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Amiodarone (cordarone) - Uses, dosages, side effects ...

Amiodarone is a class III antiarrhythmic drug that has both alpha and beta-receptor-blocking properties.

It is among the WHO's list of essential medicines.

It is used to treat the following conditions.

Ventricular arrhythmias:
- It is used to treat recurrent hemodynamically unstable ventricular tachycardia not responding to other antiarrhythmic agents or patients intolerant of other agents, and patients with life-threatening recurrent ventricular fibrillation.
Off Label Use of Amiodarone in Adults:
- Atrial fibrillation
- Electrical storm and continuous ventricular tachycardia (VT), hemodynamically stable
- Nonsustained VT with symptoms
- Pharmacologic conversion of atrial fibrillation to and maintenance of normal sinus rhythm
- Prevention of implantable cardioverter/ defibrillator (ICD) shocks
- Prevention of postoperative atrial fibrillation and atrial flutter associated with cardiothoracic surgery
- Primary prevention of sudden cardiac death caused due to ventricular arrhythmias
- Supraventricular tachycardia (eg, atrioventricular nodal reentrant tachycardia [AVNRT], atrioventricular reentrant tachycardia [AVRT], focal atrial tachycardia [AT])
- Ventricular premature beats, symptomatic

Amiodarone Dose in Adults

Supraventricular arrhythmias:

Note: Amiodarone is a preferred antiarrhythmic for patients with structural heart disease.

Atrial fibrillation:

Off-label use as an alternative agent in the treatment of Pharmacologic cardioversion:

Note: Amiodarone can also slow ventricular response

The use of amiodarone (Intravenous and oral) is not mainly effective for cardioversion of atrial fibrillation to normal sinus rhythm when compared to other antiarrhythmics (eg, flecainide).
The more common regimens utilized include:
- 150 mg intravenous over 10 minutes, then 1 mg/minute for the next 6 hours, followed by 0.5 mg/minute for 18 hours, then change to oral maintenance dosing.
- 600 to 800 mg orally daily in divided doses for a total load of up to 10 g, then a maintenance dose is given of200 mg once daily.
- 400 mg orally every 8 to 24 hours for a total load of 6 to 10 g, then a maintenance dose of 100 to 200 mg once daily is given.
- A maintenance dose of 100 mg orally once daily is commonly used mainly for elderly patients or patients with low body mass.

Note: Loading regimen can be given 2 to 6 weeks prior to direct current cardioversion to reduce the risk of recurrence

Off-label use in the treatment of Maintenance of sinus rhythm:

400 to 600 mg orally daily in divided doses for 2 - 4 weeks, afterwards maintenance dose of 100 to 200 mg once daily.
Another proposed dosage is 400 mg orally every 8 to 24 hours for a total load of ~6 to 10 g, then a maintenance dose of 100 to 200 mg once daily.

Off-label use as an alternative agent in the Prevention of postoperative atrial fibrillation and atrial flutter associated with cardiothoracic surgery:

Note:

Some experts use beta-blockers instead of amiodarone.

But, in patients who cannot use beta-blockers, amiodarone may be used.

200 mg orally 3 times daily for 7 days before surgery, followed by 200 mg daily until hospital discharge.
Preoperative regimen:
- 150 mg intravenous loading dose, then 0.4 mg/kg/hour (~0.5 mg/minute for a 70 kg patient) for 3 days prior to surgery and for 5 days postoperatively.
Postoperative regimen:
- Starting at postoperative recovery: 1,000 mg intravenous given over 24 hours for 2 days

Intravenous followed by Oral:

Postoperative regimen:
- It is started 6 hours postoperatively, 1,050 mg Intravenous loading dose over 24 hours, then 400 mg orally 3 times daily on postop days 1 to 4.

Off-label use in the treatment of heart rate control:

300 mg is given intravenously over 1 hour, then 10 to 50 mg/hour over 24 hours followed by an oral maintenance dose; the usual maintenance dose is 100 to 200 mg once daily.
Some experts use a more typical regimen of 150 mg intravenously over at least 10 minutes, followed by 0.5 to 1 mg/minute.
Repeat boluses of 150 mg Intravenous over at least 10 minutes as needed can also be given.
Mean daily doses of greater than 2.1 g/day have been associated with hypotension.

Off-label use in the treatment of Supraventricular tachycardia (eg, atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, and focal atrial tachycardia):

Note:

Amiodarone is sometimes reserved for use when other therapies have failed or are contraindicated.

In general, most patients do not require long-term treatment with antiarrhythmic therapy.

Pharmacologic cardioversion:
- Loading dose:
  - 400 to 600 mg orally daily in divided doses for 2- 4 weeks.
  - In an admitted patient with a monitoring setting, loading doses up to 1,200 mg daily in divided doses may be considered.
  - Some experts suggest a total oral load of ~6 to 10 g.
- Maintenance dose:
  - 100 to 200 mg orally daily.
- 150 mg I/V over 10 minutes, then 1 mg/minute for 6 hours, then 0.5 mg/minute for 18 hours or may change to oral dosing.

Ventricular arrhythmias:

Off-label use in the treatment of hemodynamically stable electrical storm and incessant ventricular tachycardia (VT):

150 mg intravenous over 10 minutes (can be repeated if necessary), followed by 1 mg/minute Intravenous infusion for 6 hours, followed by 0.5 mg/minute for 18 additional hours or till switched to oral therapy.

Note: Coadministration with a beta-blocker (eg, propranolol) is advised.

Maintenance dose:
- 400 mg orally every 8 to 12 hours for 1- 2 weeks, followed by 200 to 400 mg OD.
- A total oral load of ~6 to 10 g is also recommended in some cases.

Off-label use in the treatment of symptomatic Nonsustained VT:

Note: Think of adding a beta-blocker or non-dihydropyridine calcium channel blocker (eg, diltiazem) before starting antiarrhythmic therapy.

400 mg every orally 8 - 12 hours for 1 to 2 weeks, followed by 200 to 400 mg once daily.
A total of ~6 to 10 g during the first 1 to 2 weeks of therapy may be given
A slower oral loading regimen of 200 mg twice daily for the first 28 days, followed by 200 mg once daily may also be used.

Off-label use in the treatment of Prevention of implantable cardioverter/ defibrillator (ICD) shocks:

Note:

Antiarrhythmic therapy for this indication does not show to reduce mortality but may improve quality of life by reducing the frequency of ICD shocks.

Amiodarone is the preferred antiarrhythmic for this use.

400 mg orally twice daily for 14 days, followed by 400 mg once daily for 28 days, then 200 mg once daily in combination with a beta-blocker or
some experts recommend 400 mg orally every 8 to 24 hours for a total oral load of 6 to 10 g, then 200 to 400 mg once daily.

Off-label use in the treatment of Primary prevention of sudden cardiac death due to ventricular arrhythmias:

Note:

Think of the addition of a beta-blocker before starting antiarrhythmic therapy.

For patients eligible for an ICD with left ventricular dysfunction, but who cannot or refuse to have ICD implantation, amiodarone can be used.

400 mg orally every 8 to 24 hours for 1 to 2 weeks for a total load of 6 to 10 g, then a maintenance dose of 200 to 400 mg once daily

Secondary prevention of sudden cardiac death due to ventricular arrhythmias (eg, ventricular fibrillation [VF] or hemodynamically unstable VT):

Note:

ICD implantation is preferred over antiarrhythmic therapy.
In patients who do not meet ICD implant criteria, have contraindications, or refuse ICD implantation, antiarrhythmics can be used.
Beta-blockers are given prior to or at the time of antiarrhythmic therapy initiation.
- 400 mg orally every 8 to 12 hours for 1 to 2 weeks, then a maintenance dose of 200 to 400 mg once daily or
- 400 mg orally every 8 to 24 hours for a total load of 6 to 10 g, then 200 to 400 mg once daily.

Use in the treatment of Sudden cardiac arrest due to VF or pulseless VT:

Unresponsive to cardiopulmonary resuscitation, defibrillation, and epinephrine:
- 300 mg rapid intravenous or intraosseous bolus.
- If pulseless VT or VF doesn't subside after subsequent defibrillation attempts or recurs, administer a supplemental dose of 150 mg.

Note: In this setting, administering undiluted is recommended.

Upon return of spontaneous circulation:
- 1 mg/minute intravenous for 6 hours, then 0.5 mg/minute for 18 hours or until starting oral therapy.

Note: If amiodarone could not be given during resuscitation but the return of spontaneous circulation is achieved, some experts recommend empiric antiarrhythmic therapy with amiodarone.

Use in the hemodynamically stable Sustained monomorphic VT:

150 mg intravenous over 10 minutes, then 1 mg/minute for 6 hours, then 0.5 mg/minute for at least 18 hours or
until switched to oral therapy.
Breakthrough hemodynamically stable VT:
- 150 mg is given intravenously over 10 minutes
Maintenance regimen:
- 400 mg orally every 8 to 12 hours for 1 to 2 weeks, then a maintenance dose of 200-400 mg once daily.
- Some experts suggest 400 mg every 8 to 24 hours for a total oral load of ~6 to 10 g, then 200- 400 mg orally once daily.

Off-label use in the treatment of symptomatic ventricular premature beats:

Note: For patients who do not respond to beta-blocker or non-dihydropyridine calcium channel blocker therapy (eg, diltiazem) and cannot take class Ic antiarrhythmic agents.

400 mg orally every 8 to 12 hours for 1 - 2 weeks, then when adequate control is achieved, lessen to 200 to 400 mg once daily; use the lowest effective dose to avoid adverse effects.

Switching to oral amiodarone after Intravenous administration:
Use the following as a guide:
- <1-week Intravenous infusion:
  - 400 - 1,200 mg daily in divided doses till a loading dose of ~6 to 10 g has been given, then start maintenance dose of 200 to 400 mg OD.
- 1- to 2-week Intravenous infusion:
  - 400 to 800 mg daily in divided doses until a loading dose of ~6 to 10 g has been administered, then start a maintenance dose of 200 to 400 mg OD.
- >2-week Intravenous infusion:
  - 200 to 400 mg OD

Switching to Intravenous amiodarone after oral administration:
- During long-term amiodarone therapy (ie, greater than 4 months), the mean plasma elimination half-life of the active metabolite of amiodarone is almost 61 days.
- Replacement therapy might not be necessary for such patients if oral therapy is discontinued for a period <2 weeks, because any reduction in serum amiodarone concentrations during this period may not be clinically significant.

Amiodarone Dose in Children

Use in the treatment of Perfusing tachycardias:

Infants, Children, and Adolescents:
- 5 mg/kg (maximum: 300 mg/dose) is given as a loading dose intravenously over 20 to 60 minutes.
- It can be repeated twice up to a maximum total dose of 15 mg/kg during acute treatment.

Use in the treatment of Shock refractory VF or pulseless VT:

Infants, Children, and Adolescents:
- 5 mg/kg (maximum: 300 mg/dose) rapid bolus intravenous or intraosseous.
- It might be repeated twice up to a maximum total dose of 15 mg/kg during acute treatment.

Use in the treatment of Tachyarrhythmia, including junctional ectopic tachycardia (JET), paroxysmal supraventricular tachycardia (PSVT):

Infants, Children, and Adolescents:
- Loading dose:
  - 10 to 15 mg/kg/day orally in 1 to 2 divided doses daily for 4 - 14 days or
  - until satisfactory control of arrhythmia or prominent adverse effects occur.
  - The dosage should be reduced to 5 mg/kg/day given OD for several weeks.
  - If arrhythmia does not repeat, reduce to the lowest effective dosage possible.
  - The usual daily minimal dose is 2.5 mg/kg/day.
  - The maintenance doses may be given for 5 - 7 days/week

Note:

In infants, some experts suggest BSA-directed dosing.
Loading dose:
- 600 to 800 mg/1.73 m² /day orally in 1 to 2 divided doses.
maintenance dose:
- 200 to 400 mg/1.73 m² /day once daily.

Note:

Prolongation of the corrected QT interval was more likely in infants less than 9 months of age who received higher loading doses (20 mg/kg/day vs 10 mg/kg/day in 2 divided doses)

Loading dose:
- 5 mg/kg intravenous (maximum: 300 mg/dose) given over 60 minutes;

Continuous Intravenous infusion (if needed)
- Dosing based on mcg/kg/minute:
  - 5 mcg/kg/minute.
  - Increase slowly as clinically needed.
  - The usual required dose is 10 mcg/kg/minute ranging from 5 - 15 mcg/kg/minute.
  - A maximum daily dose of 2200 mg can be given
- Dosing based on mg/kg/day:
  - 10 mg/kg/day.
  - Increase the dose incrementally as needed.
  - The usual range is 10 to 20 mg/kg/day.
  - A maximum daily dose of 2,200 mg can be given.

Pregnancy risk Factor: D

In some studies on animal reproduction, adverse events were observed.
Amiodarone crosses the placenta (10% - 50%) and can cause fetal harm if given to pregnant women.
Some of the reported effects are:
- Neonatal bradycardia and QT prolongation. Periodic ventricular extrasystoles.
- Neonatal hypothyroidism, with or without goitre.
- Neonatal hyperthyroxinemia
- Neurodevelopmental abnormalities that are not related to thyroid function.
- Synchronous head titubation and jerk nystagmus
- Retardation of fetal growth
- Premature birth.
Pregnant women should only use intravenous or oral amiodarone to treat arrhythmias that are not responding to other treatments.

Amiodarone use during breastfeeding:

Breast milk contains amiodarone as well as its active metabolite.
Breastfeeding can cause significant infant exposure and possible toxicity.
Because of its long half-life, amiodarone can remain in breast milk for several days after discontinuation.
If treatment is required, the manufacturer suggests that breastfeeding be stopped.

Amiodarone dose in Renal disease:

No dosage adjustment is required.
Hemodialysis:
- Not dialyzable (0% to 5%).
- A supplemental dose is not required
Peritoneal dialysis:
- Not dialyzable (0% to 5%).
- A supplemental dose is not required

Amiodarone dose in Liver disease:

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

Common Side Effects of Amiodarone Include:

Cardiovascular:
- Hypotension
Endocrine & metabolic:
- Phospholipidemia
Gastrointestinal:
- Nausea
- Vomiting
Ophthalmic:
- Epithelial keratopathy

Respiratory:
- Pulmonary toxicity

Less Common Side Effects of Amiodarone Include:

Cardiovascular:
- Bradycardia
- atrioventricular block
- sinus bradycardia
- exacerbation of cardiac arrhythmia
- cardiac failure
- cardiac arrhythmia
- edema
- flushing
- sinus node dysfunction
- ventricular tachycardia
- atrial fibrillation
- cardiogenic shock
- nodal arrhythmia
- prolonged Q-T interval on ECG
- torsades de pointes
- ventricular fibrillation
Central nervous system:
- Abnormal gait
- ataxia
- fatigue
- involuntary body movements
- malaise
- dizziness
- paresthesia
- altered sense of smell
- headache
- insomnia
- sleep disorder
Dermatologic:
- Skin photosensitivity
- solar dermatitis
- Stevens-Johnson syndrome
Endocrine & metabolic:
- Hypothyroidism
- decreased libido
- hyperthyroidism
Gastrointestinal:
- Anorexia
- constipation
- altered salivation
- dysgeusia
- abdominal pain
- diarrhea
Hematologic & oncologic:
- Disorder of hemostatic components of blood
- thrombocytopenia
Hepatic:
- Abnormal hepatic function tests
- hepatic disease
- increased serum alanine aminotransferase
- increased serum aspartate aminotransferase
Neuromuscular & skeletal:
- Tremor
Ophthalmic:
- Blurred vision
- visual halos around lights
- visual disturbance
- optic neuritis
Renal:
- Renal insufficiency
Respiratory:
- Pneumonitis
- pulmonary fibrosis
- acute respiratory distress syndrome
- pulmonary edema

Miscellaneous:
- Fever

Frequency not defined:

Cardiovascular:
- Asystole
Central nervous system:
- Peripheral neuropathy
Ophthalmic:
- Dry eye syndrome
- Photophobia
Respiratory:
- Hypersensitivity pneumonitis
- Pneumonitis (alveolar)

Contraindication to Amiodarone Include:

Allergy to amiodarone, Iodine or any other component of the formulation
- Sick sinus syndrome.
- Atrioventricular block, second or third-degree.
- Bradycardia can cause syncope if the pacemaker is not working.
- Cardiogenic shock

Notice:

FDA-approved product labels state that amiodarone should not be used in patients suffering from iodine hypersensitivity.
- Patients with allergies to shellfish and contrast media are not included in this group. These reactions are often not caused by iodine.
- Patients with severe shellfish allergies or other contrast media should be cautious.

Warnings and precautions

Bradycardia and Hypotension
- Hypotension and bradycardia may occur (infusion rate related).
Dermatologic toxicities:
- Can cause severe cutaneous or life-threatening reactions, such as Stevens-Johnson Syndrome and toxic epidermal necrolysis.
- If you notice signs or symptoms such as skin rash frequently with blisters, or mucosal lesions, stop using the medication immediately.
Extravasation:
- Perhaps a vesicant.
- Before infusion, ensure proper placement of the catheter or needle.
- Avoid extravasation.
Hepatotoxicity: [US Boxed Warning Tablet]
- Hepatotoxicity can be fatal.
- If the patient's baseline or periodic liver transaminases are elevated, discontinue the medication or reduce it.
- Patients with liver injury symptoms should stop receiving treatment.
- Patients who received IV amiodarone have reported elevated levels of bilirubin.
Neurotoxicity:
- Rarely, peripheral neuropathy has been associated with chronic administration.
- Although it may disappear when amiodarone stops being prescribed, the process may take some time.
Ocular effects
- It is recommended to have regular ophthalmic exams (including fundoscopy and slit lamp)
- Optic neuropathy or optic neuritis may cause permanent blindness.
- Ophthalmic evaluations are recommended for patients suffering from optic neuropathy or optic neuritis.
- Reevaluate amiodarone therapy if you are diagnosed with optic neuropathy or optic neuritis.
- Corneal microdeposits can affect most adults. They may cause visual impairments up to 10% in some patients (blurred vision or halos).
- Microdeposits that are symptomatic may be reversible. They should not be considered a reason for discontinuing treatment.
- Corneal refractive surgery with laser is usually contraindicated for amiodarone users (from manufacturers' of surgical devices).
Photosensitivity
- Avoid too much exposure to the sun as it can cause photosensitivity.
- Blue-grey discolouration may occur on the skin after long-term treatment.
- Patients with fair skin or excessive sun exposure are at greater risk.
Proarrhythmic effects [US Boxed Warning (tablet),]
- Amiodarone can exacerbate arrhythmias.
- Initiate treatment in a setting that offers continuous ECGs and cardiac support
- Other arrhythmias include significant heart block, sinus bradycardia and new ventricular fibrillation. There has also been an increase in resistance to cardioversion and polymorphic right ventricular tachycardia due to QTc prolongation (torsades-de-pointes).
- Concomitant use with antiarrhythmic drugs or drugs prolonging the QTc interval may increase the risk.
- The effects of proarrhythmic symptoms may last for a long time.
Toxicity in the lungs: [US Boxed Warning]
- There have been reports of pulmonary toxicity (hypersensitivity or interstitial/alveolar pneumonitis), including fatalities.
- Before initiation, take a baseline chest radiograph and pulmonary function test, including diffusion capacity.
- Do a clinical evaluation and take a repeat chest X-ray every 3 to 6 months.
- If you experience signs and symptoms of pulmonary toxicities, consider alternative therapies.
Thyroid effects:
- Hyperthyroidism and hypothyroidism can occur.
- Hyperthyroidism can lead to thyrotoxicosis, including fatalities, and/or arrhythmia breakthroughs or aggravation.
- Hyperthyroidism is possible if you notice any signs of arrhythmia.
- Sometimes severe hypothyroidism may occur after the resolution of previous amiodarone-induced hyperthyroidism. Myxedema (which may prove fatal) has also been reported.
- Reduce the dosage or stop taking amiodarone if you have hyper- or hypothyroidism.
- Thyroid nodules, and/or thyroid carcinoma have been reported.
- Thyroid disease patients should be cautious
- Thyroid function should be monitored prior to treatment and periodically thereafter, particularly in the elderly and in patients with underlying thyroid dysfunction.
Arrhythmias:
- Use it in the right way: [US Boxed Warnings Tablet]
  - Because of the high risk of significant toxicities, this medication is not recommended for patients suffering from life-threatening arrhythmias.
  - Alternative therapies should be explored before you start taking amiodarone.
  - When amiodarone starts, patients should be admitted to the hospital.
  - The 2015 ACLS Guidelines recommend that Intravenous Amiodarone be considered as an antiarrhythmic to treat pulseless VT/VF not responsive to CPR, defibrillation and vasopressor treatment.
  - Amiodarone should only be used in patients with non-life-threatening arrhythmias, such as atrial fibrillation.

Cardiac devices (eg, implanted defibrillators, pacemakers):
- Chronic administration of antiarrhythmic medications may affect pacing thresholds or defibrillation.
- Take note of when you are starting amiodarone therapy and how it is going.
Electrolyte imbalance:
- Before and during therapy, correct electrolyte imbalances, particularly hypokalemia, hypomagnesemia or hypocalcemia.
- Myocardial Infarction
  - Beta-blocker therapy should be started in the event of acute myocardial injury, even if concomitant amiodarone treatment provides beta-blockade.
  - Wolff-Parkinson-White (WPW) syndrome:
    - Patients with WPW syndrome or pre-excited atrial fibrillation/flutter should not take amiodarone as ventricular fibrillation could result.

Amiodarone: Drug Interaction

Note: Drug Interaction Categories:

Risk Factor C: Monitor When Using Combination
Risk Factor D: Consider Treatment Modification
Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy).
Abiraterone Acetate	High risk of Inhibitors causing an increase in serum CYP2C8 Substrates concentrations
Alfuzosin	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Aminolevulinic Acid Topical	Photosensitizing agents may increase the photosensitizing effects of Aminolevulinic Acid Topical.
Antipsychotic Agents, Second Generation (Atypical)	Blood Pressure Lowering Agents can increase the hypotensive effects of Antipsychotic Agents (Second Gen [Atypical]).
Aprepitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
ARIPiprazole	CYP3A4 Inhibitors, Weak, may increase serum levels of ARIPiprazole. Monitoring for increased aripiprazole-pharmacologic effects is important. Aripiprazole dosage adjustments may be necessary depending on the indication and/or concomitant therapy. For more information, consult the full interaction monograph.
ARIPiprazole	CYP2D6 inhibitors (Weak), may increase serum levels of ARIPiprazole. Monitoring for increased aripiprazole-pharmacologic effects is important. Aripiprazole dosage adjustments may be necessary depending on the indication and concomitant therapy. For more information, consult the full interaction monograph.
Atazanavir	May increase the serum concentration of Amiodarone.
AtorvaSTATin	Amiodarone could increase serum AtorvaSTATin concentrations.
Barbiturates	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Benperidol	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Beta-Blockers	Beta-Blockers may have a bradycardic effect that Amiodarone might enhance. It could even cause cardiac arrest. Amiodarone can increase serum Beta-Blockers. Exceptions: Levobunolol; Metipranolol.
Blood Pressure Lowering Agents	May enhance the hypotensive effect of HypotensionAssociated Agents.
Bosentan	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Bradycardia-Causing Agents	May increase the bradycardic effects of Bradycardia-Causing agents.
Brentuximab Vedotin	Brentuximab Vedotin may be increased by P-glycoprotein/ABCB1 inhibitors. Concentrations of the monomethyl auristatin E component (MMAE) may increase.
Bretylium	May increase the bradycardic effects of Bradycardia Causing Agents. Patients receiving AV-blocking drugs may experience a reduction in AV blockade due to Bretylium.
Brimonidine (Topical	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Calcium Channel Blockers (Nondihydropyridine)	May increase the bradycardic effects of Amiodarone. A sinus arrest has been reported.
Celiprolol	The serum concentration of Celiprolol may be increased by P-glycoprotein/ABCB1 inhibitors
Clopidogrel	Clopidogrel's active metabolite(s), Amiodarone, may be lower in serum.
Cobicistat	May increase serum Amiodarone concentrations
Cyclophosphamide	Amiodarone may have an adverse/toxic effect. Particularly, the risk for pulmonary toxicities may be increased.
CYP2C8 inhibitors (Moderate)	Might decrease the metabolism of CYP2C8 substrates (High Risk with Inhibitors).
CYP3A4 Inducers, Moderate	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
CYP3A4 inhibitors (Moderate)	Might decrease the metabolism of CYP3A4 substrates (High Risk with Inhibitors).
Darunavir	May increase serum Amiodarone concentrations
Deferasirox	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Deferasirox	High risk of Inhibitors causing an increase in serum CYP2C8 Substrates concentrations
Diazoxide	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
DULoxetine	DULoxetine may increase hypotensive effects by lowering blood pressure.
Duvelisib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Etravirine	May lower the serum level of Amiodarone.
Everolimus	Everolimus serum concentration may be increased by P-glycoprotein/ABCB1 inhibitors
Flibanserin	Flibanserin may be increased by CYP3A4 inhibitors (Weak).
Fosamprenavir	May increase serum Amiodarone concentrations
Fosaprepitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Fosnetupitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Herbs with hypotensive properties	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Hypotension-Associated Agents	Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.
Ivabradine	Bradycardia-Causing agents may increase the bradycardic effects of Ivabradine.
Lacosamide	Bradycardia-Causing Agents can increase the AV-blocking effects of Lacosamide.
Lacosamide	Lacosamide's toxic/adverse effects may be exacerbated by antiarrhythmic agents (Class III). The risk of bradycardia, heart attacks, and prolonged PR intervals may increase, specifically.
Larotrectinib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Larotrectinib	The serum concentration of Larotrectinib may be increased by P-glycoprotein/ABCB1 inhibitors
Levodopa-Containing Products	Blood Pressure Lowering Agents can increase the hypotensive effects of Levodopa - Containing Products.
Lidocaine (Systemic)	Amiodarone could increase serum Lidocaine (Systemic) concentrations
Lidocaine (Topical)	May increase the arrhythmogenic effects of Antiarrhythmic Drugs (Class III). Antiarrhythmic agents (Class III) can increase serum levels of Lidocaine Topical. This applies specifically to dronedarone and amiodarone.
Lormetazepam	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Midodrine	May increase the bradycardic effects of Bradycardia Causing Agents.
Mipomersen	Mipomersen's hepatotoxic effects may be enhanced by Amiodarone.
Molsidomine	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Naftopidil	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Naldemedine	The serum concentrations of Naldemedine may be increased by P-glycoprotein/ABCB1 inhibitors.
Naloxegol	The serum concentrations of Naloxegol may be increased by P-glycoprotein/ABCB1 inhibitors.
Netupitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Nicergoline	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Nicorandil	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
NiMODipine	CYP3A4 Inhibitors, Weak may increase NiMODipine serum concentrations.
Nitroprusside	The hypotensive effects of Nitroprusside may be enhanced by blood pressure-lowering agents.
Ombitasvir, Paritaprevir, and Ritonavir	May increase serum Amiodarone concentrations
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir	May increase serum Amiodarone concentrations. Management: Canadian labelling suggests avoiding this combination.
Orlistat	May lower the serum level of Amiodarone.
Palbociclib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Pentoxifylline	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Perhexiline	Perhexiline serum concentration may be increased by CYP2D6 inhibitors (Weak).
P-glycoprotein/ABCB1 Inhibitors	Increases serum concentrations of P-glycoprotein/ABCB1 substrates. P-glycoprotein inhibitors can also increase the distribution of P-glycoprotein substrates to certain cells/tissues/organs in which p-glycoprotein exists in high amounts (e.g. brain, testes and T-lymphocytes).
P-glycoprotein/ABCB1 Substrates	P-glycoprotein/ABCB1 inhibitors may increase serum levels of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors can also increase the distribution of P-glycoprotein substrates in specific cells/tissues/organs that have high levels (e.g. brain, T-lymphocytes and testes). Exceptions: Loperamide.
Phenytoin	Could lower the serum level of Amiodarone. Amiodarone could increase the serum level of Phenytoin.
Pholcodine	Pholcodine may increase hypotensive effects by lowering blood pressure.
Phosphodiesterase 5 Inhibitors	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Porfimer	Photosensitizing agents may increase the photosensitizing effects of Porfimer.
Prostacyclin Analogues	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Prucalopride	The serum concentrations of Prucalopride may be increased by P-glycoprotein/ABCB1 inhibitors.
QT-prolonging Agents (Indeterminate Risk - Avoid)	QTc-prolonging effects of QTprolonging agents (highest risk) may be increased. When using these agents together, monitor for QTc interval prolongation or ventricular arrhythmias. Patients at higher risk for QTc prolongation might have additional risk factors.
QT-prolonging Agents (Indeterminate Risk - Caution)	QTc-prolonging effects of QT-prolonging agents may be increased (highest risk). When using these agents together, monitor for QTc interval prolongation or ventricular arrhythmias. Patients at higher risk for QTc prolongation might have additional risk factors.
Quinagolide	Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Ranolazine	Ranolazine may be increased by P-glycoprotein/ABCB1 inhibitors.
Ranolazine	Increased serum concentrations of P-glycoprotein/ABCB1 Substrates may be possible.
RifAXIMin	The serum concentrations of RifAXIMin may be increased by P-glycoprotein/ABCB1 inhibitors
Ruxolitinib	May increase the bradycardic effects of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labels recommend that bradycardia-causing agents be avoided to the greatest extent possible.
Sarilumab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Silodosin	The serum concentrations of Silodosin may be increased by P-glycoprotein/ABCB1 inhibitors.
Siltuximab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Simeprevir	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Terlipressin	May increase the bradycardic effects of Bradycardia Causing Agents.
Thyroid Products	Thyroid Products may be less effective if Amiodarone is used.
TiZANidine	Amiodarone could increase TiZANidine serum levels
Tocilizumab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Tocilizumab	May increase the bradycardic effects of Bradycardia Causing Agents.
Verteporfin	Photosensitizing agents may increase the photosensitizing effects of Verteporfin.
Risk Factor D (Consider therapy modifications)
Afatinib	The serum concentrations of Afatinib may be increased by P-glycoprotein/ABCB1 inhibitors. If afatinib is not tolerated, reduce the dose by 10 mg. Canadian labelling states that it is best to avoid combination therapy. If you must use the P-gp inhibitor, do so simultaneously with or after afatinib.
Amifostine	Amifostine's hypotensive effects may be enhanced by blood pressure lowering agents. Treatment: Blood pressure lowering drugs should be stopped 24 hours before amifostine administration. Amifostine should be avoided if blood pressure lowering medication cannot be withheld.
Amisulpride	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Amisulpride. Management: You may consider other combinations. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Azithromycin (Systemic)	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Azithromycin Systemic. Management: You may consider other combinations. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Betrixaban	The serum concentration of Betrixaban may be increased by P-glycoprotein/ABCB1 inhibitors. Management: Reduce the initial dose of betrixaban to 80 mg, followed by 40 mg daily if taken with a Pglycoprotein inhibitor.
Bilastine	Bilastine may be increased by P-glycoprotein/ABCB1 inhibitors. Patients with severe or moderate renal impairment who are on p-glycoprotein inhibitors should consider other options.
Bile Acid Sequestrants	May reduce the bioavailability and potency of Amiodarone.
Cardiac Glycosides	Amiodarone can increase serum levels of Cardiac Glycosides. Management: When starting concomitant Amiodarone therapy, reduce the dosage of cardiac glycosides from 30% to 50% and/or decrease the frequency of administration. Monitor for elevated serum levels and toxic effects of cardiac Glycosides.
Ceritinib	Amiodarone could increase Ceritinib's bradycardic effects. Amiodarone could increase Ceritinib's QTc-prolonging effects. You should consider other combinations. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Chloroquine	QT-prolonging agents (highest risk) can increase the QTc-prolonging effects of Chloroquine. Management: You may consider other combinations. Monitor for QTc interval prolongation or ventricular arrhythmias if the combination is used. Patients at higher risk for QTc prolongation might have additional risk factors.
Cimetidine	Could increase serum Amiodarone concentrations. Management: Look for 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.
Clofazimine	Clofazimine's QTc-prolonging effects may be enhanced by QT-prolonging agents (highest risk). Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the combination is used. Patients at higher risk for QTc prolongation might have additional risk factors.
CloZAPine	CloZAPine's QTc-prolonging effects may be enhanced by QT-prolonging agents (highest risk). Management: You may consider other combinations. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Colchicine	The serum Colchicine concentration may be increased by P-glycoprotein/ABCB1 inhibitors. The distribution of Colchicine into specific tissues, such as the brain, may be increased. Patients with impaired renal and hepatic function, who are also taking a p–glycoprotein inhibitor, should not be given colchicine. Reduce the dose of colchicine for those with normal renal or hepatic function. See the full monograph for details.
CycloSPORINE Systemic	CycloSPORINE (Systemic) may be increased by amiodarone. Management: If amiodarone is combined, monitor for an increase in serum concentrations or toxicity of Cyclosporine. It is likely that cyclosporine dosages will need to be reduced.
Strong CYP2C8 inhibitors	Might decrease the metabolism of CYP2C8 substrates (High Risk with Inhibitors).
CYP3A4 Inducers - Strong	May increase the metabolism of CYP3A4 substrates (High Risk with Inducers). Management: You may consider a different drug to replace one of the interacting drugs. Some combinations might be contraindicated. Consult appropriate manufacturer labelling.
Strong CYP3A4 inhibitors	Might decrease the metabolism of CYP3A4 substrates (High Risk with Inhibitors).
Dabigatran Etexilate	Amiodarone can increase serum Dabigatran Etexilate concentrations. Management: This combination can be reduced or avoided. Specific recommendations may vary depending on the U.S. and Canadian labelling, renal function, indication for dabigatran, and other factors. Refer to the full monograph and dabigatran labelling.
Dabrafenib	High risk of Inducers causing a decrease in serum CYP3A4 substrates. Management: If possible, seek alternatives to the CYP3A4 substrate. Concomitant therapy should be avoided if possible. Monitor the clinical effects of the substrate carefully (especially therapeutic effects).
Dabrafenib	High risk of Inducers causing a decrease in serum CYP2C8 substrates. Management: If possible, seek alternatives to the CYP2C8 substrate. Concomitant therapy should be avoided if possible. Monitor the clinical effects of the substrate carefully (especially therapeutic effects).
Dasatinib	QTc-prolonging agents (highest risk) could increase Dasatinib's QTc-prolonging effects. You should consider other combinations. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Doxepin-Containing Product	QT-prolonging agents (highest risk) can increase the QTcprolonging effects of Doxepin-Containing products. Management: You may consider other combinations. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
DOXOrubicin (Conventional	P-glycoprotein/ABCB1 inhibitors may increase serum levels of DOXOrubicin (Conventional). Treatment: If you are treated with doxorubicin, consider alternative P-glycoprotein inhibitors. These combinations should be avoided according to one U.S. manufacturer, Pfizer Inc.
Droperidol	Droperidol's QTc-prolonging effects may be enhanced by QT-prolonging agents (highest risk). Management: You may consider other combinations. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Edoxaban	The serum concentrations of Edoxaban may be increased by P-glycoprotein/ABCB1 inhibitors. Management: See full monograph for details. Patients receiving edoxaban to treat venous embolism are advised to take lower doses when taking it with P-gp inhibitors. For patients with atrial fibrillation, edoxaban should not be adjusted in the same way.
Encorafenib	QTc-prolonging agent QT-prolonging agents may have an enhanced effect (highest risk). Management: Look for alternatives to this combination. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Enzalutamide	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Avoid concurrent use of enzalutamide and CYP3A4 substrates with a narrow therapeutic index. You should exercise caution when using enzalutamide or any other CYP3A4 sub-substance.
Escitalopram	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Escitalopram. Management: You may consider other combinations. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Flecainide	Amiodarone could increase the QTc-prolonging effects of Flecainide. Amiodarone could increase Flecainide serum concentration. Flecainide dosage should be reduced by 50%. Monitoring for QTc interval prolongation or ventricular arrhythmias is important. Also, monitoring for elevated flecainide levels may be an option. Patients at higher risk for QTc prolongation might have additional risk factors.
Fosphenytoin	May increase the QTc-prolonging effects of Amiodarone. Fosphenytoin can decrease Amiodarone's serum concentration. Amiodarone may increase the serum concentration of Fosphenytoin. Manage: Look for alternatives whenever possible. Monitor patients receiving this combination for QT interval prolongation or changes in cardiac rhythm, and for decreased serum concentrations/effects of amiodarone and increased concentrations/effects of phenytoin.
Gadobenate Dimeglumine	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Gadobenate Dimeglumine. Management: You may consider other combinations. Monitor for QTc interval prolongation or ventricular arrhythmias if the combination is used. Patients at higher risk for QTc prolongation might have additional risk factors.
Gilteritinib	QTc-prolonging agent QT-prolonging agents may have an enhanced effect (highest risk). Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or arrhythmias if you are using this combination.
Halofantrine	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Halofantrine. Management: You may consider other combinations. Monitor for QTc interval prolongation or ventricular arrhythmias if the combination is used. Patients at higher risk for QTc prolongation might have additional risk factors.
Haloperidol	Amiodarone could increase the QTc-prolonging effects of Haloperidol. Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the drug combination is combined. Patients at higher risk for QTc prolongation might have additional risk factors.
Inotuzumab Ozogamicin	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Inotuzumab Ozogamicin. Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the combination is used. Patients at higher risk for QTc prolongation might have additional risk factors.
Lofexidine	May increase the QTc-prolonging effects of Amiodarone. Management: Look for alternatives to this combination. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Lomitapide	Lomitapide may be increased by CYP3A4 inhibitors (Weak). Management: Patients taking lomitapide 5 mg/day can continue to take this dose. Patients who are taking lomitapide 10mg/day or more must reduce their lomitapide dosage by half. You can then adjust the lomitapide dose to 30 mg/day for adults.
Loratadine	Amiodarone can increase Loratadine's serum concentration. Management: This combination may cause QT interval prolongation or Torsades de Pointes. Consider an alternative to Loratadine if you are able.
Lorlatinib	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Do not use lorlatinib concurrently with any CYP3A4 Substrates. Even a slight decrease in serum concentrations could cause therapeutic failure or serious clinical consequences.
Lovastatin	Amiodarone can increase Lovastatin serum concentrations. Management: Patients on amiodarone should be considered using a non-interacting statin (pravastatin). Limit the daily dose of lovastatin to 40 mg if combined and monitor for signs of toxicities such as myalgia, elevations in liver function tests, or rhabdomyolysis.
Methadone	Amiodarone could increase the QTc-prolonging effects of Methadone. Management: You may want to consider other combinations of this drug. Monitor for QTc interval prolongation or ventricular arrhythmias if the drug combination is combined. Patients at higher risk for QTc prolongation might have additional risk factors.
Midostaurin	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Midostaurin. Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the combination is used. Patients at higher risk for QTc prolongation might have additional risk factors.
MiFEPRIStone	High risk of Inhibitors causing an increase in serum CYP2C8 substrates. Management: Keep CYP2C8 Substrates at the lowest dose and watch for any adverse effects, including myopathy, during and after mifepristone treatment.
MiFEPRIStone	High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid dihydroergotamine and ergotamine.
Mitotane	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Treatment: Patients receiving mitotane may require significant adjustments in the dosage of CYP3A4 Substrates.
Obinutuzumab	This may increase the hypotensive effects of Blood Pressure Lowering Agents. Management: You may temporarily withhold blood pressure-lowering medication beginning 12 hours before obinutuzumab injection and continuing for 1 hour after infusion.
OLANZapine	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of OLANZapine. Management: You may consider other combinations. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Ondansetron	Amiodarone could increase the QTc-prolonging effects of Ondansetron. Management: You may consider other combinations. Monitor for QTc interval prolongation or ventricular arrhythmias if the combination is used. Patients at higher risk for QTc prolongation might have additional risk factors.
Osimertinib	Osimertinib's QTc-prolonging effects may be enhanced by QT-prolonging agents (highest risk). Management: You may consider other combinations. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Pentamidine (Systemic)	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Pentamidine Systemic. Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the combination is used. Patients at higher risk for QTc prolongation might have additional risk factors.
Pilsicainide	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Pilsicainide. Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the combination is used. Patients at higher risk for QTc prolongation might have additional risk factors.
Pitolisant	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates Management: Avoid combining pitolisant and a CYP3A4 substrate with a low therapeutic index. Pitolisant should not be combined with other CYP3A4 sub-substances.
Propafenone	Propafenone's QTc-prolonging effects may be enhanced by Amiodarone. Management: Look for alternatives to this drug combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the drug combination is combined. Patients at higher risk for QTc prolongation might have additional risk factors.
QT-prolonging Class IA Antiarrhythmics (Highest Risk)	May increase the QTc-prolonging effects of Amiodarone. Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the drug combination is combined. Patients at higher risk for QTc prolongation might have additional risk factors.
QT-prolonging Class III Antiarrhythmics (Highest Risk)	May increase the QTc-prolonging effects of Amiodarone. Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the drug combination is combined. Patients at higher risk for QTc prolongation might have additional risk factors.
QT-prolonging Kinase Inhibitors (Highest Risk)	May increase the QTc-prolonging effects of Amiodarone. Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the drug combination is combined. Patients at higher risk for QTc prolongation might have additional risk factors.
QT-prolonging Miscellaneous Agents (Highest Risk)	May increase the QTc-prolonging effects of Amiodarone. Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the drug combination is combined. Patients at higher risk for QTc prolongation might have additional risk factors.
Moderate Risk QT-prolonging CYP3A4 Inhibitors	May increase the QTc-prolonging effects of Amiodarone. QT-prolonging Moderate CYP3A4 Drug Inhibitors (Moderate risk) could increase serum Amiodarone concentration. Management: You may consider other options for this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the drug combination is combined. Patients at higher risk for QTc prolongation might have additional risk factors. Ceritinib, Erythromycin Systemic; Nilotinib and Ribociclib are exceptions.
Red Yeast Rice	Red Yeast Rice serum concentrations may be increased by amiodarone. Management: Patients on amiodarone should be considered using a non-interacting statin (pravastatin). Limit the daily dose of lovastatin to 40 mg if combined and monitor for signs of toxic effects (eg, myalgia or liver function test elevations, rhabdomyolysis).
RifAMPin	This could lead to a decrease in serum levels of Amiodarone's active metabolite(s). Desethylamiodarone levels may be lower. RifAMPin could decrease Amiodarone's serum concentration. Management: Look for alternatives. When used together, monitor closely for decreased amiodarone concentrations/effects. Adjusting the dose may be necessary.
RisperiDONE	QT-prolonging agents (highest risk) could increase RisperiDONE's CNS depressant effects. QT-prolonging agents (Highest risk) could increase the QTc prolonging effect of RisperiDONE. Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the drug combination is combined. Patients at higher risk for QTc prolongation might have additional risk factors.
Simvastatin	Simvastatin may be increased by amiodarone. Management: Patients on amiodarone should be considered using a non-interacting statin (pravastatin). Simvastatin should be taken in combination at 20 mg per day. Monitor for simvastatin toxicities, such as myalgia, elevated liver function tests, and rhabdomyolysis.
Siponimod	Bradycardia-Causing Drugs can increase Siponimod's bradycardic effects. Management: Siponimod should not be taken with bradycardia-causing drugs.
Sodium Iodide I131	Amiodarone can decrease the therapeutic effects of Sodium Iodide II131.
Sodium Stibogluconate	QT-prolonging agents (highest risk) can increase the QTc-prolonging effects of Sodium Stibogluconate. Management: Look for alternatives to this combination. Monitor for QTc interval prolongation or ventricular arrhythmias if the combination is used. Patients at higher risk for QTc prolongation might have additional risk factors.
St John's Wort	High risk of Inducers causing a decrease in serum CYP3A4 Substrates. Management: You may consider a different drug to replace one of the interacting drugs. Some combinations might be contraindicated. Consult appropriate manufacturer labelling.
Stiripentol	High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Avoid stiripentol use with CYP3A4 Substrates that have a narrow therapeutic Index. This is to avoid adverse effects and toxicities. Monitoring of any CYP3A4 substrate that is used with stiripentol should be closely done.
Talazoparib	Amiodarone can increase serum Talazoparib concentrations. Management: Reduce the daily dose of talazoparib to 0.75 mg if concurrent use is impossible. Increase the talazoparib dosage to the same dose as before you started amiodarone after a time of 3 to 5 times the half-life of amiodarone.
Vemurafenib	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Vemurafenib. You should consider other combinations. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Venetoclax	Venetoclax may be increased by P-glycoprotein/ABCB1 inhibitors. Treatment: Patients who are concomitantly treated with P-glycoprotein inhibitors (P-gp), should consider a venetoclax dose decrease of at least 50%.
Vitamin K antagonists (eg warfarin)	Vitamin K Antagonists may have an anticoagulant effect that Amiodarone might enhance. Amiodarone could increase serum Vitamin K Antagonists. Monitoring: If amiodarone has been started, it is important to monitor patients closely for signs of an increase in anticoagulant effects. Although there are no published guidelines for dose adjustment, it is worth considering an empiric reduction in warfarin dosage of 30 to 50%.
Risk Factor X (Avoid Combination)
Agalsidase Alfa	Amiodarone could decrease the therapeutic effects of Agalsidase Alfa.
Agalsidase Beta	Amiodarone could decrease the therapeutic effects of Agalsidase Beta.
Aminolevulinic Acid Systemic	The photosensitizing effects of Aminolevulinic Acid Systemic may be enhanced by the use of photosensitizing agents.
Bromperidol	Bromperidol's hypotensive effects may be enhanced by Blood Pressure Lowering agents. Bromperidol could decrease the hypotensive effects of Blood Pressure Lowering agents.
Citalopram	QT-prolonging agents (highest risk) can increase the QTc-prolonging effects of Citalopram.
Clarithromycin	Clarithromycin may have a QTc-prolonging agent (highest risk) that can increase its QTc-prolonging effects.
Conivaptan	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Daclatasvir	May increase the bradycardic effects of Amiodarone.
Domperidone	QTc-prolonging Agents (Highest risk) could increase the QTc-prolonging effects of Domperidone.
Erythromycin (Systemic)	Amiodarone could increase the QTc-prolonging effects of Erythromycin Systemic. Amiodarone's QTc-prolonging effects may be enhanced by Erythromycin Systemic. Systemic Erythromycin may increase Amiodarone's serum concentration.
Fingolimod	May increase the QTc-prolonging effects of Amiodarone.
Flupentixol	Flupentixol may have a QTc-prolonging agent (highest risk) that can increase its QTc-prolonging effects.
Fusidic Acid (Systemic).	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Gemifloxacin	May increase the QTc-prolonging effects of Amiodarone.
Grapefruit Juice	May lower serum levels of Amiodarone's active metabolite(s). Grapefruit Juice can increase serum Amiodarone concentrations.
Idelalisib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Indinavir	May increase serum Amiodarone concentrations
Levofloxacin-Containing Products (Systemic)	May increase the QTc-prolonging effects of Amiodarone.
Lofepramine	May increase the arrhythmogenic effects of Amiodarone.
Lopinavir	May increase the QTc-prolonging effects of Amiodarone. Lopinavir could increase Amiodarone's serum concentration. Lopinavir/Ritonavir could increase serum Amiodarone concentrations. Management: If you cannot avoid this combination, be sure to monitor for elevated amiodarone serum levels and effects, as well as evidence of prolonged QT interval.
Moxifloxacin Systemic	QT-prolonging agents (Highest risk) can increase the QTc-prolonging effects of Moxifloxacin Systemic.
Nelfinavir	May increase serum Amiodarone concentrations
Nilotinib	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Nilotinib.
PAZOPanib	P-glycoprotein/ABCB1 inhibitors may increase serum levels of PAZOPanib.
Pimozide	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Pimozide. Management: You may consider other combinations. These toxicities are more likely to occur in patients with other risk factors, such as older age, female sexual activity, bradycardia and hypokalemia.
Piperaquine	Piperaquine may have a QTc-prolonging agent (highest risk) that can increase its QTc-prolonging effects.
Probucol	Probucol may have a QTc-prolonging agent (highest risk) that can increase its QTc-prolonging effects.
QUEtiapine	QTc-prolonging agents (highest risk) could increase the QTc-prolonging effects of QUEtiapine.
Ribociclib	QT-prolonging agents (highest risk) could increase Ribociclib's QTc-prolonging effects.
Ritonavir	May increase serum Amiodarone concentrations. Management: Ritonavir US prescribing instructions lists this combination as contraindicated. Combining amiodarone and lopinavir/ritonavir should be avoided. However, if you must use the combination, be sure to monitor for elevated amiodarone serum levels and other side effects.
Saquinavir	May increase the QTc-prolonging effects of Amiodarone. Saquinavir could increase Amiodarone's serum concentration.
Sofosbuvir	May increase the bradycardic effects of Amiodarone.
Sparfloxacin	QT-prolonging agents (highest risk) could increase the QTc-prolonging effects of Sparfloxacin.
Thioridazine	QT-prolonging agents (highest risk) can increase the QTc-prolonging effects of Thioridazine.
Tipranavir	May increase serum Amiodarone concentrations
Topotecan	Topotecan serum concentrations may be increased by P-glycoprotein/ABCB1 inhibitors
VinCRIStine (Liposomal)	The serum VinCRIStine (Liposomal) concentration may be increased by P-glycoprotein/ABCB1 inhibitors
Voriconazole	Amiodarone could increase the QTc-prolonging effects of Voriconazole. Voriconazole could increase Amiodarone's serum concentration.

Monitor:

Blood pressure
Heart rate (ECG) and rhythm throughout therapy
Assess the patient for signs of lethargy, oedema of the hands or feet, weight loss, and pulmonary toxicity (baseline pulmonary function tests and chest X-ray
Continue monitoring chest X-rays 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 to 6 months).
If signs or symptoms of thyroid disease or arrhythmia breakthrough/ exacerbation occur then an immediate re-evaluation is necessary.
Amiodarone partially inhibits the peripheral conversion of thyroxine to triiodothyronine.
Serum T and reverse triiodothyronine concentrations may be increased and serum T may be decreased
Most patients remain clinically euthyroid, however, clinical hypothyroidism or hyperthyroidism may occur.
Monitor infusion site.
Perform regular ophthalmic exams.

Patients with implantable cardiac devices:

Monitor pacing or defibrillation thresholds with the initiation of amiodarone and during treatment.
Consult individual institutional policies and procedures.

How to administer Amiodarone?

Oral administration:

Use drug in a single or divided dose (if the dose is greater than 1000 mg) with or without regard to meals.

Intravenous administration:

It should be through a central line. If infused via a peripheral line, an in-line filter should be used to reduce the incidence of phlebitis.
It may be infused undiluted in patients with pulseless ventricular tachycardia and ventricular fibrillation.
The infusions should be administered via an infusion pump, drop counting may result in less dosage.
If the infusion is to be administered over more than one hour, a concentration of 2 mg/ml or less could be used.
The rate of infusion should be reduced if the patient develops hypotension or bradycardia.
It is a vesicant, proper needle and catheter placement before and during intravenous infusion should be maintained to avoid extravasation.

Extravasation management:

Stop the infusion immediately and disconnect if extravasation occurs.
Gently aspirate extravasated solution.

Do NOT flush the line.

Initiate hyaluronidase antidote for refractory cases.
Remove the needle or cannula and apply dry warm compresses.
The extremity should be elevated.

Hyaluronidase:

Inject a total of 1 mL (15 units/mL) intradermal as 5 separate 0.2 mL injections (using a 25-gauge needle) into the area of extravasation.

Mechanism of action of Amiodarone:

It is a class 3 antiarrhythmic agent with alpha and beta-blocking properties.
It reduces SA and AV nodal conduction, and extends the action potential, and refractory time in myocardial tissue.
It also affects the sodium and potassium channels.

It has been the beginning of action usually within 24 hours of intravenous administration, and 2 to 3 weeks after oral administration. Antiarrhythmic effects take 2 to 3 weeks. Children and patients who have received an intravenous loading dose are less likely to experience the antiarrhythmic effect.

Peak effects can be seen within a week to five months. In children, the effects last for a few weeks to several months. In adults, the effects can last for many months.

AbsorptionAfter oral administration, the effects are slow and irregular. The drug contains more than 96% protein. It is metabolized in the liver by CYP2C8 or 3A4 to the active metabolite.

Enterohepatic recirculation may also be possible. It has been bioavailability of oral administration is 50%. Half-life elimination is shorter in children than it is for adults.

The half-life elimination single oral tablet dose lasts for 58 days. The range of tablets can be taken between 15 and 142 days. The half-life of chronic oral therapy is between 40 and 55 days.

After a single intravenous injection, the half-life is between 9 and 36 days. the half-life of the metabolite N-desethylamiodarone is the active metabolite. It is available in single and chronic doses. The duration of a single dose is 36, and chronic therapy is 61.

When reaching peak serum concentration-time taken to absorb the drug from oral administration is between 3 and 7 hours. It is excreted in the urine and faeces.

Amiodarone international Brands: