Amiodarone: Mechanism of Action, Uses, Side Effects
Amiodarone is a benzofuran derivative, anti-arrhythmic drug used commonly in a variety of settings. Most known for its approved indication in life-threatening ventricular arrhythmias, it is also used off-label in the outpatient and inpatient setting for atrial fibrillation. Because of its ability to cause serious toxicity and possibly death.
Amiodarone is used to treat and prevent certain types of serious, life-threatening ventricular arrhythmias (a certain type of abnormal heart rhythm when other medications did not help or could not be tolerated. Amiodarone is in a class of medications called antiarrhythmics. It works by relaxing overactive heart muscles. Amiodarone use should be reserved for its approved indications, according to prescribing information.
Amiodarone mechanism of action
Amiodarone is considered a class III anti-arrhythmic drug. It blocks potassium currents that cause repolarization of the heart muscle during the third phase of the cardiac action potential. As a result, amiodarone increases the duration of the action potential as well as the effective refractory period for cardiac cells (myocytes). Therefore, cardiac muscle cell excitability is reduced, preventing and treating abnormal heart rhythms.
Unique from other members of the class III anti-arrhythmic drug class, amiodarone also interferes with the functioning of beta-adrenergic receptors, sodium channels, and calcium channels channels. These actions, at times, can lead to undesirable effects, such as hypotension, bradycardia, and Torsades de pointes (TdP). In addition to the above, amiodarone may increase activity of peroxisome proliferator-activated receptors, leading to steatogenic changes in the liver or other organs. Finally, amiodarone has been found to bind to the thyroid receptor due to its iodine content, potentially leading to amiodarone induced hypothyroidism or thyrotoxicosis.
How should this medicine be used?
Amiodarone comes as a tablet to take by mouth. It is usually taken once or twice a day. You may take amiodarone either with or without food, but be sure to take it the same way each time. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take amiodarone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
What special precautions should I follow?
Before taking amiodarone,
• tell your doctor and pharmacist if you are allergic to amiodarone, iodine, any other medications, or any of the ingredients in amiodarone tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: antidepressants (‘mood elevators’) such as trazodone (Oleptro); anticoagulants (‘blood thinners’) such as dabigatran (Pradaxa) and warfarin (Coumadin, Jantoven); certain cholesterol lowering medications such as atorvastatin (Lipitor, in Caduet, in Liptruzet), cholestyramine (Prevalite), lovastatin (Altoprev, in Advicor), and simvastatin (Zocor, in Simcor, in Vytorin); cimetidine; clopidogrel (Plavix); cyclosporine (Gengraf, Neoral, Sandimmune); dextromethorphan (a medication in many cough preparations); fentanyl (Actiq, Duragesic, Fentora, others); HIV protease inhibitors such as indinavir (Crixivan) and ritonavir (Norvir, in Kaletra, in Viekira Pak); ledipasvir and sofosbuvir (Harvoni); lithium (Lithobid); loratadine (Claritin); medications for diabetes or seizures; methotrexate (Otrexup, Rasuvo, Trexall); narcotic medications for pain; rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); and sofosbuvir (Solvaldi) with simeprevir (Olysio). Many other medications may interact with amiodarone, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may have to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort.
• tell your doctor if you have diarrhea or have or have ever had any of the conditions mentioned in the Amiodarone Safety Information section or problems with your blood pressure.
• tell your doctor if you are pregnant or plan to become pregnant. Talk to your doctor if you plan to become pregnant during your treatment because amiodarone may remain in your body for some time after you stop taking it. If you become pregnant while taking amiodarone, call your doctor immediately. Amiodarone can cause fetal harm.
• tell your doctor if you are breastfeeding. Do not breastfeed while you are taking amiodarone.
• talk to your doctor about the risks of taking this medication if you are 65 years of age or older. Older adults should not usually take amiodarone because it is not as safe or effective as other medication(s) that can be used to treat the same condition.
• if you are having surgery, including dental surgery or laser eye surgery, tell your doctor or dentist that you are taking amiodarone.
• plan to avoid unnecessary or prolonged exposure to sunlight or sunlamps and to wear protective clothing, sunglasses, and sunscreen. Amiodarone may make your skin sensitive to sunlight. Exposed skin may turn blue-gray and may not return to normal even after you stop taking this medication.
• you should know that amiodarone may cause vision problems including permanent blindness. Be sure to have regular eye exams during your treatment and call your doctor if your eyes become dry, sensitive to light, if you see halos, or have blurred vision or any other problems with your vision.
• you should know that amiodarone may remain in your body for several months after you stop taking it. You may continue to experience side effects of amiodarone during this time. Be sure to tell every health care provider who treats you or prescribes any medication for you during this time that you have recently stopped taking amiodarone.
What special dietary instructions should I follow?
Do not drink grapefruit juice while you are taking this medication.
What should I do if I forget a dose?
Skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What are the side effects of amiodarone?
Amiodarone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
• loss of appetite
• decreased sex drive
• difficulty falling asleep or staying asleep
• changes in ability to taste and smell
• changes in amount of saliva
Some side effects can be serious. If you experience any of the following symptoms, or those listed in the Amiodarone Safety Information section, call your doctor immediately or get emergency medical treatment:
• weight loss or gain
• intolerance to heat or cold
• thinning hair
• excessive sweating
• changes in menstrual cycle
• swelling in the front of the neck (goiter)
• swelling of the hands, feet, ankles, or lower legs
• uncontrollable shaking of a part of the body
• decreased concentration
• movements that you cannot control
• poor coordination or trouble walking
• numbness or tingling in the hands, legs, and feet
• muscle weakness
Amiodarone may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from light, excess heat and moisture (not in the bathroom).
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.
It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org
In case of emergency/overdose
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services at 911.
Symptoms of overdose may include:
• slow heartbeat
• blurred vision
Amiodarone Safety Information
Amiodarone may cause lung damage that can be serious or life-threatening. Tell your doctor if you have or have ever had any type of lung disease or if you have ever developed lung damage or breathing problems while taking amiodarone. If you experience any of the following symptoms, call your doctor immediately: fever, shortness of breath, wheezing, other breathing problems, cough, or coughing or spitting up blood.
Amiodarone may also cause liver damage. Tell your doctor if you have or have ever had liver disease. If you experience any of the following symptoms, call your doctor immediately: nausea, vomiting, dark colored urine, excessive tiredness, yellowing of the skin or eyes, itching, or pain in the upper right part of the stomach.
Amiodarone may cause your arrhythmia (irregular heart rhythm) to worsen or may cause you to develop new arrhythmias. Tell your doctor if you have ever been dizzy or lightheaded or have fainted because your heartbeat was too slow and if you have or have ever had low levels of potassium or magnesium in your blood; heart or thyroid disease; or any problems with your heart rhythm other than the arrhythmia that is being treated. Tell your doctor and pharmacist if you are taking any of the following medications: antifungals such as fluconazole (Diflucan), ketoconazole (Nizoral), and itraconazole (Onmel, Sporanox); azithromycin (Zithromax, Zmax); beta blockers such as propranolol (Hemangeol, Inderal, Innopran); calcium channel blockers such as diltiazem (Cardizem, Cartia, Diltzac, Tiazac, others), and verapamil (Calan, Covera, Verelan, in Tarka); cisapride (Propulsid; not available in the US); clarithromycin (Biaxin); clonidine (Catapres, Kapvay); diuretics (‘water pills’); dofetilide (Tikosyn); erythromycin (E.E.S., E-Mycin, Erythrocin); fluoroquinolone antibiotics such as ciprofloxacin (Cipro), levofloxacin (Levaquin), lomefloxacin (not available in the US), moxifloxacin (Avelox), norfloxacin (not available in the US), ofloxacin, and sparfloxacin (not available in the US); other medications for irregular heartbeat such as digoxin (Lanoxin), disopyramide (Norpace), flecainide, ivabradine (Corlanor), phenytoin (Dilantin, Phenytek), procainamide, quinidine (in Nuedexta), and sotalol (Betapace, Sorine, Sotylize); and thioridazine. If you have any of the following symptoms, call your doctor immediately: lightheadedness; fainting; fast, slow, or pounding heartbeat; or feeling that your heart has skipped a beat.
You will probably be hospitalized for one week or longer when you begin your treatment with amiodarone. Your doctor will monitor you carefully during this time and for as long as you continue to take amiodarone. Your doctor will probably start you on a high dose of amiodarone and gradually decrease your dose as the medication begins to work. Your doctor may decrease your dose during your treatment if you develop side effects. Follow your doctor’s directions carefully.
Do not stop taking amiodarone without talking to your doctor. You may need to be closely monitored or even hospitalized when you stop taking amiodarone. Amiodarone may remain in your body for some time after you stop taking it, so your doctor will watch you carefully during this time.
Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests, such as blood tests, X-rays, and electrocardiograms (EKGs, tests that record the electrical activity of the heart) before and during your treatment to be sure that it is safe for you to take amiodarone and to check your body’s response to the medication.
Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with amiodarone and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also obtain the Medication Guide from the FDA website: http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm.
What other information should I know?
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.