bradycardia and conduction disturbances.301

Cautions for Amiodarone Hydrochloride

Contraindications

  • Cardiogenic shock.1 355

  • Severe sinus node dysfunction resulting in marked sinus bradycardia (unless a functioning pacemaker is present).1 355

  • Second- or third-degree AV block (unless a functioning pacemaker is present).1 355 (See Effects on Cardiac Conduction under Cautions.)

  • Bradycardia that has caused syncope (unless a functioning pacemaker is present).1

  • Known hypersensitivity to amiodarone or any ingredient in the formulation, including iodine.1 355

Warnings/Precautions

Warnings

Mortality

Potentially fatal toxicities and severe adverse effects;1 106 355 use principally for documented life-threatening ventricular arrhythmias.1

Amiodarone therapy should be administered only by physicians experienced in the management of life-threatening arrhythmias who have access to laboratory facilities necessary to adequately monitor efficacy and adverse effects, including continuous ECG monitoring and electrophysiologic techniques for evaluating the patient in both ambulatory and hospital settings.1 106 355

Pulmonary Effects

Possible acute-onset (days to weeks) pulmonary injury; findings may include pulmonary infiltrates and/or mass on radiograph, pulmonary alveolar hemorrhage, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, or hypoxia, sometimes leading to respiratory failure and/or death.1 355

Potentially fatal pulmonary toxicity1 3 9 25 136 324 325 326 327 333 338 370 may result from pulmonary interstitial pneumonitis (or alveolitis) or hypersensitivity pneumonitis (see Hypersensitivity Reactions under Cautions).1 325 326 338 339 345 346 Toxicity is usually reversible following discontinuance of the drug (with or without corticosteroid therapy).1 3 75 136 138 139 140 142 272 308 327 329 333 336 337 338 350

Baseline pulmonary function testing (prior to initiating therapy)1 25 325 326 327 328 335 338 and periodic (e.g., every 3–6 months) chest radiographs, clinical evaluation, and pulmonary function testing recommended.1 25 148 284 325 327 338

If hypersensitivity pneumonitis occurs, discontinue amiodarone and initiate corticosteroid therapy.1 350

If interstitial pneumonitis occurs, reduce dosage or discontinue therapy, especially if other acceptable antiarrhythmic therapies are available.1 326 327 328 333 338 Supportive treatment, including mechanical ventilation, may be required.136 140 142

Use with caution, if at all, in patients with preexisting pulmonary disease35 (e.g., chronic obstructive disease,252 reduced pulmonary diffusion capacity35 138 324 ); poorer prognosis if pulmonary toxicity develops in such patients.1

If new respiratory symptoms develop, consider the possibility of amiodarone-induced pulmonary toxicity; 1 136 140 326 327 clinical and radiographic evaluation, as well as scintigraphic and pulmonary function testing (including diffusion capacity), if necessary, are recommended.1 138 151 324 326 327 328 333 336 337 338 Carefully assess respiratory symptoms and rule out other causes of respiratory impairment (e.g., CHF, pulmonary embolism, malignancy, infectious causes) before discontinuing therapy.1 136 138 140 327 328 338

Bronchiolitis obliterans organizing pneumonia (possibly fatal) and pleuritis reported during postmarketing experience.1

Hepatic Effects

Possible liver function test abnormalities;1 3 9 10 25 30 75 83 108 141 153 154 157 158 159 163 355 abnormalities are usually minor,1 25 75 not accompanied by clinical symptoms,1 3 9 10 70 72 75 153 158 159 161 and generally return to normal following dosage reduction or discontinuance of the drug.9 72 75 141 154 159

Rarely, potentially fatal hepatic injury (i.e., clinical hepatitis, cholestatic hepatitis, hepatocellular necrosis, cirrhosis) 1 3 35 155 156 160 162 341 342 355 has occurred.1 3 25 35 155 156 158 160 161 162 163 164 355

Monitor serum hepatic enzyme concentrations at regular intervals.1 153 157 160 164 355 Reduce oral dosage, decrease IV infusion rate, or discontinue therapy if enzyme concentrations are >3 times normal values in patients with normal pretreatment values or twice baseline pretreatment values in patients with elevated pretreatment values or if hepatomegaly or progressive hepatic injury occurs.1 156 162 163 164 355

Possible acute centrolobular confluent hepatic necrosis during IV therapy; may be related to a much higher loading dose concentration and more rapid infusion rate than recommended.355 Closely monitor initial concentration and rate of IV infusion; do not exceed recommended initial drug concentration and infusion rate.355 (See Rate of Administration under Dosage and Administration.)

Arrhythmogenic Effects

Possible worsening of existing arrhythmias1 3 9 10 25 35 75 132 141 175 287 355 or occurrence of new arrhythmias.1 35 166 167 168 175 176 355 Arrhythmogenic effects include progression of VT to VF,1 132 355 sustained VT,1 25 141 175 176 355 increased resistance to cardioversion,1 25 122 175 304 atrial fibrillation,355 nodal arrhythmia,355 and atypical VT (torsades de pointes).1 3 9 25 75 132 171 173 265 355

Monitor for QTc prolongation during IV infusion of amiodarone.355

If new signs of arrhythmia appear, consider possibility of hyperthyroidism.1 355 (See Thyroid Effects under Cautions.)

Chronic administration of antiarrhythmic drugs (e.g., amiodarone) in patients with an implanted cardiac device (e.g., defibrillator, pacemaker) may change electrical conduction properties of the heart and potentially affect pacing and/or defibrillating thresholds.1 Therefore, manufacturer recommends assessment to ensure appropriate device parameters before and during amiodarone therapy.1

Electrolyte Abnormalities

Electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia) may increase arrhythmogenic effects (see Arrhythmogenic Effects under Cautions).1 3 41 Evaluate patient for potassium or magnesium deficiency; if present, correct deficiency prior to initiation of therapy.1 249

Monitor electrolyte and acid-base balance in patients with severe or prolonged diarrhea and in patients receiving diuretics concomitantly.45 47 50 355

Effects on Cardiac Conduction

Possible AV, intraventricular,1 3 4 25 26 30 35 355 or SA block;168 SA node dysfunction (e.g., symptomatic sinus bradycardia),1 3 4 9 10 25 26 30 35 50 75 154 169 175 355 393 sinus arrest with suppression of escape foci);1 141 166 167 168 169 or bradycardia (usually associated with IV therapy).355

Administer IV amiodarone in a setting where a temporary pacemaker is available for patients with known predisposition to bradycardia or AV block.355

Ocular Effects

Optic neuropathy1 25 153 154 184 185 186 187 355 and/or optic neuritis may occur at any time during amiodarone therapy; usually results in visual impairment1 294 311 355 357 and may progress to permanent blindness.1 355 357

Baseline and routine (e.g., after the first 6 months and then annually and/or as necessary) ophthalmologic examinations recommended, including slit-lamp and funduscopic tests.1 25 31 355 431

Careful monitoring recommended for patients experiencing visual disturbances or those receiving long-term therapy.1 186 188 If visual impairment occurs (e.g., changes in visual acuity, decreases in peripheral vision), prompt ophthalmologic examination recommended.1 355 357

If optic neuropathy and/or optic neuritis develops, reevaluate therapy; consider risks and complications against the possible benefits of antiarrhythmic therapy.1 355

Thyroid Effects

Thyroid nodules or thyroid cancer reported during postmarketing experience, sometimes accompanied by hyperthyroidism.1 355

Possible altered thyroid function test results:1 4 9 10 25 35 83 153 154 230 231 232 233 234 235 236 237 238 239 240 253 355 374 385 increased serum thyroxine (T4) and reverse triiodothyronine (rT3) concentrations, decreased serum T3 concentrations.1 4 9 10 25 35 83 153 230 231 232 233 234 235 237 253 283 355 393

Possible hypothyroidism or hyperthyroidism.1 3 4 9 10 25 26 70 83 153 154 230 231 233 234 235 236 237 238 239 240 253 370 374 355 393 Amiodarone-induced hyperthyroidism may result in thyrotoxicosis and/or arrhythmia breakthrough or aggravation; fatalities have occurred.1 355

Thyroid function tests recommended prior to initiating therapy and at periodic intervals (approximately every 3–6 months) thereafter,1 25 35 231 234 235 236 237 253 355 particularly in geriatric patients1 283 355 and/or in patients with a history of thyroid nodules, goiter, or other thyroid dysfunction.1 4 234 237 283 355

If hypothyroidism occurs, reduce amiodarone dosage1 25 154 283 355 and/or carefully supplement with thyroid agents if necessary;1 25 72 83 153 154 230 231 235 283 355 374 discontinuance of amiodarone may be required.1 231 283 344 355 368 374

If hyperthyroidism occurs, aggressive therapy (including dosage reduction or discontinuance of amiodarone) is indicated, since clinical manifestations (i.e., cardiac arrhythmias) may be potentially serious and may be fatal.1 72 153 154 230 253 283 344 355 368 374 Antithyroid drugs, adrenergic blockers, and/or temporary corticosteroid therapy may be necessary.1 355 However, antithyroid agents appear to be of limited benefit when used alone, since high intrathyroidal iodine stores (typically observed in patients receiving long-term amiodarone therapy)1 238 239 355 445 antagonize the inhibitory effects of antithyroid drugs on thyroidal iodine utilization.446 Radioactive iodine treatment contraindicated because of low radioiodine uptake in amiodarone-associated hyperthyroidism.1 355 In patients in whom aggressive treatment of amiodarone-induced toxicity has failed or the drug cannot be discontinued because it is the only drug effective against the resistant arrhythmia, thyroidectomy may be an option.1 355 However, experience with surgical management is limited and such treatment could induce thyroid storm; therefore, careful surgical and anesthetic management is required.1 355

Fetal/Neonatal Morbidity

Possible adverse effects on fetal thyroid function and overall development.25 35 89 91 Possible congenital goiter/hypothyroidism and hyperthyroidism.1 330 354 355 Women should avoid becoming pregnant during amiodarone therapy.431 Use during pregnancy only when the potential benefits justify the possible risks to the fetus.1 88 89 355 If amiodarone is used during pregnancy or the patient becomes pregnant while taking the drug, apprise patient of potential hazard to fetus.1 355

Hypotension

Hypotension associated with IV therapy;355 mean daily IV dosages >2.1 g associated with increased risk of hypotension.355 Hypotension may be refractory in some cases, resulting in death.1 355 Monitor initial rate of infusion closely; do not exceed recommended rate. (See Rate of Administration under Dosage and Administration.)355

Hypotension (possibly severe) reported during open-heart surgery (during and/or following cardiopulmonary bypass) in amiodarone-treated patients.1 170 216 267

Arrhythmia Recurrence

Possible recurrence of life-threatening arrhythmias after dosage reduction or discontinuance of therapy; time to recurrence may range from weeks to months.1 Prolonged hospitalization1 35 or intensive ambulatory monitoring (e.g., via telemetric ECG),284 possibly with periodic determination of plasma amiodarone concentrations, may be required.35

Sensitivity Reactions

Hypersensitivity Reactions

Possible hypersensitivity pneumonitis.1 326 330 338 346 If hypersensitivity pneumonitis occurs, initiate corticosteroid therapy and discontinue amiodarone.1 350 Rechallenge may result in more rapid and more severe adverse effects than rechallenge with amiodarone in patients with interstitial pneumonitis.1 (See Pulmonary Effects under Cautions.)

Anaphylactic/anaphylactoid reaction (including shock) and angioedema reported during postmarketing experience.1 355

Dermatologic Reactions

Possible photosensitivity.1 70 72 153 373 Reactions generally begin within 2 hours of exposure to sunlight 9 153 190 195 and last for 1–3 days;190 195 may last a week in severe cases.190 Reactions may occur up to 4 months following discontinuance of the drug.9 140

Possible pigmentary changes (blue-gray discoloration) to exposed areas of the body (e.g., face, hands) in patients receiving long-term therapy,1 3 9 25 30 35 108 153 154 190 191 192 193 196 385 in patients with fair complexions,1 or following excessive exposure to sunlight.1 9 25 35 153 191 193 Usually slowly reversible following discontinuance of the drug.1 191

Sunscreen agents,1 25 35 72 153 190 195 283 protective clothing,1 35 190 195 and avoidance of excessive exposure to sunlight25 35 190 are recommended.1 25 35 190 195

Toxic epidermal necrolysis (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, skin cancer, and pruritus reported during postmarketing experience.1 355

General Precautions

Ocular Effects

Corneal microdeposits occur in almost all patients.1 3 9 25 35 70 72 75 141 153 176 185 186 187 393 Usually not associated with visual disturbances;1 9 35 185 however, halo vision,1 25 70 73 75 141 153 154 175 176 184 187 188 blurred vision,1 3 10 25 154 185 188 photophobia,1 25 75 176 184 187 and dry eyes may occur.1 175 176

Corneal deposits are related to dosage and duration of therapy.9 25 72 153 183 185 186 Reversible following dosage reduction or discontinuance of therapy.1 9 25 56 70 72 153 154 185 186 187 Asymptomatic, nonprogressive deposits do not necessitate dosage reduction or drug discontinuance.1 284

Routine ophthalmologic examinations, including slit-lamp and funduscopic tests, recommended.1 355

Most manufacturers of corneal refractive laser surgery devices consider the procedure to be contraindicated in patients receiving amiodarone.1 355

Nervous System Effects

Possible peripheral neuropathy 1 3 9 25 35 72 75 162 176 177 178 179 180 268 and proximal myopathy.3 9 25 75 153 162 176 177 268

Delirium, hallucination, confusional state, pseudotumor cerebri, disorientation, and parkinsonian symptoms (e.g., akinesia, bradykinesia) reported during postmarketing experience.1

Cardiac Failure

Possible new or worsened heart failure;1 9 25 35 70 75 108 299 355 rarely requires discontinuance of the drug.1

Pulmonary Precautions

Possible ARDS following cardiothoracic or other surgery.1 309 334 355 Closely monitor forced inspiratory oxygen and tissue oxygenation.1 355 Preoperative pulmonary function testing recommended for patients undergoing cardiothoracic surgery.309

Symptomatic Bradycardia in Patients Receiving HCV Treatment

Symptomatic bradycardia, including cases requiring pacemaker intervention, reported in patients receiving amiodarone concomitantly with an HCV treatment regimen containing sofosbuvir in conjunction with another HCV direct-acting antiviral (DAA), including ledipasvir, simeprevir, or daclatasvir.453 454 455 456 457 Fatal cardiac arrest reported in a patient receiving amiodarone concomitantly with fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir).453 454 455 456 457

In most reported cases, bradycardia occurred within hours to days after HCV treatment initiated in patients receiving amiodarone (also has been observed up to 2 weeks after initiation of HCV treatment) and resolved after HCV treatment discontinued.454 455 456 457 Mechanism for this adverse cardiovascular effect unknown.453 454 455 456 457

Patients who may be at increased risk for symptomatic bradycardia if amiodarone used concomitantly with HCV treatment regimen containing sofosbuvir with another DAA include those also receiving a β-adrenergic blocking agent, those with underlying cardiac comorbidities, and/or those with advanced liver disease.454 455 456 457

Concomitant use of amiodarone with HCV treatment regimen containing sofosbuvir with another DAA not recommended.454 455 456 457

If there are no alternative HCV treatment options and regimen of sofosbuvir with another DAA must be used in a patient receiving amiodarone, advise patient about the risk of serious symptomatic bradycardia before initiating HCV treatment.454 455 456 457 Perform cardiac monitoring in an inpatient setting during first 48 hours of concomitant use of amiodarone and regimen of sofosbuvir with another DAA;454 455 456 457 subsequently, perform heart rate monitoring daily (outpatient or self-monitoring) through at least the first 2 weeks of concomitant use.454 455 456 457 Similar cardiac monitoring recommended in patients who discontinued amiodarone just prior to initiation of regimen of sofosbuvir with another DAA or if alternative antiarrhythmic agent cannot be used and amiodarone must be initiated in a patient already receiving regimen of sofosbuvir with another DAA.454 455 456 457

Advise patients receiving amiodarone concomitantly with regimen of sofosbuvir with another DAA to immediately contact a clinician if signs or symptoms of bradycardia (e.g., near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion, memory problems) develop.454 455 456 457

Specific Populations

Pregnancy

Category D.1 128 355 (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Amiodarone and desethylamiodarone are distributed into milk.1 2 78 89 91 355 Discontinue nursing.1 91 355

Pediatric Use

Safety and efficacy not established;1 355 however, amiodarone has been used in children.35 40 69 189 280 281 282 502 503

Large amounts of benzyl alcohol (e.g., 100–400 mg/kg daily) have been associated with toxicity in neonates;355 408 409 410 411 412 413 414 each mL of amiodarone hydrochloride injection contains 20.2 mg of benzyl alcohol.355

Amiodarone hydrochloride injection leaches DEHP plasticizer from IV tubing;355 408 exposure to DEHP may adversely affect male reproductive tract development during fetal, infant, and toddler stages of development.408 415 Consider dosing methods to reduce potential exposure to DEHP (see Pediatric Patients under Dosage and Administration).408

Geriatric Use

Response similar to that in younger adults.1 355

Possible increased susceptibility to bradycardia and conduction disturbances.301

Possible thyroid effects.283 (See Thyroid Effects under Cautions.)

Select dosage with caution, usually starting at low end of dosage range, because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1 355

Hepatic Impairment

Effects of hepatic impairment on amiodarone elimination have not been evaluated;1 2 35 however, amiodarone is extensively metabolized,9 25 76 80 101 probably in the liver.9 35 64 76 81 Consider dosage reduction in patients with substantial hepatic impairment.35 283 284

Renal Impairment

Possible excessive accumulation of iodine and possible resultant thyroid effects.284 314 315

Common Adverse Effects

IV administration: hypotension.355

Oral therapy: adverse nervous system (e.g., malaise and fatigue,1 tremor and/or involuntary movements,1 3 9 10 25 70 75 153 175 178 180 268 lack of coordination,1 abnormal gait and/or ataxia,1 3 9 75 154 175 176 178 180 268 dizziness,1 3 10 paresthesia1 9 10 70 75 175 176 177 178 179 ) and GI (e.g., nausea,1 3 9 25 70 75 141 153 154 175 176 vomiting,1 3 175 constipation,1 9 25 70 75 141 153 154 175 176 anorexia1 3 9 25 70 75 141 153 176 ) effects.

Interactions for Amiodarone Hydrochloride

Metabolized by CYP3A4 and CYP2C8.1 355

Elimination half-life of amiodarone is long and variable; potential for interactions exists with drugs administered after discontinuance of amiodarone therapy.1 35 208 215 355

Drugs, Foods, and Dietary or Herbal Supplements Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions with substrates, inhibitors, or inducers of CYP3A4 are likely.1 355 Inhibits CYP isoenzymes 1A2, 2C9, 2D6, and 3A4;1 355 potential pharmacokinetic interaction with drugs metabolized by these isoenzymes (increased plasma concentrations).1 355 Amiodarone is a substrate for CYP3A4 and CYP2C8; drugs and other substances that inhibit these isoenzymes may decrease metabolism and increase serum concentrations of amiodarone.1 355

Drugs with P-Glycoprotein-Mediated Clearance

Amiodarone inhibits the P-glycoprotein transport system, which may result in unexpectedly high plasma concentrations of drugs that are substrates for this transport system.1 355

Drugs Affecting QT Interval

Potential pharmacodynamic interaction (additive effects on the QTc interval).1 355 433

Antiarrhythmic Agents

Cautious use and close monitoring for possible adverse effects recommended if amiodarone is used concomitantly with other antiarrhythmic agents,1 355 particularly class IA antiarrhythmic agents.207 228 255 264 265 266

Reserve concomitant use for the management of life-threatening arrhythmias unresponsive to monotherapy.1 355

In general, reduce dosage of other antiarrhythmic agent(s) by 30–50% several days after initiating amiodarone therapy;1 355 assess necessity of continuing the other antiarrhythmic agent(s) after antiarrhythmic effect of amiodarone has been established.1 355

In patients already receiving amiodarone, reduce initial dosage of other antiarrhythmic agent(s) by approximately 50%.1 355

Specific Drugs, Foods, and Dietary or Herbal Supplements

Drug, Food, or Supplement

Interaction

Comments

Agalsidase beta

Theoretical risk of inhibited intracellular α-galactosidase activity439

Some clinicians recommend avoidance of concurrent use of biosynthetic forms of α-galactosidase and amiodarone439

Anesthetics, general

Potential serious cardiovascular (e.g., hypotension) and cardiac (e.g., sinus bradyarrhythmias, AV block) effects1 167 170 216 267

Close perioperative monitoring is recommended1 355

Anticoagulants, oral

Decreased warfarin clearance; 203 204 207 208 316 increased PT in almost all patients.1 203 208 210 301 316 355 390

Can result in serious or fatal hemorrhage1 203 204 207 208 209 211 212 214 316 355

Reduce anticoagulant dosage by 33–50% when initiating amiodarone1 204 207 209 214 283 355

Frequent PT determinations and close observation for adverse effects recommended; adjust anticoagulant dosage as necessary1 203 204 207 209 316 390 355

PT may not return to normal for 1–4 months following discontinuance of amiodarone203 204 207 209 210 316 390

Azole antifungals

Additive effects in prolonging QTc interval; serious cardiac arrhythmias (e.g., torsades de pointes) reported1 355 432

Assess risks versus benefits1 355

β-adrenergic blocking agents (e.g., propranolol)

Possible potentiation of sinus bradycardia, sinus arrest, and AV block1 25 263 355

Concomitant therapy may be considered in patients with severe sinus bradycardia or sinus arrest following insertion of artificial pacemaker;1 355 monitor cardiac function432

Calcium-channel blocking agents (e.g., diltiazem, verapamil)

Possible potentiation of sinus bradycardia, sinus arrest, and AV block1 35 256 301 355

Concomitant therapy may be considered in patients with severe sinus bradycardia or sinus arrest following insertion of artificial pacemaker1 355

Cardiac glycosides

Increased serum digoxin concentrations and digoxin toxicity1 9 25 35 203 204 207 217 218 219 220 221 222 223 301 355

When initiating amiodarone therapy, reassess need for continued cardiac glycoside therapy; discontinue digoxin or reduce digoxin dosage by 50%1 25 35 207 217 223 355

Monitor serum digoxin concentrations carefully and reduce digoxin dosage as necessary1 9 35 204 218 219 222 223 355 432

Close observation for signs of cardiac glycoside toxicity recommended 1 9 204 218 355

Monitor thyroid function carefully due to potential for altered cardiac glycoside sensitivity in patients with amiodarone-induced changes in thyroid function218 224 225

Cholestyramine

Decreased plasma amiodarone concentrations and half-life1 203 262 355

Cimetidine

Increased plasma amiodarone concentrations1 355

Cisapride (no longer commercially available in the US)

Additive effects in prolonging QTc interval; serious cardiac arrhythmias (e.g., torsades de pointes) reported432

Concurrent use contraindicated432

Clopidogrel

Potential interaction resulting in ineffective inhibition of platelet aggregation by clopidogrel1 355

Cyclosporine

Increased plasma cyclosporine concentrations resulting in elevated serum creatinine concentrations1 355

Dextromethorphan

Possible inhibition of dextromethorphan metabolism with prolonged administration (>2 weeks) of oral amiodarone1 355

Disopyramide

Additive effects in prolonging QTc interval; possible serious cardiac arrhythmias (e.g., torsades de pointes)1 355

Dolasetron

Possible additive effects in prolonging QTc interval432 438

Use concomitantly with caution; monitor cardiac function432 438

Fentanyl

Possible hypotension, bradycardia, and decreased cardiac output1 355

Flecainide

Decreased flecainide clearance226

Reduce flecainide dosage by 30–50% several days after initiating amiodarone therapy1 226 355

Monitor patient and plasma flecainide concentrations closely; adjust flecainide dosage as necessary1 226 320 355

Fluoroquinolone anti-infectives (e.g., ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin)

Additive effects in prolonging QTc interval; possible serious cardiac arrhythmias (e.g., torsades de pointes)1 355 432

Avoid concomitant use 366 432 434 435 436

Grapefruit juice

Increased amiodarone concentrations.1 355

Avoid concomitant use.1 355

Halofantrine (no longer commercially available in the US)

Additive effects in prolonging QTc interval; possible serious cardiac arrhythmias (e.g., torsades de pointes)444

Avoid concomitant use444

HCV antivirals

Regimen containing sofosbuvir with another DAA (e.g., ledipasvir, simeprevir, daclatasvir): May result in serious symptomatic bradycardia (mechanism unknown);453 454 455 456 457 effect on plasma concentrations of the drugs is unknown454 455 456 457

Simeprevir-containing regimen that does not include sofosbuvir: Modestly increased plasma concentrations of oral amiodarone due to intestinal CYP3A4 inhibition by simeprevir456

Fixed combination of ombitasvir, paritaprevir, and ritonavir (ombitasvir/paritaprevir/ritonavir) with dasabuvir: Increased plasma concentrations of amiodarone458

Regimen containing sofosbuvir with another DAA: Concomitant use not recommended;454 455 456 457 if concomitant use necessary, patient counseling and cardiac monitoring required454 455 456 457 (see Symptomatic Bradycardia in Patients Receiving HCV Treatment under Cautions)

Simeprevir-containing regimen that does not include sofosbuvir: Use concomitantly with caution;456 amiodarone therapeutic drug monitoring recommended, if available456

Ombitasvir/paritaprevir/ritonavir with dasabuvir: Use concomitantly with caution;458 amiodarone therapeutic drug monitoring recommended, if available458

HIV protease inhibitors

HIV protease inhibitors used with low-dose ritonavir (ritonavir-boosted) or without low-dose ritonavir (unboosted): Possible increased plasma concentrations of amiodarone and the HIV protease inhibitor1 200 355

Ritonavir-boosted saquinavir or ritonavir-boosted tipranavir: Concomitant use not recommended200

Other ritonavir-boosted HIV protease inhibitors or unboosted HIV protease inhibitors: Use concomitantly with caution;200 monitor for amiodarone toxicity;200 consider monitoring ECG and amiodarone plasma concentrations200

HMG-CoA reductase inhibitors (statins)

Increased risk of myopathy and/or rhabdomyolysis, particularly when used with higher dosages of certain statins (e.g., simvastatin)1 355 371 417 448 449 450 451

Reduce dosage of lovastatin (to ≤40 mg daily) or simvastatin (to ≤20 mg daily) during concomitant therapy with amiodarone371 417 448

Lidocaine

Increased serum lidocaine concentrations; potential increase in adverse effects (e.g., sinus bradycardia, seizures)1 355

Loratadine

Additive effects in prolonging QTc interval; serious cardiac arrhythmias (e.g., torsades de pointes)1 355

Macrolide antibiotics

Additive effects in prolonging QTc interval; serious cardiac arrhythmias (e.g., torsades de pointes)1 355

Assess risks versus benefits1 355

Methotrexate

Possible inhibition of methotrexate metabolism with prolonged administration (>2 weeks) of oral amiodarone1 355

Phenytoin

Increased serum phenytoin concentrations;1 203 205 206 355 possible phenytoin toxicity (e.g., nystagmus, ataxia, lethargy)1 203 205 206

Possible decreased plasma amiodarone concentrations1 355

Monitor serum phenytoin concentrations and closely observe patient for signs of phenytoin toxicity; reduce phenytoin dosage as necessary1 205

Pimozide

Additive effects in prolonging QTc interval; possible serious cardiac arrhythmias (e.g., torsades de pointes)433

Concomitant use contraindicated433

Procainamide

Increased plasma procainamide and N-acetylprocainamide (NAPA) concentrations;1 203 227 possible increases in QTc and QRS intervals and acceleration of ventricular tachycardia313

Reduce procainamide dosage by 20–33% when amiodarone therapy is initiated or discontinue procainamide therapy1 227 313 355

Quinidine

Increased serum quinidine concentrations;1 35 227 228 355 possible marked QT prolongation and torsades de pointes207 228 264

Reduce quinidine dosage by 33–50% when amiodarone therapy is initiated or discontinue quinidine therapy1 227 355

Monitor serum quinidine concentrations carefully and reduce quinidine dosage as necessary; observe patient closely for signs of toxicity, including QT prolongation1 227 228 355

Rifampin

Decreased plasma amiodarone and desethylamiodarone concentrations1 355

St. John’s wort (Hypericum perforatum)

Potential decrease in amiodarone concentrations1 355

Trazodone

Additive effects in prolonging QTc interval; serious cardiac arrhythmias (e.g., torsades de pointes)1 355

Ziprasidone

Possible additive effects in prolonging QTc interval; possible serious cardiac arrhythmias (e.g., torsades de pointes)437

Avoid concomitant use437

Amiodarone Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Slowly1 2 10 25 35 40 49 55 58 59 61 62 65 78 79 80 81 99 and variably absorbed from the GI tract following oral administration;1 2 5 25 26 35 49 55 56 58 59 60 61 62 65 70 76 77 78 79 80 81 99 absolute bioavailability averages 50%1 25 55 58 59 60 61 78 79 80 355 (range: 22–86%).2 3 25 55 58 59 60 78 99 Considerable interindividual variation in plasma concentrations attained with a given dosage.1 5 56 60 70 75 Following oral administration, peak plasma concentrations usually occur within 3–7 hours.1 2 10 25 35 55 58 59 60 61 62 64 65 73 78 79 80 81 99

Onset

Following oral administration, onset of antiarrhythmic activity is highly variable;1 2 3 23 25 42 59 64 68 72 however, a therapeutic response generally is not evident until 1–3 weeks after beginning therapy, even when loading doses are administered.1 2 3 5 23 25 42 59 64 68 72

Duration

Antiarrhythmic effects generally persist for 10–150 days following withdrawal of long-term therapy;1 2 3 4 5 23 24 26 49 56 59 67 72 79 duration of antiarrhythmic activity is variable and unpredictable1 and appears to depend on length of therapy2 26 and type of arrhythmia.5 23

Food

Food increases rate and extent of absorption.1 283

Distribution

Extent

Following chronic oral administration, amiodarone and N-desethylamiodarone are distributed extensively into many body tissues and fluids.1 2 10 25 35 55 56 62 78 81 84 86 94 98 99 290 Tissue concentrations generally exceed concurrent plasma concentrations of the drug.2 10 35 55 62 78 82 84 85 After long-term therapy, concentrations of the metabolite usually are substantially higher than concentrations of unchanged drug in almost all tissues, except adipose tissue.2 5 35 55 78 81 82 84 86 99

Following IV administration, amiodarone is rapidly and widely distributed.85

Amiodarone and N-desethylamiodarone cross the placenta to a limited extent.1 2 78 88 89 91 355 Amiodarone and N-desethylamiodarone are distributed into milk.1 2 78 89 91 355

Plasma Protein Binding

Approximately 96%.1 2 87 90 355

Elimination

Metabolism

Extensively metabolized,9 25 76 80 101 probably in the liver9 35 64 76 81 and possibly in the intestinal lumen and/or GI mucosa,35 64 76 to at least one major metabolite,1 2 25 35 76 77 78 81 96 101 355 N-desethylamiodarone. This metabolite appears to possess substantial electrophysiologic and antiarrhythmic activity similar to amiodarone’s.1 86 99 100 101 273 285 355

Elimination Route

Excreted almost completely in feces as unchanged drug and N-desethylamiodarone, presumably via biliary elimination.1 3 9 25 35 59 77 78 80 95 98 355

Half-life

Half-life of amiodarone appears to be substantially more prolonged following multiple rather than single doses.2 4 9 26 55 58 59 64 65 78 81 99 291

Following a single IV dose, the terminal elimination phase half-life of amiodarone averages 25 days (range 9–47 days);2 5 55 355 elimination half-life of N-desethylamiodarone equals or exceeds that of amiodarone.355

Following chronic oral administration, amiodarone has an initial elimination half-life of about 2.5–10 days, followed by a terminal elimination half-life averaging 53 days;1 55 elimination half-life of N-desethylamiodarone averages 57–61 days.1 25 55 93 97 99 101

Clearance may be more rapid in pediatric patients.2 9 40 69

Clearance may be decreased in geriatric patients (>65 years of age).355

Stability

Storage

Oral

Tablets

Tightly sealed containers at 20–25°C; protect from light.1 443 The manufacturer of one commercially available amiodarone tablet preparation (Pacerone) states the tablets may be exposed to 15–30°C.443

Parenteral

Injection Concentrate

20–25°C; protect from light and excessive heat.355 Store ampuls in carton to protect from light until used.355 Light protection not necessary during administration.355 c

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Do not use evacuated glass containers for amiodarone hydrochloride infusions (incompatibility with a buffer in the container may cause precipitation).c Polysorbate 80, a component of IV amiodarone injection, can cause leaching of diethylhexyl phthalate (DEHP) from IV tubing, including PVC tubing; leaching increases at lower than recommended flow rates and at higher than recommended infusion concentrations.355

Solution Compatibilityc

Manufacturer states physically compatible in PVC container with amiodarone loss of <10% at 2 hours at room temperature and physically compatible in polyolefin or glass container with no amiodarone loss at 24 hours at room temperature.c

Compatible

Dextrose 5% in water

Variable

Sodium chloride 0.9%

Drug Compatibility
Admixture Compatibilityc

Compatible

Dobutamine HCl

Lidocaine HCl

Potassium chloride

Procainamide HCl

Verapamil HCl

Variable

Furosemide

Quinidine gluconate

Y-Site Compatibility c

Compatible

Amikacin sulfate

Amphotericin B

Atracurium besylate

Atropine sulfate

Calcium chloride

Calcium gluconate

Caspofungin acetate

Ceftaroline fosamil

Ceftriaxone sodium

Cefuroxime sodium

Ciprofloxacin

Clindamycin phosphate

Dexmedetomidine HCl

Dobutamine HCl

Dopamine HCl

Doripenem

Doxycycline hyclate

Epinephrine HCl

Eptifibatide

Erythromycin lactobionate

Esmolol HCl

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Fluconazole

Gentamicin sulfate

Hetastarch in lactated electrolyte injection (Hextend)

Insulin, regular

Isoproterenol HCl

Labetalol HCl

Lepirudin

Lidocaine HCl

Lorazepam

Methylprednisolone sodium succinate

Metoprolol tartrate

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nesiritide

Nitroglycerin

Norepinephrine bitartrate

Penicillin G potassium

Phentolamine mesylate

Phenylephrine HCl

Potassium chloride

Procainamide HCl

Tirofiban HCl

Tobramycin sulfate

Vancomycin HCl

Vasopressin

Vecuronium bromide

Incompatible

Aminophylline

Ampicillin sodium-sulbactam sodium

Argatroban

Bivalirudin

Ceftazidime

Digoxin

Heparin sodium

Imipenem-cilastatin sodium

Micafungin sodium

Piperacillin sodium-tazobactam

Potassium phosphates

Sodium bicarbonate

Sodium phosphates

Variable

Cefazolin sodium

Furosemide

Magnesium sulfate

Sodium nitroprusside

Actions

  • Exhibits greater efficacy and a lower incidence of proarrhythmic effects than class I or other class III antiarrhythmic drugs. 406 407

  • Delays repolarization by prolonging the action potential duration and effective refractory period in cardiac tissue.1 2 3 4 5 6 7 12 13 17 18 19 21 22 25 26 38 355

  • Inhibits transmembrane influx of extracellular sodium ions via fast sodium channels.5 13 32 35 44 355 Combines with fast sodium channels in their inactive state and inhibits recovery after repolarization in a time- and voltage-dependent manner.21 25 32 35 44 46

  • Noncompetitively inhibits α- and β-adrenergic responses to sympathetic stimulation and catecholamine administration.1 3 4 5 6 9 10 11 13 14 15 16 19 21 24 25 34 35 51

  • Depresses sinus node function1 3 4 5 6 9 10 11 14 15 18 20 21 25 26 28 29 30 33 34 35 39 49 50 and automaticity.1 5 6 9 25

  • Relaxes cardiac and vascular smooth muscle, thereby dilating both systemic and coronary arteries.1 3 4 9 10 13 14 17 35 53 54

  • Inhibits extrathyroidal deiodinases,231 237 269 resulting in decreased peripheral conversion of thyroxine (T4) to triiodothyronine (T3).1 4 9 25 35 83 154 231 232 233 234 235 237 253 269 298 355

  • Contains 37.3% iodine; each 200-mg tablet or each mL of the injection contains approximately 75 or 18.7 mg of iodine, respectively.1 2 13 355

  • Inhibits phospholipase (e.g., phospholipase A1, A2, and C)150 270 activity in vitro;35 150 157 270 326 339 production of amiodarone-phospholipid complexes within certain organs may be involved in the development of adverse effects.9 25 35 150 156 157 158 159 161 162 163 164 177 179 183 185 186 187 191 192 193 196 270

  • Inhibits α-galactosidase activity.439

Advice to Patients

  • Importance of patients taking medication exactly as prescribed.431 Importance of not taking a double dose to make up for a missed dose but instead taking the next scheduled dose.431

  • Importance of not interrupting or discontinuing therapy without consulting a clinician, even if improvement is evident, as condition may worsen.431

  • Importance of seeking medical attention immediately or proceeding to a hospital emergency department if too many oral doses are ingested.431

  • If serious adverse effects occur, importance of informing a clinician before discontinuing the drug.431

  • Importance of patients informing clinician of history of BP abnormalities, lung, liver, or thyroid disorders prior to treatment initiation.431

  • Importance of clinicians informing patients of potential toxicities (e.g., lung, liver) that may occur during therapy.355

  • Importance of patients informing clinician of any episodes of shortness of breath, wheezing, coughing, spitting up blood, chest pain, any other breathing disorders, or aggravation of cardiovascular disease.4 431

  • Importance of patients informing clinician of symptoms of thyroid dysfunction such as weakness, weight gain or loss, heat or cold intolerance, hair thinning, sweating, menstrual cycle changes, swelling of the neck (goiter), nervousness, irritability, restlessness, decreased concentration, depression in geriatric patients, or tremor.431

  • Importance of patients contacting their clinician if nausea or vomiting, dark urine, fatigue, yellowing of the skin or whites of eyes, or stomach pain occurs.431

  • Importance of patients contacting their clinician if heart pounding, irregular heart beat, rapid or slow heartbeat, lightheadedness, or faintness occurs.431

  • Importance of patients contacting their clinician if visual disturbances (e.g., blurred vision, visual halos, ocular photosensitivity) occur.431

  • Importance of advising patients that most manufacturers of corneal refractive laser surgery devices consider the procedure to be contraindicated in patients receiving amiodarone.1 355

  • Importance of regular laboratory monitoring (e.g., pulmonary, thyroid, and liver function) and clinical (e.g., cardiac, ophthalmologic) evaluation.1 355

  • Importance of patients informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, dietary supplements and/or herbal products, as well as any concomitant illnesses.1 355

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 355 Importance of avoiding pregnancy during therapy.431

  • Importance of using sunscreen agents1 25 35 72 153 190 195 283 and protective clothing1 35 190 195 431 and of avoiding excessive exposure to sunlight or sun lamps.25 35 190 431

  • Importance of taking amiodarone in a consistent manner relative to food intake.1 431

  • Importance of not consuming grapefruit juice during oral amiodarone therapy.1 355 431

  • Importance of advising patients of other important precautionary information.1 355 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Amiodarone Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

100 mg

Pacerone

Upsher-Smith

200 mg*

Amiodarone Hydrochloride Tablets

Cordarone (scored)

Wyeth

Pacerone (scored)

Upsher-Smith

400 mg*

Amiodarone Hydrochloride Tablets

Pacerone (scored)

Upsher-Smith

Parenteral

Concentrate for injection, for IV infusion

50 mg/mL*

Amiodarone Hydrochloride Injection

AHFS DI Essentials. © Copyright 2017, Selected Revisions November 14, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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