Version May 2024
Amiodarone is intended for use only in patients with indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity.
Amiodarone can cause pulmonary toxicity (hypersensitivity pneumonitis or interstitial/alveolar pneumonitis) that has resulted in clinically manifest disease at rates as high as 17% in some series of patients. Pulmonary toxicity has been fatal about 10% of the time. Obtain a baseline chest X-ray and pulmonary function tests, including diffusion capacity, when amiodarone therapy is initiated. Repeat history, physical exam, and chest X-ray every 3 to 6 months.
Amiodarone can cause hepatotoxicity, which can be fatal. Obtain baseline and periodic liver transaminases and discontinue or reduce dose if the increase exceeds 3 times normal or doubles in a patient with an elevated baseline. Discontinue amiodarone if the patient experiences signs or symptoms of clinical liver injury.
Amiodarone can exacerbate arrhythmias. Initiate amiodarone in a clinical setting where continuous ECGs and cardiac resuscitation are available.
Supraventricular tachycardia: Limited data available: Oral: Loading dose: 10 to 20 mg/kg/day in 2 divided doses for 7 to 10 days; dosage should then be reduced to 5 to 10 mg/kg/day once daily and continued for 2 to 7 months; dosing based on a study of 50 infants (<9 months of age) and neonates (as young as 1 day of life); Note: Patients who received a higher loading dose (20 mg/kg/day) were more likely to have a prolongation of the corrected QT interval (Ref).
Tachyarrhythmia, including junctional ectopic tachycardia (JET), paroxysmal supraventricular tachycardia (PSVT): Limited data available; the following dosing is based on studies that included neonates, infants, and children.
Loading dose: IV: 5 mg/kg given over 60 minutes; Note: Most studies used bolus infusion time of 60 minutes to avoid hypotension; may repeat initial loading dose to a maximum total initial load: 10 mg/kg; do not exceed total daily bolus of 15 mg/kg/day (Ref).
Continuous IV infusion (if needed): Note: Reported dosing units for regimens are variable (mcg/kg/minute and mg/kg/day); use caution to ensure appropriate dose and dosing units are used; taper infusion as soon as clinically possible and switch to oral therapy if necessary.
Dosing based on mcg/kg/minute: Initial: 5 mcg/kg/minute; increase incrementally as clinically needed; usual required dose: 10 mcg/kg/minute; range: 5 to 15 mcg/kg/minute (Ref).
Dosing based on mg/kg/day: Initial: 10 mg/kg/day; increase incrementally as clinically needed; range: 10 to 20 mg/kg/day (Ref).
Resuscitation after hospital discharge (Pediatric Advanced Life Support [PALS]):
Perfusing tachycardias: Neonates: IV, Intraosseous: Loading dose: 5 mg/kg over 20 to 60 minutes; may repeat twice up to maximum total dose of 15 mg/kg during acute treatment (Ref).
Ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), shock-refractory: Neonates: IV, Intraosseous: 5 mg/kg rapid bolus; may repeat twice up to a maximum total dose of 15 mg/kg during acute treatment (Ref).
Perfusing tachycardias: Infants, Children, and Adolescents: IV, Intraosseous: Loading dose: 5 mg/kg (maximum dose: 300 mg/dose) over 20 to 60 minutes; may repeat twice up to maximum total dose of 15 mg/kg during acute treatment (Ref).
Ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), shock-refractory: Infants, Children, and Adolescents: IV, Intraosseous: 5 mg/kg (maximum dose: 300 mg/dose) rapid bolus; may repeat twice up to a maximum total dose of 15 mg/kg during acute treatment (Ref).
Tachyarrhythmia, including junctional ectopic tachycardia (JET), paroxysmal supraventricular tachycardia (PSVT): Limited data available:
Infants, Children, and Adolescents:
Oral: Loading dose: 10 to 15 mg/kg/day in 1 to 2 divided doses/day for 4 to 14 days or until adequate control of arrhythmia or prominent adverse effects occur; dosage should then be reduced to 5 mg/kg/day given once daily for several weeks; if arrhythmia does not recur, reduce to lowest effective dosage possible; usual daily minimal dose: 2.5 mg/kg/day; maintenance doses may be given for 5 of 7 days/week.
Note: For infants, some have suggested BSA-directed dosing: Loading dose: 600 to 800 mg/1.73 m2/day in 1 to 2 divided doses (equivalent to 347 to 462 mg/m2/day); maintenance dose: 200 to 400 mg/1.73 m2/day once daily (equivalent to 116 to 231 mg/m2/day) (Ref).
Note: Prolongation of the corrected QT interval was more likely in infants <9 months of age who received higher loading doses (20 mg/kg/day vs 10 mg/kg/day in 2 divided doses) (n=50; mean age: 1 ± 1.5 months) (Ref).
IV: Loading dose: 5 mg/kg (maximum dose: 300 mg/dose) given over 60 minutes; Note: Most studies used bolus infusion time of 60 minutes to avoid hypotension; may repeat initial loading dose to a maximum total initial load: 10 mg/kg; do not exceed total daily bolus of 15 mg/kg/day (Ref).
Note: Dividing the 5 mg/kg loading dose into 1 mg/kg aliquots (each administered over 5 to 10 minutes) has been used; an additional 1 to 5 mg/kg loading dose was given in the same manner, if needed, after 30 minutes (Ref).
Continuous IV infusion (if needed); Note: Reported dosing units for regimens are variable (mcg/kg/minute and mg/kg/day); use caution to ensure appropriate dose and dosing units are used; taper infusion as soon as clinically possible and switch to oral therapy if necessary.
Dosing based on mcg/kg/minute: Initial: 5 mcg/kg/minute; increase incrementally as clinically needed; usual required dose: 10 mcg/kg/minute; range: 5 to 15 mcg/kg/minute; maximum daily dose: 2,200 mg/day (Ref).
Dosing based on mg/kg/day: Initial: 10 mg/kg/day; increase incrementally as clinically needed; range: 10 to 20 mg/kg/day; maximum daily dose: 2,200 mg/day (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; pharmacokinetic data implies that no dosage adjustment would be necessary. The commercially available premix injectable solution contains the excipient cyclodextrin which may accumulate in patients with renal insufficiency; the clinical significance of this finding is unknown (Ref); monitor patients closely. Close monitoring is recommended in adults with renal abnormalities who are elderly and/or have left ventricular dysfunction.
Hemodialysis: Not dialyzable; supplemental dose is not necessary (Ref)
Peritoneal dialysis: Not dialyzable; supplemental dose is not necessary (Ref)
Baseline: There are no dosage adjustments provided in the manufacturer's labeling. Although no dosage recommendations exist for adults with hepatic abnormalities, close monitoring is recommended in the elderly and those with left ventricular dysfunction.
Hepatoxicity during therapy: There are no dosage adjustments provided in the manufacturer's labeling; based on experience in adult patients, dosage adjustment or discontinuation is suggested when hepatic enzymes exceed 3 times normal or double in a patient with an elevated baseline.
(For additional information see "Amiodarone: Drug information")
Supraventricular arrhythmias:
Note: Amiodarone is a preferred antiarrhythmic for patients with structural heart disease.
Atrial fibrillation:
Pharmacologic cardioversion (off-label use) (alternative agent):
Note: Although amiodarone may slow ventricular response, the use of amiodarone (both IV and oral) is not particularly effective for cardioversion of atrial fibrillation to normal sinus rhythm as compared to other antiarrhythmics (eg, flecainide). Various IV and oral regimens have been described and may be used clinically. The more common regimens utilized include:
IV: 150 mg over 10 minutes, then 1 mg/minute for 6 hours, then 0.5 mg/minute for 18 hours. Continue for a total loading dose of up to 10 g; may finish load with oral dosing. Change to oral maintenance dose when clinically indicated (Ref).
Oral: 400 mg every 8 to 24 hours for a total loading dose of ~6 to 10 g (total of IV plus oral doses), then change to a maintenance dose (Ref). Note: May initiate loading regimen 2 to 6 weeks prior to direct current cardioversion to reduce the risk of atrial fibrillation recurrence (Ref). Also see "Switching to Oral Amiodarone After IV Administration."
Maintenance of sinus rhythm (off-label use): Oral: 100 to 200 mg once daily (Ref). Use the lower maintenance dose for elderly patients or patients with low body mass (Ref).
Prevention of postoperative atrial fibrillation and atrial flutter associated with cardiothoracic surgery (off-label use) (alternative agent):
Note: In patients who cannot receive a beta-blocker, amiodarone may be used. A variety of regimens have been used in clinical trials, including oral and IV regimens:
IV only:
Preoperative regimen: 150 mg once, followed by 0.4 mg/kg/hour (~0.5 mg/minute for a 70 kg patient) for 3 days prior to surgery and for 5 days postoperatively (Ref).
Postoperative regimen: Starting at postoperative recovery: 1 g infused over 24 hours for 2 days (Ref).
IV followed by Oral:
Postoperative regimen: IV: Starting 6 hours postoperatively: 1,050 mg IV loading dose over 24 hours, followed by 400 mg orally 3 times daily on postop days 1 through 4 (Ref).
Oral only: 200 mg 3 times daily for 7 days prior to surgery, followed by 200 mg once daily until hospital discharge (Ref).
Rate control (alternative agent) (off-label use):
IV: 300 mg over 1 hour followed by 10 to 50 mg/hour over 24 hours (Ref) or 150 mg over 10 to 30 minutes, then 1 mg/minute for 6 hours, then 0.5 mg/minute for 18 hours; administer repeat boluses of 150 mg over 10 to 30 minutes as needed but no more than 8 additional boluses should be administered in any 24-hour period (Ref). Note: Mean daily doses >2.1 g/day have been associated with hypotension.
Oral: 400 mg every 8 to 24 hours for a total loading dose of ~6 to 10 g (total of IV plus oral doses), then change to a maintenance dose (Ref); usual maintenance dose: 100 to 200 mg once daily (Ref). Also see "Switching to Oral Amiodarone After IV Administration."
Supraventricular tachycardia (eg, atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, focal atrial tachycardia) (off-label use):
Note: Amiodarone is usually reserved for use when other therapies have failed or are contraindicated. In general, most patients do not require long-term treatment with antiarrhythmic therapy.
Pharmacologic cardioversion:
IV: 150 mg over 10 minutes, followed by 1 mg/minute for 6 hours, then 0.5 mg/minute for 18 hours or transition to oral dosing (Ref).
Oral : 400 to 600 mg daily in divided doses for 2 to 4 weeks; in an inpatient monitored setting, initial oral doses up to 1.2 g daily in divided doses may be considered; administer a total loading dose of ~6 to 10 g (total of IV plus oral doses) then transition to a maintenance dose (Ref); usual maintenance dose: 100 to 200 mg once daily (Ref). Also see "Switching to Oral Amiodarone After IV Administration."
Ventricular arrhythmias:
Electrical storm and incessant ventricular tachycardia, hemodynamically stable (off-label use):
IV: 150 mg over 10 minutes (may repeat if necessary), followed by 1 mg/minute IV infusion for 6 hours, then 0.5 mg/minute for 18 additional hours or until switched to oral therapy. Note: Coadministration with a beta-blocker (eg, propranolol) is recommended (Ref).
Oral (following IV therapy): 400 mg every 8 to 12 hours for 1 to 2 weeks (loading dose of ~6 to 10 g [total of IV plus oral doses]), followed by 200 to 400 mg once daily (Ref). Also see "Switching to Oral Amiodarone After IV Administration."
Nonsustained ventricular tachycardia, symptomatic (off-label use):
Note: Consider addition of a beta-blocker or nondihydropyridine calcium channel blocker (eg, diltiazem) before starting antiarrhythmic therapy (Ref).
Oral: 400 mg every 8 to 12 hours for 1 to 2 weeks (total loading dose of ~6 to 10 g), followed by 200 to 400 mg once daily (Ref). A more gradual oral loading regimen of 200 mg twice daily for the first 4 weeks, followed by 200 mg once daily may also be considered (Ref).
Prevention of implantable cardioverter defibrillator shocks (off-label use):
Note: Antiarrhythmic therapy for this indication has not been shown to reduce mortality, but may improve quality of life by reducing frequency of implantable cardioverter defibrillator (ICD) shocks. Amiodarone is the preferred antiarrhythmic for this use (Ref).
Oral: 400 mg twice daily for 2 weeks, followed by 400 mg once daily for 4 weeks, then 200 mg once daily in combination with a beta-blocker (Ref) or 400 mg every 8 to 24 hours for a total loading dose of ~6 to 10 g, then 200 to 400 mg once daily (Ref).
Primary prevention of sudden cardiac death due to ventricular arrhythmias (off-label use):
Note: Consider addition of a beta-blocker before starting antiarrhythmic therapy. For patients eligible for an ICD with left ventricular dysfunction, but who cannot or refuse to have ICD implantation, amiodarone can be utilized (Ref).
Oral: 400 mg every 8 to 24 hours for 1 to 2 weeks for a total loading dose of ~6 to 10 g, then a maintenance dose of 200 to 400 mg once daily (Ref).
Secondary prevention of sudden cardiac death due to ventricular arrhythmias (eg, ventricular fibrillation or hemodynamically unstable ventricular tachycardia):
Note: ICD implantation is preferred over antiarrhythmic therapy. In patients who do not meet ICD implant criteria, have contraindications, or refuse ICD implantation, antiarrhythmics can be utilized. Beta-blockers are recommended prior to or at the time of antiarrhythmic therapy initiation (Ref).
Oral: 400 mg every 8 to 24 hours for 1 to 2 weeks (loading dose of ~6 to 10 g [total of IV plus oral doses]), followed by a maintenance dose of 200 to 400 mg once daily (Ref). Also see "Switching to Oral Amiodarone After IV Administration."
Sudden cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia (unresponsive to CPR, defibrillation, and epinephrine):
IV push, Intraosseous (IO): Initial: 300 mg (undiluted) rapid bolus; if ventricular fibrillation or pulseless ventricular tachycardia continues after subsequent defibrillation attempt or reoccurs after initially achieving return of spontaneous circulation, administer supplemental dose of 150 mg (Ref).
Upon return of spontaneous circulation (ROSC): Continuous IV infusion: 1 mg/minute for 6 hours, then 0.5 mg/minute for 18 hours or until switched to oral therapy for secondary prevention of sudden cardiac death due to ventricular arrhythmias (Ref). Note: If amiodarone was not given during resuscitation but ROSC is achieved, some experts recommend empiric antiarrhythmic therapy with amiodarone (Ref).
Sustained monomorphic ventricular tachycardia, hemodynamically stable (off-label use):
IV: 150 mg over 10 minutes, then 1 mg/minute for 6 hours, followed by 0.5 mg/minute for at least 18 hours or until switched to an oral maintenance regimen (see "Switching to Oral Amiodarone After IV Administration").
Breakthrough hemodynamically stable ventricular tachycardia: IV: 150 mg over 10 minutes (mean daily doses >2.1 g/day have been associated with hypotension).
Oral (following IV therapy): 400 mg every 8 to 24 hours for 1 to 2 weeks (loading dose of ~6 to 10 g [total of IV plus oral doses]), followed by a maintenance dose of 200 to 400 mg once daily (Ref); if arrhythmia remains controlled on 200 mg once daily, consider reducing dose further to 100 mg once daily to reduce the risk of adverse effects (Ref). Also see "Switching to Oral Amiodarone After IV Administration."
Ventricular premature beats, symptomatic (off-label use):
Note: For patients who are refractory to beta-blocker or nondihydropyridine calcium channel blocker therapy (eg, diltiazem) and cannot take class Ic antiarrhythmic agents (Ref).
Oral: 400 mg every 8 to 12 hours for 1 to 2 weeks (total loading dose of ~6 to 10 g), then when adequate control is achieved, decrease to 200 to 400 mg once daily; use lowest effective dose to minimize adverse effects (eg, may consider 100 mg once daily) (Ref).
Switching to oral amiodarone after IV administration: Use the following as a guide:
<1-week IV infusion: 400 to 1,200 mg daily in divided doses until loading dose of ~6 to 10 g (total of IV plus oral doses) has been administered, then start maintenance dose of 100 to 400 mg once daily (depending on indication).
1- to 2-week IV infusion: 400 to 800 mg daily in divided doses until loading dose of ~6 to 10 g (total of IV plus oral doses) has been administered, then start maintenance dose of 100 to 400 mg once daily (depending on indication).
>2-week IV infusion: 100 to 400 mg once daily (depending on indication) (Ref).
Note: Conversion from IV to oral therapy has not been formally evaluated. Some experts recommend a 1- to 2-day overlap when converting from IV to oral therapy, especially when treating ventricular arrhythmias (Ref).
Switching to IV amiodarone after oral administration: Due to the long half-life, replacement therapy may not be necessary when oral maintenance doses are temporarily discontinued for only a few days. If oral maintenance doses must be withheld for ≥5 to 7 days, may consider administering ~50% (range of 30% to 70%) of the oral daily dose IV (based on bioavailability) as a slow bolus infusion once daily (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Poorly dialyzed (amiodarone and N-desethylamiodarone): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Poorly dialyzed (amiodarone and N-desethylamiodarone): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
Dosage adjustment is probably necessary in substantial hepatic impairment. No specific guidelines available. If hepatic enzymes exceed 3 times normal or double in a patient with an elevated baseline, consider decreasing the dose or discontinuing amiodarone.
Amiodarone may cause a range of effects on conduction and/or blood pressure. Acute hemodynamic changes (bradycardia and hypotension) may occur, particularly with IV administration. A variety of longer-term changes in conduction/heart rate are associated with amiodarone use, most commonly bradycardia, even in patients receiving low-dose chronic oral therapy. Significant disruptions in initiation and conduction, including cases of atrioventricular block, as well as sinoatrial arrest have been reported in adult and pediatric patients (Ref). Cardiac conduction disorder (enhanced accessory pathway conduction) has also been reported (Ref).
Mechanism: Dose-related; related to pharmacologic action (ie, beta-blocking and calcium channel blocking activity are responsible for bradycardia and sinoatrial blockade as well as some of the hypotensive effects) (Ref). Formulation-related; acute hypotension with rapid IV administration has been attributed in part to polysorbate 80 (Ref).
Onset: Acute hypotension during IV administration: Rapid; generally has an onset within 90 minutes but may occur up to 12 hours after initiation (Ref). Other hypotensive adverse reactions: Intermediate; generally reported in the first 12 months of therapy, while bradycardia may develop over months to years (Ref).
Risk factors:
Acute hypotension:
• Age >65 years with history of myocardial infarction (Ref)
• Pediatric patients: Age <3 months; baseline blood pressure below the third percentile for age and height; rapid IV bolus administration (ie, ≤20 minutes) (Ref)
• Formulations containing polysorbate 80 (Ref)
Drug-induced phospholipidosis is a common finding, reflecting a chemical reaction between amiodarone and phospholipids (amiodarone is a potent inhibitor of phospholipase A), but alone this is not indicative of hepatic impairment. Severe, acute hepatotoxicity has been associated with IV administration (Ref). Chronic toxicity may take the form of micronodular hepatic cirrhosis, hepatic fibrosis, or (less commonly) cholestasis (Ref). Hepatotoxicity may be irreversible in some cases (Ref).
Mechanism:
Acute toxicity: Idiosyncratic, immunologic, and formulation-related (ie, polysorbate 80) mechanisms have been proposed (Ref).
Chronic toxicity: Idiosyncratic; may be related to mitochondrial dysfunction and free-radical induced injury (Ref).
Onset:
Acute toxicity following IV administration: Rapid; may occur within 24 hours of initiation (Ref).
Chronic toxicity: Delayed; most cases occur after at least a year of therapy (Ref).
Risk factors:
Acute toxicity:
• High doses (Ref)
• IV administration (Ref)
• Hepatic congestion (Ref)
Chronic toxicity:
• Cumulative dose (potential risk factor) (Ref)
Amiodarone may exacerbate arrhythmias; also associated with new-onset ventricular tachycardia, and polymorphic ventricular tachycardia associated with prolonged QT interval on ECG and torsades de pointes (TdP). However, relative to other agents in this class, amiodarone is associated with relatively low rates of proarrhythmia (specifically a low rate of TdP).
Mechanism: Exhibits multiple effects on cardiac conduction, resulting in a net increase in the QTc interval, consistent with type III antiarrhythmic activity (Ref). Several electrophysiologic properties may contribute to the relative lack of proarrhythmia, including a lack of reverse use dependence, concurrent blockade of the L-type calcium channels, and less QT dispersion (heterogeneity of ventricular repolarization) (Ref). May increase resistance to cardioversion in some patients (Ref). The major metabolite (desethylamiodarone) increases defibrillation threshold in a dose-dependent fashion; this effect is seen with monophasic and biphasic waveforms (Ref).
Onset: Intermediate; generally proarrhythmic events occur sporadically later in therapy (Ref). Rare cases have been reported after short-term, low-dose therapy (200 mg/day for 4 to 5 days) (Ref).
Risk factors:
• Concurrent administration of multiple medications (≥2) that prolong the QT interval or medications with drug interactions that increase serum concentrations of QT-prolonging medications (Ref)
• Electrolyte disturbances (hypokalemia, hypomagnesemia) (Ref)
• Females (Ref)
• In the treatment of atrial fibrillation, structural heart disease, and concurrent use of medications to control heart rate (beta-blockers and digitalis) were noted to increase the risk of TdP following an IV loading dose (Ref)
Pulmonary toxicity may occur with amiodarone use and include a variety of clinical syndromes which may be categorized by onset. Acute events include pneumonitis, pulmonary alveolar hemorrhage, and acute respiratory distress syndrome (ARDS). Pulmonary adverse reactions associated with longer-term therapy (subacute or chronic) include chronic eosinophilic pneumonia, chronic organizing pneumonia, acute fibrinous organizing pneumonia, and pulmonary fibrosis (Ref).
Mechanism:
Acute toxicity:
Non-dose-related; idiosyncratic. Related to production of superoxide radicals and release of active iodide species (Ref). Diffuse alveolar hemorrhage may occur in patients with preexisting immune dysfunction represented by autoantibodies (Ref). Some cases of acute toxicity may represent an acute vasculitis, possibly related to autoantibodies (Ref).
Chronic toxicity: More significant pulmonary toxicity, primarily pulmonary fibrosis, is mediated by a combination of direct toxicity to specific pulmonary cells, immune activation, and activation of angiotensin (Ref).
Onset:
Acute toxicity: Intermediate; may occur as early as 2 days to 2 weeks (Ref).
Chronic toxicity: Delayed; pulmonary fibrosis is usually identified after months to years of therapy (Ref).
Risk factors:
Acute toxicity:
• Cardiothoracic surgery (Ref)
• Exposure to a high inspiratory fraction of inhaled oxygen (FiO2) (Ref)
• Pulmonary angiography (Ref)
Chronic toxicity:
• Daily and cumulative doses (Ref)
• Chronic kidney disease (Ref)
• Older adults (particularly >60 years of age) (Ref)
• Preexisting lung disease/chronic obstructive pulmonary disease (Ref)
Amiodarone is associated with complex effects on thyroid function, resulting in either hyperthyroidism or hypothyroidism. Most euthyroid patients exhibit transient abnormalities of thyroid tests without overt symptoms and return to a baseline in 3 to 6 months (Ref). In a subset of patients, often in those with underlying thyroid disease, these effects may result in clinical thyroid disease, including rare cases of thyrotoxicosis, thyroid storm, or myxedema (including myxedema coma) (Ref). Hypothyroidism (sometimes severe) may be subsequent to resolution of preceding amiodarone-induced hyperthyroidism.
Mechanism: Dose-related. Effects may be considered in two categories: Those which are mediated by the high iodine content or those which are related to other effects of amiodarone.
Hyperthyroidism: Two types of amiodarone-induced thyrotoxicosis are generally recognized: Type 1 occurs in patients with underlying thyroid pathology (autonomous nodular goiter or Graves' disease) and is associated with increased synthesis of T4 and T3 in the thyroid gland (Ref). The high iodine content of amiodarone appears to be an important factor in loss of regulation in these susceptible individuals (Ref). Type 2 results from a subacute thyroiditis, causing release of thyroid hormones into the circulation without an increase in synthesis (Ref). Thyroiditis is considered a direct effect of amiodarone and not related to iodine content (Ref).
Hypothyroidism : Amiodarone inhibits the conversion of T4 to T3 (de-iodination), decreases binding of T3 to its nuclear receptor, and may exert direct toxicity on thyroid follicular cells (thyroiditis) (Ref).
Onset: Delayed; most cases of hyperthyroidism occur between 3 months and 4 years of therapy (Ref). In an evaluation of FDA Adverse Reactions Reporting data, median time to diagnosis of hyperthyroidism is 720 days (range: 225 to 1,145 days) (Ref). Most cases of hypothyroidism occur within the first 6 to 7 months of therapy (Ref). In a pediatric series, the majority of thyroid dysfunction was noted within 35 days of amiodarone initiation (Ref).
Risk factors:
• Dietary iodine intake (Ref)
• Thyroid autoantibodies (hypothyroidism) (Ref)
• Thyroid disease (including Graves’ disease or preexisting multinodular goiter) (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported for the oral dosage form unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Hypotension (refractory in rare cases)
Gastrointestinal: Nausea, vomiting (oral: >10%; IV: <2%)
Ophthalmic: Epithelial keratopathy (98% to 99%; vortex; Raizman 2017)
Respiratory: Pulmonary toxicity (including hypersensitivity pneumonitis and interstitial/alveolar pneumonitis: ≤17%)
1% to 10%:
Cardiovascular: Bradycardia (2% to 4%), cardiac arrhythmia, cardiac failure (IV, oral), edema, exacerbation of cardiac arrhythmia (2% to 5%), flushing, prolonged QT interval on ECG (associated with worsening arrhythmia), shock (IV: <2%), sinus node dysfunction, torsades de pointes (IV: <2%), ventricular fibrillation (IV: <2%)
Dermatologic: Skin photosensitivity, solar dermatitis, Stevens-Johnson syndrome (IV, oral: <2%) (Blumenthal 2015)
Endocrine & metabolic: Decreased libido, hyperthyroidism (2%), hypothyroidism
Gastrointestinal: Abdominal pain, altered salivation, anorexia, constipation, diarrhea (IV: <2%), dysgeusia
Hematologic & oncologic: Disorder of hemostatic components of blood
Hepatic: Abnormal hepatic function tests (IV, oral), hepatic disease
Nervous system: Abnormal gait, altered sense of smell, ataxia, dizziness, fatigue, headache, insomnia, involuntary body movements, malaise, paresthesia, sleep disorder
Neuromuscular & skeletal: Tremor
Ophthalmic: Blurred vision, visual disturbance, visual halos around lights
Renal: Renal insufficiency (IV: <2%)
Respiratory: Acute respiratory distress syndrome (IV, oral: ≤2%; incidence may be higher in patients following anesthesia with high FiO2 exposure) (Teerakanok 2016), pulmonary fibrosis
<1%:
Dermatologic: Alopecia, blue-gray skin pigmentation (incidence may be higher ~8%) (Rappersberger 1989), skin rash
Hematologic & oncologic: Spontaneous ecchymoses
Hepatic: Hepatic necrosis (acute: IV)
Frequency not defined: Cardiovascular: Asystole (IV), atrioventricular block (IV), cardiogenic shock (IV), ventricular tachycardia (IV, oral)
Postmarketing (oral and/or IV):
Cardiovascular: Cardiac conduction disorder (including bundle branch block, infra-HIS block, and antegrade conduction via an accessory pathway) (Schützenberger 1987), sinoatrial block, vasculitis
Dermatologic: Bullous dermatitis, eczema, erythema multiforme (Chen 2013), erythema of skin (palmer) (Serrao 2007), exfoliative dermatitis, toxic epidermal necrolysis (Yung 2002), urticaria (Stafford 2007)
Endocrine & metabolic: Myxedema (including myxedema coma) (Hawatmeh 2018), SIADH (Marcelino 2019), thyroid nodule, thyrotoxicosis (Inoue 2018)
Gastrointestinal: Cholestasis (Bratton 2019), pancreatitis (including acute pancreatitis) (Alonso 2015), xerostomia
Genitourinary: Epididymitis (Dasu 2019), impotence, orchitis (Dasu 2019)
Hematologic & oncologic: Agranulocytosis (Gershinsky 2019), aplastic anemia (Ba 2019), granulocytosis, granuloma (of bone) (Mukhopadhyay 2004), hemolytic anemia, immune thrombocytopenia (Chhatrala 2021), malignant neoplasm of skin (Maoz 2009), malignant neoplasm of thyroid (Inaba 2012), neutropenia (Groneberg 2001), pancytopenia (Erie 2010), thrombocytopenia
Hepatic: Cholestatic hepatitis (Rumessen 1986), hepatic cirrhosis (Puli 2005), hepatotoxicity (idiosyncratic) (Chalasani 2014)
Hypersensitivity: Anaphylactic shock (Kurt 2012), anaphylaxis (Okuyan 2012), angioedema (Burches 2000), nonimmune anaphylaxis
Immunologic: Drug reaction with eosinophilia and systemic symptoms
Local: Infusion site reaction (including cellulitis, edema, erythema, granuloma, hypoesthesia, induration, inflammation, pain, phlebitis (IV concentrations of >3 mg/mL have been associated with peripheral vein phlebitis), pigment changes, pruritus, skin sloughing, thrombophlebitis, thrombosis, urticaria (Russell 2006)
Nervous system: Delirium (Athwal 2003), demyelinating disease (polyneuropathy) (Pulipaka 2002), drug-induced Parkinson's disease (Bondon-Guitton 2011), hallucination, hypoesthesia, increased intracranial pressure, intracranial hypertension (Tan 2020), myasthenia, peripheral neuropathy (chronic treatment, partially to completely reversible with discontinuation) (Roseti 2010)
Neuromuscular & skeletal: Back pain, lupus-like syndrome (Yachoui 2015), muscle spasm, myopathy, rhabdomyolysis
Ophthalmic: Corneal deposits, dry eye syndrome (Ikäheimo 2002), optic neuritis, optic neuropathy (Wang 2016)
Renal: Acute kidney injury (Mohamed 2020)
Respiratory: Bronchiolitis obliterans organizing pneumonia, bronchospasm (Yavuzgil 2005), hemoptysis (Busch 2019), hypoxia, pleural effusion (Hawatmeh 2017), pleurisy, pulmonary alveolar hemorrhage (Saeed 2019), pulmonary infiltrates
Miscellaneous: Drug-induced phospholipidosis, fever, mass (pulmonary) (Jarand 2007)
Hypersensitivity to amiodarone, iodine, or any component of the formulation; sick sinus syndrome, second- or third-degree atrioventricular block, bradycardia leading to syncope without a functioning pacemaker; cardiogenic shock
Note: The FDA-approved product labeling states amiodarone is contraindicated in patients with iodine hypersensitivity. This does not include most patients with allergic reactions to shellfish or contrast media, which are usually not due to iodine itself (Beall 2007; Brouse 2005; Lakshmanadoss 2012). However, exercise caution in patients with severe allergies to shellfish or contrast media (Brouse 2005).
Canadian labeling (oral formulation): Additional contraindications (not in US labeling): Evidence of hepatitis; pulmonary interstitial abnormalities; thyroid dysfunction
Concerns related to adverse effects:
• Extravasation: May be a vesicant; ensure proper needle or catheter placement prior to infusion. Avoid extravasation.
• Ocular effects: Regular ophthalmic examination (including slit lamp and fundoscopy) is recommended. May cause optic neuropathy and/or optic neuritis resulting in visual impairment (peripheral vision loss, changes in acuity) at any time during therapy; permanent blindness has occurred. If symptoms of optic neuropathy and/or optic neuritis occur, prompt ophthalmic evaluation is recommended. If diagnosis of optic neuropathy and/or optic neuritis is confirmed, reevaluate amiodarone therapy. Corneal microdeposits occur in a majority of adults and may cause visual disturbances in up to 10% of patients (blurred vision, halos); asymptomatic microdeposits may be reversible and are not generally considered a reason to discontinue treatment. Corneal refractive laser surgery is generally contraindicated in amiodarone users (from manufacturers of surgical devices).
• Photosensitivity: Avoid excessive exposure to sunlight; may cause photosensitivity. During long-term treatment, a blue-gray discoloration of exposed skin may occur; risk increased in patients with fair complexion or excessive sun exposure; may be related to cumulative dose and duration of therapy.
Disease-related concerns:
• Arrhythmias: Appropriate use: The 2015 ACLS guidelines recommend the consideration of IV amiodarone as the preferred antiarrhythmic for the treatment of pulseless ventricular tachycardia/ventricular fibrillation unresponsive to CPR, defibrillation, and vasopressor therapy (AHA [Link 2015]). In patients with non-life-threatening arrhythmias (eg, atrial fibrillation), amiodarone should be used only if the use of other antiarrhythmics has proven ineffective or are contraindicated.
• Cardiac devices (eg, implanted defibrillators, pacemakers): Chronic administration of antiarrhythmic drugs may affect defibrillation or pacing thresholds. Assess when initiating amiodarone and during therapy.
• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia, hypomagnesemia, or hypocalcemia, prior to use and throughout therapy.
• Myocardial infarction: In the setting of acute myocardial infarction (MI), beta-blocker therapy should be initiated even though concomitant amiodarone therapy provides beta-blockade. In the Cardiac Arrhythmia Suppression Trial (CAST), post-MI patients with asymptomatic, nonlife-threatening ventricular arrhythmias did not benefit and may have been harmed by attempts to suppress arrhythmia with flecainide or encainide. Although use of amiodarone post-MI was not associated with an increase in mortality in 2 trials, antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.
• Wolff-Parkinson-White (WPW) syndrome: Amiodarone should not be used in patients with WPW syndrome and preexcited atrial fibrillation/flutter since ventricular fibrillation may result (AHA/ACC/HRS [January 2014]).
Special populations:
• Surgical patients: Use caution and close perioperative monitoring in surgical patients; may enhance myocardial depressant and conduction effects of halogenated inhalational anesthetics; adult respiratory distress syndrome (ARDS) has been reported postoperatively (fatal in rare cases). Hypotension upon discontinuation of cardiopulmonary bypass during open-heart surgery have been reported (rare); relationship to amiodarone is unknown.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.
• Commercially prepared premixed infusion: Contains the excipient cyclodextrin (sulfobutyl ether beta-cyclodextrin), which may accumulate in patients with renal insufficiency, although the clinical significance of this finding is uncertain (Luke 2010).
• Long-term use: There has been limited experience in patients receiving IV amiodarone for >3 weeks.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling. Commercially prepared premixed amiodarone solutions do not contain polysorbate 80 and may have a lower incidence of hypotension.
Other warnings/precautions:
• Discontinuation of therapy: Patients may still be at risk for amiodarone-related adverse reactions or drug interactions after the drug has been discontinued. The pharmacokinetics are complex (due to prolonged duration of action and half-life) and difficult to predict.
Vials for injection contain benzyl alcohol which has been associated with “gasping syndrome” in neonates. Commercially-prepared premixed solutions do not contain benzyl alcohol.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous, as hydrochloride:
Nexterone: 150 mg/100 mL in Dextrose (100 mL); 360 mg/200 mL in Dextrose (200 mL)
Generic: 150 mg/3 mL (3 mL); 450 mg/9 mL (9 mL); 900 mg/18 mL (18 mL)
Tablet, Oral, as hydrochloride:
Pacerone: 100 mg
Pacerone: 200 mg [scored; contains fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow)]
Pacerone: 400 mg [scored; contains corn starch]
Pacerone: 400 mg [DSC] [contains quinoline (d&c yellow #10) aluminum lake]
Generic: 100 mg, 200 mg, 400 mg
Yes
Solution (Amiodarone HCl Intravenous)
150 mg/3 mL (per mL): $0.70 - $1.53
450 mg/9 mL (per mL): $0.64 - $1.03
900 mg/18 mL (per mL): $1.00
Solution (Nexterone Intravenous)
150MG/100ML 4.21% (per mL): $0.42
360MG/200ML 4.14% (per mL): $0.28
Tablets (Amiodarone HCl Oral)
100 mg (per each): $7.43
200 mg (per each): $3.30 - $3.48
400 mg (per each): $1.60 - $7.48
Tablets (Pacerone Oral)
100 mg (per each): $7.43
200 mg (per each): $7.27
400 mg (per each): $14.96
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 50 mg/mL (3 mL, 9 mL, 18 mL)
Solution, Intravenous, as hydrochloride:
Generic: 150 mg/3 mL (3 mL)
Tablet, Oral, as hydrochloride:
Generic: 100 mg, 200 mg
5 mg/mL Oral Suspension (ASHP Standard Concentration) (ASHP 2017)
A 5 mg/mL oral suspension may be made with tablets and either a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Ora-Sweet SF and Ora-Plus adjusted to a pH between 6-7 using a sodium bicarbonate solution (5 g/100 mL of distilled water). Crush five 200 mg tablets in a mortar and reduce to a fine powder. Add small portions of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 200 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 200 mL. Label “shake well” and “protect from light.” Stable for 42 days at room temperature or 91 days refrigerated (preferred) (Nahata 1999; Nahata 2014).
Oral: Administer at same time in relation to meals; do not administer with grapefruit juice. In adults, may administer in divided doses with meals if GI upset occurs or if taking large daily dose.
IV: Adjust administration rate to patient's clinical condition and urgency; give slowly to patients who have a pulse (ie, perfusing arrhythmia). With perfusing arrhythmias (eg, atrial fibrillation, stable ventricular tachycardia), do not exceed recommended IV concentrations or rates of infusion listed below (severe hepatic toxicity may occur). Slow the infusion rate if hypotension or bradycardia develops. An in-line filter has been recommended during administration to reduce the incidence of phlebitis associated with dilution-induced precipitation (consult individual institutional policies and procedures) (Ref).
May be a vesicant; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation. If extravasation occurs, stop infusion immediately and disconnect (leave needle/cannula in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote for refractory cases (see Management of Drug Extravasations for more details); remove needle/cannula; apply dry warm compresses (Ref); elevate extremity.
Pulseless VT or VF: Infants, Children, and Adolescents: Administer via rapid IV bolus; adult data in this setting suggest administration of undiluted drug may be preferred (Ref). Note: PALS guidelines (Ref) do not specify dilution of bolus dose and The Handbook of Emergency Cardiovascular Care (Ref) and the ACLS guidelines do not make any specific recommendations regarding dilution of amiodarone in this setting.
Perfusing arrhythmias: Information based on adult data: Injection must be diluted before IV use. Administer via central venous catheter, if possible; increased phlebitis may occur with peripheral infusions >3 mg/mL in D5W; the use of a central venous catheter with concentrations >2 mg/mL for infusions >1 hour is recommended. Must be infused via volumetric infusion device; drop size of IV solution may be reduced and underdosage may occur if drop counter-infusion sets are used. PVC tubing is recommended for administration regardless of infusion duration. Incompatible with heparin; flush with saline prior to and following infusion. Note: IV administration at lower flow rates (potentially associated with use in pediatrics) and higher concentrations than recommended may result in leaching of plasticizers (DEHP) from intravenous tubing. DEHP may adversely affect male reproductive tract development. Alternative means of dosing and administration (1 mg/kg aliquots) may need to be considered.
Neonates: Administer loading dose over 60 minutes; may be followed by continuous infusion (Ref).
Infants, Children, and Adolescents: Administer loading dose over 20 to 60 minutes (Ref); may be followed by continuous IV infusion
Oral: Administer consistently with regard to meals. Take in divided doses with meals if GI upset occurs or if taking large daily dose (≥1,000 mg). If GI intolerance occurs with single-dose therapy, use twice daily dosing.
IV: For infusions >1 hour, use concentrations ≤2 mg/mL unless a central venous catheter is used; commercially prepared premixed solutions in concentrations of 1.5 mg/mL and 1.8 mg/mL are available. Use only volumetric infusion pump; use of drop counting may lead to underdosage. Administer through an IV line located as centrally as possible. For peripheral infusions, an in-line filter has been recommended during administration to reduce the incidence of phlebitis (consult individual institutional policies and procedures). During pulseless VT/VF, administering undiluted is preferred (Ref). The Handbook of Emergency Cardiovascular Care (Ref) and the ACLS guidelines do not make any specific recommendations regarding dilution of amiodarone in this setting.
Adjust administration rate to urgency (give more slowly when perfusing arrhythmia present). Slow the infusion rate if hypotension or bradycardia develops. Infusions >2 hours must be administered in a non-PVC container (eg, glass or polyolefin). PVC tubing is recommended for administration regardless of infusion duration. Incompatible with heparin; flush with saline prior to and following infusion. Note: IV administration at lower flow rates (potentially associated with use in pediatrics) and higher concentrations than recommended may result in leaching of plasticizers (DEHP) from intravenous tubing. DEHP may adversely affect male reproductive tract development. Alternative means of dosing and administration (1 mg/kg aliquots) may need to be considered.
May be a vesicant; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately; leave needle/cannula in place temporarily but do NOT flush the line; gently aspirate extravasated solution, then remove needle/cannula; elevate extremity; apply dry warm compresses; initiate hyaluronidase antidote for refractory cases in addition to supportive management (Ref).
Hyaluronidase: Intradermal or SUBQ: Inject a total of 1 mL (15 units/mL) as 5 separate 0.2 mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through the infiltrated catheter; may repeat in 30 to 60 minutes if no resolution (Ref).
Note: Premixed solutions available.
IV infusion: 1.8 mg/mL
Tablets: Store at 20°C to 25°C (68°F to 77°F); protect from light.
Injection: Store undiluted vials and premixed solutions (Nexterone) at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Protect from light during storage; protect from excessive heat. There is no need to protect solutions from light during administration. When vial contents are admixed in D5W to a final concentration of 1-6 mg/mL, amiodarone is stable for 24 hours in glass or polyolefin bottles and for 2 hours in polyvinyl chloride (PVC) bags; do not use evacuated glass containers as buffer may cause precipitation. Nexterone is available as premixed solutions. Although amiodarone adsorbs to PVC tubing, all clinical studies used PVC tubing and the recommended doses account for adsorption; in adults, PVC tubing is recommended. Discard any unused portions of premixed solutions.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Cordarone: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/018972s054lbl.pdf#page=13
Pacerone: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088668.pdf
Oral: Management of life-threatening recurrent ventricular arrhythmias [eg, recurrent ventricular fibrillation (VF) or recurrent hemodynamically unstable ventricular tachycardia (VT)] unresponsive to other therapy or in patients intolerant to other therapy (FDA approved in adults).
IV: Initiation of management and prophylaxis of frequently recurrent VF and hemodynamically unstable VT unresponsive to other therapy; VF and VT in patients requiring amiodarone who are not able to take oral therapy (All indications: FDA approved in adults).
Note: Also has been used to treat supraventricular arrhythmias unresponsive to other therapy. Amiodarone is recommended in the PALS guidelines for SVT (unresponsive to vagal maneuvers and adenosine). It is recommended in both the PALS and ACLS guidelines for cardiac arrest with pulseless VT or VF (unresponsive to defibrillation, CPR, and vasopressor administration) and control of hemodynamically-stable monomorphic VT or wide-complex tachycardia of uncertain origin. The drug is also recommended in the ACLS guidelines for re-entry SVT (unresponsive to vagal maneuvers and adenosine); control of rapid ventricular rate due to conduction via an accessory pathway in pre-excited atrial arrhythmias; control of stable narrow-complex tachycardia; and control of polymorphic VT with a normal QT interval.
Amiodarone may be confused with amantadine, aMILoride, inamrinone.
Cordarone may be confused with Cardura, Cordran.
Nexterone may be confused with Cardene IV.
The Institute for Safe Medication Practices (ISMP) includes this medication (IV formulation) among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
Beers Criteria: Amiodarone is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older as first-line therapy for atrial fibrillation (unless patient has concomitant heart failure or substantial left ventricular hypertrophy) due to increased toxicities compared to other antiarrhythmics used in atrial fibrillation (Beers Criteria [AGS 2023]).
Amyben [brand name for amiodarone (Great Britain)] may be confused with Ambien [US, Argentina, Israel]
Substrate of CYP1A2 (minor), CYP2C19 (minor), CYP2C8 (minor), CYP2D6 (minor), CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C9 (weak), CYP2D6 (weak), CYP3A4 (weak), P-glycoprotein/ABCB1
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification
Agalsidase Alfa: Amiodarone may diminish the therapeutic effect of Agalsidase Alfa. Risk X: Avoid combination
Agalsidase Beta: Amiodarone may diminish the therapeutic effect of Agalsidase Beta. Management: Avoid concomitant use of amiodarone with agalsidase beta when possible as amiodarone could antagonize intracellular alpha-galactosidase activity. Risk D: Consider therapy modification
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Amisulpride (Oral): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride (Oral). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even greater risk. Risk D: Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Atazanavir: May increase the serum concentration of Amiodarone. Risk X: Avoid combination
Atorvastatin: Amiodarone may increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Beta-Blockers: Amiodarone may enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Risk C: Monitor therapy
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
Bile Acid Sequestrants: May decrease the bioavailability of Amiodarone. Management: Consider alternatives to this combination due to the risk of subtherapeutic amiodarone serum concentrations. If amiodarone is coadministered with colesevelam, administer amiodarone at least 4 hours before colesevelam. Risk D: Consider therapy modification
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Calcium Channel Blockers (Nondihydropyridine): May enhance the bradycardic effect of Amiodarone. Sinus arrest has been reported. Risk C: Monitor therapy
CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Carbetocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Cardiac Glycosides: Amiodarone may increase the serum concentration of Cardiac Glycosides. Management: Reduce the dose of cardiac glycosides by 30% to 50% or reduce the frequency of administration when initiating concomitant amiodarone therapy. Monitor for increased serum concentrations and toxic effects of cardiac glycosides. Risk D: Consider therapy modification
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy
Ceritinib: Amiodarone may enhance the bradycardic effect of Ceritinib. Amiodarone may enhance the QTc-prolonging effect of Ceritinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Chloroquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Cimetidine: May increase the serum concentration of Amiodarone. Risk X: Avoid combination
Citalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. Risk X: Avoid combination
Clarithromycin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. Risk X: Avoid combination
Clofazimine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
ClomiPRAMINE: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
CloZAPine: Amiodarone may enhance the QTc-prolonging effect of CloZAPine. Amiodarone may increase the serum concentration of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider therapy modification
CycloPHOSphamide: May enhance the adverse/toxic effect of Amiodarone. Specifically, the risk of pulmonary toxicity may be enhanced. Risk C: Monitor therapy
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP2C8 Inhibitors (Strong): May increase the serum concentration of Amiodarone. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Amiodarone. CYP3A4 Inducers (Strong) may decrease the serum concentration of Amiodarone. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Amiodarone. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Amiodarone. Management: Consider alternatives to use of amiodarone and strong CYP3A4 inhibitors. If combined, monitor for increased amiodarone concentrations and toxicities. Risk D: Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Dabrafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Daclatasvir: May enhance the bradycardic effect of Amiodarone. Risk X: Avoid combination
Dasatinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Domperidone: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination
Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
DroPERidol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of DroPERidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy
Encorafenib: May enhance the QTc-prolonging effect of Amiodarone. Encorafenib may decrease the serum concentration of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, and decreased amiodarone concentrations. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination
Erythromycin (Systemic): Amiodarone may enhance the QTc-prolonging effect of Erythromycin (Systemic). Erythromycin (Systemic) may enhance the QTc-prolonging effect of Amiodarone. Erythromycin (Systemic) may increase the serum concentration of Amiodarone. Risk X: Avoid combination
Escitalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Etelcalcetide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy
Fexinidazole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Fingolimod: May enhance the QTc-prolonging effect of Amiodarone. Risk X: Avoid combination
Flecainide: Amiodarone may enhance the QTc-prolonging effect of Flecainide. Amiodarone may increase the serum concentration of Flecainide. Management: Decrease flecainide dose by 50%. Monitor for QTc interval prolongation and ventricular arrhythmias, and consider monitoring for elevated flecainide concentrations. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Fluorouracil Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Flupentixol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. Risk X: Avoid combination
Fosphenytoin: May decrease the serum concentration of Amiodarone. Amiodarone may increase the serum concentration of Fosphenytoin. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Gemifloxacin: May enhance the QTc-prolonging effect of Amiodarone. Risk X: Avoid combination
Gilteritinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
Grapefruit Juice: May increase the serum concentration of Amiodarone. Risk X: Avoid combination
Halofantrine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Haloperidol: Amiodarone may enhance the QTc-prolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
HydrOXYzine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Imipramine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Indinavir: May increase the serum concentration of Amiodarone. Risk X: Avoid combination
Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Lacosamide: Antiarrhythmic Agents (Class III) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy
Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid combination
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Levofloxacin-Containing Products (Systemic): May enhance the QTc-prolonging effect of Amiodarone. Risk X: Avoid combination
Levoketoconazole: QT-prolonging CYP3A4 Substrates may enhance the QTc-prolonging effect of Levoketoconazole. Levoketoconazole may increase the serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid combination
Lidocaine (Systemic): Amiodarone may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
Lofepramine: May enhance the arrhythmogenic effect of Amiodarone. Risk X: Avoid combination
Lofexidine: May enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification
Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification
Loratadine: Amiodarone may increase the serum concentration of Loratadine. Management: Due to reported QT interval prolongation and Torsades de Pointes with this combination, consider an alternative to loratadine when possible. If concomitant use cannot be avoided, monitor QT interval and for signs of dyshythmias (eg, syncope). Risk D: Consider therapy modification
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Lovastatin: Amiodarone may increase the serum concentration of Lovastatin. Management: Consider using a non-interacting statin (pravastatin, pitavastatin) in patients on amiodarone. If combined, limit the lovastatin dose to 40 mg daily and monitor for lovastatin toxicities (eg, myalgia, liver function test elevations, rhabdomyolysis). Risk D: Consider therapy modification
Macitentan: Amiodarone may increase the serum concentration of Macitentan. Risk C: Monitor therapy
Meglumine Antimoniate: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Methadone: Amiodarone may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Midostaurin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Mipomersen: Amiodarone may enhance the hepatotoxic effect of Mipomersen. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Risk X: Avoid combination
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy
Nelfinavir: May increase the serum concentration of Amiodarone. Risk X: Avoid combination
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nilotinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib. Risk X: Avoid combination
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: May increase the serum concentration of Amiodarone. Risk X: Avoid combination
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
OLANZapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Ondansetron: Amiodarone may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Orlistat: May decrease the serum concentration of Amiodarone. Risk C: Monitor therapy
Osimertinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Oxygen: May enhance the adverse/toxic effect of Amiodarone. Specifically, amiodarone pulmonary toxicity may be enhanced. Risk C: Monitor therapy
Oxytocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Pacritinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pacritinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
PAZOPanib: Amiodarone may enhance the QTc-prolonging effect of PAZOPanib. Amiodarone may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Phenytoin: May decrease the serum concentration of Amiodarone. Amiodarone may increase the serum concentration of Phenytoin. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pilsicainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Pimozide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk X: Avoid combination
Piperaquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Posaconazole: May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid combination
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification
Probucol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. Risk X: Avoid combination
Propafenone: Amiodarone may enhance the QTc-prolonging effect of Propafenone. Risk X: Avoid combination
Propofol: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
QT-prolonging Agents (Indeterminate Risk - Avoid): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Agents (Indeterminate Risk - Caution): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IA Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, consider dose reductions of the class IA antiarrhythmic (30% to 50%) and monitor for QTc interval prolongation and ventricular arrhythmias. Risk D: Consider therapy modification
QT-prolonging Class III Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Miscellaneous Agents (Highest Risk): May enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Amiodarone. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of Amiodarone. QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase the serum concentration of Amiodarone. Management: Consider alternatives to this combination. If combined, monitor for increased amiodarone toxicities, including QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QUEtiapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. Risk X: Avoid combination
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quizartinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy
Red Yeast Rice: Amiodarone may increase the serum concentration of Red Yeast Rice. Management: Consider using a non-interacting statin (eg, pravastatin, pitavastatin) in patients on amiodarone. If combined, limit the adult red yeast rice dose to the equivalent of lovastatin 40 mg daily and monitor for toxicities (eg, myalgia, rhabdomyolysis). Risk D: Consider therapy modification
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
Ribociclib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib. Risk X: Avoid combination
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification
RisperiDONE: QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Ritonavir: May increase the serum concentration of Amiodarone. Management: Ritonavir US prescribing information lists this combination as contraindicated. Amiodarone use should be avoided with lopinavir/ritonavir, but if the combination must be used, monitor closely for increased amiodarone serum concentrations and effects. Risk X: Avoid combination
Rivaroxaban: Amiodarone may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
Saquinavir: May enhance the QTc-prolonging effect of Amiodarone. Saquinavir may increase the serum concentration of Amiodarone. Risk X: Avoid combination
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Simvastatin: Amiodarone may increase serum concentrations of the active metabolite(s) of Simvastatin. Amiodarone may increase the serum concentration of Simvastatin. Management: Consider using a non-interacting statin (pravastatin) in patients on amiodarone. If combined, limit the adult simvastatin dose to 20 mg daily and monitor for evidence of simvastatin toxicities (eg, myalgia, liver function test elevations, rhabdomyolysis). Risk D: Consider therapy modification
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider therapy modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Sodium Iodide I131: Amiodarone may diminish the therapeutic effect of Sodium Iodide I131. Management: Discontinue amiodarone at least 6 months before sodium iodide I-131 administration, and avoid concurrent use. Risk X: Avoid combination
Sofosbuvir: May enhance the bradycardic effect of Amiodarone. Management: Use alternative to a sofosbuvir-containing combo or to amiodarone when possible. If alternatives not possible, monitor in inpatient setting for first 48 hours of coadministration with daily outpatient monitoring for at least 2 weeks. Risk D: Consider therapy modification
Sparfloxacin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin. Risk X: Avoid combination
Sulfonylureas: Amiodarone may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
SUNItinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of SUNItinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Tacrolimus (Systemic): May enhance the QTc-prolonging effect of Amiodarone. Amiodarone may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Talazoparib: Amiodarone may increase the serum concentration of Talazoparib. Management: In breast cancer, if concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. In prostate cancer, monitor patients for increased adverse events. Risk D: Consider therapy modification
Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Terbutaline: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Thioridazine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Thyroid Products: Amiodarone may diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
Tipranavir: May increase the serum concentration of Amiodarone. Risk X: Avoid combination
TiZANidine: Amiodarone may increase the serum concentration of TiZANidine. Risk C: Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
TOLBUTamide: CYP2C9 Inhibitors (Weak) may increase the serum concentration of TOLBUTamide. Risk C: Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Toremifene: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Toremifene. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification
Vemurafenib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider therapy modification
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Amiodarone may enhance the anticoagulant effect of Vitamin K Antagonists. Amiodarone may increase the serum concentration of Vitamin K Antagonists. Management: Monitor patients extra closely for evidence of increased anticoagulant effects if amiodarone is started. Consider empiric reduction of 30% to 50% in warfarin dose, though no specific guidelines on dose adjustment have been published. Risk D: Consider therapy modification
Voriconazole: Amiodarone may enhance the QTc-prolonging effect of Voriconazole. Voriconazole may increase the serum concentration of Amiodarone. Risk X: Avoid combination
Food increases the rate and extent of absorption of amiodarone. Grapefruit juice increases bioavailability of oral amiodarone by 50% and decreases the conversion of amiodarone to N-DEA (active metabolite); altered effects are possible. Management: Take consistently with regard to meals; grapefruit juice should be avoided during therapy.
Take consistently with regard to meals. Amiodarone is a potential source of large amounts of inorganic iodine; ~3 mg of inorganic iodine per 100 mg of amiodarone is released into the systemic circulation. Recommended daily allowance for iodine in adults is 150 mcg.
Grapefruit juice is not recommended.
Amiodarone and the active metabolite, N-desethylamiodarone, cross the placenta (Plomp 1992).
In utero exposure may cause fetal harm. Reported risks include neonatal bradycardia, QT prolongation, and periodic ventricular extrasystoles; neonatal hypothyroidism (with or without goiter); neonatal hyperthyroxinemia; neurodevelopmental abnormalities independent of thyroid function; jerk nystagmus with synchronous head titubation; fetal growth retardation; and/or premature birth.
Oral or IV amiodarone should be used in pregnancy only to treat arrhythmias refractory to other treatments or when other treatments are contraindicated (ACC/AHA/HRS [Page 2015]).
Amiodarone (administered either maternally or directly to the fetus) may be considered for the in utero management of fetal atrial flutter and in life-threatening cases of sustained fetal supraventricular tachycardia refractory to first and second line agents, but because of potential toxicity, risks and benefits should be assessed (AHA [Donofrio 2014]; Kang 2015).
If in utero exposure occurs, newborns should be monitored for thyroid disorders and cardiac arrhythmias.
Heart rate and rhythm, blood pressure, ECG, chest x-ray, pulmonary function tests, thyroid function tests; serum glucose, electrolytes (especially potassium and magnesium), triglycerides, liver enzymes; ophthalmologic exams including fundoscopy and slit-lamp examinations, physical signs and symptoms of thyroid dysfunction (lethargy, edema of hands and feet, weight gain or loss), and pulmonary toxicity (dyspnea, cough; oxygen saturation, blood gases). Monitor pacing or defibrillation thresholds in patients with implantable cardiac devices (eg, pacemakers, defibrillators) at initiation of therapy and periodically during treatment. Monitor infusion site.
Therapeutic: Chronic oral dosing: 1 to 2.5 mg/L (SI: 2 to 4 micromoles/L) (parent); desethyl metabolite (active) is present in equal concentration to parent drug; serum concentrations may not be of great value for predicting toxicity and efficacy; toxicity may occur even at therapeutic concentrations
Class III antiarrhythmic agent which inhibits adrenergic stimulation (alpha- and beta-blocking properties), affects sodium, potassium, and calcium channels, prolongs the action potential and refractory period in myocardial tissue; decreases AV conduction and sinus node function
Onset of action: Oral: 2 days to 3 weeks; IV: (electrophysiologic effects) within hours; Antiarrhythmic effects: 2 to 3 days to 1 to 3 weeks; mean onset of effect may be shorter in children vs adults and in patients receiving IV loading doses
Peak effect: 1 week to 5 months
Duration after discontinuing therapy: Variable, 2 weeks to months: Children: less than a few weeks; Adults: Several months
Note: Duration after discontinuation may be shorter in children than adults
Absorption: Oral: Slow and variable
Distribution:
IV: Rapid redistribution with a decrease to 10% of peak values within 30 to 45 minutes after completion of infusion
IV single dose: Vdss: Mean range: 40 to 84 L/kg
Oral: Vd: 66 L/kg (range: 18 to 148 L/kg)
Protein binding: >96%
Metabolism: Hepatic via CYP2C8 and 3A4 to active N-desethylamiodarone metabolite; possible enterohepatic recirculation
Bioavailability: Oral: ~50% (range: 35% to 65%)
Half-life elimination: Note: Half-life is shortened in children vs adults
Amiodarone:
Single dose: 58 days (range: 15 to 142 days)
Oral chronic therapy: Mean range: 40 to 55 days (range: 26 to 107 days)
IV single dose: Mean range: 9 to 36 days
N-desethylamiodarone (active metabolite):
Single dose: 36 days (range: 14 to 75 days)
Oral chronic therapy: 61 days
IV single dose: Mean range: 9 to 30 days
Time to peak, serum: Oral: 3 to 7 hours
Excretion: Feces; urine (<1% as unchanged drug)
Hepatic function impairment: After a single dose of amiodarone injection in cirrhotic patients, Cmax was significantly lower and average concentration values were seen for desethylamiodarone, but mean amiodarone levels were unchanged.
Older adult: Clearance is lower and half-life is increased.
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