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

Amiodarone is a medication primarily used to treat certain types of irregular heartbeats (arrhythmias). It belongs to a class of drugs known as antiarrhythmics, and it works by affecting the electrical activity in the heart muscle, helping to stabilize the heart rhythm.

Amiodarone is often prescribed for life-threatening ventricular arrhythmias, such as ventricular tachycardia or ventricular fibrillation, as well as for atrial fibrillation/flutter. It's typically reserved for cases where other medications have not been effective or are not suitable due to 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:

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

Off-Label Use: Amiodarone is sometimes used in a different way from what it's originally made for.
Pharmacologic Cardioversion: Amiodarone isn't the top choice for changing heart rhythm back to normal (like from atrial fibrillation to regular heartbeat). Other medicines like flecainide are more effective for this.
Intravenous Regimen:
- Start with 150 mg over 10 minutes.
- Then, give 1 mg per minute for 6 hours.
- After that, lower the dose to 0.5 mg per minute for 18 hours.
- Then, switch to taking it by mouth for maintenance.
Oral Regimen:
- Take 600 to 800 mg each day, split into smaller doses, until you've taken up to 10 grams total.
- Then, take a lower amount each day (maintenance dose), like 200 mg once daily.
- Another way is to take 400 mg every 8 to 24 hours until you've taken around 6 to 10 grams total, then switch to a lower maintenance dose, like 100 to 200 mg once daily.
- Sometimes, a maintenance dose of just 100 mg once daily is used, especially for older or smaller patients.
Starting Before Cardioversion: Doctors might start the loading doses of amiodarone a few weeks before doing direct current cardioversion to lower the chance of the heart problem coming back.

Amiodarone off-label use in the treatment of Maintenance of sinus rhythm:

Oral Regimen:

Start with 400 to 600 mg every day, divided into smaller doses, for 2 to 4 weeks.
After that, switch to a lower maintenance dose of 100 to 200 mg once daily.
Alternatively, some experts suggest taking 400 mg every 8 to 24 hours until you've taken around 6 to 10 grams total.
Then, maintain with 100 to 200 mg once daily.
This helps keep the heart rhythm normal, even though it's not the main use of amiodarone.

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

Alternative to Beta-Blockers: Amiodarone is sometimes used when beta-blockers can't be given.

Clinical Regimens:

Oral Regimen:
- Take 200 mg three times a day for 7 days before surgery.
- Then, take 200 mg daily until leaving the hospital.
Intravenous Regimen (Preoperative):
- Before surgery: Give a loading dose of 150 mg, then give about 0.5 mg per minute for 3 days before surgery and 5 days after.
Intravenous Regimen (Postoperative):
- Right after surgery: Infuse 1,000 mg over 24 hours for 2 days.
Intravenous to Oral Regimen (Postoperative):
- After surgery, start 6 hours later with 1,050 mg given intravenously over 24 hours.
- Then, take 400 mg orally three times a day for 4 days after surgery.

These methods aim to prevent irregular heartbeats after heart surgery, especially when beta-blockers aren't an option.

Amiodarone off-label use in the treatment of heart rate control:

Comparison with Calcium Channel Blockers: Amiodarone takes longer to control heart rate compared to calcium channel blockers like diltiazem (7 hours vs. 3 hours, respectively).

Intravenous Regimen:

Start with 300 mg given over 1 hour.
Then, give 10 to 50 mg per hour over 24 hours.
After that, switch to taking it by mouth as a maintenance dose.
Usual maintenance dose is 100 to 200 mg once daily.

Alternative Intravenous Regimen:

Some experts suggest starting with 150 mg over at least 10 minutes.
Then, give 0.5 to 1 mg per minute.
Additional 150 mg boluses over at least 10 minutes may be given as needed.

Caution with High Doses:

Mean daily doses over 2.1 grams have been linked with low blood pressure (hypotension).

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

Amiodarone is typically used when other treatments haven't worked or can't be used.
Most patients don't need to take antiarrhythmic medicines for a long time.

Pharmacologic Cardioversion:

Oral Regimen:
- Loading Dose: Take 400 to 600 mg each day, divided into smaller doses, for 2 to 4 weeks. In a hospital, doses up to 1,200 mg daily in divided doses may be considered.
- Some experts suggest taking around 6 to 10 grams total orally.
- Maintenance Dose: After the loading period, take 100 to 200 mg once daily.
Intravenous Regimen:
- Start with 150 mg over 10 minutes.
- Then, give 1 mg per minute for 6 hours.
- After that, lower the dose to 0.5 mg per minute for 18 hours.
- Alternatively, switch to taking it by mouth.

Ventricular arrhythmias:

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

Intravenous Regimen:

Start with 150 mg over 10 minutes (may repeat if needed).
Then, give 1 mg per minute intravenously for 6 hours.
After that, lower the dose to 0.5 mg per minute for 18 additional hours or until switching to oral therapy.
It's recommended to use amiodarone with a beta-blocker like propranolol.

Maintenance Dose (Oral):

Begin with 400 mg every 8 to 12 hours for 1 to 2 weeks.
Then, reduce to 200 to 400 mg once daily.
Some experts suggest taking around 6 to 10 grams total orally during the first 1 to 2 weeks.
Another approach is to start with 200 mg twice daily for the first 4 weeks, then switch to 200 mg once daily.

Nonsustained VT, Symptomatic:

Consider adding a beta-blocker or a calcium channel blocker like diltiazem before starting antiarrhythmic therapy.
Oral Regimen:
- Begin with 400 mg every 8 to 12 hours for 1 to 2 weeks.
- Then, reduce to 200 to 400 mg once daily.
- Some experts suggest taking around 6 to 10 grams total orally during the first 1 to 2 weeks.
- Alternatively, start with 200 mg twice daily for the first 4 weeks, then switch to 200 mg once daily.

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

Antiarrhythmic therapy for this purpose doesn't reduce mortality but may improve quality of life by lowering the frequency of ICD shocks.
Amiodarone is the preferred antiarrhythmic for this use.

Oral Regimen:

Start with 400 mg twice daily for 2 weeks.
Then, take 400 mg once daily for 4 weeks.
Finally, maintain with 200 mg once daily.
It's recommended to combine amiodarone with a beta-blocker.
Some experts suggest starting with 400 mg every 8 to 24 hours for a total oral load of around 6 to 10 grams.
Then, switch to 200 to 400 mg once daily for maintenance.

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

Before starting antiarrhythmic therapy, it's advisable to consider adding a beta-blocker.
For patients who are eligible for an implantable cardioverter defibrillator (ICD) due to left ventricular dysfunction but cannot or refuse to have ICD implantation, amiodarone can be used.

Oral Regimen:

Start with 400 mg every 8 to 24 hours for 1 to 2 weeks to achieve a total load of around 6 to 10 grams.
Then, switch to a maintenance dose of 200 to 400 mg once daily.
This helps prevent sudden cardiac death by controlling ventricular arrhythmias.

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

If unresponsive to CPR, defibrillation, and epinephrine:

Intravenous Push or Intraosseous:
- Initial: Administer a rapid bolus of 300 mg.
- If pulseless VT or VF continues after subsequent defibrillation attempt or recurs, give a supplemental dose of 150 mg.
- It's preferred to administer undiluted.

Upon return of spontaneous circulation:

Intravenous Infusion:
- Give 1 mg per minute for 6 hours.
- Then, reduce to 0.5 mg per minute for 18 hours or until switching to oral therapy.
- For maintenance dosing, refer to guidelines for secondary prevention of sudden cardiac death due to ventricular arrhythmias.

Note: If amiodarone wasn't given during resuscitation but return of spontaneous circulation is achieved, some experts suggest starting empiric antiarrhythmic therapy with amiodarone.

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

Sustained Monomorphic Ventricular Tachycardia (VT), Hemodynamically Stable:
- Intravenous Regimen:
  - Start with 150 mg over 10 minutes.
  - Then, administer 1 mg per minute for 6 hours.
  - After that, reduce to 0.5 mg per minute for at least 18 hours or until switching to oral therapy.
Breakthrough Hemodynamically Stable VT:
- Intravenous Regimen:
  - Give 150 mg over 10 minutes.
  - Be cautious as mean daily doses over 2.1 grams have been linked with low blood pressure.
Maintenance Regimen (Oral):
- Start with 400 mg every 8 to 12 hours for 1 to 2 weeks.
- Then, maintain with 200 to 400 mg once daily.
- Some experts suggest starting with 400 mg every 8 to 24 hours for a total oral load of around 6 to 10 grams.
- Then, switch to 200 to 400 mg once daily for maintenance.

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

This is for patients who don't respond well to beta-blockers or non-dihydropyridine calcium channel blockers like diltiazem, and cannot take class Ic antiarrhythmic agents.

Oral Regimen:

Begin with 400 mg every 8 to 12 hours for 1 to 2 weeks.
Once adequate control is achieved, decrease the dose to 200 to 400 mg once daily.
It's important to use the lowest effective dose to minimize adverse effects.
This approach helps manage symptomatic ventricular premature beats in patients who don't respond to other medications or can't take certain types of antiarrhythmic agents.

Switching to oral amiodarone after Intravenous administration:

For intravenous infusions lasting less than a week:

Administer 400 to 1,200 mg daily in divided doses until a loading dose of approximately 6 to 10 grams has been given.
Then, start a maintenance dose of 200 to 400 mg once daily, depending on the indication.

For intravenous infusions lasting one to two weeks:

Use 400 to 800 mg daily in divided doses until the loading dose of approximately 6 to 10 grams has been administered.
Then, transition to a maintenance dose of 200 to 400 mg once daily, based on the indication.

For intravenous infusions lasting more than two weeks:

Administer 200 to 400 mg once daily, depending on the indication, for maintenance.

Note: There hasn't been a formal evaluation of converting from intravenous to oral therapy. Some experts suggest a 1- to 2-day overlap when transitioning, particularly when treating ventricular arrhythmias.

Switching to Intravenous amiodarone after oral administration:

Patients who have been on long-term amiodarone (≥4 months) have a mean plasma-elimination half-life of the active metabolite of about 61 days.
If oral therapy is discontinued for a period of less than 2 weeks, replacement therapy may not be necessary.
This is because any reduction in serum amiodarone concentrations during this period might not be clinically significant.
However, individual patient factors and the clinical situation should always be considered when making treatment decisions.

Amiodarone Dose in Children

Amiodarone Use in the treatment of Perfusing tachycardias:

In perfusing tachycardias, such as in infants, children, and adolescents:

Intravenous or Intraosseous (I.O.) Administration:
- Start with a loading dose of 5 mg/kg, with a maximum of 300 mg per dose.
- Administer over 20 to 60 minutes.
- This loading dose can be repeated twice, up to a maximum total dose of 15 mg/kg during acute treatment.

This regimen is based on guidelines from the Pediatric Advanced Life Support (PALS).

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

In infants, children, and adolescents:

Intravenous or Intraosseous (I.O.) Administration:
- Administer a rapid bolus of 5 mg/kg, with a maximum of 300 mg per dose.
- This dose can be repeated twice, up to a maximum total dose of 15 mg/kg during acute treatment.

These recommendations are provided by the Pediatric Advanced Life Support (PALS) guidelines.

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

In infants, children, and adolescents, dosing can vary based on oral and intravenous administration:

Oral Administration:

Loading Dose: 10 to 15 mg/kg/day given in 1 to 2 divided doses for 4 to 14 days, or until adequate control or prominent adverse effects occur.
After achieving control, dosage should be reduced to 5 mg/kg/day given once daily for several weeks.
If the arrhythmia does not recur, further reduction to the lowest effective dosage is recommended.
Usual daily minimal dose is 2.5 mg/kg/day, and maintenance doses may be given for 5 of 7 days per week.
For infants, some suggest dosing based on body surface area (BSA), with a loading dose of 600 to 800 mg/1.73 m^2/day and a maintenance dose of 200 to 400 mg/1.73 m^2/day.

Intravenous Administration:

Loading Dose: 5 mg/kg (maximum 300 mg/dose) given over 60 minutes.
It can be repeated once to a maximum total initial load of 10 mg/kg.
Total daily bolus should not exceed 15 mg/kg/day.
For continuous intravenous infusion, dosing can be based on either mcg/kg/minute or mg/kg/day:
- Dosing based on mcg/kg/minute: Start with 5 mcg/kg/minute and increase as needed, usual required dose is 10 mcg/kg/minute (range: 5 to 15 mcg/kg/minute), with a maximum daily dose of 2200 mg/day.
- Dosing based on mg/kg/day: Start with 10 mg/kg/day and increase as needed, usual range is 10 to 20 mg/kg/day, with a maximum daily dose of 2200 mg/day.

When using continuous intravenous infusion, ensure proper dosing units are used and taper infusion as soon as clinically possible. Transition to oral therapy if necessary.

Pregnancy risk Factor: D

Adverse effects have been seen in some animal studies on reproduction.
When a pregnant woman takes amiodarone, it can cross to the baby through the placenta (about 10% to 50% of it), possibly harming the fetus.
Risks include things like slow heartbeat in newborns, longer QT intervals, and extra heartbeats; low thyroid function in newborns (with or without a swollen thyroid gland); too much thyroid hormone in newborns; problems with brain development that aren't related to thyroid function; unusual eye movements and head movements in newborns; babies being born too small or too early.
Doctors should only give oral or intravenous amiodarone to pregnant women if they have severe heart rhythm problems that other treatments haven't helped, or if they can't use other treatments.

Amiodarone use during breastfeeding:

Amiodarone and its active form can pass into breast milk.
This could expose the baby to the medicine and cause problems.
Because amiodarone stays in the body for a long time, it might still be in breast milk for several days even after the mother stops taking it.
The company that makes the medicine suggests that mothers should stop breastfeeding if they need to take amiodarone.

Amiodarone dose in renal disease:

No changes are needed in the dosage of amiodarone for patients undergoing hemodialysis or peritoneal dialysis.
Amiodarone is not effectively removed by either method (with dialyzability ranging from 0% to 5%), so there's no need for additional doses after dialysis.

Amiodarone dose in Liver disease:

In cases of significant liver problems, dosage adjustments might be needed for amiodarone.
However, there aren't specific guidelines available for this situation.
If a patient's liver enzymes are three times higher than normal or double what they were before starting amiodarone, it might be necessary to lower the dose or stop taking the medication altogether.

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:

Amiodarone is not suitable for people who have a hypersensitivity to amiodarone itself, iodine, or any part of the medication.
It's also not recommended for those with certain heart conditions like sick sinus syndrome, second- or third-degree atrioventricular block, or bradycardia that leads to fainting without having a working pacemaker.
Additionally, it's contraindicated in cases of cardiogenic shock.
While the FDA-approved label says amiodarone should not be given to patients allergic to iodine, most allergies to shellfish or contrast media aren't due to iodine itself, but it's still wise to be cautious in those with severe allergies to these substances.
In Canada, there are additional contraindications for the oral formulation, including evidence of hepatitis, pulmonary interstitial abnormalities, and thyroid dysfunction.

Warnings and precautions

Bradycardia and Hypotension

Amiodarone can lead to low blood pressure and slow heart rate, especially if given too quickly.
This hypotension (low blood pressure) with rapid administration is often linked to an ingredient called polysorbate 80.
However, commercially-prepared premixed solutions usually don't contain polysorbate 80, which might reduce the risk of hypotension.

Dermatologic toxicities:

Amiodarone can lead to severe skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis, which can be life-threatening or fatal.
If you notice any symptoms or signs such as a spreading skin rash with blisters or lesions on the mucous membranes, it's important to stop taking amiodarone right away.

Extravasation:

Amiodarone can cause tissue damage if it leaks into the surrounding tissue during administration, so it's essential to make sure the needle or catheter is correctly placed before giving the medication.
It's crucial to avoid extravasation, which is when the medication leaks outside of the vein.

Hepatotoxicity: [US Boxed Warning Tablet]

Amiodarone can cause liver damage, which could be fatal.
It's crucial to monitor liver enzyme levels before starting treatment and regularly afterward.
If the liver enzymes increase to more than three times the normal level, or double in a patient with already elevated levels, the dose should be reduced or the medication discontinued.
Treatment should also be stopped if signs or symptoms of liver injury appear.
Elevated bilirubin levels have been reported in patients receiving intravenous amiodarone.
While the US Boxed Warning specifically mentions the tablet form, these effects may also occur with intravenous use, depending on how long the medication is used.

Neurotoxicity:

In some cases, long-term use of amiodarone can lead to peripheral neuropathy, a condition affecting the nerves outside the brain and spinal cord.
If this occurs, stopping amiodarone may help, but the improvement might be slow and not complete.

Ocular effects

Regular eye exams, including slit lamp and fundoscopy, are important for those taking amiodarone because it can affect the eyes.
It may cause optic neuropathy or neuritis, leading to vision problems like peripheral vision loss or changes in acuity, and in severe cases, permanent blindness.
If you experience symptoms like these, it's crucial to get an eye exam promptly.
Even if there are no symptoms, corneal microdeposits, which are common in most adults taking amiodarone, can sometimes cause visual disturbances in around 10% of patients, such as blurred vision or halos around lights.
While these microdeposits might not cause symptoms and can sometimes reverse, it's generally recommended to avoid corneal refractive laser surgery if you're taking amiodarone.

Photosensitivity

It's important to limit exposure to sunlight while taking amiodarone because it can cause photosensitivity, making your skin more sensitive to the sun.
Over time, especially with prolonged treatment, you might notice a blue-gray discoloration of your skin in areas exposed to the sun.
This risk is higher in people with fair skin or those who spend a lot of time in the sun.
The extent of discoloration might be related to how much amiodarone you've taken and how long you've been taking it.

Proarrhythmic effects [US Boxed Warning (tablet),]

Amiodarone can sometimes worsen existing heart rhythm problems, so it's crucial to start treatment in a medical setting where continuous heart monitoring and resuscitation equipment are available.
Other types of heart rhythm disturbances, such as heart block, slow heart rate, new ventricular fibrillation, ongoing ventricular tachycardia, difficulty in reverting to normal rhythm, and a specific type of ventricular tachycardia associated with prolonged QT interval (called torsades de pointes), have been reported.
The risk of these effects may increase if amiodarone is used with other antiarrhythmic drugs or medications that also prolong the QT interval.
These proarrhythmic effects can last for a long time.
While the US Boxed Warning specifically mentions the tablet form, these effects may also occur with intravenous use, depending on how long the medication is used.

Toxicity in the lungs: [US Boxed Warning]

Amiodarone can cause lung problems, including hypersensitivity pneumonitis or interstitial/alveolar pneumonitis, which can sometimes be fatal.
Before starting treatment, it's important to have a baseline chest X-ray and pulmonary function tests, including diffusion capacity.
These tests should be repeated every 3 to 6 months along with a thorough history, physical exam, and chest X-ray.
If any signs or symptoms of lung problems develop, alternative therapy should be considered.
While the US Boxed Warning specifically mentions the tablet form, these effects may also occur with intravenous use, depending on how long the medication is used.

Thyroid effects:

Amiodarone can affect the thyroid gland, leading to either overactivity (hyperthyroidism) or underactivity (hypothyroidism).
Hyperthyroidism can cause thyrotoxicosis, which may be severe and even fatal, and can worsen or trigger heart rhythm problems.
If new signs of arrhythmia appear, it's important to consider the possibility of hyperthyroidism.
On the other hand, hypothyroidism, which can also be severe, may develop either as a direct effect of amiodarone or after resolving hyperthyroidism caused by amiodarone.
In some cases, hypothyroidism can be life-threatening.
If hyper- or hypothyroidism occurs, the dose of amiodarone may need to be reduced or the medication discontinued.
Additionally, amiodarone has been associated with thyroid nodules and thyroid cancer.
Patients with thyroid disease should be closely monitored before starting amiodarone and regularly thereafter, especially elderly patients and those with existing thyroid problems.

Arrhythmias:

Amiodarone is a potent medication reserved for patients with life-threatening arrhythmias due to its potential for significant toxicity.
Before resorting to amiodarone, alternative treatments should be attempted.
When initiating amiodarone therapy, patients should be hospitalized for close monitoring.
According to the 2015 ACLS guidelines, Intravenous amiodarone is recommended as the preferred antiarrhythmic for treating pulseless ventricular tachycardia or ventricular fibrillation that does not respond to CPR, defibrillation, and vasopressor therapy.
For non-life-threatening arrhythmias like atrial fibrillation, amiodarone should only be used if other antiarrhythmic drugs have failed or are not suitable.
While these warnings are specifically for the tablet form, similar effects may also occur with intravenous administration, depending on the duration of use.

Cardiac devices (eg, implanted defibrillators, pacemakers):

When using amiodarone, it's important to consider its potential impact on the functioning of cardiac devices such as implanted defibrillators or pacemakers.
Chronic use of antiarrhythmic medications like amiodarone can affect the thresholds required for defibrillation or pacing by these devices.
Therefore, it's crucial to assess these thresholds both when starting amiodarone therapy and periodically throughout treatment.

Electrolyte imbalance:

Before starting amiodarone therapy and during treatment, it's essential to address any electrolyte imbalances, particularly low levels of potassium, magnesium, or calcium.
These imbalances can affect the heart's rhythm and function, so correcting them is crucial for safe and effective use of amiodarone.
Regular monitoring of electrolyte levels throughout therapy can help maintain proper balance and minimize the risk of complications.

Myocardial Infarction

Even in the context of acute myocardial infarction, it's important to start beta-blocker therapy, even if amiodarone therapy is also being used and provides beta-blockade.
Beta-blockers play a critical role in managing acute myocardial infarction by reducing the workload on the heart, preventing further damage, and improving outcomes.
Therefore, they should be initiated as part of the standard treatment regimen, regardless of concurrent amiodarone therapy.

Wolff-Parkinson-White (WPW) syndrome:

Even in the context of acute myocardial infarction, it's important to start beta-blocker therapy, even if amiodarone therapy is also being used and provides beta-blockade.
Beta-blockers play a critical role in managing acute myocardial infarction by reducing the workload on the heart, preventing further damage, and improving outcomes.
Therefore, they should be initiated as part of the standard treatment regimen, regardless of concurrent amiodarone therapy.

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, and Rhythm:
- Continuously monitor blood pressure, heart rate, and cardiac rhythm throughout therapy.
- Look out for signs of lethargy, edema in hands or feet, weight loss, and pulmonary issues.
Pulmonary Function and Chest X-ray:
- Conduct baseline pulmonary function tests and chest X-rays before starting treatment.
- Continue monitoring chest X-rays annually during therapy.
Liver Function Tests:
- Perform liver function tests every six months to assess liver health.
Electrolyte Levels:
- Regularly monitor serum electrolytes, especially potassium and magnesium.
Thyroid Function Tests:
- Evaluate thyroid function before initiating treatment.
- Periodically assess thyroid function tests, with some experts recommending evaluations every 3 to 6 months.
Infusion Site Monitoring:
- Keep a check on the infusion site to prevent any complications.
Ophthalmic Exams:
- Schedule regular ophthalmic exams to detect any ocular issues.

Patients with Implantable Cardiac Devices:

Device Threshold Monitoring:
- Monitor pacing or defibrillation thresholds when starting amiodarone and throughout treatment.
- Follow institutional policies and procedures for specific guidance.

How to administer Amiodarone?

Oral Administration:

Consistency with Meals:
- Administer consistently with regard to meals.
- Take in divided doses with meals if gastrointestinal (GI) upset occurs or if taking a large daily dose (≥1,000 mg).
- If GI intolerance occurs with single-dose therapy, switch to twice daily dosing.

Intravenous Administration:

Infusion Concentration and Rate:
- For infusions >1 hour, use concentrations ≤2 mg/mL unless a central venous catheter is used.
- Adjust administration rate based on urgency, slowing down if hypotension or bradycardia develops.
- Consider using commercially-prepared premixed solutions.
Container and Tubing Recommendations:
- Infusions >2 hours must be in a non-PVC container (e.g., glass or polyolefin).
- Use PVC tubing for administration regardless of infusion duration.
Incompatible with Heparin:
- Flush with saline prior to and following infusion.
Extravasation Management:
- If extravasation occurs, stop infusion immediately and disconnect.
- Gently aspirate extravasated solution and apply dry warm compresses.
- Elevate the extremity and consider hyaluronidase antidote for refractory cases.

Hyaluronidase Administration:

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

Mechanism of action of Amiodarone:

Amiodarone is a Class III antiarrhythmic medication that works by inhibiting adrenergic stimulation, which means it blocks the effects of adrenaline.
It has both alpha- and beta-blocking properties.
Additionally, amiodarone affects sodium, potassium, and calcium channels in the heart, which helps to regulate the heart's rhythm.
By prolonging the action potential and refractory period in myocardial tissue, it helps to stabilize irregular heartbeats.
Amiodarone also reduces atrioventricular (AV) conduction and the function of the sinus node, which is the heart's natural pacemaker.

Onset of Action:

Oral: 2 days to 3 weeks.
Intravenous: Within hours, especially regarding electrophysiologic effects.
Antiarrhythmic effects may manifest between 2 to 3 days to 1 to 3 weeks, with a potentially shorter onset in children and patients receiving Intravenous loading doses.

Peak Effect:

Typically observed between 1 week to 5 months after initiation.

Duration after Discontinuing Therapy:

Variable, ranging from 2 weeks to several months. In children, the effects may resolve in less than a few weeks, while in adults, it may last several months.

Absorption:

Oral absorption is slow and variable.

Distribution:

Intravenous: Rapid redistribution with a significant decrease within 30 to 45 minutes post-infusion.
Volume of Distribution (V): Ranges from 40 to 84 L/kg for Intravenous single dose and 66 L/kg for Oral administration.

Protein Binding:

More than 96%.

Metabolism:

Primarily hepatic via enzymes CYP2C8 and 3A4 to active N-desethylamiodarone metabolite, with possible enterohepatic recirculation.

Bioavailability:

Approximately 50%, with a range of 35% to 65%.

Half-Life Elimination:

For Amiodarone: Single dose ranges from 15 to 142 days; Oral chronic therapy ranges from 26 to 107 days.
For N-desethylamiodarone (active metabolite): Single dose ranges from 14 to 75 days; Oral chronic therapy is 61 days.

Time to Peak, Serum: