Amiodarone

1. Health Canada Product Monograph — Amiodarone

• Amiodarone is used to treat life-threatening, recurrent ventricular tachycardia that has not responded to other antiarrhythmic drugs or when other drugs could not be tolerated.
• Amiodarone is also used to treat recurrent ventricular fibrillation, a dangerous chaotic heart rhythm, under the same circumstances.
• Because of its serious potential side effects, amiodarone is reserved for hemodynamically unstable, life-threatening ventricular arrhythmias and should be started in hospital.

• Amiodarone can cross the placenta and has been linked to congenital goiter, underactive thyroid, and overactive thyroid in newborns when used during pregnancy.
• Amiodarone should be used during pregnancy only if the expected benefit to the mother clearly outweighs the potential risk to the baby.
• Animal studies have shown that amiodarone can cause harm to a developing fetus at high doses.

• Amiodarone passes into breast milk in amounts that could expose a nursing infant to a significant dose of the drug.
• Breastfeeding is generally not recommended while taking amiodarone, and mothers are usually advised to discontinue nursing.

• Amiodarone has not been specifically studied in large numbers of patients 65 and older, but clinical experience has not shown differences in response between older and younger patients.
• Older adults should generally start at the lower end of the dosing range, since they are more likely to have reduced liver, kidney, or heart function, or to be taking other medications.

• The safety and effectiveness of amiodarone in children have not been established, so its use in children is not recommended.

• Amiodarone therapy must be started in hospital, under continuous heart monitoring, and continued under a cardiologist's supervision.
• Treatment usually begins with a loading dose of 800 to 1600 mg per day, given for one to three weeks, sometimes longer, until the arrhythmia is controlled.
• Loading doses of 1000 mg or more per day are usually divided and taken with meals to reduce stomach upset.
• Once the arrhythmia is controlled, the dose is typically reduced to 600 to 800 mg per day for about one month.
• After that, the usual long-term maintenance dose is 200 to 400 mg per day, occasionally up to 600 mg per day, taken once daily or in divided doses if stomach upset occurs.
• The lowest effective dose should always be used, and dosing must be individualized based on how the patient responds and tolerates the drug, since amiodarone builds up in the body and leaves very slowly.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Overdose of amiodarone may cause severe slowing of the heart rate and dangerous disturbances in heart conduction, particularly in older adults or those taking digitalis-type medications.
• A single very large ingestion has caused sweating and a mild rapid heart rate followed by slight slowing of the heart rate over the following days.
• There is no specific antidote for amiodarone overdose; treatment relies on inducing vomiting or gastric lavage to reduce absorption if the overdose is recent, plus general supportive care.
• Cardiac rhythm and blood pressure should be closely monitored after an overdose, with a temporary pacemaker or medication used if severe slowing of the heart rate occurs.
• Amiodarone and its main breakdown product are not removed by dialysis.

• Nausea and vomiting may occur, especially when starting treatment at high doses.
• Constipation and loss of appetite may occur.
• Abdominal pain, indigestion, diarrhea, or an unusual taste in the mouth may occur.
• Sun sensitivity, causing easier sunburn, is common.
• Blue-grey discoloration of sun-exposed skin may develop with long-term use.
• Skin rash may occur.
• Tiredness, tremor, or shaky movements may occur.
• Loss of coordination or an unsteady walk may occur.
• Dizziness and tingling sensations may occur.
• Corneal deposits in the eye are very common with long-term use and can cause visual halos or blurred vision.
• Other visual disturbances may occur.
• Sleep disturbances, memory or concentration problems, and general weakness may occur.
• Decreased sex drive or difficulty with sexual function may occur.
• Hair loss may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Amiodarone can cause serious lung damage, including inflammation and scarring of the lungs, which can be fatal in some cases.
• Amiodarone can cause or worsen liver disease, including rare cases of severe liver failure.
• Amiodarone can worsen or trigger dangerous heart rhythm problems, including new or worsened ventricular arrhythmias.
• Severe slowing of the heart rate or heart block may occur, sometimes requiring a pacemaker.
• Worsening or new congestive heart failure may occur.
• Amiodarone can cause thyroid problems, either an underactive or an overactive thyroid, both of which can be serious and may require dose adjustment or stopping the drug.
• Overactive thyroid caused by amiodarone can trigger a dangerous return or worsening of the heart arrhythmia and has been linked to death in rare cases.
• Permanent vision loss from optic nerve damage has been reported rarely.
• Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported.
• Peripheral nerve damage causing numbness, weakness, or pain in the hands and feet may occur and may not fully resolve after stopping the drug.
• Life-threatening bradycardia and heart block can occur when amiodarone is combined with certain hepatitis C antiviral medications.
• Seek urgent medical attention for new or worsening shortness of breath, cough, or fever, yellowing of the skin or eyes, fainting, a very slow or irregular heartbeat, or sudden vision changes.

• Use with caution in patients with any history of thyroid problems, and monitor thyroid function before starting and periodically during treatment.
• Use with caution in patients with pre-existing lung disease, and obtain baseline chest x-rays and lung function tests before starting.
• Use with caution in patients with liver disease, and monitor liver enzymes regularly during treatment.
• Use with caution in patients with existing heart failure, since amiodarone can worsen this condition.
• Use with caution in patients undergoing surgery, since general anesthesia can interact with amiodarone's effects on the heart.
• Use with caution in patients scheduled for corneal refractive laser surgery, since most device manufacturers list amiodarone use as a reason to avoid the procedure.
• Use with caution in patients who drink grapefruit juice, and advise them to avoid it during treatment.
• Regular eye examinations, including slit-lamp exams, are recommended during long-term treatment.
• Use with caution in older adults, who typically need lower starting doses.

• Contraindicated in patients with known hypersensitivity to amiodarone or any component of the tablet, including iodine.
• Contraindicated in cardiogenic shock.
• Contraindicated in severe sinus-node dysfunction causing a very slow heart rate.
• Contraindicated in second- or third-degree heart block, unless the patient has a pacemaker.
• Contraindicated in patients with a history of fainting caused by slow heart rate episodes, unless a pacemaker is in place.
• Contraindicated in patients with active hepatitis or liver inflammation.
• Contraindicated in patients with pre-existing lung scarring or interstitial lung disease.

• Warfarin and other blood thinners have their effect significantly increased by amiodarone, raising the risk of serious bleeding; doses usually need to be reduced and monitored closely.
• Digoxin blood levels rise substantially when combined with amiodarone, so the digoxin dose usually needs to be reduced and levels monitored.
• Other antiarrhythmic drugs, such as quinidine, procainamide, and flecainide, can reach higher blood levels when combined with amiodarone, requiring dose reduction.
• Beta-blockers and calcium channel blockers such as verapamil and diltiazem can combine with amiodarone to cause dangerously slow heart rates or heart block.
• Certain hepatitis C antiviral medications, including sofosbuvir-based regimens, can cause severe slow heart rates when combined with amiodarone and are generally not recommended together.
• Statins such as simvastatin and atorvastatin have an increased risk of muscle damage when combined with amiodarone.
• Cyclosporine blood levels can rise when combined with amiodarone, increasing the risk of kidney problems.
• Drugs that prolong the QT interval, including certain antibiotics such as fluoroquinolones and macrolides, and antifungal medications, increase the risk of dangerous heart rhythm problems when combined with amiodarone.
• Phenytoin blood levels can rise with amiodarone use, while phenytoin can lower amiodarone blood levels.
• Cholestyramine can reduce amiodarone blood levels by binding it in the gut.
• Cimetidine can raise amiodarone blood levels.
• Rifampin can lower amiodarone blood levels by speeding up its breakdown.
• St. John's wort may reduce amiodarone's effectiveness and should be avoided.
• Stimulant laxatives should be avoided, since the low potassium they can cause increases the risk of dangerous heart rhythms with amiodarone.

• Grapefruit juice significantly increases amiodarone blood levels and should not be taken during treatment.
• Food increases the absorption of amiodarone, so amiodarone should be taken consistently either always with food or always without food, rather than switching back and forth.
• Amiodarone can be taken with or without food, as long as the pattern chosen is kept consistent from dose to dose.

• Amiodarone is usually taken once daily, though it may be split into two doses with meals if stomach upset occurs at higher doses.
• Take amiodarone at a consistent time and consistent relationship to meals each day, since changing this can alter how much drug is absorbed.

• Store amiodarone tablets between 15°C and 25°C, in a tightly closed container.
• Protect amiodarone tablets from light and excessive heat.

• Amiodarone is a powerful medication for life-threatening heart rhythm problems, and it can cause serious side effects affecting the lungs, liver, thyroid, eyes, and skin.
• Keep all scheduled blood tests, chest x-rays, eye exams, and follow-up visits, since these checks catch problems early.
• Avoid grapefruit juice and tell every healthcare provider and pharmacist that you take amiodarone, since it interacts with many other medications.
• Seek urgent care for new breathing problems, yellowing skin or eyes, fainting, or an irregular heartbeat.