Amiodarone

Amiodarone is used to treat certain types of serious (possibly fatal) irregular heartbeat (such as persistent ventricular fibrillation/tachycardia). It is used to restore normal heart rhythm and maintain a regular, steady heartbeat.

• Amiodarone is known as an anti-arrhythmic drug. It works by blocking certain electrical signals in the heart that can cause an irregular heartbeat.
• Amiodarone is available under the following different brand names: Pacerone, Cordarone, and Nexterone.

Side effects associated with the use of Amiodarone, include the following:

• Increased liver AST or ALT levels
• Low blood pressure (hypotension)
• Dizziness
• Headache
• Feeling unwell (malaise)
• Abnormal gait/problems with coordination
• Fatigue
• Impaired memory
• Involuntary movement
• Sleep disturbances
• Sensitivity to sunlight
• Hypothyroidism
• Constipation
• Loss of appetite
• Congestive heart failure (CHF)
• Slow heart rate
• AV block
• SA node dysfunction
• Hyperthyroidism
• Hepatitis and cirrhosis
• Visual disturbances
• Optic neuritis

Other side effects of amiodarone include:

Postmarketing side effects of amiodarone reported include:

• Corneal microdeposits
• Demyelinating polyneuropathy
• Hypersensitivity: Anaphylactic/anaphylactoid reaction (including shock), skin swelling, hives
• Pulmonary: Eosinophilic pneumonia, acute respiratory distress syndrome/ARDS (in postoperative setting), bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest, and ARDS), bronchiolitis obliterans organizing pneumonia (possibly fatal), fever, shortness of breath, cough, coughing up blood, wheezing, hypoxia, pulmonary infiltrates and/or mass, pulmonary alveolar hemorrhage, pleural effusion, pleuritis
• Gastrointestinal: Hepatitis, cholestatic hepatitis, cirrhosis, pancreatitis, dry mouth
• Nephrology: Renal impairment, renal insufficiency, acute renal failure
• Neurology: Pseudotumor cerebri, parkinsonian symptoms, such as restlessness and slow movement (sometimes reversible with discontinuation of therapy)
• Endocrine: syndrome of inappropriate antidiuretic hormone (SIADH), thyroid nodules/thyroid cancer
• Dermatology: Toxic epidermal necrolysis (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, drug rash with eosinophilia and systemic symptoms (DRESS), eczema, skin cancer, vasculitis, itching, bullous dermatitis
• Hematology: Hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, agranulocytosis, granuloma
• Musculoskeletal: Muscle disease, muscle weakness, muscle wasting, demyelinating polyneuropathy
• Psychiatric: Hallucination, confusion, disorientation, delirium
• Genitourinary: Epididymitis, impotence

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheartedness, or passing out.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosages of Amiodarone:

Dosage Forms and Strengths

Injectable solution

• 50 mg/mL
• 150 mg/100mL (Nexterone)
• 360 mg/200mL (Nexterone)

Conventional IV preparation contains polysorbate 80 and benzyl alcohol

The newer IV formulation (Nexterone) does not contain polysorbate 80 or benzyl alcohol

Tablet

• 100 mg
• 200 mg
• 400 mg

Dosage Considerations – Should be Given as Follows:

Stable Monomorphic or Polymorphic Ventricular Tachycardia (VT) (Off-label)

• 150 mg intravenous (IV) bolus in 10 minutes; may repeat every 10 minutes as necessary, THEN
• 1 mg/min IV for 6 hours, THEN
• 0.5 mg/min IV for 18 hours; not to exceed 2.2 g/24 hours
• For breakthrough episodes of ventricular fibrillation (VF, or V-Fib) or hemodynamically unstable VT, repeat the initial Load
• Dosing considerations
  • Initiate in hospital with experienced personnel

ACLS, Pulseless Ventricular Fibrillation/Ventricular Tachycardia (Off-label)

• 300 mg intravenous (IV) or intraosseous push after dose epinephrine if no initial response to defibrillation
• May follow the initial dose with 150 mg IV every 3-5 minutes
• Dosing considerations
  • Rapid IV push if pulseless/no blood pressure (BP)

Ventricular Arrhythmias

Oral

• Load: 800-1600 mg orally once/day for 1-3 weeks until response; once adequate arrhythmia control is achieved, reduce dose to 600-800 mg/day for 1 month; THEN reduce to a maintenance dose
• Maintenance dose: 400 mg orally once per day

Intravenous (IV)

• 150 mg over the first 10 min (15mg/min), followed by 360 mg over the next 6 hours (1 mg/min), then 540 mg over the remaining 18 hours (0.5 mg/min), for a total of 1000 mg over 24 hours before administering maintenance infusion
• Maintenance: 0.5 mg/min for a total 720 mg/24hr at a concentration of 1-6 mg/mL (360 mg/200mL), or 1.8 mg/mL Nexterone at rate of 278 mL/min
• Duration of therapy: May continue to administer 0.5 mg/min for 2-3 weeks regardless of patient's age, renal function, or ventricular function

Conversion to oral amiodarone after intravenous (IV) administration

• Less than 1 week IV infusion: 800-1600 mg/day
• 1-3 week IV infusion: 600-800 mg/day
• Greater than 3 week IV infusion: 400 mg/day

Pediatric

Drug-Resistant Refractory Cardiac Arrhythmias (Off-label)

Oral

• Age less than 1 year: 600-800 mg/1.73 m² every 24 hours or divided every 12 hours; continue therapy for 4-14 days and/or until adequate control is achieved; if initial treatment is effective, decrease dosage to 200-400 mg/1.73 m² every 24 hours or divided every 12 hours
• Age over 1 year: Until adequate control, 10-15 mg/kg/day orally once/day or divided every 12 hours; if effective, reduce to 5 mg/kg/day orally once/day or divided every 12 hours

Intravenous (IV)

• Loading dose (limited data): 5 mg/kg IV over 30-60 min
• Maintenance dose: 0.005 mg/kg/min IV infusion; may increase to 20 mcg/kg/min per 24 hours; consider converting to oral therapy within 24-48 hours

Pulseless Ventricular Tachycardia or Ventricular Fibrillation (PALS dosing) (Off-label)

• 5 mg/kg intravenous/intraosseous (IV/IO) rapid bolus; not to exceed 300 mg/dose; may repeat twice to a maximum of 15 mg/kg during acute treatment

Supraventricular Tachycardia (Off-label)

• Infants/children/adolescents: 5 mg/kg intravenous (IV) over 1 hour initially; follow with 5 mg/kg/day for 47 hours
• Maintenance: 10-20 mg/kg/day for 7-10 days; follow with 3-20 mg/kg/day

Dosing Considerations, Pediatric

• In a pediatric trial of 61 patients, aged 30 days to 15 years, hypotension (36%), bradycardia (20%), and atrioventricular block (15%) were common dose-related adverse events and were severe or life-threatening in some cases
• Injection site reactions were seen in 5 (25%) of the 20 patients receiving amiodarone HCI injection through a peripheral vein, irrespective of dose regimen
• Conventional IV amiodarone contains the preservative benzyl alcohol; there have been reports of fatal “gasping syndrome” in neonates (children aged less than 1 month) following the administration of IV solutions containing the preservative benzyl alcohol
• Nexterone does not contain benzyl alcohol

Dosing Considerations, Geriatric

• Recommended to start dosing at the lower end of the dosing range because the elderly may be predisposed to toxicity

Dosing Considerations, Susceptible organisms

• Gram-positive cocci, gram-negative bacilli, gram-positive bacilli, gram-negative cocci, anaerobes

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Amiodarone has severe interactions with at least 30 different drugs.
• Amiodarone has serious interactions with at least 131 different drugs.
• Amiodarone has moderate interactions with at least 240 different drugs.
• Amiodarone has mild interactions with at least 46 different drugs.

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns, or for more information about this medicine.

Warnings

• Indicated only for life-threatening arrhythmias:
  • Indicated only for life-threatening arrhythmias because of risk for substantial toxicity; poses major management problems that could be life-threatening in patients at risk of sudden death; therefore, make every effort to utilize alternative agents first
  • The difficulty of using amiodarone effectively and safely poses a significant risk to patients
  • Patients must be hospitalized while an IV loading dose administered; response generally requires at least 1 week
  • Absorption and elimination variable, maintenance dosing difficult, and often requires dosage decrease or temporary discontinuation
  • A retrospective survey of 192 patients with ventricular tachyarrhythmias showed 84 patients required dose reduction and 18 required at least temporary discontinuation (because of adverse reactions); several trials have reported 15-20% overall frequencies of discontinuation because of adverse reactions
  • The time to recurrence of previously controlled life-threatening arrhythmia after discontinuation or dose adjustment is unpredictable (ranges from weeks to months); the patient is at great risk during this transition and may require hospitalization
• Fatal toxicities:
• Fatal toxicities may be caused by pulmonary toxicity, hepatotoxicity, and proarrhythmic effect
• Pulmonary toxicity:
  • Presents as hypersensitivity pneumonitis or interstitial/alveolar pneumonitis (10-17% incidence with 400 mg/day)
  • May present without symptoms as abnormal diffusion capacity in a much higher percentage of patients
  • Fatal in approximately 10% of cases
• Liver injury:
  • Common but usually mild and evidenced only by abnormal liver enzymes
  • Overt liver disease can occur and has been fatal in a few cases
• Proarrhythmic effect:
  • Like other antiarrhythmics, can exacerbate the arrhythmia (e.g., by making the arrhythmia less well tolerated or more difficult to reverse)
  • 2-5% incidence; includes significant heart block or sinus bradycardia
  • Manage arrhythmias in a proper clinical setting
  • Effects are prolonged when they occur because of the long drug half-life
• This medication contains amiodarone. Do not take Pacerone, Cordarone, or Nexterone if you are allergic to amiodarone or any ingredients contained in this drug. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity
• Severe sinus node dysfunction, 2°/3° AV block or bradycardia causing syncope (except with functioning artificial pacemaker), cardiogenic shock
• Avoid during breastfeeding

Effects of Drug Abuse

• No information provided

Short-Term Effects

• Acute-onset (days to weeks) pulmonary injury was reported in patients treated with IV amiodarone; findings have included pulmonary infiltrates and masses on X-ray, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia; some cases have progressed to respiratory failure or death
• See "What Are Side Effects Associated with Using Amiodarone?"

Long-Term Effects

• Peripheral neuropathy is reported rarely with chronic administration; may resolve upon discontinuation of therapy
• See "What Are Side Effects Associated with Using Amiodarone?"

Cautions

• It is to be administered only by physicians experienced in the treatment of life-threatening arrhythmias, who are thoroughly familiar with the risks and benefits of amiodarone therapy, and have access to facilities adequate for monitoring effectiveness and side effects of treatment; because of the long half-life of amiodarone and its metabolite desethylamiodarone, the potential for adverse reactions or interactions, as well as observed adverse effects, can persist following amiodarone withdrawal
• Adjust dosage based on adverse reaction and therapeutic response
• Avoid excessive exposure to sunlight; may cause photosensitivity
• Attempts to substitute other antiarrhythmic agents when amiodarone must be stopped are difficult due to the complex pharmacokinetics of the drug, including prolonged duration of action and half-life and difficulties predicting them, which in turn increases the risk for drug interactions
• Hypothyroidism has been reported in 2 to 10% of patients receiving amiodarone and may be primary or after resolution of preceding amiodarone-induced hyperthyroidism; manage hypothyroidism by reducing the dose of or discontinuing amiodarone and considering the need for thyroid hormone supplement
• Risks of acute myocardial infarction (MI), AV block, cardiomegaly; especially with intravenous (IV) administration
• Bradycardia and atrioventricular block were reported; treat bradycardia by slowing infusion rate or discontinuing therapy; in some patients, inserting a pacemaker is required; treat patients with a known predisposition to bradycardia or AV block in a setting where a temporary pacemaker is available
• Hypotension is the most common adverse reaction; in some cases, hypotension may be refractory and result in a fatal outcome; treat hypotension initially by slowing the infusion; additional standard therapy may include vasopressor drugs, positive inotropic agents, and volume expansion; monitor initial rate of infusion closely, not to exceed the recommended rate
• Chronic administration of antiarrhythmic drugs may affect defibrillation or pacing thresholds in patients with implanted defibrillators, and pacemakers; assess when therapy is initiated and throughout
• Correct hypokalemia, hypomagnesemia, or hypocalcemia before initiating treatment as these disorders can exaggerate the degree of QTc prolongation and increase the potential for TdP; give special attention to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or in patients receiving concomitant diuretics and laxatives, systemic corticosteroids, amphotericin B (IV) or other drugs affecting electrolyte levels
• May increase risks of pulmonary fibrosis; liver disease; hypotension, bradycardia, hyperthyroidism; optic neuropathy; pleural effusion; pneumonitis (including eosinophilic pneumonia)
• Acute-onset (days to weeks) pulmonary injury was reported in patients treated with IV amiodarone; findings have included pulmonary infiltrates and masses on X-ray, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia; some cases have progressed to respiratory failure or death
• Postoperatively, occurrences of adult respiratory distress syndrome were reported in patients receiving amiodarone therapy who have undergone either cardiac or non-cardiac surgery; although patients usually respond well to vigorous respiratory therapy, in rare instances the outcome has been fatal; until further studies are performed, monitor FiO2 and determinants of oxygen delivery to tissues (e.g., SaO2, PaO2) while taking amiodarone
• Use caution when administering concomitantly with drugs that prolong QTc interval
• Corneal microdeposits appear in the majority of adults treated; usually discernible only by slit-lamp examination, but give rise to symptoms such as visual halos or blurred vision in up to 10% of patients; corneal microdeposits are reversible upon reduction of dose or termination of treatment; asymptomatic microdeposits alone are not a reason to reduce the dose or discontinue treatment
• Causes increased INR; use caution when initiating therapy in patients treated with warfarin
• Close perioperative monitoring is recommended in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction effects of halogenated inhalational anesthetics
• Fatal cutaneous reactions reported, including Stevens-Johnson syndrome and toxic epidermal necrolysis; discontinue therapy if symptoms of progressive skin rash occur
• Monitor hepatic enzymes regularly in patients receiving relatively high maintenance doses
• Peripheral neuropathy is reported rarely with chronic administration; may resolve upon discontinuation of therapy
• Bradycardia, some requiring pacemaker insertion reported when ledipasvir/sofosbuvir or sofosbuvir with simeprevir initiated in patients on amiodarone; bradycardia generally occurred within hours to days, but in some cases up to 2 weeks after initiating antiviral treatment; monitor heart rate in patients taking or recently discontinuing amiodarone when starting antiviral treatment
• Drug interaction overview:
  • Serious symptomatic bradycardia when co-administered with ledipasvir/sofosbuvir or with sofosbuvir with simeprevir; postmarketing cases of symptomatic bradycardia, some requiring pacemaker insertion and at least one fatal, have been reported when ledipasvir/sofosbuvir or sofosbuvir with simeprevir were initiated in patients on amiodarone; bradycardia generally occurred within hours to days, but in some cases up to 2 weeks after initiating antiviral treatment and resolved after discontinuation of antiviral treatment; monitor heart rate in patients taking or recently discontinuing amiodarone when starting antiviral treatment
  • Concomitant use of drugs with depressant effects on sinus and AV node (e.g., digoxin, beta-blockers, verapamil, diltiazem, ivabradine, clonidine) can potentiate electrophysiologic and hemodynamic effects of amiodarone, resulting in bradycardia, sinus arrest, and AV block; monitor heart rate in patients on amiodarone and concomitant drugs that slow heart rate

Pregnancy and Lactation

• Amiodarone can cause fetal harm when administered to a pregnant woman
• Fetal exposure may increase the potential for adverse experiences including cardiac, thyroid, neurodevelopmental, neurological, and growth effects in the neonate
• Inform patients of the potential hazard to the fetus if amiodarone is administered during pregnancy or if the patient becomes pregnant while in therapy
• Amiodarone and one of its major metabolites, DEA, are excreted in human milk, suggesting that breastfeeding could expose the nursing infant to a significant dose of the drug
• The risk of exposing an infant to amiodarone and DEA must be weighed against the potential benefit of arrhythmia suppression in the mother
• Advise the mother to discontinue nursing