Elsaad products
Member Login


New Products
Newsletter
 
 
Our Products
 
Product Name
:
Amiodarone-ELSaad (tab)
Chemical Name
:
Amiodarone
Therapeutic Category
:
Cardiovascular drugs
Pharmacologic Category
:
Antiarrhythmic Agent, Class III
Pharmaceutical Form
:
Tablets
Composition
:
amiodarone 200mg
Dosing
 
Dosing: Adult

Note: Lower loading and maintenance doses are preferable in women and all patients with low body weight.

Atrial fibrillation pharmacologic cardioversion (ACC/AHA/ESC Practice Guidelines) (unlabeled use):

Oral: Inpatient: 1.2-1.8 g/day in divided doses until 10 g total, then 200-400 mg/day maintenance. Outpatient: 600-800 mg/day in divided doses until 10 g total, then 200-400 mg/day maintenance; although not supported by clinical evidence, a maintenance dose of 100 mg/day is commonly used especially for the elderly or patients with low body mass (Fuster, 2006; Zimetbaum, 2007). Note: Other regimens have been described and may be used clinically:

400 mg 3 times/day for 5-7 days, then 400 mg/day for 1 month, then 200 mg/day

or

10 mg/kg/day for 14 days, followed by 300 mg/day for 4 weeks, followed by maintenance dosage of 200 mg/day (Roy, 2000)

I.V.: 5-7 mg/kg over 30-60 minutes, then 1.2-1.8 g/day continuous infusion or in divided oral doses until 10 g total. Maintenance: See oral dosing.

Atrial fibrillation prophylaxis following open heart surgery (unlabeled use): Note: A variety of regimens have been used in clinical trials, including oral and intravenous regimens:

Oral: Starting in postop recovery, 400 mg twice daily for up to 7 days. Alternative regimen of amiodarone: 600 mg/day for 7 days prior to surgery, followed by 200 mg/day until hospital discharge, has also been shown to decrease the risk of postoperative atrial fibrillation.

I.V.: Starting at postop recovery, 1000 mg infused over 24 hours for 2 days has been shown to reduce the risk of postoperative atrial fibrillation.

Recurrent atrial fibrillation (unlabeled use): No standard regimen defined; examples of regimens include: Oral: Initial: 10 mg/kg/day for 14 days; followed by 300 mg/day for 4 weeks, followed by maintenance dosage of 200 mg/day (Roy, 2000). Other regimens have been described and are used clinically (ie, 400 mg 3 times/day for 5-7 days, then 400 mg/day for 1 month, then 200 mg/day).

Ventricular arrhythmias: Oral: 800-1600 mg/day in 1-2 doses for 1-3 weeks, then when adequate arrhythmia control is achieved, decrease to 600-800 mg/day in 1-2 doses for 1 month; maintenance: 400 mg/day; lower doses are recommended for supraventricular arrhythmias.

Pulseless VT or VF (ACLS, 2010): I.V. push, I.O.: Initial: 300 mg; if pulseless VT or VF continues after subsequent defibrillation attempt or recurs, administer supplemental dose of 150 mg. Note: In this setting, administering undiluted is preferred (Dager, 2006; Skrifvars, 2004). The Handbook of Emergency Cardiovascular Care (Hazinski, 2010) and the 2010 ACLS guidelines, do not make any specific recommendations regarding dilution of amiodarone in this setting. Experience limited with I.O. administration of amiodarone (ACLS, 2010).

Upon return of spontaneous circulation, follow with an infusion of 1 mg/minute for 6 hours, then 0.5 mg/minute for 18 hours (mean daily doses >2.1 g/day have been associated with hypotension).

Stable VT or SVT (unlabeled use): First 24 hours: 1050 mg according to following regimen

Step 1: 150 mg (100 mL) over first 10 minutes (mix 3 mL in 100 mL D5W)

Step 2: 360 mg (200 mL) over next 6 hours (mix 18 mL in 500 mL D5W): 1 mg/minute

Step 3: 540 mg (300 mL) over next 18 hours: 0.5 mg/minute

Note: After the first 24 hours: 0.5 mg/minute utilizing concentration of 1-6 mg/mL

Breakthrough stable VT or SVT: 150 mg supplemental doses in 100 mL D5W or NS over 10 minutes (mean daily doses >2.1 g/day have been associated with hypotension)

I.V. to oral therapy conversion: Use the following as a guide:

<1 week I.V. infusion: 800-1600 mg/day

1- to 3-week I.V. infusion: 600-800 mg/day

>3 week I.V. infusion: 400 mg

Note: Conversion from I.V. to oral therapy has not been formally evaluated. Some experts recommend a 1-2 day overlap when converting from I.V. to oral therapy especially when treating ventricular arrhythmias.

Recommendations for conversion to intravenous amiodarone after oral administration: During long-term amiodarone therapy (ie, ≥4 months), the mean plasma-elimination half-life of the active metabolite of amiodarone is 61 days. Replacement therapy may not be necessary in such patients if oral therapy is discontinued for a period <2 weeks, since any changes in serum amiodarone concentrations during this period may not be clinically significant.

Dosing: Pediatric

Arrhythmias (unlabeled use):

Loading dose: Oral: 10-20 mg/kg/day in 1-2 doses for 4-14 days or until adequate control of arrhythmia or prominent adverse effects occur; alternative loading dose in children <1 year: 600-800 mg/1.73 m2/day in 1-2 divided doses/day.

Maintenance dose: Oral: Dose may be reduced to 5 mg/kg/day for several weeks (or 200-400 mg/1.73 m2/day given once daily); if no recurrence of arrhythmia, dose may be further reduced to 2.5 mg/kg/day; maintenance doses may be given 5-7 days/week.

Arrhythmias (unlabeled use, dosing based on limited data):

Loading dose: I.V.: 5 mg/kg over 30 minutes; may repeat up to 3 times if no response.

Maintenance dose: I.V.: Continuous infusion: 10-20 mg/kg/day followed by conversion to oral therapy as appropriate

Note: I.V. administration at low flow rates (potentially associated with use in pediatrics) may result in leaching of plasticizers (DEHP) from intravenous tubing. DEHP may adversely affect male reproductive tract development. Alternative means of dosing and administration (1 mg/kg aliquots) may need to be considered.

Pulseless VT or VF (PALS dosing): I.V.: 5 mg/kg (maximum: 300 mg/dose) rapid I.V. bolus or I.O.; repeat up to a maximum daily dose of 15 mg/kg. (Note: Maximum recommended daily dose in adolescents is 2.2 g.)

Perfusing tachycardias (PALS dosing): I.V.: Loading dose: 5 mg/kg (maximum: 300 mg/dose) I.V. over 20-60 minutes or I.O.; may repeat up to maximum dose of 15 mg/kg/day. (Note: Maximum recommended daily dose in adolescents is 2.2 g.)

Dosing: Geriatric

Refer to adult dosing. No specific guidelines available. Dose selection should be cautious, at low end of dosage range, and titration should be slower to evaluate response. Although not supported by clinical evidence, a maintenance dose of 100 mg/day is commonly used especially for the elderly or patients with low body mass (Fuster, 2006; Zimetbaum, 2007).

Dosing: Renal Impairment

No dosage adjustment necessary.

Hemodialysis: Not dialyzable (0% to 5%); supplemental dose is not necessary

Peritoneal dialysis: Not dialyzable (0% to 5%); supplemental dose is not necessary

Dosing: Hepatic Impairment

Dosage adjustment is probably necessary in substantial hepatic impairment. No specific guidelines available. If hepatic enzymes exceed 3 times normal or double in a patient with an elevated baseline, consider decreasing the dose or discontinuing amiodarone.

Use
 

Management of life-threatening recurrent ventricular fibrillation (VF) or hemodynamically-unstable ventricular tachycardia (VT) refractory to other antiarrhythmic agents or in patients intolerant of other agents used for these conditions

Adverse Reactions
 

>10%:

Cardiovascular: Hypotension (I.V. 16%, refractory in rare cases)

Central nervous system (3% to 40%): Abnormal gait/ataxia, dizziness, fatigue, headache, malaise, impaired memory, involuntary movement, insomnia, poor coordination, peripheral neuropathy, sleep disturbances, tremor

Dermatologic: Photosensitivity (10% to 75%)

Endocrine & Metabolic: Hypothyroidism (1% to 22%)

Gastrointestinal: Nausea, vomiting, anorexia, and constipation (10% to 33%)

Hepatic: AST or ALT level >2x normal (15% to 50%)

Ocular: Corneal microdeposits (>90%; causes visual disturbance in <10%)

1% to 10%:

Cardiovascular: CHF (3%), bradycardia (3% to 5%), AV block (5%), conduction abnormalities, SA node dysfunction (1% to 3%), cardiac arrhythmia, flushing, edema. Additional effects associated with I.V. administration include asystole, atrial fibrillation, cardiac arrest, electromechanical dissociation, pulseless electrical activity (PEA), ventricular tachycardia, and cardiogenic shock.

Dermatologic: Slate blue skin discoloration (<10%)

Endocrine & metabolic: Hyperthyroidism (3% to 10%; more common in iodine-deficient regions of the world), libido decreased

Gastrointestinal: Abdominal pain, abnormal salivation, abnormal taste (oral), diarrhea, nausea (I.V.)

Hematologic: Coagulation abnormalities

Hepatic: Hepatitis and cirrhosis (<3%)

Local: Phlebitis (I.V., with concentrations >3 mg/mL)

Ocular: Visual disturbances (2% to 9%), halo vision (<5% occurring especially at night), optic neuritis (1%)

Respiratory: Pulmonary toxicity has been estimated to occur at a frequency between 2% and 7% of patients (some reports indicate a frequency as high as 17%). Toxicity may present as hypersensitivity pneumonitis; pulmonary fibrosis (cough, fever, malaise); pulmonary inflammation; interstitial pneumonitis; or alveolar pneumonitis. ARDS has been reported in up to 2% of patients receiving amiodarone, and postoperatively in patients receiving oral amiodarone.

Miscellaneous: Abnormal smell (oral)

<1% (Limited to important or life-threatening): Acute intracranial hypertension (I.V.), acute renal failure, acute respiratory distress syndrome, agranulocytosis, alopecia, anaphylactic shock, angioedema, aplastic anemia, bone marrow granuloma, bronchiolitis obliterans organizing pneumonia (BOOP), bronchospasm, cholestatic hepatitis, confusion, delirium, demyelinating polyneuropathy, disorientation, drug rash with eosinophilia and systemic symptoms (DRESS), dyspnea, encephalopathy, eczema, eosinophilic pneumonia, epididymitis (noninfectious), erectile dysfunction, erythema multiforme, exfoliative dermatitis, fever, granuloma, hallucination, hemolytic anemia, hemoptysis, hyperglycemia, hypertriglyceridemia, hypotension (oral), hypoxia, impotence, injection site reactions, leukocytoclastic vasculitis, muscle weakness, myopathy, neutropenia, optic neuropathy, pancreatitis, pancytopenia, parkinsonian symptoms, photophobia, pleural effusion, pleuritis, proarrhythmia, pruritus, pseudotumor cerebri, pulmonary alveolar hemorrhage, pulmonary edema, pulmonary infiltrates, pulmonary mass, QT interval increased, rash, renal impairment, renal insufficiency, respiratory failure, rhabdomyolysis, SIADH, sinus arrest, skin cancer, spontaneous ecchymosis, Stevens-Johnson syndrome, thrombocytopenia, thyroid nodules, thyroid cancer, thyrotoxicosis, torsade de pointes (rare), toxic epidermal necrolysis, urticaria, vasculitis, ventricular fibrillation, wheezing

Contraindications
 
Hypersensitivity to amiodarone, iodine, or any component of the formulation; severe sinus-node dysfunction; second- and third-degree heart block (except in patients with a functioning artificial pacemaker); bradycardia causing syncope (except in patients with a functioning artificial pacemaker); cardiogenic shock
Warnings / Precautions Drug
 

Boxed warnings:

• Arrhythmias: Appropriate use: See “Disease-related concerns” below.

• Hepatotoxicity: See “Concerns related to adverse effects” below.

• Proarrhythmic effects: See “Concerns related to adverse effects” below.

• Pulmonary toxicity: See “Concerns related to adverse effects” below.

Concerns related to adverse effects:

• Bradycardia/hypotension: May cause hypotension and bradycardia (infusion-rate related). Hypotension with rapid administration has been attributed to the emulsifier polysorbate 80. Commercially-prepared premixed solutions do not contain polysorbate 80 and may have a lower incidence of hypotension.

• Hepatotoxicity: [U.S. Boxed Warning]: Liver toxicity is common, but usually mild with evidence of increased liver enzymes; severe liver toxicity can occur and has been fatal in a few cases.

• Optic neuritis/neuropathy: May cause optic neuropathy and/or optic neuritis, usually resulting in visual impairment. Corneal microdeposits occur in a majority of patients, and may cause visual disturbances in some patients (blurred vision, halos); these are not generally considered a reason to discontinue treatment. Corneal refractive laser surgery is generally contraindicated in amiodarone users (from manufacturers of surgical devices).

• Photosensitivity: Avoid excessive exposure to sunlight; may cause photosensitivity.

• Proarrhythmic effects: [U.S. Boxed Warning]: Amiodarone can exacerbate arrhythmias, by making them more difficult to tolerate or reverse; other types of arrhythmias have occurred, including significant heart block, sinus bradycardia new ventricular fibrillation, incessant ventricular tachycardia, increased resistance to cardioversion, and polymorphic ventricular tachycardia associated with QTc prolongation (torsade de pointes [TdP]). Risk may be increased with concomitant use of other antiarrhythmic agents or drugs that prolong the QTc interval. Proarrhythmic effects may be prolonged.

• Pulmonary toxicity: [U.S. Boxed Warning]: Lung damage (abnormal diffusion capacity) may occur without symptoms; monitor for pulmonary toxicity (eg, chronic interstitial pneumonitis, organizing pneumonia, acute respiratory distress syndrome, solitary pulmonary mass). Educate patients about monitoring for symptoms (eg, nonproductive cough, dyspnea, pleuritic pain, hemoptysis, wheezing, weight loss, fever, malaise). Evaluate new respiratory symptoms; pre-existing pulmonary disease does not increase risk of developing pulmonary toxicity, but if pulmonary toxicity develops then the prognosis is worse. Use of lower doses may be associated with a decreased incidence, but pulmonary toxicity has been reported in patients treated with low doses. The lowest effective dose should be used as appropriate for the acuity/severity of the arrhythmia being treated.

Disease-related concerns:

• Arrhythmias: Appropriate use: [U.S. Boxed Warnings]: Only indicated for patients with life-threatening arrhythmias because of risk of toxicity. Alternative therapies should be tried first before using amiodarone. Patients should be hospitalized when amiodarone is initiated. Currently, the 2005 ACLS guidelines recommend I.V. amiodarone as the preferred antiarrhythmic for the treatment of pulseless VT/VF. In patients with non-life-threatening arrhythmias (eg, atrial fibrillation), amiodarone should be used only if the use of other antiarrhythmics has proven ineffective or are contraindicated.

• Cardiac devices (eg, implanted defibrillators, pacemakers): Chronic administration of antiarrhythmic drugs may affect defibrillation or pacing thresholds. Assess when initiating amiodarone and during therapy.

• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Thyroid disease: Use very cautiously and with close monitoring in patients with thyroid disease; may cause hyper- or hypothyroidism. Hyperthyroidism may result in thyrotoxicosis and may aggravate or cause breakthrough arrhythmias. If any new signs of arrhythmia appear, hyperthyroidism should be considered. Thyroid function should be monitored prior to treatment and periodically thereafter, particularly in the elderly and in patients with underlying thyroid dysfunction.

Concurrent drug therapy issues:

• Drugs metabolized by CYP enzymes: Amiodarone is a potent inhibitor of CYP enzymes and transport proteins (including p-glycoprotein), which may lead to increased serum concentrations/toxicity of a number of medications.

• Drugs with QT prolongation potential: Particular caution must be used when a drug with QTc-prolonging potential relies on metabolism via enzymes amiodarone inhibits, since the effect of elevated concentrations may be additive with the effect of amiodarone. Carefully assess risk:benefit of coadministration of other drugs which may prolong QTc interval.

• Warfarin: Use caution when initiating amiodarone in patients on warfarin. Cases of increased INR with or without bleeding have occurred in patients treated with warfarin; monitor INR closely after initiating amiodarone in these patients.

Special populations:

• Elderly: Monitor thyroid function prior to treatment and periodically thereafter. May be inappropriate in this age group due to a risk of QTc-interval prolongation, torsade de pointes, and lack of efficacy in the elderly (Beers Criteria).

• Surgical patients: Caution in surgical patients; may enhance hemodynamic effect of anesthetics; associated with increased risk of adult respiratory distress syndrome (ARDS) postoperatively.

Dosage form specific issues:

• Benzyl alcohol: Vials for injection contain benzyl alcohol which has been associated with “gasping syndrome” in neonates. Commercially-prepared premixed solutions do not contain benzyl alcohol.

• Commercially-prepared premixed infusion: Contains the excipient cyclodextrin (sulfobutyl ether beta-cyclodextrin), which may accumulate in patients with renal insufficiency.

Other warnings/precautions:

• CAST trial: In the Cardiac Arrhythmia Suppression Trial (CAST), recent (>6 days but <2 years ago) myocardial infarction patients with asymptomatic, nonlife-threatening ventricular arrhythmias did not benefit and may have been harmed by attempts to suppress the arrhythmia with flecainide or encainide. An increased mortality or nonfatal cardiac arrest rate (7.7%) was seen in the active treatment group compared with patients in the placebo group (3%). The applicability of the CAST results to other populations is unknown. Use of amiodarone post-MI was not associated with an increase in mortality in two post-MI trials. Antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.

• Discontinuation of therapy: Patients may still be at risk for amiodarone–related drug interactions after the drug has been discontinued. The pharmacokinetics are complex (due to prolonged duration of action and half-life) and difficult to predict.

Interactions
 

Agalsidase Alfa: Amiodarone may diminish the therapeutic effect of Agalsidase Alfa. Risk X: Avoid combination

Agalsidase Beta: Amiodarone may diminish the therapeutic effect of Agalsidase Beta. Risk X: Avoid combination

Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

Antiarrhythmic Agents (Class Ia): Amiodarone may enhance the QTc-prolonging effect of Antiarrhythmic Agents (Class Ia). Amiodarone may increase the serum concentration of Antiarrhythmic Agents (Class Ia). Management: Risk of QTc prolongation and Torsades de Pointes may be increased; consider alternative therapy when possible. Risk D: Consider therapy modification

Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Azithromycin: May enhance the QTc-prolonging effect of Amiodarone. Management: A careful risk:benefit assessment should be conducted. Patients should be carefully monitored for the development of this effect as QTc prolongation can result in torsades de pointes. Risk D: Consider therapy modification

Azithromycin (Systemic): May enhance the QTc-prolonging effect of Amiodarone. Management: A careful risk:benefit assessment should be conducted . Patients should be carefully monitored for the development of this effect as QTc prolongation can result in torsades de pointes. Risk D: Consider therapy modification

Beta-Blockers: Amiodarone may enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the bioavailability of Amiodarone. Risk D: Consider therapy modification

Boceprevir: May increase the serum concentration of Amiodarone. Risk C: Monitor therapy

Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Monitor patients closely for signs/symptoms of corticosteroid excess. Risk D: Consider therapy modification

Calcium Channel Blockers (Nondihydropyridine): May enhance the bradycardic effect of Amiodarone. Sinus arrest has been reported. Risk D: Consider therapy modification

Cardiac Glycosides: Amiodarone may increase the serum concentration of Cardiac Glycosides. Risk D: Consider therapy modification

Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of Amiodarone. Management: Consider alternatives to cimetidine. If this combination cannot be avoided, monitor for increased amiodarone concentrations/effects with cimetidine initiation/dose increase or decreased concentrations/effects with cimetidine discontinuation/dose decrease. Risk D: Consider therapy modification

Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

Ciprofloxacin (Systemic): May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy

Clopidogrel: Amiodarone may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk C: Monitor therapy

Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Risk D: Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination

CycloSPORINE: Amiodarone may decrease the metabolism of CycloSPORINE. Risk D: Consider therapy modification

CycloSPORINE (Systemic): Amiodarone may decrease the metabolism of CycloSPORINE (Systemic). Risk D: Consider therapy modification

CYP2A6 Substrates: CYP2A6 Inhibitors (Moderate) may decrease the metabolism of CYP2A6 Substrates. Risk C: Monitor therapy

CYP2C8 Inducers (Highly Effective): May increase the metabolism of CYP2C8 Substrates (High risk). Risk C: Monitor therapy

CYP2C8 Inhibitors (Moderate): May decrease the metabolism of CYP2C8 Substrates (High risk). Risk C: Monitor therapy

CYP2C8 Inhibitors (Strong): May decrease the metabolism of CYP2C8 Substrates (High risk). Risk D: Consider therapy modification

CYP2C9 Substrates (High risk): CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy

CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification

CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy

Dabigatran Etexilate: Amiodarone may increase the serum concentration of Dabigatran Etexilate. Management: Canadian (but not U.S.) dabigatran prescribing information recommends limiting dabigatran dose for VTE prevention following hip/knee replacement to 150 mg/day. No dose adjustment is recommended for dabigatran in atrial fibrillation. Risk D: Consider therapy modification

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. According to Canadian labeling, dabigatran dose for prevention of venous thromboembolism post hip or knee replacement should be reduced to 150 mg/day in patients receiving amiodarone, verapamil, or quinidine. Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Deferasirox: May increase the serum concentration of CYP2C8 Substrates (High risk). Risk C: Monitor therapy

Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination

Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: A lower starting dose of eplerenone (25 mg once daily for adults) is recommended in patients with hypertension who are also taking drugs that are moderate inhibitors of CYP3A4. Risk D: Consider therapy modification

Eribulin: May enhance the QTc-prolonging effect of Antiarrhythmic Agents (Class III). Risk C: Monitor therapy

Etravirine: May decrease the serum concentration of Amiodarone. Risk C: Monitor therapy

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification

FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients extra closely for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate. Risk D: Consider therapy modification

Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy

Fingolimod: May enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class III). Management: Obtain baseline ECG (if not recently available) if initiating fingolimod during treatment with class III antiarrhythmic agents. Monitor for bradycardia and AV block. The Canadian labeling recommends avoiding concomitant use of these agents. Risk C: Monitor therapy

Flecainide: Amiodarone may increase the serum concentration of Flecainide. Management: Decrease flecainide dose by 50% in the presence of amiodarone. Monitor for adverse effects of flecainide and consider monitoring for elevated serum concentrations during concomitant therapy. Risk D: Consider therapy modification

Fosphenytoin: May decrease the serum concentration of Amiodarone. Amiodarone may increase the serum concentration of Fosphenytoin. Risk C: Monitor therapy

Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification

Grapefruit Juice: May decrease serum concentrations of the active metabolite(s) of Amiodarone. Grapefruit Juice may increase the serum concentration of Amiodarone. Risk X: Avoid combination

HMG-CoA Reductase Inhibitors: Amiodarone may decrease the metabolism of HMG-CoA Reductase Inhibitors. Management: Dose of HMG-CoA reductase inhibitor may need to be reduced (e.g., simvastatin prescribing information recommends limiting adult maximum dose to 10 mg/day). Avoid Simcor (simvastatin/niacin) as fixed simvastatin doses exceed recommended maximum doses. Exceptions: Pitavastatin; Pravastatin. Risk D: Consider therapy modification

Lidocaine: Amiodarone may decrease the metabolism of Lidocaine. Risk C: Monitor therapy

Lidocaine (Systemic): Amiodarone may decrease the metabolism of Lidocaine (Systemic). Risk C: Monitor therapy

Lidocaine (Topical): Amiodarone may decrease the metabolism of Lidocaine (Topical). Risk C: Monitor therapy

Loratadine: Amiodarone may increase the serum concentration of Loratadine. Management: Due to reported QT interval prolongation and Torsades de Pointes with this combination, consider an alternative to loratadine when possible. Risk D: Consider therapy modification

Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Risk D: Consider therapy modification

Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Orlistat: May decrease the absorption of Amiodarone. Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: P-glycoprotein/ABCB1 Substrates may increase the serum concentration of P-glycoprotein/ABCB1 Inhibitors. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

P-glycoprotein/ABCB1 Substrates: May increase the serum concentration of P-glycoprotein/ABCB1 Inhibitors. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

Phenytoin: May decrease the serum concentration of Amiodarone. Amiodarone may increase the serum concentration of Phenytoin. Risk C: Monitor therapy

Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy

Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Protease Inhibitors: May decrease the metabolism of Amiodarone. Risk X: Avoid combination

QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification

QUEtiapine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination

Rifamycin Derivatives: May increase the metabolism of Amiodarone. Risk C: Monitor therapy

Rivaroxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rivaroxaban. Risk C: Monitor therapy

Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk X: Avoid combination

Sodium Iodide I131: Amiodarone may diminish the therapeutic effect of Sodium Iodide I131. Risk D: Consider therapy modification

Telaprevir: May enhance the adverse/toxic effect of Amiodarone. Telaprevir may increase the serum concentration of Amiodarone. Risk C: Monitor therapy

Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination

Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Toremifene: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Toremifene. The risk for potentially dangerous arrhythmias may be increased. Risk X: Avoid combination

TraMADol: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy

Vandetanib: QTc-Prolonging Agents may enhance the arrhythmogenic effect of Vandetanib. Risk X: Avoid combination

Vemurafenib: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Vemurafenib. Risk X: Avoid combination

Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Amiodarone may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination

Pregnancy
 

D

Pregnancy Implications

May cause fetal harm when administered to a pregnant woman, leading to congenital goiter and hypo- or hyperthyroidism

Lactation
 
Enters breast milk/not recommended
Monitoring Parameters
 
Blood pressure, heart rate (ECG) and rhythm throughout therapy; assess patient for signs of lethargy, edema of the hands or feet, weight loss, and pulmonary toxicity (baseline pulmonary function tests and chest X-ray; continue monitoring chest X-ray annually during therapy); liver function tests (semiannually); monitor serum electrolytes, especially potassium and magnesium. Assess thyroid function tests before initiation of treatment and then periodically thereafter (some experts suggest every 3-6 months). If signs or symptoms of thyroid disease or arrhythmia breakthrough/exacerbation occur then immediate re-evaluation is necessary. Amiodarone partially inhibits the peripheral conversion of thyroxine (T4) to triiodothyronine (T3); serum T4 and reverse triiodothyronine (rT3) concentrations may be increased and serum T3 may be decreased; most patients remain clinically euthyroid, however, clinical hypothyroidism or hyperthyroidism may occur.
Mechanism of Action
 
Class III antiarrhythmic agent which inhibits adrenergic stimulation (alpha- and beta-blocking properties), affects sodium, potassium, and calcium channels, prolongs the action potential and refractory period in myocardial tissue; decreases AV conduction and sinus node function
Pharmacodynamics / Kinetics
 

Absorption: Slow and variable

Onset of action: Oral: 2 days to 3 weeks; I.V.: May be more rapid

Peak effect: 1 week to 5 months

Duration after discontinuing therapy: 7-50 days

Note: Mean onset of effect and duration after discontinuation may be shorter in children than adults

Distribution: Vd: 66 L/kg (range: 18-148 L/kg)

Protein binding: 96%

Metabolism: Hepatic via CYP2C8 and 3A4 to active N-desethylamiodarone metabolite; possible enterohepatic recirculation

Bioavailability: Oral: 35% to 65%

Half-life elimination: Terminal: 40-55 days (range: 26-107 days); shorter in children

Time to peak, serum: 3-7 hours

Excretion: Feces; urine (<1% as unchanged drug)

 
   
 
Powered by: TSS-EST.COM