PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Anti-arrhythmics, Class III

    BOXED WARNING

    AV block, bradycardia, cardiac arrhythmias, QT prolongation, requires an experienced clinician, sick sinus syndrome, torsade de pointes

    According to the manufacturer black box warnings, amiodarone is only indicated for use in patients with life-threatening arrhythmias due to the potential for drug toxicity; use requires an experienced clinician who is familiar with the drug's risks and experienced in the treatment of life-threatening arrhythmias. Also included in the black box warnings provided by the manufacturer is information regarding the difficulties associated with effectively and safely using amiodarone. The manufacturer recommends that patients be hospitalized during administration of the loading dose. Because of the variability of the absorption and elimination of amiodarone, maintenance dose selection is difficult, and most patients require dosage decrease or discontinuation. Introduction of another antiarrhythmic agent after discontinuation of amiodarone introduces further risk due to the gradual and unpredictable elimination of amiodarone. Amiodarone is contraindicated in patients with severe sinus node dysfunction or sick sinus syndrome, advanced AV block (second or third degree), and when episodes of bradycardia have caused syncope (except when used in conjunction with a pacemaker). Amiodarone, like other antiarrhythmics, can worsen cardiac arrhythmias, a risk that may be enhanced by the presence of concomitant antiarrhythmics. Arrhythmia exacerbation during amiodarone therapy has been reported in approximately 2—5% in most series, and has included new ventricular fibrillation, incessant ventricular tachycardia, increased resistance to cardioversion, and polymorphic ventricular tachycardia associated with QTc prolongation (and torsade de pointes). In addition, amiodarone has caused symptomatic bradycardia or sinus arrest with suppression of escape foci in 2—4% of patients. Amiodarone should be avoided where possible in patients with congenital or acquired QT prolongation syndromes or a history of torsade de pointes. Amiodarone has also been associated with QT prolongation, with or without torsade de pointes, in patients receiving concomitant therapy with certain fluoroquinolones, macrolide antibiotics, and systemic azole antifungals. According to the manufacturer, the need to coadminister amiodarone with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits (see Drug Interactions).

    Amiodarone-induced lung toxicity, chronic obstructive pulmonary disease (COPD), pneumonitis, pulmonary disease, pulmonary fibrosis, respiratory distress syndrome, respiratory insufficiency, surgery

    Potentially fatal amiodarone-induced lung toxicity may occur during therapy. Hypersensitivity pneumonitis and/or interstitial/alveolar pulmonary fibrosis has resulted in clinically significant disease at rates of 10—17% in some series of patients with ventricular arrhythmias given doses of approximately 400 mg/day. Therefore, amiodarone should be used with extreme caution, if at all, in patients with preexisting pulmonary disease (i.e., chronic obstructive pulmonary disease (COPD), reduced diffusion capacity, respiratory insufficiency). Post-marketing reports of early, acute-onset (days to weeks) pulmonary injury have been reported in patients receiving IV amiodarone. Clinical manifestations have included pulmonary infiltrates and/or mass on X-ray, pulmonary alveolar hemorrhage, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, hypoxia, and/or respiratory failure. Although most patients respond to vigorous respiratory therapy, death has been reported rarely. Rare cases of acute respiratory distress syndrome (ARDS) have been reported postoperatively in patients receiving oral amiodarone who have undergone cardiac or noncardiac surgery. Thorough pulmonary function testing including diffusion capacity, radiographic and clinical evaluation should be performed prior to and throughout the course of amiodarone therapy to assess the potential development of pulmonary toxicity.

    Amiodarone-induced liver toxicity, hepatic disease, hepatitis, hepatotoxicity

    Amiodarone should be used cautiously in patients with preexisting structurally degenerative hepatic disease (e.g., cirrhosis), as the metabolism and/or elimination of amiodarone and active metabolite DEA could be reduced, potentially increasing the risk of hepatotoxicity. Asymptomatic elevations in hepatic enzyme concentrations are seen frequently in patients taking amiodarone. Although rare, fatal hepatotoxicity (e.g., hepatic failure, hepatitis) has occurred secondary to amiodarone therapy and is accompanied by severely elevated hepatic enzymes. Baseline and periodic evaluation of hepatic enzymes is recommended for all patients receiving amiodarone. The manufacturer recommends considering dosage reduction or discontinuation of amiodarone therapy if amiodarone-induced liver toxicity occurs as manifested by elevated serum hepatic enzyme concentrations three times the upper limit of normal (ULN) or two times the ULN in a patient with elevated baseline hepatic enzymes. Acute, centrolobular confluent hepatocellular necrosis leading to hepatic coma, renal failure, and death has been associated with the administration of amiodarone injection at a concentration much higher and an infusion rate much faster than that recommended by the manufacturer.

    DEA CLASS

    Rx

    DESCRIPTION

    Class III Antiarrhythmic agent; used for many indications including refractory life-threatening ventricular arrhythmias, pharmacological cardioversion/maintenance of AFIB, prevention of atrial fibrillation after cardiac surgery, treatment of cardiac arrest associated with VFIB or pulseless VT; possesses many ADRs, some of which are severe and potentially fatal, but not associated with proarrhythmias as frequently as other antiarrhythmics; ADRs are less frequent at lower daily dosages.

    COMMON BRAND NAMES

    Cordarone, Nexterone, Pacerone

    HOW SUPPLIED

    Amiodarone/Amiodarone Hydrochloride/Cordarone/Nexterone Intravenous Inj Sol: 1mL, 50mg, 100mL, 150mg, 200mL, 360mg
    Amiodarone/Amiodarone Hydrochloride/Cordarone/Pacerone Oral Tab: 100mg, 200mg, 400mg

    DOSAGE & INDICATIONS

    For the treatment of life-threatening recurrent ventricular fibrillation or hemodynamically unstable (symptomatic) sustained ventricular tachycardia, including post-myocardial infarction (MI) patients.
    NOTE: See resuscitation indication for ECC/AHA dosage and administration guidelines for ventricular fibrillation or pulseless ventricular tachycardia.
    NOTE: Amiodarone is FDA-approved for the treatment and prophylaxis of frequently recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia in patients refractory to other therapy.
    Oral dosage
    Adults

    Initially, 800 to 1600 mg/day PO in single or divided doses for a minimum of 1 to 3 weeks in a monitored setting until an initial therapeutic response is achieved (suppression of life-threatening ventricular ectopy and reduction of total ventricular ectopy), followed by 600 to 800 mg/day PO in one or divided doses for about one month. Then reduce dosage again to the lowest effective maintenance dose, usually 400 mg/day PO in one or divided doses. Some patients can be controlled on lower doses (e.g., 200 to 300 mg/day PO). Amiodarone did not increase overall mortality in two controlled clinical trials (CAMIAT and EMIAT) of post-MI patients followed up to 2 years. Patients in CAMIAT qualified with ventricular arrhythmias, and those randomized to amiodarone received weight- and response-adjusted doses of 200 to 400 mg/day. Patients in EMIAT qualified with an ejection fraction less than 40%, and those randomized to amiodarone received fixed doses of 200 mg/day. Both studies had weeks-long loading dose schedules.

    Children†

    Loading doses of 10 to 15 mg/kg/day PO or 600 to 800 mg/1.73 m2/day PO should be employed for 4 to 14 days or until adequate control of arrhythmias or prominent adverse effects occur. The loading dose should be given in 1 to 2 divided doses per day. Dosage should then be reduced to 5 mg/kg/day or 200 to 400 mg/1.73 m2 given PO once daily for several weeks. If arrhythmias do not recur, reduce to lowest effective dose possible. Use the minimal effective dose, which is usually about 2.5 mg/kg/day. Doses for children less than 1 year should be calculated based on BSA (body surface area).

    Intravenous dosage
    Adults

    If the patient is being treated for pulseless ventricular tachycardia/fibrillation or stable ventricular tachycardia during the emergency ACLS setting, see dosage guidelines for CPR. The approved IV dosage recommended by the manufacturer for life-threatening ventricular arrhythmias for the first 24 hours is the following infusion regimen: initial IV rapid infusion of 150 mg over the first 10 minutes. Then begin a slow IV infusion of 1 mg/min for the next 6 hours (total dose infused = 360 mg). Then, the infusion rate is lowered to 0.5 mg/min for the next 18 hours (total dose infused = 540 mg). After the first 24 hours, a maintenance IV infusion of 0.5 mg/minute (720 mg/day) is recommended. Adjust infusion rate to achieve effective arrhythmia suppression. Intravenous amiodarone is not intended for maintenance therapy and should not be administered for longer than 3 weeks. NOTE: The dose of amiodarone may be individualized, however, during controlled clinical trials doses more than 2100 mg were associated with an increased risk of hypotension.

    Conversion from intravenous to oral therapy
    Adults

    If the duration of IV infusion was less than 1 week, the initial oral dose is 800 to 1600 mg/day PO. If the duration of IV infusion was 1 to 3 weeks, the initial oral dose is 600 to 800 mg/day PO. If the duration of IV infusion was longer than 3 weeks, the initial oral dose is 400 mg/day PO.

    For the treatment of ventricular arrhythmias during cardiopulmonary resuscitation† (CPR).
    For cardiac arrest associated with ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) unresponsive to CPR.
    Intravenous and Intraosseous† dosage
    Adults

    300 mg IV, which may be followed by 150 mg IV. The same dosage may be given via the intraosseous route when IV access is not available. In a study of prehospital cardiac arrest associated with VF, amiodarone 300 mg was diluted with 20 mL of 5% Dextrose Injection and given rapidly by peripheral IV catheter with 5% Dextrose Injection infusing. Clinical practice guidelines suggest amiodarone for patients who are unresponsive to CPR, defibrillation, and a vasopressor; CPR should not be interrupted to administer drug therapy.

    Neonates, Infants, Children, and Adolescents

    5 mg/kg/dose IV; may repeat dose twice up to 15 mg/kg IV (Max single dose: 300 mg IV). May administer IV push for ventricular fibrillation or pulseless ventricular tachycardia. The same dosage may be given via the intraosseous route when IV access is not available.

    For hemodynamically stable ventricular tachycardia (monomorphic or polymorphic) or wide-complex tachycardia of unknown origin during CPR (perfusing ventricular arrhythmias).
    Intravenous or Intraosseous† dosage
    Adults

    150 mg IV (diluted in 100 mL of 5% Dextrose Injection) over 10 minutes, followed by 1 mg/minute continuous IV infusion for 6 hours then 0.5 mg/minute continuous IV infusion for 18 hours. Supplemental 150 mg IV doses may be repeated every 10 minutes as needed up to a maximum cumulative dosage of 2.2 g IV per 24 hours. The same dosage may be given via the intraosseous route when IV access is not available.

    Neonates, Infants, Children, and Adolescents

    5 mg/kg/dose IV; may repeat dose twice up to 15 mg/kg IV (Max single dose: 300 mg IV). Slower administration (e.g., over 20 to 60 minutes) is recommended for patients with a perfusing rhythm. The same dosage may be given via the intraosseous route when IV access is not available.

    For the treatment of atrial fibrillation†, atrial flutter†, or paroxysmal supraventricular tachycardia (PSVT)†.
    Intravenous dosage
    Adults

    150 mg IV over 10 minutes, followed by 1 mg/minute continuous IV infusion for 6 hours then 0.5 mg/minute continuous IV infusion for 18 hours. After 24 hours, change to oral dosing or consider decreasing rate to 0.25 mg/minute. Clinical practice guidelines suggest oral amiodarone as a reasonable option for pharmacological cardioversion of atrial fibrillation. For maintenance of sinus rhythm, consider amiodarone only after consideration of its risks and when other agents have failed or are contraindicated.

    Neonates, Infants, Children, and Adolescents

    5 mg/kg/dose IV as a bolus/loading dose infused over 1 hour followed by a continuous infusion of 5 mcg/kg/minute IV titrated to a maximum of 15 mcg/kg/min IV. A second bolus ranging from 1 to 5 mg/kg/dose has been administered to some patients (Max initial bolus: 10 mg/kg IV). Dosing protocols administering the bolus dose in smaller aliquots of 1 to 2 mg/kg/dose IV over 5 to 10 minutes have been recommended in order to reduce patient exposure to plasticizers, such as DEHP, which may be leached out of IV tubing, including polyvinyl chloride (PVC) tubing, by certain formulations of amiodarone.

    Oral dosage
    Adults

    400 to 800 mg/day PO in divided doses for 2 to 4 weeks to a total load of up to 10 g then 100 to 200 mg PO once daily. Clinical practice guidelines suggest oral amiodarone as a reasonable option for pharmacological cardioversion of atrial fibrillation. For maintenance of sinus rhythm, consider amiodarone only after consideration of its risks and when other agents have failed or are contraindicated. The SAFE-T trial comparing amiodarone and sotalol to restore and maintain sinus rhythm utilized an amiodarone dosing regimen of 800 mg/day PO for 14 days, then 600 mg/day for 14 days, then 300 mg/day for the first year, and 200 mg/day thereafter. Results from the SAFE-T trial indicate the superiority of amiodarone over sotalol for maintaining sinus rhythm in patients with persistent atrial fibrillation. Various loading and maintenance dosage regimens for oral amiodarone have been utilized. One source recommends a loading dose of 800 to 1600 mg/day PO for 1 to 3 weeks, followed by 800 mg/day for the next 2 to 4 weeks, with a maintenance dose of 300 mg/day or less. Another source describes utilizing a loading dose of 800 mg PO twice daily for 2 weeks followed by 400 mg/day for the next 2 weeks, with a maintenance dose of 200 mg/day. The Canadian Trial of Atrial Fibrillation (CTAF) utilized a dosage regimen of 10 mg/kg PO once daily for 2 weeks, followed by 300 mg once daily for 4 weeks, followed by a maintenance dose of 200 mg PO once daily. The CTAF study demonstrated greater efficacy of amiodarone compared to sotalol or propafenone in preventing recurrent atrial fibrillation.

    Children and Adolescents

    10 mg/kg/day PO for 7 to 10 days followed by 3 to 5 mg/kg/day PO once daily has been used in 13 patients ranging in age from 2 years to 15 years. Combination therapy with propranolol was used in 2 patients; ten of 13 patients had complete response to therapy. In another report, amiodarone 10 mg/kg PO for 10 days followed-up by a maintenance dose of 5 mg/kg/day (7.5 mg/kg/day in children younger than 2 years) was administered. The dose was maintained for at least 1 month and if the arrhythmia did not recur, attempts to decrease the dose were made every 3 to 4 months. Once a stable dose was achieved, it was administered 5 days/week. If amiodarone was initially effective but the arrhythmia later recurred, the dose was titrated up to a max of 25 mg/kg/day. The mean maintenance dose was 7.7 mg/kg/day (range 1.5 to 25 mg/kg/day) with a mean duration of therapy of 2.3 years. Alternatively, an initial dose of 800 mg/1.73 m2 PO per day for 2 weeks has been used, followed by 400 mg/1.73 m2 PO per day, given 5 days per week. Patients received the drug for an average of 4.1 months with partial or complete response occurring in 93% of patients. Although the reported efficacy rates of amiodarone in pediatric patients are high (84% to 93% for SVT), it is often reserved for the treatment of life-threatening arrhythmias or arrhythmias resistant to other therapies due to the concern for serious adverse reactions with long-term use.

    Neonates and Infants

    A loading dose of 10 or 20 mg/kg/day PO divided twice daily for 7 to 10 days followed-up by a maintenance dose of 5 to 20 mg/kg/day PO has been administered. Propranolol (2 to 4 mg/kg/day) was added in patients who did not initially respond to amiodarone. In one study, the dose for the load was given at the discretion of the treating physician, but those infants with tachycardias that were difficult to control were typically given the higher dose. In another study, the mean initial doses for arrhythmia suppression and maintenance based on body weight and body surface area in patients younger than 1 year of age with various arrhythmias were 15.3 mg/kg/day and 8.2 mg/kg/day and 261 mg/m2/day and 204 mg/m2/day, respectively. These doses were significantly higher than doses required in patients older than 1 year of age when compared on a mg/kg basis but not when compared on a mg/m2 basis. The authors recommended that dosing be based on body surface area in this age group rather than weight. Alternatively, an initial dose of 800 mg/1.73 m2 PO per day for 2 weeks, followed-up by 400 mg/1.73 m2 PO per day given 5 days per week, has been used in a study in pediatric patients with various arrhythmias (n = 135, age 0 to 15 years). Although the reported efficacy rates of amiodarone in pediatric patients are high (84% to 93% for SVT), it is often reserved for the treatment of life-threatening arrhythmias or arrhythmias resistant to other therapies due to the concern for serious adverse reactions with long-term use.

    For primary atrial fibrillation prophylaxis† in patients receiving cardiac surgery†.
    NOTE: Amiodarone is listed as an alternative treatment option to other frontline treatment strategies (e.g., beta-blockers) for the prevention of atrial fibrillation after coronary artery bypass graft (CABG) surgery.
    Oral dosage
    Adults

    Initially, 600 mg PO once daily for 7 days preoperatively, then 200 mg once daily postoperatively until hospital discharge. In a double-blind, placebo-controlled study, the efficacy of oral amiodarone for the prevention of atrial fibrillation was assessed in patients with normal sinus rhythm who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass. Sixty-four patients received 200 mg PO three times per day for seven days (beginning an average of 13 days prior to surgery), then 200 mg once daily during hospitalization and until discharge (mean total cumulative dosage 4.8 g). Patients with a resting heart rate < 50 bpm or uncontrolled heart failure were excluded. Postoperative atrial fibrillation occurred in 25% of patients in the amiodarone group and 53% in the placebo group (p = 0.003). Patients in the amiodarone group were hospitalized for significantly fewer days than patients assigned to placebo (6.5 vs. 7.9 days, p = 0.04). Further evidence supporting the efficacy of amiodarone in prevention of atrial fibrillation was reported in the PAPABEAR trial. Patients undergoing nonemergent CABG and/or valve replacement or repair were randomized to receive either oral amiodarone 10 mg/kg/day, in 2 divided doses, for 6 days before and 6 days after surgery for a total of 13 perioperative days, or placebo. Postoperative atrial tachyarrhythmias occurred significantly less often in the amiodarone group than the placebo group (16.1% vs. 29.5%, respectively). Although the use of amiodarone in post-CABG patients has been established as an alternative therapy, less favorable results have been documented with intraoperative amiodarone use during CABG surgery. A study of intraoperative IV amiodarone to prevent atrial fibrillation in patients undergoing CABG, showed that it did not prevent new onset of atrial fibrillation and had no beneficial effects on outcome (e.g., perioperative complications, early mortality, duration of hospital stay).

    For the prevention of sudden cardiac death in patients with heart failure†.
    Oral dosage
    Adults

    600 to 800 mg PO once daily for 7 to 14 days; then, a maintenance dose of 200 to 400 mg PO daily has been studied. Although studies indicate amiodarone suppresses ventricular arrhythmias and improves left ventricular ejection fraction (LVEF) in heart failure patients, its effect on mortality remains inconclusive. Because of the neutral effects on mortality, clinical practice guidelines recommend the use of amiodarone for the treatment of arrhythmias in patients with heart failure.

    †Indicates off-label use

    MAXIMUM DOSAGE

    No specific maximum dosage guidelines are available. Amiodarone dosage is individualized according to clinical goals, phase of dosage titration, and close monitoring of efficacy and safety parameters.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dosage reduction with cautious monitoring of drug efficacy and safety (e.g., hepatic function) is prudent (see Contraindications section). Amiodarone and DEA (active metabolite) are primarily eliminated by hepatic metabolism.

    Renal Impairment

    No dosage adjustment is needed.
     
    Intermittent hemodialysis 
    No dosage adjustment is needed.

    ADMINISTRATION

    Oral Administration

    May be taken without regard to meals. Administer consistently with or without food due to the variable effect of food on oral absorption. To minimize gastrointestinal side effects, administer with meals.

    Oral Liquid Formulations

    Extemporaneous suspension: Shake well before administering. Measure dosage with calibrated measuring device.

    Extemporaneous Compounding-Oral

    Extemporaneous 5 mg/mL amiodarone oral suspension preparation:
    Crush five (5) 200 mg amiodarone tablets in a mortar and grind to a fine powder.
    Mix together a 1:1 mixture of a vehicle consisting of 100 mL of Ora-Plus and 100 mL of Ora-Sweet or Ora-Sweet SF.
    Add an adequate amount of bicarbonate solution (5 g/100 mL in distilled water) to the vehicle mixture to adjust the pH to between 6 and 7.
    Add a small amount of the vehicle mixture to the crushed tablets and mix to form a uniform paste.
    Add geometric amounts of the vehicle to almost the desired volume while mixing.
    Transfer the contents of the mortar to a graduated cylinder and add remaining vehicle to a total volume of 200 mL.
    Storage: The resulting suspension is stable for 42 days at 25 degrees C or 91 days at 4 degrees C when stored in plastic bottles.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Dilution
    For rapid infusion during cardiopulmonary resuscitation (CPR): The need for dilution is no longer specified when administering amiodarone during cardiac arrest, a situation in which any delay in therapy should be avoided. Specific information regarding the use of undiluted amiodarone in pediatric patients is not available; for small doses, dilution may be necessary for accurate measurement and administration.
    Dilute amiodarone in 5% Dextrose Injection only.
    Commercially available premixed solutions are available; no further dilution is required for premixed solutions.
    For rapid loading infusion: Add 150 mg (3 mL) of amiodarone 50 mg/mL injection to 100 mL 5% Dextrose Injection (final concentration = 1.5 mg/mL).
    For slow loading infusion: Add 900 mg (18 mL) of amiodarone 50 mg/mL injection to 500 mL 5% Dextrose Injection (final concentration = 1.8 mg/mL).
    For maintenance infusion: Dilute amiodarone 50 mg/mL injection to a final concentration of 1 to 6 mg/mL.
    Data regarding concentration for infusion in pediatric patients is not available.
    For infusions lasting more than 1 hour, do not exceed a concentration more than 2 mg/mL unless administered via a central venous catheter. Intravenous amiodarone concentrations more than 3 mg/mL have been associated with a high incidence of peripheral vein phlebitis.
    Infusions lasting more than 2 hours must be administered in polyolefin or glass bottles containing 5% Dextrose Injection. Do not use evacuated glass containers for admixing, as incompatibility with a buffer in the container may cause precipitation.
    Storage: Amiodarone diluted in 5% Dextrose Injection is stable at concentrations of 1 to 6 mg/mL for 2 hours in polyvinyl chloride (PVC) and for 24 hours in polyolefin or glass bottles at room temperature. Nexterone premixed solution is for single-use only; discard any unused portion.
     
    General Administration
    Only administer using a volumetric infusion pump. Use an in-line filter during administration.
    Administer via a central venous catheter whenever possible.
    Use PVC tubing during administration. The recommended adult dosing regimens have taken into account the amount of amiodarone adsorbed to PVC tubing.
    A warning by the FDA has noted the concern that IV amiodarone has been found to leach out plasticizers, such as di-(2-ethylhexyl)phthalate (DEHP) from IV tubing, including PVC tubing, which may lead to safety concerns for pediatric patients. Conventional amiodarone injection contains polysorbate 80, which is also known to leach DEHP from PVC tubing. The degree of leaching increases when infusing high concentrations and low flow rates. It is important to administer at recommended dosage and infusion rates. Nexterone premixed containers do not contain polysorbate 80.
    Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is complete.
     
    IV Push During CPR
    When administering amiodarone peripherally via IV push, follow peripheral injection of resuscitation drugs with a bolus injection of 10 to 20 mL IV fluid. Elevate the extremity for 10 to 20 seconds following peripheral injection to facilitate drug delivery to the central circulation. Although peak drug serum concentrations are lower and onset of action is delayed when drugs are administered via peripheral vs. central sites, CPR should not be interrupted for central line placement. Drugs generally reach the central circulation within 1 to 2 minutes when administered peripherally.
     
    IV Infusion
    For rapid IV loading infusion, breakthrough ventricular fibrillation, or hemodynamically unstable (symptomatic) ventricular tachycardia: Infuse IV at a rate of 15 mg/minute to minimize the potential for hypotension. The infusion rate should not exceed 30 mg/minute.
    For slow IV loading infusion: Infuse IV at a rate of 1 mg/minute.
    Maintenance infusion: Infuse IV at a rate of 0.5 mg/minute. Rate may be adjusted to achieve effective arrhythmia suppression.

    Other Injectable Administration

    Intraosseous Administration
    NOTE: Amiodarone is not FDA-approved for intraosseous administration.
    During cardiopulmonary resuscitation, the same dosage as that for IV administration may be given via the intraosseous route when IV access is not available.

    STORAGE

    Cordarone:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Nexterone:
    - Avoid excessive heat (above 104 degrees F)
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Protect from freezing
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in carton until time of use
    Pacerone:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Iodine hypersensitivity

    Due to the incorporation of iodine into its chemical structure, amiodarone is contraindicated in patients with known iodine hypersensitivity.

    AV block, bradycardia, cardiac arrhythmias, QT prolongation, requires an experienced clinician, sick sinus syndrome, torsade de pointes

    According to the manufacturer black box warnings, amiodarone is only indicated for use in patients with life-threatening arrhythmias due to the potential for drug toxicity; use requires an experienced clinician who is familiar with the drug's risks and experienced in the treatment of life-threatening arrhythmias. Also included in the black box warnings provided by the manufacturer is information regarding the difficulties associated with effectively and safely using amiodarone. The manufacturer recommends that patients be hospitalized during administration of the loading dose. Because of the variability of the absorption and elimination of amiodarone, maintenance dose selection is difficult, and most patients require dosage decrease or discontinuation. Introduction of another antiarrhythmic agent after discontinuation of amiodarone introduces further risk due to the gradual and unpredictable elimination of amiodarone. Amiodarone is contraindicated in patients with severe sinus node dysfunction or sick sinus syndrome, advanced AV block (second or third degree), and when episodes of bradycardia have caused syncope (except when used in conjunction with a pacemaker). Amiodarone, like other antiarrhythmics, can worsen cardiac arrhythmias, a risk that may be enhanced by the presence of concomitant antiarrhythmics. Arrhythmia exacerbation during amiodarone therapy has been reported in approximately 2—5% in most series, and has included new ventricular fibrillation, incessant ventricular tachycardia, increased resistance to cardioversion, and polymorphic ventricular tachycardia associated with QTc prolongation (and torsade de pointes). In addition, amiodarone has caused symptomatic bradycardia or sinus arrest with suppression of escape foci in 2—4% of patients. Amiodarone should be avoided where possible in patients with congenital or acquired QT prolongation syndromes or a history of torsade de pointes. Amiodarone has also been associated with QT prolongation, with or without torsade de pointes, in patients receiving concomitant therapy with certain fluoroquinolones, macrolide antibiotics, and systemic azole antifungals. According to the manufacturer, the need to coadminister amiodarone with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits (see Drug Interactions).

    Cardiogenic shock, heart failure, hypotension, hypovolemia, ventricular dysfunction

    Due to potential negative inotropic effects, amiodarone generally should be used cautiously in patients with congestive heart failure or left ventricular dysfunction (LVD). However, amiodarone may be preferred to alternative antiarrhythmics in patients with severe ventricular impairment due to its lower incidence of adverse hemodynamic and proarrhythmic effects relative to other antiarrhythmic agents. When antiarrhythmic therapy is necessary, amiodarone may be useful for the treatment of atrial and ventricular arrhythmias in patients with heart failure or LV dysfunction (EF < 40%). Amiodarone is contraindicated for use in cardiogenic shock due to its adverse effect profile which includes hypotension, heart failure, and cardiogenic shock. Intravenous amiodarone should be used with caution in patients at risk for hypotension; blood pressure should be monitored closely and volume expansion with blood or plasma should be used when appropriate in patients with pre-existing hypotension or hypovolemia.

    Amiodarone-induced lung toxicity, chronic obstructive pulmonary disease (COPD), pneumonitis, pulmonary disease, pulmonary fibrosis, respiratory distress syndrome, respiratory insufficiency, surgery

    Potentially fatal amiodarone-induced lung toxicity may occur during therapy. Hypersensitivity pneumonitis and/or interstitial/alveolar pulmonary fibrosis has resulted in clinically significant disease at rates of 10—17% in some series of patients with ventricular arrhythmias given doses of approximately 400 mg/day. Therefore, amiodarone should be used with extreme caution, if at all, in patients with preexisting pulmonary disease (i.e., chronic obstructive pulmonary disease (COPD), reduced diffusion capacity, respiratory insufficiency). Post-marketing reports of early, acute-onset (days to weeks) pulmonary injury have been reported in patients receiving IV amiodarone. Clinical manifestations have included pulmonary infiltrates and/or mass on X-ray, pulmonary alveolar hemorrhage, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, hypoxia, and/or respiratory failure. Although most patients respond to vigorous respiratory therapy, death has been reported rarely. Rare cases of acute respiratory distress syndrome (ARDS) have been reported postoperatively in patients receiving oral amiodarone who have undergone cardiac or noncardiac surgery. Thorough pulmonary function testing including diffusion capacity, radiographic and clinical evaluation should be performed prior to and throughout the course of amiodarone therapy to assess the potential development of pulmonary toxicity.

    Amiodarone-induced liver toxicity, hepatic disease, hepatitis, hepatotoxicity

    Amiodarone should be used cautiously in patients with preexisting structurally degenerative hepatic disease (e.g., cirrhosis), as the metabolism and/or elimination of amiodarone and active metabolite DEA could be reduced, potentially increasing the risk of hepatotoxicity. Asymptomatic elevations in hepatic enzyme concentrations are seen frequently in patients taking amiodarone. Although rare, fatal hepatotoxicity (e.g., hepatic failure, hepatitis) has occurred secondary to amiodarone therapy and is accompanied by severely elevated hepatic enzymes. Baseline and periodic evaluation of hepatic enzymes is recommended for all patients receiving amiodarone. The manufacturer recommends considering dosage reduction or discontinuation of amiodarone therapy if amiodarone-induced liver toxicity occurs as manifested by elevated serum hepatic enzyme concentrations three times the upper limit of normal (ULN) or two times the ULN in a patient with elevated baseline hepatic enzymes. Acute, centrolobular confluent hepatocellular necrosis leading to hepatic coma, renal failure, and death has been associated with the administration of amiodarone injection at a concentration much higher and an infusion rate much faster than that recommended by the manufacturer.

    Diarrhea, electrolyte imbalance, hypokalemia, hypomagnesemia

    Correct any electrolyte imbalance including hypokalemia, hypomagnesemia, or hypocalcemia prior to initiation of amiodarone. Give special attention to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or in patients receiving concomitant diuretics, laxatives, systemic corticosteroids, intravenous amphotericin B, or other drugs affecting electrolyte levels. Electrolyte imbalance may predispose the patient to the development of proarrhythmias as well as potentially decrease the efficacy of amiodarone.

    Goiter, hyperthyroidism, hypothyroidism, thyroid disease, thyrotoxicosis

    Amiodarone should be used cautiously in patients with preexisting thyroid disease (including thyrotoxicosis, thyroid nodules, goiter, or other thyroid dysfunction) as the drug may exacerbate or cause either hypothyroidism or hyperthyroidism. Older patients may be more sensitive to the thyrotoxic effects of amiodarone. Amiodarone-induced hyperthyroidism usually poses a greater hazard to the patient than hypothyroidism because of the possibility of arrhythmia breakthrough or arrhythmia exacerbation, which may result in fatality. If any new signs of arrhythmia appear, the possibility of hyperthyroidism should be considered. A careful assessment of the potential risks and benefits of administering amiodarone must be made in patients with thyroid dysfunction to minimize the risk of arrhythmias. Appropriate baseline and periodic evaluation of thyroid function tests is recommended for all patients treated with amiodarone. There have been post-marketing reports of thyroid nodules/thyroid cancer in patients treated with amiodarone; in some instances, hyperthyroidism has also been present. Although human data are lacking, animal studies (rat model) show a statistically significant, dose-related increase in the incidence of thyroid tumors (follicular adenoma and/or carcinoma). The incidence of thyroid tumors in rats was significantly greater than the incidence in control animals even at the lowest dose tested (5 mg/kg/day, approximately 0.08 times the maximum recommended human maintenance dosage).

    Cataracts, Fabry disease, optic neuritis, visual disturbance

    Visual impairment or disturbances, including halo vision, blurred vision, photophobia, and dry eyes, occur in up to 10% of the patients receiving amiodarone therapy. Lens opacities (i.e., cataracts), scotomata, corneal degeneration, and macular degeneration have been reported. The lens opacities are minute, white-yellow punctate deposits within the pupillary aperture. Optic nerve changes have also been reported and are described as papillopathy, optic neuritis, or neuropathy. In some cases, patients have progressed to permanent blindness. Cases of optic neuropathy and/or optic neuritis, usually resulting in visual disturbance, have been reported in patients treated with amiodarone. In some cases, visual impairment has progressed to permanent blindness. Regular ophthalmic examination, including funduscopy and slit-lamp examination, is recommended in all patients during administration of amiodarone. An ophthalmic examination is also recommended if symptoms of visual impairment appear. If optic neuropathy and/or neuritis is detected, the use of amiodarone should be reconsidered. The use of amiodarone should be approached with caution in patients with Fabry disease, particularly those with ocular symptoms. Amiodarone can cause a keratopathy that is clinically and ultrastructurally indistinguishable from keratopathy caused by Fabry disease; this drug-induced keratopathy is reversible with drug cessation. In addition, amiodarone poses a theoretical risk of decreased intracellular alpha-galactosidase A activity.

    Geriatric

    Geriatric subjects over 65 years of age have a slower clearance of amiodarone compared to younger subjects, with a prolongation in half-life from about 20 days to 47 days. Elderly patients may be more sensitive to the thyrotoxic and neurotoxic effects of amiodarone. Insufficient data are available to evaluate the dose-response of amiodarone in elderly patients. Initiate amiodarone dosage cautiously in elderly patients, starting at the lower end of the adult dosage range; monitor clinical response closely. According to the Beers Criteria, amiodarone is considered a potentially inappropriate medication (PIM) for use in geriatric patients and should be avoided as first-line treatment of atrial fibrillation in this population, unless the patient has heart failure or substantial left ventricular hypertrophy. Amiodarone is effective for maintaining sinus rhythm but has greater toxicities than other anti-arrhythmics used in atrial fibrillation. Amiodarone may be a reasonable first-line agent in patients with concomitant heart failure or substantial left ventricular hypertrophy if rhythm control is preferred over rate control. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to the OBRA guidelines, antiarrhythmics can have serious adverse effects (e.g., impairment of mental function, appetite, behavior, heart function, or falls) in older individuals. The only approved indication for amiodarone is to treat documented life-threatening recurrent ventricular arrhythmias that do not respond to other antiarrhythmics or when alternative agents are not tolerated. However, a common off-label use of amiodarone is the treatment of atrial fibrillation. The literature suggests that in many higher risk individuals, alternative approaches are equally effective and less toxic. It is essential to carefully consider risks and benefits, use the lowest possible dose for the shortest possible duration, closely monitor patients receiving long-term treatments, and seek and identify adverse consequences. Toxicity increases with higher doses and longer duration of use. Potentially fatal toxicities include pulmonary toxicity (hypersensitivity pneumonitis, interstitial/alveolar pneumonitis) and hepatic injury. Amiodarone may also cause hypothyroidism, exacerbate existing arrhythmias, worsen heart failure, and impair mental function and behavior. Clinically significant interactions may occur, such as with digoxin or warfarin.

    Neurological disease, peripheral neuropathy

    Use amiodarone with caution in any patient with a significant neurological disease or disorder, including peripheral neuropathy, due to the potential neurotoxic and central nervous system effects of the drug. Chronic administration of oral amiodarone in rare instances may lead to the development of peripheral neuropathy that may resolve when amiodarone is discontinued, but resolution has been slow and incomplete.

    Sunlight (UV) exposure

    Dermatologic reactions occur in roughly 15% of patients who receive amiodarone, with photosensitivity being the most common (10% of patients). Individuals who experience this effect seem to be particularly sensitive to long-wave ultraviolet-A (UVA) light, and may experience this symptom even through glass windows and/or cotton clothing. Sunscreens do not prevent this effect unless they also absorb UVA light. Opaquing screens such as zinc oxide or titanium dioxide provide adequate protection. Avoidance of sunlight (UV) exposure and protective clothing should be used to help prevent this adverse reaction.

    Halothane anesthesia

    Close perioperative monitoring is recommended in patients who are on amiodarone therapy and are undergoing surgery that requires general anesthesia. These patients may be more sensitive to the myocardial depressant and conduction effects of halothane anesthesia. Most manufacturers of corneal refractive laser surgery devices contraindicate the use of this procedure in patients taking amiodarone. Rare episodes of hypotension occurring upon the discontinuation of cardiopulmonary bypass have been reported in patients receiving amiodarone.

    Benzyl alcohol hypersensitivity, children, infants, neonates

    Although IV amiodarone is used off-label in pediatric patients including in the PALS guidelines, the manufacturer has not established safety and efficacy in children and infants and therefore does not recommend its use in pediatric patients. Limited data are available for IV amiodarone use in pediatric patients. In a pediatric trial of 61 infants and children, aged 30 days to 15 years, hypotension (36%), bradycardia (20%), and atrio-ventricular block (15%) were common dose-related adverse events and were severe or life-threatening in some cases (manufacturer data). Injection site reactions were seen in five (25%) of twenty patients receiving IV amiodarone via a peripheral vein irrespective of dose regimen. In addition, a warning was issued by the FDA regarding the concern that IV amiodarone has been found to leach out plasticizers, such as DEHP from IV tubing, including polyvinyl chloride (PVC) tubing, which may lead to safety concerns for pediatric patients. The degree of leaching increases when infusing amiodarone at high concentrations and low flow rates. An expert panel recently concluded that, based on data from animal studies, there was concern that exposure to DEHP may adversely affect male reproductive tract development during fetal, infant, and toddler stages of development if the exposure in these immature stages is several fold higher than in adults, a situation that might be associated with intensive medical procedures such as those used in critically ill infants. The maximum anticipated exposure to DEHP following IV amiodarone administration under conditions of pediatric administration is estimated to be about 1.9 mg/kg/day for a 3 kg infant, which produces a safety margin of between about two-fold and seven-fold. If the use of IV amiodarone in pediatric patients is medically warranted, in order to reduce the potential exposure of these patients to plasticizers, alternative methods of dosing and administration (e.g., bolus IV dosing in 1mg/kg aliquots) may be considered (see Dosage). An additional precaution for IV amiodarone is that it contains the preservative benzyl alcohol, which can cause adverse effects in neonates or in other patients with a benzyl alcohol hypersensitivity. There have been reports of fatal 'gasping syndrome' in neonates following the administration of IV solutions containing benzyl alcohol; symptoms include a striking onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse. This warning is not associated with Nexterone, a formulation of amiodarone injection approved in January 2009 that is free of polysorbate 80 and benzyl alcohol.

    Pregnancy

    Amiodarone crosses the placenta and can cause fetal harm when administered to a pregnant woman. Inform the patient of the potential hazard to the fetus if amiodarone is administered during pregnancy or if the patient becomes pregnant while taking amiodarone. Reported risks include neonatal bradycardia; QT prolongation; periodic ventricular extrasystoles; neonatal hypothyroidism (with or without goiter) detected antenatally or in the newborn and reported even after a few days of exposure; neonatal hyperthyroxinemia; neurodevelopmental abnormalities independent of thyroid function, including speech delay and difficulties with written language and arithmetic, delayed motor development, and ataxia; jerk nystagmus with synchronous head titubation; fetal growth retardation; and premature birth. When pregnant rabbits were administered amiodarone at doses approximately 2.7 times the maximum recommended human maintenance dose (MRHD), abortions occurred in more than 90% of the animals. Doses of 0.8 times the MRHD were associated with slight displacement of the testes and increased incidence of incomplete ossification of some skull and digital bones. At doses 1.6 times the MRHD, fetal body weights were reduced, and at doses 3.2 times the MRHD, fetal resorption was increased.

    Breast-feeding

    Amiodarone and a major metabolite, desethylamiodarone (DEA), are excreted in human milk, suggesting that breast-feeding could expose the nursing infant to a significant dose of the drug. Nursing offspring of lactating rats administered amiodarone have been shown to be less viable and have reduced body-weight gains. Weigh the risk of exposing the infant to amiodarone and DEA against the potential benefit of arrhythmia suppression in the mother. When amiodarone therapy is indicated, discontinue breast-feeding.

    Infertility

    Very high concentrations of amiodarone and desethylamiodarone may be found in testes. There are reports of an elevated follicle-stimulating hormone and luteinizing hormone levels, suggestive of testicular dysfunction, in men on long-term amiodarone treatment. Consider the long half-life of amiodarone and its metabolite while planning pregnancy after discontinuation of amiodarone treatment. Amiodarone reduces fertility in animal models (males and females) at approximately 1.4 times the maximum human recommended dosage; the potential for infertility in humans is unknown.

    ADVERSE REACTIONS

    Severe

    pulmonary fibrosis / Delayed / 4.0-9.0
    bradycardia / Rapid / 2.0-5.0
    arrhythmia exacerbation / Early / 2.0-5.0
    heart failure / Delayed / 3.0-3.0
    acute respiratory distress syndrome (ARDS) / Early / 2.0-2.0
    ventricular fibrillation / Early / 0-2.0
    atrial fibrillation / Early / 0-2.0
    torsade de pointes / Rapid / 0-2.0
    hepatic failure / Delayed / 0-1.0
    bronchospasm / Rapid / Incidence not known
    respiratory arrest / Rapid / Incidence not known
    bronchiolitis obliterans / Delayed / Incidence not known
    pleural effusion / Delayed / Incidence not known
    eosinophilic pneumonia / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    hepatic necrosis / Delayed / Incidence not known
    cirrhosis / Delayed / Incidence not known
    coma / Early / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    asystole / Rapid / Incidence not known
    cardiac arrest / Early / Incidence not known
    AV block / Early / Incidence not known
    optic neuritis / Delayed / Incidence not known
    corneal degeneration / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    macular degeneration / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    periarteritis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    cyanosis / Early / Incidence not known
    thrombosis / Delayed / Incidence not known
    skin necrosis / Early / Incidence not known
    akinesia / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    epididymitis / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known

    Moderate

    constipation / Delayed / 2.0-25.0
    pneumonitis / Delayed / 2.0-15.0
    hypothyroidism / Delayed / 2.0-10.0
    elevated hepatic enzymes / Delayed / 4.0-9.0
    ataxia / Delayed / 4.0-9.0
    involuntary movements / Delayed / 4.0-9.0
    edema / Delayed / 1.0-3.0
    hyperthyroidism / Delayed / 1.0-3.0
    blurred vision / Early / 0-1.0
    photophobia / Early / 0-1.0
    peripheral neuropathy / Delayed / 0-1.0
    corneal deposits / Delayed / 10.0
    dyspnea / Early / Incidence not known
    hemoptysis / Delayed / Incidence not known
    wheezing / Rapid / Incidence not known
    hypoxia / Early / Incidence not known
    respiratory depression / Rapid / Incidence not known
    cholestasis / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    thyrotoxicosis / Delayed / Incidence not known
    goiter / Delayed / Incidence not known
    scotomata / Delayed / Incidence not known
    cataracts / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    bleeding / Early / Incidence not known
    phlebitis / Rapid / Incidence not known
    erythema / Early / Incidence not known
    hallucinations / Early / Incidence not known
    pseudotumor cerebri / Delayed / Incidence not known
    delirium / Early / Incidence not known
    confusion / Early / Incidence not known
    myopathy / Delayed / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 25.0-25.0
    anorexia / Delayed / 25.0-25.0
    nausea / Early / 25.0-25.0
    vomiting / Early / 25.0-25.0
    photosensitivity / Delayed / 10.0-10.0
    paresthesias / Delayed / 4.0-9.0
    fatigue / Early / 4.0-9.0
    dizziness / Early / 4.0-9.0
    malaise / Early / 4.0-9.0
    tremor / Early / 4.0-9.0
    flushing / Rapid / 1.0-3.0
    insomnia / Early / 1.0-3.0
    headache / Early / 1.0-3.0
    dysgeusia / Early / 1.0-3.0
    abdominal pain / Early / 1.0-3.0
    libido decrease / Delayed / 1.0-3.0
    xerophthalmia / Early / 0-1.0
    ecchymosis / Delayed / 0-1.0
    alopecia / Delayed / 0-1.0
    rash (unspecified) / Early / 0-1.0
    fever / Early / Incidence not known
    cough / Delayed / Incidence not known
    arthralgia / Delayed / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    skin discoloration / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    xerostomia / Early / Incidence not known
    weakness / Early / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Severe) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation including amiodarone.
    Acalabrutinib: (Major) Decrease the acalabrutinib dose to 100 mg PO once daily if coadministered with amiodarone. Coadministration may result in increased acalabrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Acalabrutinib is a CYP3A4 substrate; amiodarone is a moderate CYP3A4 inhibitor. In physiologically based pharmacokinetic (PBPK) simulations, the Cmax and AUC values of acalabrutinib were increased by 2- to almost 3-fold when acalabrutinib was coadministered with moderate CYP3A inhibitors.
    Acebutolol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone.
    Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Amiodarone is an inhibitor of CYP1A2 isoenzymes, and could theoretically reduce CYP1A2-mediated caffeine metabolism. The clinical significance of this potential interaction is not known.
    Acetaminophen; Butalbital; Caffeine: (Minor) Amiodarone is an inhibitor of CYP1A2 isoenzymes, and could theoretically reduce CYP1A2-mediated caffeine metabolism. The clinical significance of this potential interaction is not known.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Minor) Amiodarone inhibits CYP2D6 and may interfere with the conversion of codeine to the active metabolite, morphine. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with any other drugs that inhibit CYP2D6. (Minor) Amiodarone is an inhibitor of CYP1A2 isoenzymes, and could theoretically reduce CYP1A2-mediated caffeine metabolism. The clinical significance of this potential interaction is not known.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of amiodarone and dihydrocodeine warrants caution due to the potential for increased side effects of dihydrocodeine. Amiodarone is an inhibitor and dihydrocodeine is a substrate of CYP2D6; therefore, coadministration may lead to increased dihydrocodeine concentrations. (Minor) Amiodarone is an inhibitor of CYP1A2 isoenzymes, and could theoretically reduce CYP1A2-mediated caffeine metabolism. The clinical significance of this potential interaction is not known.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Minor) Amiodarone is an inhibitor of CYP1A2 isoenzymes, and could theoretically reduce CYP1A2-mediated caffeine metabolism. The clinical significance of this potential interaction is not known.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Minor) Amiodarone is an inhibitor of CYP1A2 isoenzymes, and could theoretically reduce CYP1A2-mediated caffeine metabolism. The clinical significance of this potential interaction is not known.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly. (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Acetaminophen; Codeine: (Minor) Amiodarone inhibits CYP2D6 and may interfere with the conversion of codeine to the active metabolite, morphine. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with any other drugs that inhibit CYP2D6.
    Acetaminophen; Dextromethorphan: (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly. (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly. (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Acetaminophen; Hydrocodone: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Acetaminophen; Oxycodone: (Major) Coadministration of amiodarone, an inhibitor of CYP3A4 and CYP2D6, and oxycodone, a substrate of CYP3A4 and CYP2D6, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Acetaminophen; Propoxyphene: (Moderate) Propoxyphene is a substrate and an inhibitor of CYP2D6. Increased serum concentrations of propoxyphene would be expected from concurrent use of a CYP2D6 inhibitor, such as amiodarone.
    Acetaminophen; Tramadol: (Moderate) Use of amiodarone concurrently with tramadol may inhibit tramadol metabolism. Decreased efficacy and possibly increased side effects may occur due to increased tramadol serum concentrations and decreased serum concentrations of the active metabolite.
    Afatinib: (Major) If the concomitant use of amiodarone and afatinib is necessary, consider reducing the afatinib dose by 10 mg per day if the original dose is not tolerated; resume the previous dose of afatinib as tolerated after discontinuation of amiodarone. Afatinib is a P-glycoprotein (P-gp) substrate and inhibitor in vitro, and amiodarone is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration of another P-gp inhibitor, ritonavir (200 mg twice daily for 3 days), 1 hour before afatinib (single dose) increased the afatinib AUC and Cmax by 48% and 39%, respectively; there was no change in the afatinib AUC when ritonavir was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with ritonavir, and 111% and 105% when ritonavir was administered 6 hours after afatinib. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise.
    Agalsidase Beta: (Minor) There are no known drug interactions with agalsidase beta; drug interactions studies were not performed. Theoretically, there is a possible drug interaction between agalsidase beta and amiodarone due to a risk of decreased intracellular alpha galactosidase A activity induced by amiodarone; coadministration of amiodarone with agalsidase beta is not recommended because a decreased response to agalsidase beta therapy could result.
    Albuterol: (Minor) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Albuterol; Ipratropium: (Minor) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Alfentanil: (Moderate) Alfentanil is a substrate of CYP3A4. Amiodarone is an inhibitor of CYP3A4. If these drugs are coadministered, monitor patients for adverse effects of alfentanil, such as hypotension, nausea, itching, and respiratory depression. Also, adverse cardiovascular effects, such as hypotension and atropine-resistant bradycardia can occur in patients receiving amiodarone who subsequently are administered anesthetics, including alfentanil. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after amiodarone discontinuation.
    Alfuzosin: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval. In addition, alfuzosin is primarily metabolized by CYP3A4 hepatic enzymes and amiodarone is a CYP3A4 inhibitor. Concurrent use may increase systemic exposure to alfuzosin and further increase the risk for QT prolongation.
    Aliskiren; Amlodipine: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as amiodarone, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when amiodarone is coadministered with amlodipine; therapeutic response should be monitored.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics. (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as amiodarone, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when amiodarone is coadministered with amlodipine; therapeutic response should be monitored.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Alprazolam: (Moderate) Amiodarone is a CYP3A4 inhibitors and may theoretically inhibit CYP3A4 metabolism of alprazolam.
    Amiloride; Hydrochlorothiazide, HCTZ: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Amitriptyline: (Major) If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Carefully asses treatmentt risks versus benefits. Amiodarone is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Drugs with a possible risk for QT prolongationthat should be used cautiously with amiodarone include tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations) or in patients with other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of such combined therapies.
    Amitriptyline; Chlordiazepoxide: (Major) If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Carefully asses treatmentt risks versus benefits. Amiodarone is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Drugs with a possible risk for QT prolongationthat should be used cautiously with amiodarone include tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations) or in patients with other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of such combined therapies. (Moderate) CYP3A4 inhibitors, such as amiodarone, may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity.
    Amlodipine: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as amiodarone, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when amiodarone is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Atorvastatin: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as amiodarone, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when amiodarone is coadministered with amlodipine; therapeutic response should be monitored. (Moderate) Monitor for signs and symptoms of myopathy in patients receiving amiodarone concurrently with atorvastatin. Amiodarone may inhibit hepatic CYP3A4 isoenzymes, and therefore has the potential to increase serum concentrations of atorvastatin.
    Amlodipine; Benazepril: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as amiodarone, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when amiodarone is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics. (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as amiodarone, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when amiodarone is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics. (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as amiodarone, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when amiodarone is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Olmesartan: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as amiodarone, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when amiodarone is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Telmisartan: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as amiodarone, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when amiodarone is coadministered with amlodipine; therapeutic response should be monitored.
    Amlodipine; Valsartan: (Moderate) Amlodipine is a CYP3A4 substrate. Theoretically, CYP3A4 inhibitors, such as amiodarone, may increase the plasma concentration of amlodipine via CYP3A4 inhibition; this effect might lead to hypotension in some individuals. Caution should be used when amiodarone is coadministered with amlodipine; therapeutic response should be monitored.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration of amiodarone and clarithromycin. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration of amiodarone and clarithromycin. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including amphotericin B.
    Amphotericin B lipid complex (ABLC): (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including amphotericin B.
    Amphotericin B liposomal (LAmB): (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including amphotericin B.
    Amphotericin B: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including amphotericin B.
    Amprenavir: (Major) Amprenavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as amiodarone, should be expected with concurrent use. Therapeutic monitoring of amiodarone concentrations is recommended.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include amiodarone.
    Apixaban: (Major) Use apixaban and amiodarone together with caution, especially in patients with significant renal dysfunction, as risk of bleeding may be increased. Amiodarone is a moderate CYP3A4 and P-glycoprotein (P-gp) inhibitor. Apixaban is a substrate of CYP3A4 and P-gp. One cohort study found an increased risk of major bleeding when amiodarone and a non-vitamin K oral anticoagulant were used together. The combination was associated with an adjusted incidence rate difference for major bleeding of 13.94 events per 1,000 person-years (99% CI, 9.76 to 18.13).
    Apomorphine: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 2-10 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended. Drugs with a possible risk for QT prolongation and TdP should be used cautiously with apomorphine.
    Aprepitant, Fosaprepitant: (Major) Avoid coadministration of amiodarone, a moderate CYP3A4 inhibitor, and aprepitant/fosaprepitant, a CYP3A4 substrate, due to substantially increased exposure of aprepitant. Fosaprepitant is rapidly converted to aprepitant; therefore, a similar interaction is likely. Increased amiodarone exposure may also occur with multi-day regimens of oral aprepitant, resulting in increased amiodarone-related adverse reactions, including QT prolongation. Amiodarone is a CYP3A4 substrate and aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate.
    Arformoterol: (Moderate) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Aripiprazole: (Major) Because both amiodarone and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving inhibitors of both CYP3A4 and CYP2D6 such as amiodarone. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of mild to moderate CYP3A4 and CYP2D6 inhibitors.
    Arsenic Trioxide: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. If possible, avoid coadministration or discontinue drugs that are known to prolong the QT interval prior to initiating arsenic trioxide therapy. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Artemether; Lumefantrine: (Major) Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with other drugs that prolong the QT interval such as amiodarone should be avoided. Consider ECG monitoring if amiodarone must be used with or after artemether; lumefantrine treatment. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Additionally, amiodarone is a substrate and inhibitor of the CYP3A4 isoenzyme. Both components of artemether; lumefantrine are CYP3A4 substrates; therefore, concomitant use may increase the serum concentrations of artemether; lumefantrine, thereby potentiating QT prolongation. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Asenapine: (Major) Avoid coadministration of amiodarone and asenapine. Both agents have been associated with QT prolongation and coadministration may result in additive effects on the QT interval. In addition, in vitro studies indicate that CYP1A2 is a primary metabolic pathway of asenapine. Inhibitors of this isoenzyme, such as amiodarone, may decrease the elimination of asenapine.
    Aspirin, ASA; Butalbital; Caffeine: (Minor) Amiodarone is an inhibitor of CYP1A2 isoenzymes, and could theoretically reduce CYP1A2-mediated caffeine metabolism. The clinical significance of this potential interaction is not known.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) Amiodarone inhibits CYP2D6 and may interfere with the conversion of codeine to the active metabolite, morphine. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with any other drugs that inhibit CYP2D6. (Minor) Amiodarone is an inhibitor of CYP1A2 isoenzymes, and could theoretically reduce CYP1A2-mediated caffeine metabolism. The clinical significance of this potential interaction is not known.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of amiodarone and dihydrocodeine warrants caution due to the potential for increased side effects of dihydrocodeine. Amiodarone is an inhibitor and dihydrocodeine is a substrate of CYP2D6; therefore, coadministration may lead to increased dihydrocodeine concentrations. (Minor) Amiodarone is an inhibitor of CYP1A2 isoenzymes, and could theoretically reduce CYP1A2-mediated caffeine metabolism. The clinical significance of this potential interaction is not known.
    Aspirin, ASA; Carisoprodol; Codeine: (Minor) Amiodarone inhibits CYP2D6 and may interfere with the conversion of codeine to the active metabolite, morphine. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with any other drugs that inhibit CYP2D6.
    Aspirin, ASA; Oxycodone: (Major) Coadministration of amiodarone, an inhibitor of CYP3A4 and CYP2D6, and oxycodone, a substrate of CYP3A4 and CYP2D6, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Atazanavir: (Major) Atazanavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as amiodarone, should be expected with concurrent use. Therapeutic monitoring of amiodarone concentrations is recommended.
    Atazanavir; Cobicistat: (Major) Atazanavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as amiodarone, should be expected with concurrent use. Therapeutic monitoring of amiodarone concentrations is recommended. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of amiodarone with cobicistat. Amiodarone is a substrate and inhibitor of CYP3A4 and an inhibitor CYP2D6, cobicistat is a substrate and inhibitor of CYP3A and CYP2D6. Concurrent use may result in elevated concentration of amiodarone.
    Atenolol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone.
    Atenolol; Chlorthalidone: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone. (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Atomoxetine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Both atomoxetine and amiodarone are considered drugs with a possible risk of torsade de pointes (TdP); therefore, the combination should be used cautiously and with close monitoring. In addition, because atomoxetine is primarily metabolized by CYP2D6, concurrent use of CYP2D6 inhibitors such as amiodarone may theoretically increase the risk of atomoxetine-induced adverse effects. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, increased pulse rate, QT prolongation).
    Atorvastatin: (Moderate) Monitor for signs and symptoms of myopathy in patients receiving amiodarone concurrently with atorvastatin. Amiodarone may inhibit hepatic CYP3A4 isoenzymes, and therefore has the potential to increase serum concentrations of atorvastatin.
    Atorvastatin; Ezetimibe: (Moderate) Monitor for signs and symptoms of myopathy in patients receiving amiodarone concurrently with atorvastatin. Amiodarone may inhibit hepatic CYP3A4 isoenzymes, and therefore has the potential to increase serum concentrations of atorvastatin.
    Avanafil: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including amiodarone, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
    Axitinib: (Moderate) Use caution if coadministration of axitinib with amiodarone is necessary, due to the risk of increased axitinib-related adverse reactions. Axitinib is primarily metabolized by CYP3A4, and to a lesser extent by CYP1A2, CYP2C19, and UGT1A1. Amiodarone is an inhibitor of CYP3A4, CYP1A2, and CYP2C19. Coadministration with a strong CYP3A4/5 inhibitor, ketoconazole, significantly increased the plasma exposure of axitinib in healthy volunteers. The manufacturer of axitinib recommends a dose reduction in patients receiving strong CYP3A4 inhibitors, but recommendations are not available for moderate or weak CYP3A4 inhibitors.
    Azilsartan; Chlorthalidone: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Azithromycin: (Major) If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well established risk of QT prolongation and torsade de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Reports of QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. QT prolongation was reported in a 68-year old woman receiving azithromycin and amiodarone. The patient had a history of stable congestive heart failure and a posterior communicating artery aneurysm. She was receiving amiodarone (200 mg/day) for over a year for paroxysmal atrial fibrillation. Additional medications included furosemide, enalapril, and aspirin. A regular sinus rhythm with normal P-R, QRST, and QTc intervals was noted prior to initiation of azithromycin therapy. Therapy with azithromycin was started at 500 mg PO on day 1, followed by 250 mg PO once daily for 4 days. Sinus bradycardia with marked QT prolongation and increased QT dispersion were noted on day 3 of treatment. Azithromycin was discontinued; QT and QTc intervals and QT dispersion returned to baseline in 4 days. Hypokalemia or hypomagnesemia were not noted in the patient and the amiodarone dose remained consistent at 200 mg/day.
    Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when coadministering bedaquiline and amiodarone. Both drugs are associated with QT prolongation. Furthermore, amiodarone may inhibit the CYP3A4 metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline electrocardiogram (ECG). An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Coadministration of ergotamine with inhibitors of CYP3A4, such as amiodarone, may potentially increase the risk of ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Coadministration should be done cautiously, and avoided when possible.
    Benazepril; Hydrochlorothiazide, HCTZ: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Bendroflumethiazide; Nadolol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone. (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Bepridil: (Severe) Bepridil is contraindicated for use with drugs that prolong the QT interval due to the risk of torsade de pointes (TdP), including Class III antiarrhythmic agents. Bepridil has Class I antiarrhythmic properties and is associated with a well-established risk of QT prolongation and TdP. Patients receiving other drugs which have the potential for QT prolongation, such as class III antiarrhythmics, have an increased risk of developing proarrhythmias during bepridil therapy.
    Betaxolol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone.
    Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving amiodarone. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving amiodarone. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; amiodarone inhibits P-gp.
    Bicalutamide: (Moderate) Bicalutamide is metabolized by CYP3A4. Drugs that are inhibitors of CYP3A4 activity, like amiodarone, may decrease the metabolism of bicalutamide and increase bicalutamide concentrations.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include amiodarone.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include amiodarone.
    Bisoprolol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone. (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering amiodarone with boceprevir due to an increased potential for serious and/or life-threatening amiodarone-related adverse events. If amiodarone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of amiodarone and boceprevir. Both amiodarone and boceprevir are substrates and inhibitors of the hepatic isoenzyme CYP3A4. Additionally amiodarone is an inhibitor of P-glycoprotein (PGP), an efflux transporter partially responsible for the metabolism of boceprevir. When used in combination, the plasma concentrations of both medications may be elevated.
    Bortezomib: (Minor) Amiodarone inhibits CYP3A4 and may increase the exposure to bortezomib and increase the risk for toxicity.
    Bosentan: (Moderate) Bosentan is an inducer of cytochrome P450 enzymes, specifically the CYP2C9 and CYP3A4 isoenzymes, and may decrease concentrations of drugs metabolized by these enzymes, including amiodarone.
    Brexpiprazole: (Moderate) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Amiodarone is a moderate inhibitor of CYP3A4. If amiodarone is used in combination with brexpiprazole and a moderate to strong CYP2D6 inhibitor, the brexpiprazole dose should be reduced and the patient should be carefully monitored for brexpiprazole-related adverse reactions. A reduction of the brexpiprazole dose to 25% of the usual dose is also recommended in patients who are poor metabolizers of CYP2D6 and are receiving a moderate CYP3A4 inhibitor.
    Brigatinib: (Moderate) Monitor for decreased efficacy of amiodarone if coadministration with brigatinib is necessary. Amiodarone is a CYP3A substrate and brigatinib induces CYP3A in vitro; plasma concentrations of amiodarone may decrease.
    Brimonidine; Timolol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone.
    Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of amiodarone. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; amiodarone is a moderate inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Brompheniramine; Guaifenesin; Hydrocodone: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Budesonide: (Major) Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia, including corticosteroids. Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy.
    Budesonide; Formoterol: (Major) Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia, including corticosteroids. Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. (Moderate) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Bumetanide: (Major) Monitor serum electrolytes if coadministration of bumetanide and amiodarone is necessary. Bumetanide therapy may cause electrolyte abnormalities (i.e., hypokalemia, hypomagnesemia) which may exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes.
    Bupivacaine; Lidocaine: (Major) Concomitant administration of lidocaine with amiodarone has been reported to cause sinus bradycardia and seizure. Amiodarone and its main metabolite, N-monodesethylamiodarone (DEA), appear to inhibit the metabolism of lidocaine by competitively inhibiting CYP3A4. Furthermore, DEA inhibits lidocaine metabolism in a concentration-dependent manner. Also, the metabolism of amiodarone to DEA appears to be competitively inhibited by lidocaine. Close correlations between amiodarone N-monodesethylase activities and the amounts of CYP3A4 and the rates of lidocaine N-monodesethylation have been observed from analyses of in vitro data. Inhibition of lidocaine metabolism is supported by in vivo data from 6 adults. The mean systemic concentration of lidocaine over 300 minutes after receipt of lidocaine hydrochloride 1 mg/kg intravenously before amiodarone treatment is 111.7 +/- 23.2 mcg/minute/mL. In contrast, the mean systemic concentration of lidocaine over 300 minutes after cumulative amiodarone doses of 3 g and 13 g is 135.3 +/- 34.6 and 131.7 +/- 25.5 mcg/minute/mL, respectively. As expected, the systemic exposure of the lidocaine metabolite, monoethylglycinexylidide, decreases from 19.2 +/- 6.5 to 15.8 +/- 8.3 mcg/minute/mL after 3 g of amiodarone. In addition, the systemic clearance of lidocaine decreases from 7.86 +/- 1.83 to 6.31 +/- 2.21 mL/minute/kg body weight. As compared with values before amiodarone administration, the lidocaine elimination half-life and the distribution volume at steady state remain relatively unchanged. Due to the long half-life of amiodarone, clinicians should use caution when administering lidocaine to patients who are receiving or who have recently discontinued amiodarone.
    Buprenorphine: (Major) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Antiarrhythmics with an established risk for QT prolongation and TdP include disopyramide, flecainide, propafenone, quinidine (including dextromethorphan; quinidine), procainamide, amiodarone, ibutilide, and sotalol. In addition, since the metabolism of buprenorphine is mediated by CYP3A4, co-administration of a CYP3A4 inhibitor such as amiodarone may decrease the clearance of buprenorphine resulting in prolonged or increased opioid effects. If co-administration is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
    Buprenorphine; Naloxone: (Major) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Antiarrhythmics with an established risk for QT prolongation and TdP include disopyramide, flecainide, propafenone, quinidine (including dextromethorphan; quinidine), procainamide, amiodarone, ibutilide, and sotalol. In addition, since the metabolism of buprenorphine is mediated by CYP3A4, co-administration of a CYP3A4 inhibitor such as amiodarone may decrease the clearance of buprenorphine resulting in prolonged or increased opioid effects. If co-administration is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
    Buspirone: (Moderate) CYP3A4 inhibitors, such as amiodarone,may decrease systemic clearance of buspirone leading to increased or prolonged effects. If this combination is used, a low dose of buspirone, such as 2.5 mg PO twice daily, is recommended initially. Subsequent dosage adjustments should be based on clinical response.
    Cabazitaxel: (Moderate) Cabazitaxel is a CYP3A4 and P-glycoprotein (Pgp) substrate; amiodarone is a moderate inhibitor of CYP3A4 as well as a P-gp inhibitor. A drug interaction study with repeated administration of aprepitant, another moderate CYP3A4 inhibitor, did not modify the exposure to cabazitaxel; however, formal drug interaction studies have not been conducted with P-gp inhibitors. Use caution when cabazitaxel is administered concomitantly with P-gp inhibitors.
    Cabozantinib: (Moderate) Monitor for an increase in cabozantinib-related adverse events if concomitant use with amiodarone is necessary. Cabozantinib is primarily metabolized by CYP3A4 and amiodarone is a CYP3A4 inhibitor. Coadministration with a strong CYP3A4 inhibitor, ketoconazole (400 mg daily for 27 days), increased cabozantinib (single dose) exposure by 38%. The manufacturer of cabozantinib recommends a dose reduction when used with strong CYP3A4 inhibitors; however, recommendations are not available for concomitant use with a moderate inhibitor of CYP3A4.
    Caffeine: (Minor) Amiodarone is an inhibitor of CYP1A2 isoenzymes, and could theoretically reduce CYP1A2-mediated caffeine metabolism. The clinical significance of this potential interaction is not known.
    Caffeine; Ergotamine: (Major) Coadministration of ergotamine with inhibitors of CYP3A4, such as amiodarone, may potentially increase the risk of ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Coadministration should be done cautiously, and avoided when possible. (Minor) Amiodarone is an inhibitor of CYP1A2 isoenzymes, and could theoretically reduce CYP1A2-mediated caffeine metabolism. The clinical significance of this potential interaction is not known.
    Canagliflozin: (Moderate) Canagliflozin is a substrate of drug transporter P glycoprotein (P-gp). Amiodarone is a PGP inhibitor and may theoretically increase concentrations of canagliflozin. Patients should be monitored for changes in glycemic control.
    Canagliflozin; Metformin: (Moderate) Canagliflozin is a substrate of drug transporter P glycoprotein (P-gp). Amiodarone is a PGP inhibitor and may theoretically increase concentrations of canagliflozin. Patients should be monitored for changes in glycemic control.
    Candesartan; Hydrochlorothiazide, HCTZ: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Captopril; Hydrochlorothiazide, HCTZ: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Carbamazepine: (Moderate) Adjust amiodarone and carbamazepine doses as needed based on efficacy and tolerability. Consider monitoring amiodarone serum concentrations during concurrent use. Coadministration of amiodarone and carbamazepine may result in decreased amiodarone exposure and/or increased carbamazepine exposure. Carbamazepine is a CYP3A4 substrate and strong CYP3A4 inducer; amiodarone is a CYP3A4 substrate and moderate CYP3A4 inhibitor.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Carbetapentane; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone. (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Carbinoxamine; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Cariprazine: (Moderate) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Amiodarone is an inhibitor of CYP3A4 and may reduce the hepatic metabolism of CYP3A4 substrates, although the impact of moderate CYP3A4 inhibitors on cariprazine metabolism has not been studied. Monitoring for adverse effects, such as CNS effects and extrapyramidal symptoms, is advisable during coadministration.
    Carteolol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone.
    Carvedilol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. In addition, amiodarone is an inhibitor of CYP2D6, CYP2C9, and P-glycoprotein. Concomitant administration of amiodarone and carvedilol increased the concentration of the S(-) enantiomer of carvedilol by at least 2-fold. Caution is advised as metoprolol, another beta-blocker metabolized by CYP2D6, in combination with amiodarone has resulted in severe sinus bradycardia. While the combination should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone. Patients receiving amiodarone concurrently with carvedilol should be monitored for bradycardia or heart block, especially when one agent is added to pre-existing treatment with the other.
    Celecoxib: (Minor) Since celecoxib is metabolized by cytochrome P450 2C9, concurrent administration with amiodarone, which can inhibit this enzyme, may result in increased levels of celecoxib. The clinical significance of this interactions has not been established.
    Ceritinib: (Major) Avoid coadministration of amiodarone with ceritinib if possible due to the risk of QT prolongation; because amiodarone has an extremely long half-life, an interaction is possible for days to weeks after discontinuation of amiodarone. Additionally, amiodarone exposure may be increased by ceritinib administration. If concomitant use is unavoidable, monitor for amiodarone-related adverse reactions; also, periodically monitor electrolytes and ECGs. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Amiodarone is a Class III antiarrhythmic agent. Although the frequency of torsade de pointes (TdP) is less with amiodarone than with other Class III agents, amiodarone is still associated with a well-established risk of QT prolongation and TdP.
    Cerivastatin: (Severe) Amiodarone may inhibit hepatic CYP3A4 isoenzymes, and therefore has the potential to increase serum concentrations of cerivastatin. Monitor for signs and symptoms of myopathy in patients receiving amiodarone concurrently with these HMG-CoA reductase inhibitors.
    Cevimeline: (Moderate) Cevimeline is metabolized by cytochrome P450 3A4 and CYP2D6. Inhibitors of these isoenzymes, such as amiodarone, would be expected to lead to an increase in cevimeline plasma concentrations. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Cevimeline toxicity is characterized by an exaggeration of its parasympathomimetic effects, including headache, lacrimation, sweating, nausea, vomiting, diarrhea, AV block, changes in heart rate/rhythm or blood pressure, mental confusion, and tremors.
    Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Chlordiazepoxide: (Moderate) CYP3A4 inhibitors, such as amiodarone, may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity.
    Chlordiazepoxide; Clidinium: (Moderate) CYP3A4 inhibitors, such as amiodarone, may reduce the metabolism of chlordiazepoxide and increase the potential for benzodiazepine toxicity.
    Chloroquine: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. Chloroquine administration is associated with an increased risk of QT prolongation and torsades de pointes (TdP). If possible, avoid coadministration of amiodarone and chloroquine. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Chlorothiazide: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Chlorpheniramine; Codeine: (Minor) Amiodarone inhibits CYP2D6 and may interfere with the conversion of codeine to the active metabolite, morphine. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with any other drugs that inhibit CYP2D6.
    Chlorpheniramine; Dextromethorphan: (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly. (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of amiodarone and dihydrocodeine warrants caution due to the potential for increased side effects of dihydrocodeine. Amiodarone is an inhibitor and dihydrocodeine is a substrate of CYP2D6; therefore, coadministration may lead to increased dihydrocodeine concentrations. (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of amiodarone and dihydrocodeine warrants caution due to the potential for increased side effects of dihydrocodeine. Amiodarone is an inhibitor and dihydrocodeine is a substrate of CYP2D6; therefore, coadministration may lead to increased dihydrocodeine concentrations.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone. (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Chlorpromazine: (Major) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Chlorthalidone: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Chlorthalidone; Clonidine: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics. (Moderate) Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate including amiodarone. Monitor for potential bradycardia or atrioventricular block during coadministration.
    Cholestyramine: (Major) Cholestyramine can enhance amiodarone clearance presumably via reduced enterohepatic recirculation, thereby reducing amiodarone serum concentrations. This interaction between amiodarone and cholestyramine may be of benefit to temporarily reduce amiodarone serum concentrations prior to surgery and possibly limit the cardiac depressant effects of the drug in the immediate post-surgical period, although more data are needed before this recommendation can be made.
    Cilostazol: (Major) Reduce the dose of cilostazol to 50 mg twice daily when coadministered with amiodarone, and monitor for an increase in cilostazol-related adverse reactions. Cilostazol is a CYP3A4 substrate. Amiodarone is a moderate CYP3A4 inhibitor both in vitro and in vivo. Coadministration with another moderate CYP3A4 inhibitor increased the Cmax and AUC of cilostazol (single dose) by 47% and 73%, respectively; the AUC of 4-trans-hydroxycilostazol increased by 141%.
    Cimetidine: (Moderate) Cimetidine may decrease the CYP3A4 metabolism of amiodarone, potentially resulting in increased plasma concentrations of amiodarone and the active metabolite.
    Cinacalcet: (Moderate) Cinacalcet is metabolized primarily by the CYP3A4 isoenzyme. Therefore, caution is recommended when coadministering cinacalcet with other CYP3A4 enzyme inhibitors, such as amiodarone.
    Ciprofloxacin: (Major) Concurrent use of amiodarone and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Concomitant use should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Cisapride: (Severe) Post-marketing surveillance reports have documented QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, when known and potent inhibitors of CYP3A4 are coadministered with cisapride. Amiodarone has the potential to inhibit the metabolism of cisapride through CYP3A4 and thus, should not be used with cisapride. In addition, amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Cisplatin: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and/or hypomagnesemia including cisplatin.
    Citalopram: (Major) Citalopram causes dose-dependent QT interval prolongation. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. The manufacturer of amiodarone recommends avoiding coadministraton and a careful assessment of risks versus benefits if coadministration cannot be avoided.
    Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration of amiodarone and clarithromycin. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Clindamycin: (Moderate) Concomitant use of clindamycin and amiodarone may decrease clindamycin clearance and increase the risk of adverse reactions. Clindamycin is a CYP3A4 substrate; amiodarone is a moderate inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
    Clomipramine: (Major) If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Carefully asses treatmentt risks versus benefits. Amiodarone is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Drugs with a possible risk for QT prolongationthat should be used cautiously with amiodarone include tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations) or in patients with other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of such combined therapies.
    Clonazepam: (Moderate) Amiodarone is a CYP3A4 inhibitor and may reduce the metabolism of clonazepam and increase the potential for benzodiazepine toxicity.
    Clonidine: (Moderate) Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate including amiodarone. Monitor for potential bradycardia or atrioventricular block during coadministration.
    Clorazepate: (Moderate) Amiodarone is a CYP3A4 inhibitor and may reduce the metabolism of clorazepate and increase the potential for benzodiazepine toxicity.
    Clozapine: (Major) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation such as amiodarone. In addition, amiodarone is an inhibitor of CYP2D6 and CYP3A4, two of the isoenzymes responsible for the metabolism of clozapine. Elevated plasma concentrations of clozapine occurring through CYP inhibition may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with a CYP2D6 or CYP3A4 inhibitor should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
    Cobicistat: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of amiodarone with cobicistat. Amiodarone is a substrate and inhibitor of CYP3A4 and an inhibitor CYP2D6, cobicistat is a substrate and inhibitor of CYP3A and CYP2D6. Concurrent use may result in elevated concentration of amiodarone.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of amiodarone with cobicistat. Amiodarone is a substrate and inhibitor of CYP3A4 and an inhibitor CYP2D6, cobicistat is a substrate and inhibitor of CYP3A and CYP2D6. Concurrent use may result in elevated concentration of amiodarone.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of amiodarone with cobicistat. Amiodarone is a substrate and inhibitor of CYP3A4 and an inhibitor CYP2D6, cobicistat is a substrate and inhibitor of CYP3A and CYP2D6. Concurrent use may result in elevated concentration of amiodarone. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as amiodarone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with chronic amiodarone therapy due to the risk of cobimetinib toxicity. If concurrent short-term (14 days or less) use of amiodarone is unavoidable, reduce the dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of amiodarone, resume cobimetinib at the previous dose. Use an alternative to amiodarone in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily). Cobimetinib is a P-glycoprotein (P-gp) substrate as well as a CYP3A substrate in vitro; amiodarone is a moderate inhibitor of both P-gp and CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
    Codeine: (Minor) Amiodarone inhibits CYP2D6 and may interfere with the conversion of codeine to the active metabolite, morphine. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with any other drugs that inhibit CYP2D6.
    Codeine; Guaifenesin: (Minor) Amiodarone inhibits CYP2D6 and may interfere with the conversion of codeine to the active metabolite, morphine. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with any other drugs that inhibit CYP2D6.
    Codeine; Phenylephrine; Promethazine: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with amiodarone include promethazine. Promethazine carries a possible risk of QT prolongation. Additionally, amiodarone inhibits CYP2D6 and may theoretically increase concentrations of promethazine, which is metabolized by CYP2D6. Monitor for side effects like sedation and changes in heart rate or rhythm. (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly. (Minor) Amiodarone inhibits CYP2D6 and may interfere with the conversion of codeine to the active metabolite, morphine. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with any other drugs that inhibit CYP2D6.
    Codeine; Promethazine: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with amiodarone include promethazine. Promethazine carries a possible risk of QT prolongation. Additionally, amiodarone inhibits CYP2D6 and may theoretically increase concentrations of promethazine, which is metabolized by CYP2D6. Monitor for side effects like sedation and changes in heart rate or rhythm. (Minor) Amiodarone inhibits CYP2D6 and may interfere with the conversion of codeine to the active metabolite, morphine. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with any other drugs that inhibit CYP2D6.
    Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and amiodarone in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Amiodarone can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like amiodarone in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Colesevelam: (Moderate) Colesevelam may decrease the absorption of oral antiarrhythmics. To minimize potential for interactions, consider administering oral antiarrhythmics at least 1 hour before or at least 4 hours after colesevelam.
    Conivaptan: (Moderate) Conivaptan is a substrate of CYP3A4 and coadministration with CYP3A4 inhibitors like amiodarone could lead to an increase in conivaptan serum concentrations.
    Conjugated Estrogens: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Conjugated Estrogens; Bazedoxifene: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Conjugated Estrogens; Medroxyprogesterone: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Crizotinib: (Major) Avoid coadministration of amiodarone with crizotinib due to the risk of additive QT prolongation and torsade de pointes (TdP); an increase in treatment-related adverse reactions (e.g., vision disorders, diarrhea, increased transaminases, and neuropathy) may also occur. If concomitant use is unavoidable, monitor ECGs and electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for QT prolongation. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation. Crizotinib is a CYP3A4 substrate and a moderate CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. Amiodarone, a CYP3A4 substrate, moderate CYP3A4 inhibitor, and Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP, although the frequency of TdP is less than with other Class III agents.
    Cyclobenzaprine: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Cyclobenzaprine is structurally similar to tricyclic antidepressants. Tricyclic antidepressants have been reported to prolong the QT interval, especially when given in excessive doses (or in overdosage settings). Cyclobenzaprine is associated with a possible risk of QT prolongation and torsade de pointes (TdP), particularly in the event of acute overdose.
    Cyclophosphamide: (Moderate) Use caution if cyclophosphamide is used concomitantly with amiodarone, as there may be an increased risk of pulmonary toxicity.
    Cyclosporine: (Moderate) Cyclosporine is a CYP3A4 substrate. Amiodarone is a CYP3A4 inhibitor and may decrease the clearance of cyclosporine, which may reduce cyclosporine dosage requirements or cause cyclosporine toxicity.
    Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with amiodarone, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like amiodarone in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with amiodarone, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Coadministration of dabigatran and a single oral dose of 600 mg amiodarone resulted in an increase in dabigatran AUC and Cmax by 58% and 50%, respectively. In addition, coadministration resulted in a 65% increase in renal clearance of dabigatran. Due to the long half-life of amiodarone, the increase in renal clearance may persist after discontinuation of amiodarone. Data from the RE-LY trial indicate no significant changes in dabigatran trough concentrations were seen in patients who received concomitant therapy with amiodarone. In clinical studies, dabigatran was found to have no effect on the pharmacokinetics of amiodarone. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
    Daclatasvir: (Major) Coadministration of amiodarone with daclatasvir plus sofosbuvir is not recommended due to the potential for serious symptomatic bradycardia. Cases of symptomatic bradycardia, some requiring pacemaker intervention, have been reported when amiodarone was administered with sofosbuvir and another direct-acting antiviral, including daclatasvir. One patient developed a fatal cardiac arrest after receiving amiodarone with ledipasvir; sofosbuvir. Bradycardia generally occurs within hours to days; however, cases have been observed up to 2 weeks after initiating the hepatitis C virus (HCV) treatment regimen. The mechanism of this effect is unknown. If coadministration is required, cardiac monitoring in an inpatient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment. Due to the long half-life of amiodarone, patients discontinuing amiodarone just prior to starting the HCV regimen should also undergo similar cardiac monitoring as outlined above.
    Danazol: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates, including amiodarone.
    Dapagliflozin; Saxagliptin: (Minor) Monitor patients for hypoglycemia if saxagliptin and amiodarone are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as amiodarone.
    Darifenacin: (Moderate) Amiodarone, an inhibitor of both CYP3A4 and CYP2D6, may decrease the metabolism of darifenacin and increase serum concentrations. Patients should be monitored for increased anticholinergic effects if these drugs are used concomitantly; dosage adjustments of darifenacin may be necessary.
    Darunavir: (Major) Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, like amiodarone, is expected with concurrent use. Coadminister with extreme caution, therapeutic monitoring of antiarrhythmic concentrations is recommended.
    Darunavir; Cobicistat: (Major) Darunavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, like amiodarone, is expected with concurrent use. Coadminister with extreme caution, therapeutic monitoring of antiarrhythmic concentrations is recommended. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of amiodarone with cobicistat. Amiodarone is a substrate and inhibitor of CYP3A4 and an inhibitor CYP2D6, cobicistat is a substrate and inhibitor of CYP3A and CYP2D6. Concurrent use may result in elevated concentration of amiodarone.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Coadministration of HIV treatment doses of ritonavir and amiodarone is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering amiodarone with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as amiodarone, should be expected with concurrent use. In addition, both ritonavir and amiodarone are associated with QT prolongation; concomitant use increases the risk of QT prolongation.
    Dasatinib: (Major) Avoid the concomitant use of amiodarone and dasatinib; both of these drugs may prolong the QT interval increasing the risk of torsade de pointes (TdP). Additionally, amiodarone and/or dasatinib concentrations may be increased if these drugs are used together. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Amiodarone and dasatinib are both CYP3A4 substrates and inhibitors. Concomitant use of amiodarone and dasatinib may result in increased dasatinib plasma concentrations and dasatinib-related toxicity. Concomitant use of dasatinib and a CYP3A4 substrate resulted in increased Cmax and AUC values of the CYP3A4 substrate by 37% and 20%, respectively. Therefore, coadministration of dasatinib and amiodarone may result in increased amiodarone plasma concentrations and amiodarone-related toxicity.
    Daunorubicin: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should be done only after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Deferasirox: (Moderate) Deferasirox inhibits CYP2C8. Amiodarone is a substrate for CYP2C8. The concomitant administration of deferasirox and the CYP2C8 substrate repaglinide (single dose of 0.5 mg) resulted in an increase in repaglinide Cmax by 62% and an increase in AUC 2.3-fold. Although specific drug interaction studies of deferasirox and amiodarone are not available, a similar interaction may occur. The dose of amiodarone may need to be decreased if coadministered with deferasirox.
    Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with amiodarone. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; amiodarone is a moderate inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold. Additionally, use caution with coadministration of amiodarone with drugs which may induce hypokalemia or hypomagnesemia, including deflazacort. Antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia; any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy.
    Degarelix: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with amiodarone include degarelix.
    Delavirdine: (Major) Delavirdine is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as amiodarone, should be expected with concurrent use. Coadministration of delavirdine with amiodarone should be done with caution. Therapeutic monitoring of amiodarone concentrations is recommended.
    Desflurane: (Major) In general, adverse cardiovascular effects such as hypotension and atropine-resistant bradycardia can occur in patients receiving amiodarone who subsequently are administered any general anesthetics, particularly volatile anesthetics. Close perioperative monitoring is recommended in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction effects of halogenated anesthetics, which may include QT prolongation. Due to the extremely long half-life of amiodarone, a drug interaction is also possible for days to weeks after discontinuation of amiodarone.
    Desiccated Thyroid: (Moderate) Amiodarone has a complex effect on the metabolism of thyroid hormones and can alter thyroid function tests in many patients. Since approximately 37% of amiodarone (by weight) is iodine, maintenance doses of 200-600 mg of amiodarone/day result in ingestion of 75-225 mg/day of organic iodide, resulting in much higher total iodine stores in the body. In addition, amiodarone decreases T4 5'-deiodinase activity, which decreases the peripheral conversion of T4 to T3, leading to decreased serum T3. Serum T4 levels are usually normal but may be slightly increased. TSH concentrations usually increase during amiodarone therapy, but after 3 months of continuous administration, TSH concentrations often return to normal. However, amiodarone can cause hypothyroidism or hyperthyroidism, including life-threatening thyrotoxicosis. Therefore, patients receiving levothyroxine and amiodarone should be monitored for changes in thyroid function; because of the slow elimination of amiodarone and its metabolites, abnormal thyroid function tests may persists for weeks or months after amiodarone drug discontinuation.
    Desipramine: (Major) If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Carefully asses treatmentt risks versus benefits. Amiodarone is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Drugs with a possible risk for QT prolongationthat should be used cautiously with amiodarone include tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations) or in patients with other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of such combined therapies.
    Deutetrabenazine: (Major) Avoid concomitant use of deutetrabenazine and amiodarone, if possible. If concurrent use is necessary, assess the QTc interval before and after increasing the dose of either medication with deutetrabenazine doses greater than 24 mg/day. Clinically relevant QTc prolongation may occur with deutetrabenazine. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Dexamethasone: (Major) Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia, including corticosteroids. Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Dextromethorphan: (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly. (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Dextromethorphan; Guaifenesin: (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly. (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Dextromethorphan; Promethazine: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with amiodarone include promethazine. Promethazine carries a possible risk of QT prolongation. Additionally, amiodarone inhibits CYP2D6 and may theoretically increase concentrations of promethazine, which is metabolized by CYP2D6. Monitor for side effects like sedation and changes in heart rate or rhythm. (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Dextromethorphan; Quinidine: (Major) Amiodarone coadministration increases quinidine concentrations by about 33% after 2 days, by decreasing its renal clearance or by inhibiting its hepatic metabolism. Quinidine may also be displaced from tissue and protein binding sites. Prolongation of the QT interval is well documented with quinidine, and the addition of amiodarone may increase this effect, placing the patient at an increased risk for the development of torsade de pointes. Careful clinical observation of the patient as well as close monitoring of the ECG and serum quinidine concentrations are essential with adjustment of the quinidine dosing regimen performed as necessary to avoid enhanced toxicity or pharmacodynamic effects. An empiric reduction of the quinidine dose by 33-50% is suggested within 2 days following initiation of amiodarone therapy, with consideration given to immediately discontinuing of quinidine once amiodarone therapy is begun. Combination antiarrhythmic therapy is reserved for patients with refractory life-threatening arrhythmias. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. (Minor) Amiodarone inhibits hepatic CYP2D6 and CYP3A, the pathways by which dextromethorphan is metabolized. Although the clinical significance of this interaction is not known, dextromethorphan should be used cautiously in patients receiving amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Diazepam: (Moderate) Diazepam is metabolized by oxidative metabolism, specifically, the hepatic isozymes CYP2C19 and CYP3A4. As a result, diazepam is susceptible to interactions with drugs that inhibit these hepatic enzymes, such as amiodarone. Monitor patients closely.
    Diclofenac: (Moderate) If possible, avoid concurrent use of diclofenac with inhibitors of CYP2C9, such as amiodarone; if coadministration is required, do not exceed a total daily diclofenac dose of 100 mg. When used with a CYP2C9 inhibitor the systemic exposure to diclofenac (a CYP2C9 substrate) may increase, potentially resulting in adverse events.
    Diclofenac; Misoprostol: (Moderate) If possible, avoid concurrent use of diclofenac with inhibitors of CYP2C9, such as amiodarone; if coadministration is required, do not exceed a total daily diclofenac dose of 100 mg. When used with a CYP2C9 inhibitor the systemic exposure to diclofenac (a CYP2C9 substrate) may increase, potentially resulting in adverse events.
    Dienogest; Estradiol valerate: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Diethylstilbestrol, DES: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Digoxin: (Major) Amiodarone increases orally administered digoxin serum concentration by 70% when given concomitantly. When amiodarone is coadministered with intravenous (IV) digoxin, the serum concentration of digoxin is increased by 17%. Measure serum digoxin concentrations before initiating amiodarone. According to the manufacturer of amiodarone, the digoxin dose should be reduced by 50% upon initiation of amiodarone. The manufacturer of digoxin recommends measuring the serum digoxin concentration before initiating amiodarone and reducing the serum digoxin concentration by reducing the oral dose by approximately 30 to 50%, decreasing the IV digoxin dose by 15 to 30%, or modifying the dosing frequency and continue monitoring. The mechanism of the increase in digoxin serum concentration is thought to result from inhibition of gastrointestinal P-glycoprotein (increased oral bioavailability) and/or a decrease in digoxin renal or nonrenal clearance. Because of the depressant effects of digoxin on the sinus and AV node, concurrent use can potentiate amiodarone's electrophysiologic and hemodynamic effects resulting in bradycardia, sinus arrest, and AV block. Furthermore, amiodarone may induce changes in thyroid function and alter sensitivity to cardiac glycosides, and thyroid function should be monitored closely in patients receiving both drugs simultaneously. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Close monitoring of serum digoxin concentrations and heart rate is essential to avoid enhanced toxicity.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of amiodarone and dihydrocodeine warrants caution due to the potential for increased side effects of dihydrocodeine. Amiodarone is an inhibitor and dihydrocodeine is a substrate of CYP2D6; therefore, coadministration may lead to increased dihydrocodeine concentrations.
    Dihydroergotamine: (Major) Coadministration of dihydroergotamine with inhibitors of CYP3A4, such as amiodarone, may potentially increase the risk of ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Coadministration should be done cautiously, and avoided when possible.
    Diltiazem: (Major) Based on the pharmacology of amiodarone and diltiazem, additive effects on cardiac contractility and/or AV conduction are possible. Concurrent use of amiodarone and diltiazem may result in bradycardia and depressed cardiac output; monitor clinical response. In addition, amiodarone is both a substrate and inhibitor of CYP3A4 metabolism, and may potentially interact with diltiazem via CYP3A4 metabolic pathways.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone. (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Diphenhydramine; Ibuprofen: (Minor) Amiodarone inhibits CYP2C9. Caution is recommended when administering amiodarone with CYP2C9 substrates including ibuprofen. The metabolism of ibuprofen may be decreased.
    Diphenhydramine; Naproxen: (Minor) Amiodarone inhibits CYP2C9. Caution is recommended when administering amiodarone with CYP2C9 substrates including naproxen. The metabolism of naproxen may be decreased.
    Diphenhydramine; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Disopyramide: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP) and is a substrate for CYP3A4. Life-threatening interactions have been reported with the coadministration of disopyramide with clarithromycin and erythromycin, both have a possible risk for QT prolongation and TdP and inhibit CYP3A4. The coadministration of disopyramide and CYP3A4 inhibitors may result in a potentially fatal interaction. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation andTdP and is a CYP3A4 inhibitor. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Dofetilide: (Severe) The concurrent use of amiodarone and dofetilide is contraindicated. Before switching from another antiarrhythmic drug to dofetilide therapy, the discontinued drug generally should be withheld for at least three half-lives prior to initiating dofetilide. Concurrent exposure with dofetilide could increase the risk of dofetilide-induced proarrhythmias. Because of the unpredictable pharmacokinetics of amiodarone, dofetilide should not be initiated following amiodarone therapy until amiodarone plasma levels are below 0.3 mcg/ml or until amiodarone has been withdrawn for at least 3 months (consistent with the management during dofetilide clinical trials). Amiodarone is also an inhibitor of CYP3A4 metabolism which could reduce dofetilide metabolism.
    Dolasetron: (Major) Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Amiodarone has a possible risk for QT prolongation and TdP and should be used cautiously and with close monitoring with donepezil. In addition, amiodarone inhibits CYP2D6, one of the isoenzymes involved in the metabolism of donepezil. In theory, co-administration of amiodarone and donepezil could increase donepezil concentrations, potentially resulting in dose-related toxicity. However, the clinical effect of such an interaction on the response to donepezil has not been determined.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Amiodarone has a possible risk for QT prolongation and TdP and should be used cautiously and with close monitoring with donepezil. In addition, amiodarone inhibits CYP2D6, one of the isoenzymes involved in the metabolism of donepezil. In theory, co-administration of amiodarone and donepezil could increase donepezil concentrations, potentially resulting in dose-related toxicity. However, the clinical effect of such an interaction on the response to donepezil has not been determined.
    Dorzolamide; Timolol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone.
    Doxepin: (Major) If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Carefully asses treatmentt risks versus benefits. Amiodarone is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Drugs with a possible risk for QT prolongationthat should be used cautiously with amiodarone include tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations) or in patients with other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of such combined therapies.
    Doxercalciferol: (Moderate) Amiodarone inhibits CYP450 and may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if amiodarone is coadministered with doxercalciferol.
    Doxorubicin: (Major) Avoid the concomitant use of doxorubicin and amiodarone; use of these drugs together may increase doxorubicin concentrations and increase the risk of doxorubicin-induced toxicity. Doxorubicin is a substrate of CYP2D6, CYP3A4, and P-glycoprotein (P-gp); amiodarone is a CYP2D6 inhibitor, a CYP3A4 substrate and inhibitor, and a P-gp inhibitor.
    Dronabinol, THC: (Major) Use caution if coadministration of dronabinol with amiodarone is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; amiodarone is a moderate inhibitor of CYP2C9 and 3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Dronedarone: (Severe) Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. The concomitant use of dronedarone with other drugs that prolong the QTc may induce Torsade de Pointes (TdP) and is contraindicated. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Drospirenone; Estradiol: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Drospirenone; Ethinyl Estradiol: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Duloxetine: (Moderate) Monitor for adverse effects associated with increased exposure to duloxetine if amiodarone is coadministered. Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of amiodarone and duloxetine may increase the risk of hypotension; monitor blood pressure if the combination is necessary. Amiodarone is a CYP1A2 and CYP2D6 inhibitor, while duloxetine is a CYP1A2 and CYP2D6 substrate.
    Dutasteride: (Moderate) Dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors, such as amiodarone.
    Dutasteride; Tamsulosin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of amiodarone. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as amiodarone, should be avoided. (Moderate) Dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors, such as amiodarone.
    Edoxaban: (Moderate) Coadministration of edoxaban and amiodarone may result in increased concentrations of edoxaban. Edoxaban is a P-glycoprotein (P-gp) substrate and amiodarone is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of amiodarone; monitor for increased adverse effects of edoxaban. Dosage reduction may be considered for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism.
    Efavirenz: (Major) If possible, avoid coadministration of efavirenz and amiodarone, as use of these medications together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as amiodarone. It would be prudent to monitor for changes in amiodarone efficacy.
    Efavirenz; Emtricitabine; Tenofovir: (Major) If possible, avoid coadministration of efavirenz and amiodarone, as use of these medications together may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. In addition, efavirenz induces CYP3A4 and may decrease serum concentrations of drugs metabolized by this enzyme, such as amiodarone. It would be prudent to monitor for changes in amiodarone efficacy. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as amiodarone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with amiodarone may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Amiodarone is a substrate and moderate inhibitor of CYP3A. Both elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of hepatotoxicity.
    Eletriptan: (Moderate) Use caution when coadministering eletriptan and amiodarone. Coadministration may cause an increase in systemic concentrations of eletriptan. Eletriptan is a substrate for CYP3A4, and amiodarone is a CYP3A4 inhibitor.
    Eliglustat: (Major) Coadministration of amiodarone and eliglustat is not recommended. Eliglustat is a CYP2D6 and CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Amiodarone is an inhibitor of CYP2D6 and a weak inhibitor of CYP3A and is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Amiodarone-mediated inhibition of CYP2D6 and CYP3A in a patient receiving eliglustat may result in unexpectedly high plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias).
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) The concomitant use of amiodarone and rilpivirine should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) The concomitant use of amiodarone and rilpivirine should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as amiodarone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as amiodarone. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Enalapril; Felodipine: (Moderate) Amiodarone is a CYP3A4 inhibitor, which theoretically may decrease hepatic clearance and enhance oral bioavailability of felodipine, a CYP3A4 substrate.
    Enalapril; Hydrochlorothiazide, HCTZ: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Encainide: (Major) Combination therapy with encainide and amiodarone has been reported to significantly increase the risk of proarrhythmias, necessitating close monitoring. In addition, encainide is significantly metabolized by CYP2D6 isoenzymes, and amiodarone is an inhibitor of CYP2D6.
    Enflurane: (Major) In general, adverse cardiovascular effects such as hypotension and atropine-resistant bradycardia can occur in patients receiving amiodarone who subsequently are administered any general anesthetics, particularly volatile anesthetics. Close perioperative monitoring is recommended in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction effects of halogenated anesthetics, which may include QT prolongation. Due to the extremely long half-life of amiodarone, a drug interaction is also possible for days to weeks after discontinuation of amiodarone.
    Enzalutamide: (Moderate) Monitor for decreased efficacy of amiodarone if coadministration with enzalutamide is necessary. Consider monitoring amiodarone serum concentrations during concurrent use. Coadministration may decrease amiodarone plasma concentrations. Amiodarone is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer.
    Epirubicin: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should be dont only after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Eplerenone: (Major) Eplerenone is metabolized by the CYP3A4 pathway. Amiodarone inhibits the hepatic CYP3A4 isoenzyme and therefore may increase the serum concentrations of eplerenone. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension. If these medications are given concurrently in post-myocardial infarction patients with heart failure, do not exceed an eplerenone dose of 25 mg PO once daily. If these medications are given concurrently, and eplerenone is used for hypertension, initiate eplerenone at 25 mg PO once daily. The dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Ergonovine: (Major) Coadministration of certain ergot alkaloids with inhibitors of CYP3A4, such as amiodarone, may potentially increase the risk of ergot toxicity (e.g., severe peripheral vasospasm with possible ischemia, potentially leading to gangrene, cyanosis, stroke, numbness of the extremities and/or other serious effects). Coadministration should be done cautiously until further data are available regarding the combination of these drugs with ergonovine.
    Ergotamine: (Major) Coadministration of ergotamine with inhibitors of CYP3A4, such as amiodarone, may potentially increase the risk of ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects). Coadministration should be done cautiously, and avoided when possible.
    Eribulin: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Eribulin has been associated with QT prolongation. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. If eribulin and amiodarone must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erlotinib: (Major) Avoid the coadministration of erlotinib with amiodarone due to the risk of increased erlotinib-related adverse reactions; if concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. Erlotinib is primarily metabolized by CYP3A4, and to a lesser extent by CYP1A2. Amiodarone is an inhibitor of CYP3A4 and CYP1A2. Coadministration of erlotinib with ketoconazole, a strong CYP3A4 inhibitor, increased the erlotinib AUC by 67%. Coadministration of erlotinib with ciprofloxacin, a moderate inhibitor of CYP3A4 and CYP1A2, increased the erlotinib AUC by 39% and the Cmax by 17%; coadministration with amiodarone may also increase erlotinib exposure.
    Erythromycin: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. In addition to potential pharmacokinetic interactions, erythromycin may cause QT prolongation and exhibit additive electrophysiologic effects with Class III antiarrhythmics. Concurrent use of erythromycin with amiodarone should be avoided. In addition, erythromycin may theoretically increase plasma concentrations of amiodarone via inhibition of CYP3A4. Higher antiarrhythmic plasma concentrations increases the potential risk of QT prolongation, TdP or other proarrhythmias.
    Erythromycin; Sulfisoxazole: (Major) Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. In addition to potential pharmacokinetic interactions, erythromycin may cause QT prolongation and exhibit additive electrophysiologic effects with Class III antiarrhythmics. Concurrent use of erythromycin with amiodarone should be avoided. In addition, erythromycin may theoretically increase plasma concentrations of amiodarone via inhibition of CYP3A4. Higher antiarrhythmic plasma concentrations increases the potential risk of QT prolongation, TdP or other proarrhythmias.
    Escitalopram: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as amiodarone, should be done with caution and close monitoring.
    Eslicarbazepine: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as amiodarone, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of amiodarone if coadministered with eslicarbazepine.
    Esmolol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone.
    Esomeprazole; Naproxen: (Minor) Amiodarone inhibits CYP2C9. Caution is recommended when administering amiodarone with CYP2C9 substrates including naproxen. The metabolism of naproxen may be decreased.
    Estazolam: (Moderate) Amiodarone is a CYP3A4 inhibitor. and may inhibit the metabolism of oxidized benzodiazepines including estazolam.
    Esterified Estrogens: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Esterified Estrogens; Methyltestosterone: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Estradiol: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Estradiol; Levonorgestrel: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Estradiol; Norethindrone: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Estradiol; Norgestimate: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Estrogens: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Estropipate: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Eszopiclone: (Moderate) Monitor for eszopiclone adverse effects, such as CNS depression, during coadministration with amiodarone. A decreased dose of eszopiclone may be warranted. The plasma concentrations of eszopiclone may be elevated when administered concurrently with amiodarone. Amiodarone is a CYP3A4 inhibitor, while eszopiclone is a CYP3A4 substrate.
    Ethacrynic Acid: (Major) Monitor serum electrolytes if coadministration of ethacrynic acid and amiodarone is necessary. Ethacrynic acid therapy may cause electrolyte abnormalities (i.e., hypokalemia, hypomagnesemia) which may exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes.
    Ethinyl Estradiol: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Ethinyl Estradiol; Desogestrel: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Ethinyl Estradiol; Etonogestrel: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Ethinyl Estradiol; Levonorgestrel: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Ethinyl Estradiol; Norelgestromin: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Ethinyl Estradiol; Norethindrone: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Ethinyl Estradiol; Norgestimate: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Ethinyl Estradiol; Norgestrel: (Minor) Amiodarone inhibits CYP3A4, and may increase serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) if coadministered.
    Etomidate: (Major) In general, adverse cardiovascular effects such as hypotension and atropine-resistant bradycardia can occur in patients receiving amiodarone who subsequently are administered any general anesthetics, particularly volatile anesthetics. Due to the extremely long half-life of amiodarone, a drug interaction is also possible for days to weeks after discontinuation of amiodarone. For example, when fentanyl was administered to patients receiving amiodarone, the incidence of bradycardia and other adverse cardiovascular effects was much higher than in patients not on amiodarone who received fentanyl.
    Etoposide, VP-16: (Major) Monitor for an increased incidence of etoposide-related adverse effects if used concomitantly with amiodarone. Amiodarone inhibits CYP3A4 and P-glycoprotein (P-gp), and etoposide, VP-16 is a CYP3A4 and P-gp substrate. Coadministration may cause accumulation of etoposide and decreased metabolism, resulting in increased etoposide concentrations.
    Etravirine: (Major) Etravirine is an inducer of CYP3A4; amiodarone concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor amiodarone concentrations when possible.
    Everolimus: (Major) A dose adjustment of everolimus is necessary when prescribed with amiodarone due to increased plasma concentrations of everolimus. For patients with breast cancer, neuroendocrine tumors, renal cell carcinoma, and renal angiolipoma with tubular sclerosis complex (TSC), reduce the dose of Afinitor to 2.5 mg once daily; consider increasing the dose to 5 mg based on patient tolerance. For patients with subependymal giant cell astrocytoma (SEGA) with TSC, the recommended starting dose of Afinitor/Afinitor Disperz is 2.5 mg/m2 once daily, rounded to the nearest tablet strength; subsequent dosing should be guided by therapeutic drug monitoring (TDM), with administration every other day if dose reduction is required for patients receiving the lowest available tablet strength. If amiodarone is discontinued, increase everolimus to its original dose after a washout period of 2 to 3 days. Zortress dosing for prophylaxis of organ rejection should be guided by TDM. Everolimus is a CYP3A4 substrate as well as a substrate of P-glycoprotein (P-gp); amiodarone is a moderate CYP3A4 and P-gp inhibitor. Coadministration with other moderate CYP3A4/P-gp inhibitors increased everolimus exposure by 3.5-fold to 4.4-fold.
    Ezetimibe; Simvastatin: (Major) Do not exceed a simvastatin dose of 20 mg/day in patients taking amiodarone due to increased risk of myopathy, including rhabdomyolysis. For patients chronically receiving simvastatin 80 mg/day who need to be started on amiodarone, consider switching to an alternative statin with less potential for interaction. Carefully weigh the benefits of combined use of amiodarone and simvastatin against the potential risks. Amiodarone increases the simvastatin exposure by approximately 2-fold.
    Ezogabine: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Ezogabine has been associated with QT prolongation. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. If coadministration is necessary, the manufacturer of ezogabine recommends caution during concurrent use with amiodarone.
    Famotidine; Ibuprofen: (Minor) Amiodarone inhibits CYP2C9. Caution is recommended when administering amiodarone with CYP2C9 substrates including ibuprofen. The metabolism of ibuprofen may be decreased.
    Felodipine: (Moderate) Amiodarone is a CYP3A4 inhibitor, which theoretically may decrease hepatic clearance and enhance oral bioavailability of felodipine, a CYP3A4 substrate.
    Fentanyl: (Moderate) Amiodarone inhibits CYP3A4. When fentanyl is administered to patients receiving amiodarone, the incidence of bradycardia and other adverse cardiovascular effects was much higher than in patients not on amiodarone who received fentanyl. Due to the extremely long elimination half-life of amiodarone, fentanyl should be used cautiously in patients who are receiving amiodarone or who have received amiodarone in the preceding month.
    Fesoterodine: (Moderate) Fesoterodine is rapidly hydrolyzed to its active metabolite, 5-hydroxymethyltolterodine, which is metabolized via hepatic CYP3A4 and 2D6. Amiodarone can inhibit hepatic CYP2D6 and CYP3A4 isoenzymes, which may impair both CYP metabolic pathways of 5-hydroxymethyltolterodine and result in elevated plasma concentrations of 5-hydroxymethyltolterodine and an increased risk for adverse reactions. According to the manufacturer, no dosage adjustments of fesoterodine are recommended during concurrent use of moderate CYP3A4 inhibitors.
    Fingolimod: (Severe) Concurrent use of fingolimod with Class III antiarrhythmics is contraindicated. Fingolimod initiation results in decreased heart rate, and Class III antiarrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia.
    Flecainide: (Major) Flecainide has been used in combination with amiodarone in specialized settings to treat refractory arrhythmias. Combination therapy with Class III and Class IC antiarrhythmics has been reported to increase the risk of proarrhythmias. Close monitoring of therapeutic response is warranted for patients receiving combination therapy, including serum drug concentration monitoring. Amiodarone inhibits the hepatic metabolism of flecainide via CYP2D6 inhibition. When amiodarone is added to flecainide therapy, plasma flecainide levels may increase two-fold or more in some patients, if flecainide dosage is not reduced. When flecainide is given in the presence of amiodarone, reduce the usual flecainide dose by 50% and monitor the patient closely for adverse effects. Serum drug concentration monitoring is strongly recommended to guide dosage with such combination therapy. Coadministration of amiodarone with drugs that prolong the QT interval should be done with a careful assessment of risks versus benefits. Although rare, cases of QT prolongation and torsade de pointes (TdP) have been reported during flecainide therapy; causality has not been established. Based on theoretical considerations, the manufacturer recommends allowing at least 2 to 4 plasma half-lives to elapse following flecainide discontinuation before switching to another antiarrhythmic drug.
    Flibanserin: (Severe) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as amiodarone, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
    Fluconazole: (Severe) Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP). The concurrent use of fluconazole and other drugs that prolong the QT and are CYP3A4 substrates, such as amiodarone, is contraindicated due to the risk of life-threatening arrhythmias such as TdP. Coadministration of fluconazole with amiodarone may result in an elevated plasma concentration of the interacting drug, causing an increased risk for adverse events, such as QT prolongation.
    Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include amiodarone. In addition, amiodarone inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, such as fluoxetine.
    Fluoxetine; Olanzapine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include amiodarone. In addition, amiodarone inhibits CYP2D6 and may theoretically increase concentrations of other drugs metabolized by this enzyme, such as fluoxetine. (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as olanzapine, should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration of amiodarone and olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Fluphenazine: (Minor) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Drugs with a possible risk for QT prolongation include fluphenazine.
    Flurazepam: (Moderate) Amiodarone is a CYP3A4 inhibitor and may reduce the metabolism of flurazepam and increase the potential for benzodiazepine toxicity.
    Flurbiprofen: (Minor) Amiodarone inhibits cytochrome P450 2C9. Caution is recommended when administering amiodarone with other CYP2C9 substrates, such as flurbiprofen, that have a narrow therapeutic range or where large increase in concentrations may be associated with adverse reactions.
    Fluticasone; Salmeterol: (Moderate) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluticasone; Vilanterol: (Moderate) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluvastatin: (Moderate) In theory, concurrent use CYP2C9 inhibitors, such as amiodarone, and fluvastatin, a CYP2C9 substrate, may result in reduced metabolism of fluvastatin and potential for toxicity, including myopathy and rhabdomyolysis.
    Fluvoxamine: (Major) Due to the risk of QT prolongation and torsade de pointes (TdP), avoid coadministration of amiodarone and fluvoxamine if possible. Amiodarone, a Class III antiarrhythmic agent, is associated with a well established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. QT prolongation and TdP has been reported during fluvoxamine postmarketing use. Also, fluvoxamine is a substrate of CYP1A2 and CYP2D6. Amiodarone is an inhibitor of both CYP1A2 and CYP2D6 and could reduce fluvoxamine metabolism.
    Food: (Moderate) The incidence of marijuana associated adverse effects may change following coadministration with amiodarone. Amiodarone is an inhibitor of CYP2C9 and CYP3A4, two isoenzymes responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with amiodarone, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be reduced. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile.
    Formoterol: (Moderate) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Formoterol; Mometasone: (Moderate) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fosamprenavir: (Major) Extreme caution is advised when administering fosamprenavir concurrently with amiodarone. If these drugs must be used together, therapeutic monitoring of amiodarone concentrations is recommended. Taking these drug together may cause the plasma concentrations of fosamprenavir and amiodarone to be altered. Amiodarone is a substrate and inhibitor of CYP3A4; amprenavir (the active metabolite of fosamprenavir) if a potent inhibitor, moderate inducer and substrate of CYP3A4. In addition, fosamprenavir is a substrate for the drug transporter P-glycoprotein (P-gp); amiodarone is a P-gp inhibitor.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as amiodarone. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Fospropofol: (Major) In general, adverse cardiovascular effects such as hypotension and atropine-resistant bradycardia can occur in patients receiving amiodarone who subsequently are administered any general anesthetics, particularly volatile anesthetics. Due to the extremely long half-life of amiodarone, a drug interaction is also possible for days to weeks after discontinuation of amiodarone. For example, when fentanyl was administered to patients receiving amiodarone, the incidence of bradycardia and other adverse cardiovascular effects was much higher than in patients not on amiodarone who received fentanyl.
    Furosemide: (Major) Monitor serum electrolytes if coadministration of furosemide and amiodarone is necessary. Furosemide therapy may cause electrolyte abnormalities (i.e., hypokalemia, hypomagnesemia) which can exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes.
    Gefitinib: (Major) Monitor for an increased incidence of gefitinib-related adverse effects if gefitinib and amiodarone are used concomitantly. Gefitinib is metabolized significantly by CYP3A4 and to a lesser extent by CYP2D6; amiodarone is a CYP3A4 inhibitor and a mild inhibitor of CYP2D6. Coadministration may decrease the metabolism of gefitinib and increase gefitinib concentrations. While the manufacturer has provided no guidance regarding the use of gefitinib with mild or moderate CYP3A4 inhibitors, administration of a single 250 mg gefitinib dose with a strong CYP3A4 inhibitor (itraconazole) increased the mean AUC of gefitinib by 80%. In patients with poor CYP2D6 metabolism, the mean exposure to gefitinib was 2-fold higher when compared to extensive metabolizers; the contribution of drugs that inhibit CYP2D6 on gefitinib exposure has not been evaluated.
    Gemifloxacin: (Major) According to the manufacturer, gemifloxacin should be avoided in patients receiving Class III antiarrhythmics (such as amiodarone). Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Amiodarone is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Gemtuzumab Ozogamicin: (Major) Avoid coadministration of gemtuzumab ozogamicin with amiodarone due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no human data are available.
    Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and amiodarone as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); amiodarone is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and amiodarone as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); amiodarone is an inhibitor of P-gp.
    Glycopyrrolate; Formoterol: (Moderate) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Goserelin: (Major) Amiodarone should be used cautiously and with close monitoring with goserelin. Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Granisetron: (Major) Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Grapefruit juice: (Major) Grapefruit juice has been shown to increase amiodarone peak serum concentrations and AUC when a single dose of amiodarone was administered orally. No change in ECG or arterial blood pressure measurements were identified in this single dose study; however, the impact on chronic dosing of amiodarone was not evaluated. To prevent potential drug accumulation, it would be prudent to avoid taking oral amiodarone with grapefruit juice.
    Guaifenesin; Hydrocodone: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Guaifenesin; Phenylephrine: (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Guanfacine: (Major) Amiodarone may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. Upon amiodarone discontinuation, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is primarily metabolized by CYP3A4, and amiodarone is a moderate CYP3A4 inhibitor.
    Halofantrine: (Severe) Halofantrine should be avoided in patients receiving drugs which may induce QT prolongation; these drugs include class III antiarrhythmics.
    Halogenated Anesthetics: (Major) In general, adverse cardiovascular effects such as hypotension and atropine-resistant bradycardia can occur in patients receiving amiodarone who subsequently are administered any general anesthetics, particularly volatile anesthetics. Close perioperative monitoring is recommended in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction effects of halogenated anesthetics, which may include QT prolongation. Due to the extremely long half-life of amiodarone, a drug interaction is also possible for days to weeks after discontinuation of amiodarone.
    Haloperidol: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. In addition, haloperidol is a substrate for CYP3A4 and CYP2D6. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4 or CYP2D6. Therefore, it is advisable to closely monitor for adverse events when haloperidol is co-administered with drugs that inhibit CYP3A4 and CYP2D6 and prolong the QT interval, such as amiodarone. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Halothane: (Major) In general, adverse cardiovascular effects such as hypotension and atropine-resistant bradycardia can occur in patients receiving amiodarone who subsequently are administered any general anesthetics, particularly volatile anesthetics. Close perioperative monitoring is recommended in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction effects of halogenated anesthetics, which may include QT prolongation. Due to the extremely long half-life of amiodarone, a drug interaction is also possible for days to weeks after discontinuation of amiodarone.
    Hawthorn, Crataegus laevigata: (Major) It would be prudent to avoid use of Hawthorn, Crataegus laevigata (also known as C. oxycantha) during therapy with antiarrhythmic agents whenever possible, due to the possibility of additive effects on cardiac conduction and the known effects of antiarrhythmic drugs on the heart. Following hawthorn administration to guinea pigs, the cardiac action potential duration is increased and the refractory period is prolonged. Hawthorn may also lower peripheral vascular resistance. Hawthorn thus has effects similar to the class III antiarrhythmics and would theoretically interact with drugs with similar cardiac electrophysiology (e.g., amiodarone, bretylium, dofetilide, ibutilide, sotalol). Patients should be advised to only use hawthorn with these antiarrhythmic agents after discussion with their prescriber. If co-use is advised, patients should receive periodic blood pressure and heart rate monitoring.
    Homatropine; Hydrocodone: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Hydantoins: (Major) Concomitant administration of amiodarone and phenytoin (or fosphenytoin) may result in phenytoin toxicity, secondary to a two- or three-fold increase in total, steady-state serum phenytoin concentrations likely due to a amiodarone-induced decrease in phenytoin metabolism. In addition, reduced amiodarone serum concentrations may occur during phenytoin coadministration. A similar interaction may occur with ethotoin. Close monitoring for symptoms of hydantoin anticonvulsant toxicity including nystagmus, lethargy and ataxia; and evaluation of serum concentrations with appropriate dosage reduction as necessary, is essential in patients receiving these medications. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Losartan: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics. (Minor) Coadministration of losartan with amiodarone may result in increased exposure to losartan but decreased concentrations of the active metabolite. The conversion of losartan to its active metabolite is primarily mediated by CYP2C9; amiodarone is an inhibitor of CYP2C9. When coadministered with another inhibitor of CYP2C9, the AUC of the active metabolite of losartan was decreased by 40%, but the AUC of losartan increased by 70%.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers including metoprolol with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. Because amiodarone is an inhibitor of CYP 2D6, decreased clearance of beta-blockers metabolized by CYP2D6 (metoprolol and propranolol) is possible. Caution is advised as metoprolol in combination with amiodarone has resulted in severe sinus bradycardia. While the combination should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone. (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Moexipril: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Propranolol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers including propanolol with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. Because amiodarone is an inhibitor of CYP2D6, decreased clearance of beta-blockers metabolized by CYP2D6 (metoprolol and propranolol) is possible. Caution is advised as metoprolol in combination with amiodarone has resulted in severe sinus bradycardia. While the combination should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone. (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Quinapril: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Triamterene: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrochlorothiazide, HCTZ; Valsartan: (Major) Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including thiazide diuretics.
    Hydrocodone: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Ibuprofen: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone. (Minor) Amiodarone inhibits CYP2C9. Caution is recommended when administering amiodarone with CYP2C9 substrates including ibuprofen. The metabolism of ibuprofen may be decreased.
    Hydrocodone; Phenylephrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone. (Moderate) Use phenylephrine with caution in patients receiving amiodarone. Amiodarone possesses alpha-adrenergic blocking properties and can directly counteract the effects of phenylephrine. Phenylephrine also can block the effects of amiodarone. Monitor patients for decreased pressor effect and decreased amiodarone activity if these agents are administered concomitantly.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Pseudoephedrine: (Major) Monitor for respiratory depression, sedation and decreased analgesic effect if hydrocodone and amiodarone are coadministered; consider dosage adjustments if necessary. Hydrocodone is metabolized by CYP3A4. Concomitant administration of a CYP3A4 inhibitor, such as amiodarone, may cause an increase in hydrocodone plasma concentrations, which could increase or prolong adverse effects. In addition, the metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as amiodarone, may result in a reduction in the analgesic effect of hydrocodone.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and amiodarone. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes (TdP) have been reported with the use of hydroxychloroquine. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Hydroxyzine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include amiodarone.
    Ibrutinib: (Major) If coadministered with amiodarone, initiate ibrutinib therapy at a reduced dose of 140 mg/day PO for the treatment of B-cell malignancy or 420 mg/day PO for the treatment of chronic graft-versus-host disease; monitor patients more frequently for ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection). Ibrutinib is a CYP3A4 substrate; amiodarone is a moderate CYP3A4 inhibitor. When ibrutinib was administered with multiple doses of another moderate CYP3A4 inhibitor, the Cmax and AUC values of ibrutinib were increased by 3.4-fold and 3-fold, respectively.
    Ibuprofen: (Minor) Amiodarone inhibits CYP2C9. Caution is recommended when administering amiodarone with CYP2C9 substrates including ibuprofen. The metabolism of ibuprofen may be decreased.
    Ibuprofen; Oxycodone: (Major) Coadministration of amiodarone, an inhibitor of CYP3A4 and CYP2D6, and oxycodone, a substrate of CYP3A4 and CYP2D6, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold. (Minor) Amiodarone inhibits CYP2C9. Caution is recommended when administering amiodarone with CYP2C9 substrates including ibuprofen. The metabolism of ibuprofen may be decreased.
    Ibuprofen; Pseudoephedrine: (Minor) Amiodarone inhibits CYP2C9. Caution is recommended when administering amiodarone with CYP2C9 substrates including ibuprofen. The metabolism of ibuprofen may be decreased.
    Ibutilide: (Severe) Amiodarone should not be administered concomitantly during the first four hours post-infusion of ibutilide, due to the potential for additive Class III antiarrhythmic effects. In addition, both ibutilide and amiodarone are associated with a risk of QT prolongation and torsades de pointes (TdP).
    Idarubicin: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should be dont only after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Iloperidone: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as iloperidone, should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Imatinib: (Major) Any agent that inhibits cytochrome P450 (CYP) 3A4 may decrease the metabolism of imatinib and increase imatinib concentrations leading to an increased incidence of adverse reactions. There was a significant increase in imatinib Cmax and AUC (26% and 40%, respectively) in healthy subjects when imatinib was coadministered with a single dose of ketoconazole. In addition, because imatinib inhibits CYP2C9, CYP2D6, and CYP3A4/5, the metabolism of amiodarone may be decreased by imatinib.
    Imipramine: (Major) If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Carefully asses treatmentt risks versus benefits. Amiodarone is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Drugs with a possible risk for QT prolongationthat should be used cautiously with amiodarone include tricyclic antidepressants (TCAs). TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations) or in patients with other known risk factors for QT prolongation. Limited data are available regarding the safety of TCAs in combination with other QT-prolonging drugs. One study reported the common occurrence of overlapping prescriptions for 2 or more drugs with potential for QT-prolonging effects; antidepressants were involved in nearly 50% of the cases, but there are little data to document safety of such combined therapies.
    Indacaterol: (Moderate) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Indacaterol; Glycopyrrolate: (Moderate) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Indapamide: (Major) Indapamide may induce hypokalemia, increasing the potential for proarrhythmic effects (e.g., torsade de pointes) of amiodarone. Potassium levels should be within the normal range prior and during administration of these agents. In the absence of electrolyte imbalances, these agents can be used together safely.
    Indinavir: (Severe) Coadministration of indinavir and amiodarone is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Indinavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as amiodarone, should be expected with concurrent use.
    Indomethacin: (Minor) Amiodarone inhibits CYP2C9. Caution is recommended when administering amiodarone with CYP2C9 substrates including indomethacin. The metabolism of indomethacin may be decreased.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with amiodarone due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Iohexol: (Major) When injected directly into coronary arteries, contrast media can cause bradycardia and QT interval prolongation; these reactions tend to be less common with nonionic low-osmolar contrast media. In a retrospective review of 21 patients on amiodarone therapy who underwent cardiac catheterization with iohexol, the QTc interval was significantly prolonged 12-24 hours post catheterization from a baseline QTc interval of 433 msec (95%CI 419-483 msec) to 480 msec (95%CI, 422-483 msec) (p< 0.001). No significant change in the QTc interval was seen in non-amiodarone treated control patients. Until more data are available, clinicians should closely monitor patients taking amiodarone during cardiac catheterization with radiopaque contrast agents; EKG monitoring during intra-coronary artery injection of radiopaque contrast agents is recommended.
    Iopamidol: (Major) When injected directly into coronary arteries, contrast media can cause bradycardia and QT interval prolongation; these reactions tend to be less common with nonionic low-osmolar contrast media. In a retrospective review of 21 patients on amiodarone therapy who underwent cardiac catheterization with iohexol, the QTc interval was significantly prolonged 12-24 hours post catheterization from a baseline QTc interval of 433 msec (95%CI 419-483 msec) to 480 msec (95%CI, 422-483 msec) (p< 0.001). No significant change in the QTc interval was seen in non-amiodarone treated control patients. Until more data are available, clinicians should closely monitor patients taking amiodarone during cardiac catheterization with radiopaque contrast agents; EKG monitoring during intra-coronary artery injection of radiopaque contrast agents is recommended.
    Iopromide: (Major) When injected directly into coronary arteries, contrast media can cause bradycardia and QT interval prolongation; these reactions tend to be less common with nonionic low-osmolar contrast media. In a retrospective review of 21 patients on amiodarone therapy who underwent cardiac catheterization with iohexol, the QTc interval was significantly prolonged 12-24 hours post catheterization from a baseline QTc interval of 433 msec (95%CI 419-483 msec) to 480 msec (95%CI, 422-483 msec) (p< 0.001). No significant change in the QTc interval was seen in non-amiodarone treated control patients. Until more data are available, clinicians should closely monitor patients taking amiodarone during cardiac catheterization with radiopaque contrast agents; EKG monitoring during intra-coronary artery injection of radiopaque contrast agents is recommended.
    Ioversol: (Major) When injected directly into coronary arteries, contrast media can cause bradycardia and QT interval prolongation; these reactions tend to be less common with nonionic low-osmolar contrast media. In a retrospective review of 21 patients on amiodarone therapy who underwent cardiac catheterization with iohexol, the QTc interval was significantly prolonged 12-24 hours post catheterization from a baseline QTc interval of 433 msec (95%CI 419-483 msec) to 480 msec (95%CI, 422-483 msec) (p< 0.001). No significant change in the QTc interval was seen in non-amiodarone treated control patients. Until more data are available, clinicians should closely monitor patients taking amiodarone during cardiac catheterization with radiopaque contrast agents; EKG monitoring during intra-coronary artery injection of radiopaque contrast agents is recommended.
    Irinotecan Liposomal: (Moderate) Use caution if irinotecan liposomal is coadministered with amiodarone, a CYP3A4 inhibitor, due to increased risk of irinotecan-related toxicity. The metabolism of liposomal irinotecan has not been evaluated; however, coadministration of ketoconazole, a strong CYP3A4 and UGT1A1 inhibitor, with non-liposomal irinotecan HCl resulted in increased exposure to both irinotecan and its active metabolite, SN-38.
    Irinotecan: (Moderate) Amiodarone is an inhibitor of CYP3A4 and P-glycoprotein (P-gp); irinotecan is a CYP3A4 and P-gp substrate. Coadministration may result in increased irinotecan exposure. Use caution if concomitant use is necessary and monitor for increased irinotecan side effects, including diarrhea, nausea, vomiting, and myelosuppression.
    Isavuconazonium: (Major) Concomitant use of isavuconazonium with amiodarone may result in increased serum concentrations of both drugs. Amiodarone is a substrate and inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
    Isoflurane: (Major) In general, adverse cardiovascular effects such as hypotension and atropine-resistant bradycardia can occur in patients receiving amiodarone who subsequently are administered any general anesthetics, particularly volatile anesthetics. Close perioperative monitoring is recommended in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction effects of halogenated anesthetics, which may include QT prolongation. Due to the extremely long half-life of amiodarone, a drug interaction is also possible for days to weeks after discontinuation of amiodarone.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Certain rifamycins, including rifampin, rifabutin, and rifapentine, may induce CYP3A4 metabolism of amiodarone, resulting in decreased serum concentrations of amiodarone and its active metabolite (desethylamiodarone) and potential decreased efficacy. A possible drug interaction has been reported with rifampin and amiodarone in one patient receiving therapy with ICD and amiodarone for history of atrial and ventricular arrhythmias; this patient had evidence of reduced serum amiodarone and metabolite levels, loss of antiarrhythmic efficacy, and required hospitalization.
    Isoniazid, INH; Rifampin: (Major) Certain rifamycins, including rifampin, rifabutin, and rifapentine, may induce CYP3A4 metabolism of amiodarone, resulting in decreased serum concentrations of amiodarone and its active metabolite (desethylamiodarone) and potential decreased efficacy. A possible drug interaction has been reported with rifampin and amiodarone in one patient receiving therapy with ICD and amiodarone for history of atrial and ventricular arrhythmias; this patient had evidence of reduced serum amiodarone and metabolite levels, loss of antiarrhythmic efficacy, and required hospitalization.
    Isosulfan Blue: (Major) When injected directly into coronary arteries, contrast media can cause bradycardia and QT interval prolongation; these reactions tend to be less common with nonionic low-osmolar contrast media. In a retrospective review of 21 patients on amiodarone therapy who underwent cardiac catheterization with iohexol, the QTc interval was significantly prolonged 12-24 hours post catheterization from a baseline QTc interval of 433 msec (95%CI 419-483 msec) to 480 msec (95%CI, 422-483 msec) (p< 0.001). No significant change in the QTc interval was seen in non-amiodarone treated control patients. Until more data are available, clinicians should closely monitor patients taking amiodarone during cardiac catheterization with radiopaque contrast agents; EKG monitoring during intra-coronary artery injection of radiopaque contrast agents is recommended.
    Isradipine: (Moderate) Caution should be used when CYP3A4 inhibitors, such as amiodarone, are co-administered with isradipine (CYP3A4 substrate).
    Itraconazole: (Major) Avoid coadministration of amiodarone and itraconazole due to the potential for increased amiodarone concentrations and additive effects on the QT interval. There have been reports of prolonged QT, with or without torsade de pointes (TdP) with the concomitant use of amiodarone and azole antifungals. Both itraconazole and amiodarone are associated with QT prolongation. In addition, coadministration of itraconazole (a potent CYP3A4 inhibitor) with amiodarone (a CYP3A4 substrate) may result in elevated amiodarone plasma concentrations and an increased risk for adverse events, including QT prolongation. According to the manufacturer, the need to administer amiodarone with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Further, it takes approximately 7 to 14 days after discontinuing itraconazole before the plasma concentrations are undetectable. The decline in itraconazole plasma concentrations may be even more gradual in patients with hepatic cirrhosis or who are receiving concurrent CYP3A4 inhibitors.
    Ivabradine: (Major) Avoid coadministration of ivarbadine and amiodarone as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; amiodarone is a moderate CYP3A4 inhibitor. In addition, coadministration of ivabradine with other negative chronotropes like amiodarone increases the risk for bradycardia. Increased ivabradine concentrations may further increase the risk of bradycardia exacerbation and conduction disturbances.
    Ivacaftor: (Major) Use caution when administering ivacaftor and amiodarone concurrently; increased monitoring and/or dose reduction of ivacaftor may be necessary. The manufacturer recommends administering ivacaftor at the usual recommended dose but reducing the frequency to once daily when used concurrently with a moderate CYP3A inhibitor. Ivacaftor is a CYP3A substrate, and amiodarone is a CYP3A inhibitor. Coadministration with fluconazole, a moderate CYP3A inhibitor, increased ivacaftor exposure by 3-fold. Ivacaftor is also an inhibitor of CYP3A and amiodarone is partially metabolized by CYP3A. Coadministration may increase amiodarone exposure leading to increased or prolonged therapeutic effects and adverse events.
    Ixabepilone: (Moderate) Ixabepilone is a CYP3A4 substrate, and concomitant use with mild or moderate CYP3A4 inhibitors such as amiodarone has not been studied. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. Caution is recommended if ixabepilone is coadministered with amiodarone; closely monitor patients for ixabepilone-related toxicities.
    Ketamine: (Major) In general, adverse cardiovascular effects such as hypotension and atropine-resistant bradycardia can occur in patients receiving amiodarone who subsequently are administered any general anesthetics, particularly volatile anesthetics. Due to the extremely long half-life of amiodarone, a drug interaction is also possible for days to weeks after discontinuation of amiodarone. For example, when fentanyl was administered to patients receiving amiodarone, the incidence of bradycardia and other adverse cardiovascular effects was much higher than in patients not on amiodarone who received fentanyl.
    Ketoconazole: (Major) Avoid coadministration of amiodarone and ketoconazole due to the potential for increased amiodarone concentrations and additive effects on the QT interval. There have been reports of prolonged QT, with or without torsade de pointes (TdP) with the concomitant use of amiodarone and azole antifungals. Both ketoconazole and amiodarone are associated with QT prolongation. In addition, coadministration of ketoconazole (a potent CYP3A4 inhibitor) with amiodarone (a CYP3A4 substrate) may result in elevated amiodarone plasma concentrations and an increased risk for adverse events, including QT prolongation. Per the manufacturer, the need to administer amiodarone with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Labetalol: (Major) Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects (slow sinus rate or worsen AV block), resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction. While combination amiodarone and beta-blockers should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone.
    Lansoprazole; Naproxen: (Minor) Amiodarone inhibits CYP2C9. Caution is recommended when administering amiodarone with CYP2C9 substrates including naproxen. The metabolism of naproxen may be decreased.
    Lapatinib: (Major) If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Both lapatinib and amiodarone can prolong the QT interval; therefore coadministration may further increase the risk for QT prolongation. Although the frequency of torsade de pointes (TdP) is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Lapatinib is a CYP3A4 substrate and a CYP3A4 inhibitor at clinically relevant concentrations in vitro. Also, lapatinib is a substrate and inhibitor of the efflux transporter P-glycoprotein (P-gp, ABCB1). Amiodarone is a P-glycoprotein inhibitor, a CYP3A4 substrate, and a CYP3A4 inhibitor. If lapatinib is coadministered with a CYP3A4 substrate, such as amiodarone, exercise caution and consider dose reduction of amiodarone. Concurrent administration of lapatinib with a P-glycoprotein inhibitor such as amiodarone is likely to cause elevated serum lapatinib concentrations, and caution is recommended.
    Ledipasvir; Sofosbuvir: (Major) Coadministration of amiodarone with sofosbuvir is not recommended due to the potential for serious symptomatic bradycardia. Cases of symptomatic bradycardia, including cases requiring pacemaker intervention, have been reported with the concurrent use of amiodarone with sofosbuvir-containing regimens; additionally, a fatal cardiac arrest was reported in a patient receiving a sofosbuvir-containing regimen (ledipasvir; sofosbuvir). The mechanism of this effect is unknown. If coadministration is required, cardiac monitoring in an inpatient setting for the first 48 hours of coadministration is recommended, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment. Due to the long half-life of amiodarone, patients discontinuing amiodarone just prior to starting sofosbuvir should also undergo similar cardiac monitoring as outlined above.
    Lenvatinib: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects.
    Lesinurad: (Moderate) Use lesinurad and amiodarone together with caution; amiodarone may increase the systemic exposure of lesinurad. Amiodarone is a moderate inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate. In addition, lesinurad may decrease the systemic exposure and therapeutic efficacy of amiodarone; monitor for potential reduction in efficacy. Amiodarone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Use lesinurad and amiodarone together with caution; amiodarone may increase the systemic exposure of lesinurad. Amiodarone is a moderate inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate. In addition, lesinurad may decrease the systemic exposure and therapeutic efficacy of amiodarone; monitor for potential reduction in efficacy. Amiodarone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Leuprolide: (Major) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Due to the extremely long half-life of amiodarone , a drug interaction is possible for days to weeks after discontinuation of amiodarone. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Use with caution and with close clinical monitoring with amiodarone.
    Leuprolide; Norethindrone: (Major) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Due to the extremely long half-life of amiodarone , a drug interaction is possible for days to weeks after discontinuation of amiodarone. Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Use with caution and with close clinical monitoring with amiodarone.
    Levalbuterol: (Minor) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Levobunolol: (Moderate) The concomitant use of ophthalmic beta-blockers in patients receiving antiarrhythmics which slow AV conduction, such as amiodarone, may result in additive negative dromotropic effects, especially in patients with pre-existing cardiac disease or left ventricular dysfunction.
    Levofloxacin: (Major) Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of torsade de pointes (TdP) have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. According to the manufacturer, levofloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Levomethadyl: (Severe) Levomethadyl is associated with an established risk of QT prolongation and/or torsades de pointes and is contraindicated in combination with other agents that may prolong the QT interval, such as Class III antiarrhythmics.
    Levothyroxine: (Moderate) Amiodarone has a complex effect on the metabolism of thyroid hormones and can alter thyroid function tests in many patients. Since approximately 37% of amiodarone (by weight) is iodine, maintenance doses of 200-600 mg of amiodarone/day result in ingestion of 75-225 mg/day of organic iodide, resulting in much higher total iodine stores in the body. In addition, amiodarone decreases T4 5'-deiodinase activity, which decreases the peripheral conversion of T4 to T3, leading to decreased serum T3. Serum T4 levels are usually normal but may be slightly increased. TSH concentrations usually increase during amiodarone therapy, but after 3 months of continuous administration, TSH concentrations often return to normal. However, amiodarone can cause hypothyroidism or hyperthyroidism, including life-threatening thyrotoxicosis. Therefore, patients receiving levothyroxine and amiodarone should be monitored for changes in thyroid function; because of the slow elimination of amiodarone and its metabolites, abnormal thyroid function tests may persists for weeks or months after amiodarone drug discontinuation.
    Lidocaine: (Major) Concomitant administration of lidocaine with amiodarone has been reported to cause sinus bradycardia and seizure. Amiodarone and its main metabolite, N-monodesethylamiodarone (DEA), appear to inhibit the metabolism of lidocaine by competitively inhibiting CYP3A4. Furthermore, DEA inhibits lidocaine metabolism in a concentration-dependent manner. Also, the metabolism of amiodarone to DEA appears to be competitively inhibited by lidocaine. Close correlations between amiodarone N-monodesethylase activities and the amounts of CYP3A4 and the rates of lidocaine N-monodesethylation have been observed from analyses of in vitro data. Inhibition of lidocaine metabolism is supported by in vivo data from 6 adults. The mean systemic concentration of lidocaine over 300 minutes after receipt of lidocaine hydrochloride 1 mg/kg intravenously before amiodarone treatment is 111.7 +/- 23.2 mcg/minute/mL. In contrast, the mean systemic concentration of lidocaine over 300 minutes after cumulative amiodarone doses of 3 g and 13 g is 135.3 +/- 34.6 and 131.7 +/- 25.5 mcg/minute/mL, respectively. As expected, the systemic exposure of the lidocaine metabolite, monoethylglycinexylidide, decreases from 19.2 +/- 6.5 to 15.8 +/- 8.3 mcg/minute/mL after 3 g of amiodarone. In addition, the systemic clearance of lidocaine decreases from 7.86 +/- 1.83 to 6.31 +/- 2.21 mL/minute/kg body weight. As compared with values before amiodarone administration, the lidocaine elimination half-life and the distribution volume at steady state remain relatively unchanged. Due to the long half-life of amiodarone, clinicians should use caution when administering lidocaine to patients who are receiving or who have recently discontinued amiodarone.
    Liothyronine: (Moderate) Amiodarone has a complex effect on the metabolism of thyroid hormones and can alter thyroid function tests in many patients. Since approximately 37% of amiodarone (by weight) is iodine, maintenance doses of 200-600 mg of amiodarone/day result in ingestion of 75-225 mg/day of organic iodide, resulting in much higher total iodine stores in the body. In addition, amiodarone decreases T4 5'-deiodinase activity, which decreases the peripheral conversion of T4 to T3, leading to decreased serum T3. Serum T4 levels are usually normal but may be slightly increased. TSH concentrations usually increase during amiodarone therapy, but after 3 months of continuous administration, TSH concentrations often return to normal. However, amiodarone can cause hypothyroidism or hyperthyroidism, including life-threatening thyrotoxicosis. Therefore, patients receiving levothyroxine and amiodarone should be monitored for changes in thyroid function; because of the slow elimination of amiodarone and its metabolites, abnormal thyroid function tests may persists for weeks or months after amiodarone drug discontinuation.
    Liotrix: (Moderate) Amiodarone has a complex effect on the metabolism of thyroid hormones and can alter thyroid function tests in many patients. Since approximately 37% of amiodarone (by weight) is iodine, maintenance doses of 200-600 mg of amiodarone/day result in ingestion of 75-225 mg/day of organic iodide, resulting in much higher total iodine stores in the body. In addition, amiodarone decreases T4 5'-deiodinase activity, which decreases the peripheral conversion of T4 to T3, leading to decreased serum T3. Serum T4 levels are usually normal but may be slightly increased. TSH concentrations usually increase during amiodarone therapy, but after 3 months of continuous administration, TSH concentrations often return to normal. However, amiodarone can cause hypothyroidism or hyperthyroidism, including life-threatening thyrotoxicosis. Therefore, patients receiving levothyroxine and amiodarone should be monitored for changes in thyroid function; because of the slow elimination of amiodarone and its metabolites, abnormal thyroid function tests may persists for weeks or months after amiodarone drug discontinuation.
    Lithium: (Major) If possible, avoid coadministration of amiodarone and lithium. Lithium has been shown to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Lomefloxacin: (Severe) Lomefloxacin has been associated with QT prolongation and infrequent cases of arrhythmia. Lomefloxacin should be avoided in patients receiving Class III Antiarrhythmics.
    Lomitapide: (Major) Concomitant use of lomitapide and amiodarone may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Amiodarone is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors. In addition, caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as amiodarone. The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
    Long-acting beta-agonists: (Moderate) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as beta-agonists, should only be done after careful assessment of risks versus benefits. Beta-agonists may rarely be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Loperamide: (Major) Coadministration of loperamide with amiodarone may increase the risk for QT prolongation and torsade de pointes (TdP). At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP), although the frequency of TdP is less with amiodarone than with other Class III agents. In addition, the plasma concentrations of loperamide, a substrate for CYP3A4, CYP2D6, and P-glycoprotein (P-gp), may be increased when administered concurrently with amiodarone, an inhibitor of CYP3A4, CYP2D6, and P-gp, further increasing the risk of toxicity. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. If these drugs are used together, monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Loperamide; Simethicone: (Major) Coadministration of loperamide with amiodarone may increase the risk for QT prolongation and torsade de pointes (TdP). At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP), although the frequency of TdP is less with amiodarone than with other Class III agents. In addition, the plasma concentrations of loperamide, a substrate for CYP3A4, CYP2D6, and P-glycoprotein (P-gp), may be increased when administered concurrently with amiodarone, an inhibitor of CYP3A4, CYP2D6, and P-gp, further increasing the risk of toxicity. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. If these drugs are used together, monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Lopinavir; Ritonavir: (Major) Coadministration of HIV treatment doses of ritonavir and amiodarone is contraindicated due to the potential for serious or life-threatening reactions, such as cardiac arrhythmias. Cautious consideration may be given to administering amiodarone with boosting doses of ritonavir. Ritonavir is an inhibitor of CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as amiodarone, should be expected with concurrent use. In addition, both ritonavir and amiodarone are associated with QT prolongation; concomitant use increases the risk of QT prolongation. (Major) Concurrent use of amiodarone and lopinavir; ritonavir should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Lopinavir; ritonavir is also associated with QT prolongation. In addition, lopinavir; ritonavir inhibits CYP3A4 and amiodarone is a CYP3A4 substrate. Coadministration may increase the serum concentrations of amiodarone. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Loratadine: (Moderate) Monitor for evidence of QT prolongation if loratadine is coadministered with amiodarone. QT prolongation and torsades de pointes (TdP) have been reported during concurrent administration of loratadine and amiodarone.
    Loratadine; Pseudoephedrine: (Moderate) Monitor for evidence of QT prolongation if loratadine is coadministered with amiodarone. QT prolongation and torsades de pointes (TdP) have been reported during concurrent administration of loratadine and amiodarone.
    Losartan: (Minor) Coadministration of losartan with amiodarone may result in increased exposure to losartan but decreased concentrations of the active metabolite. The conversion of losartan to its active metabolite is primarily mediated by CYP2C9; amiodarone is an inhibitor of CYP2C9. When coadministered with another inhibitor of CYP2C9, the AUC of the active metabolite of losartan was decreased by 40%, but the AUC of losartan increased by 70%.
    Lovastatin: (Major) In general, in patients taking amiodarone, the lovastatin adult dose should not exceed 40 mg/day PO. Lovastatin doses greater than 40 mg/day should only be used in patients taking amiodarone in whom the benefit is expected to outweigh the increased risk of myopathy. Amiodarone may inhibit lovastatin metabolism via hepatic CYP3A4 isoenzymes. Monitor for signs and symptoms of myopathy in patients receiving amiodarone concurrently with any dose of lovastatin.
    Lovastatin; Niacin: (Major) In general, in patients taking amiodarone, the lovastatin adult dose should not exceed 40 mg/day PO. Lovastatin doses greater than 40 mg/day should only be used in patients taking amiodarone in whom the benefit is expected to outweigh the increased risk of myopathy. Amiodarone may inhibit lovastatin metabolism via hepatic CYP3A4 isoenzymes. Monitor for signs and symptoms of myopathy in patients receiving amiodarone concurrently with any dose of lovastatin.
    Lumacaftor; Ivacaftor: (Major) Use caution when administering ivacaftor and amiodarone concurrently; increased monitoring and/or dose reduction of ivacaftor may be necessary. The manufacturer recommends administering ivacaftor at the usual recommended dose but reducing the frequency to once daily when used concurrently with a moderate CYP3A inhibitor. Ivacaftor is a CYP3A substrate, and amiodarone is a CYP3A inhibitor. Coadministration with fluconazole, a moderate CYP3A inhibitor, increased ivacaftor exposure by 3-fold. Ivacaftor is also an inhibitor of CYP3A and amiodarone is partially metabolized by CYP3A. Coadministration may increase amiodarone exposure leading to increased or prolonged therapeutic effects and adverse events.
    Lurasidone: (Major) Amiodarone is a moderate inhibitor of CYP3A4 and has the potential for interactions with substrates of CYP3A4 such as lurasidone. Concurrent use of lurasidone and amiodarone may lead to an increased risk of lurasidone-related adverse reactions. If a moderate inhibitor of CYP3A4 is being prescribed and lurasidone is added in an adult patient, the recommended starting dose of lurasidone is 20 mg/day and the maximum recommended daily dose of lurasidone is 80 mg/