Amiodarone

Do not drink grapefruit juice while you are taking this medication.

Amiodarone is part of the drug class:

• Antiarrhythmics, class III

Tell your doctor if you are pregnant or planning to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category D. Amiodarone can harm your unborn baby. Amiodarone can stay in your body for months after treatment is stopped. Therefore, talk with your doctor before you plan to get pregnant.

If you take too much amiodarone, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If amiodarone is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Amiodarone hydrochloride is a member of a class of antiarrhythmic drugs with predominantly Class III (Vaughan Williams' classification) effects. Amiodarone is a benzofuran derivative: 2-butyl-3-benzofuranyl 4-[2-(diethylamino)-ethoxy]-3,5-diiodophenyl ketone hydrochloride.

The structural formula is as follows:

Amiodarone hydrochloride, USP is a white to cream-colored crystalline powder. It is slightly soluble in water, soluble in alcohol and freely soluble in chloroform. It contains 37.3% iodine by weight.

Each Amiodarone hydrochloride tablet intended for oral administration contains 200 mg of Amiodarone hydrochloride. In addition each tablet contains the following inactive ingredients: colloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate, povidone and sodium starch glycolate.

Amiodarone is contraindicated in patients with cardiogenic shock; severe sinus-node dysfunction, causing marked sinus bradycardia; second- or third-degree atrioventricular block; and when episodes of bradycardia have caused syncope (except when used in conjunction with a pacemaker).

Amiodarone is contraindicated in patients with a known hypersensitivity to the drug or to any of its components, including iodine.

Amiodarone Hydrochloride Tablets, 200 mg are white to off-white, round-shaped, flat beveled-edge, uncoated tablets with bisect on one side and other side is plain; one side of bisect is debossed with 'ZE' and other side is debossed with '65' and are supplied as follows:

Cartons of 100 tablets (10 tablets each blister pack x 10) NDC 0904-6556-61

Storage:

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light.

Dispense in a tight, light-resistant container.

Manufactured by:

Cadila Healthcare Ltd.

India

Distributed by:

Zydus Pharmaceuticals USA Inc.

Pennington, NJ 08534

Distributed By:

MAJOR® PHARMACEUTICALS

17177 N Laurel Park Dr., Suite 233

Livonia, MI 48152

Rev.: 07/16

Medication Guide

Amiodarone Hydrochloride

(A-mi-OH-da-rone HYE-droe-KLOR-ide)

Tablets

Rx only

What is the most important information I should know about Amiodarone Hydrochloride Tablets? Amiodarone Hydrochloride Tablets can cause serious side effects that can lead to death including:

•   lung problems •   liver problems •   worsening heartbeat problems •   thyroid problems

Call your doctor or get medical help right away if you have any of the following symptoms during treatment with Amiodarone hydrochloride tablets:

•   shortness of breath, wheezing, or any other trouble breathing; coughing, chest pain, or spitting up of blood •   nausea or vomiting, brown or dark-colored urine feel more tired than usual, yellowing of your skin or the whites of your eyes (jaundice), or right upper stomach pain •   heart pounding, skipping a beat, beating fast or slowly, feel light-headed or faint •   weakness, weight loss or weight gain, heat or cold intolerance, hair thinning, sweating, changes in your menses, swelling of your neck (goiter), nervousness, irritability, restlessness, decreased concentration, depression in the elderly, or tremor.

Amiodarone hydrochloride tablets should only be used in people with life-threatening heartbeat problems called ventricular arrhythmias, for which other treatments did not work or were not tolerated.

Amiodarone Hydrochloride Tablets can cause other serious side effects. See "What are the possible side effects of Amiodarone Hydrochloride Tablets?" If you get serious side effects during treatment you may need to stop Amiodarone hydrochloride tablets, have your dose changed, or get medical treatment. Talk with your doctor before you stop taking Amiodarone.

You may still have side effects after stopping Amiodarone hydrochloride tablets because the medicine stays in your body months after treatment is stopped.

Tell all your healthcare providers that you take or took Amiodarone hydrochloride tablets.

What are Amiodarone Hydrochloride Tablets?

Amiodarone is a prescription medicine used to treat life-threatening heartbeat problems called ventricular arrhythmias, for which other treatment did not work or was not tolerated. Amiodarone hydrochloride tablets have not been shown to help people with lifethreatening heartbeat problems live longer. Amiodarone hydrochloride tablets should be started in a hospital to monitor your condition. You should have regular check-ups, blood tests, chest x-rays, and eye exams before and during treatment with Amiodarone hydrochloride tablets to check for serious side effects.

It is not known if Amiodarone hydrochloride tablets are safe and effective in children.

Who should not take Amiodarone Hydrochloride Tablets?

Do not take Amiodarone hydrochloride tablets if you:

•   have a certain heart condition called heart block with or without a slow heart rate •   have a slow heart rate with dizziness or lightheadedness, and you do not have an implanted pacemaker •   are allergic to Amiodarone, iodine, or any of the other ingredients in Amiodarone hydrochloride tablets. See the end of this Medication Guide for a complete list of ingredients in Amiodarone hydrochloride tablets.

What should I tell my doctor before taking Amiodarone Hydrochloride Tablets Before you take Amiodarone Hydrochloride Tablets tell your doctor about all of your medical conditions including if you:

•   have lung or breathing problems •   have liver problems •   have or had thyroid problems •   have blood pressure problems •   are pregnant or plan to become pregnant. Amiodarone can harm your unborn baby. •   Amiodarone can stay in your body for months after treatment is stopped. Talk with your doctor before you plan to get pregnant. •   are breastfeeding or plan to breastfeed. Amiodarone can pass into your breast milk and can harm your baby. Talk to your doctor about the best way to feed your baby. You should not breast feed while taking Amiodarone. Also, Amiodarone can stay in your body for months after treatment is stopped. •   Tell your doctor about all the medicines you take including prescription and over-the-counter medicines, vitamins and herbal supplements. Amiodarone hydrochloride tablets and certain other medicines can affect (interact) with each other and cause serious side effects. You can ask your pharmacist for a list of medicines that interact with Amiodarone hydrochloride tablets.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I take Amiodarone Hydrochloride Tablets?

•   Take Amiodarone hydrochloride tablets exactly as your doctor tells you to take it. •   Your doctor will tell you how much Amiodarone hydrochloride tablets to take and when to take it. Amiodarone hydrochloride tablets can be taken with or without food. Make sure you take Amiodarone hydrochloride tablets the same way each time. •   If you take too much Amiodarone hydrochloride tablets, call your doctor or go to the nearest hospital emergency room right away. •   If you miss a dose, wait and take your next dose at your regular time. Do not take two doses at the same. Continue with your next regularly scheduled dose.

What should I avoid while taking Amiodarone Hydrochloride Tablets?

•   Do not drink grapefruit juice during treatment with Amiodarone hydrochloride tablets. Grapefruit juice affects how Amiodarone hydrochloride tablets are absorbed in the stomach.

Avoid sunlight. Amiodarone hydrochloride tablets can make your skin sensitive to sun and the light from sunlamps and tanning beds. You could get severe sunburn. Use sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight. Talk to you doctor if you get sunburn.

What are the possible side effects of Amiodarone Hydrochloride Tablets?

See "What is the most important information I should know about Amiodarone hydrochloride tablets?"

•   vision problems that may lead to permanent blindness. You should have regular eye exams before and during treatment with Amiodarone hydrochloride tablets. Call your doctor if you have blurred vision, see halos, or your eyes become sensitive to light. Tell your doctor if you plan to have laser eye surgery. •   nerve problems. Amiodarone hydrochloride tablets can cause a feeling of "pins and needles" or numbness in the hands, legs, or feet, muscle weakness, uncontrolled movements, poor coordination, and trouble walking. •   skin problems. Amiodarone hydrochloride tablets can cause your skin to be more sensitive to the sun or turn a bluish-gray color. In most people, skin color slowly returns to normal after stopping Amiodarone hydrochloride tablets. In some people, skin color does not return to normal.

The most common side effects of Amiodarone hydrochloride tablets include:

•   nausea •   vomiting •   constipation •   loss of appetite.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Amiodarone hydrochloride tablets. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Amiodarone Hydrochloride Tablets?

•   Store Amiodarone hydrochloride tablets at room temperature. Protect from light. Keep Amiodarone hydrochloride tablets in a tightly closed container. •   Safely dispose of Amiodarone hydrochloride tablets that are out-of-date or no longer needed. •   Keep Amiodarone hydrochloride tablets and all medicines out of the reach of children.

General information about Amiodarone Hydrochloride Tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Amiodarone hydrochloride tablets for a condition for which it was not prescribed. Do not give Amiodarone hydrochloride tablets to other people, even if they have the same symptoms that you have. It may harm them.

If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Amiodarone hydrochloride tablets that was written for healthcare professionals.

Please address medical inquiries to, (MedicalAffairs@zydususa.com) Tel.: 1-877-993-8779.

What are the ingredients in Amiodarone Hydrochloride Tablets?

Active Ingredient: Amiodarone hydrochloride, USP

Inactive Ingredients: Colloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate, povidone and sodium starch glycolate.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

This product's package insert may have been updated. For current package insert, please visit www.zydususa.com.

Manufactured by:

Cadila Healthcare Ltd.

India

Distributed by:

Zydus Pharmaceuticals USA Inc.

Pennington, NJ 08534

Distributed By:

MAJOR® PHARMACEUTICALS

17177 N Laurel Park Dr., Suite 233

Livonia, MI 48152

IH5029

Rev.: 07/16

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous, as hydrochloride:

Nexterone: 150 mg/100 mL (100 mL); 360 mg/200 mL (200 mL)

Generic: 150 mg/3 mL (3 mL); 450 mg/9 mL (9 mL); 900 mg/18 mL (18 mL); 900 mg/500 mL in Dextrose 5% (500 mL)

Tablet, Oral, as hydrochloride:

Cordarone: 200 mg [DSC] [scored]

Pacerone: 100 mg

Pacerone: 200 mg [scored; contains fd&c red #40, fd&c yellow #6 (sunset yellow)]

Pacerone: 400 mg [scored; contains fd&c yellow #10 aluminum lake]

Generic: 100 mg, 200 mg, 400 mg

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

Atrial fibrillation in patients with heart failure without preexcitation who require heart rate control

Based on the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for the management of patients with atrial fibrillation, the use of amiodarone for rate control of atrial fibrillation in patients with heart failure without preexcitation is an effective and recommended treatment option for this condition. However, due to its side-effect profile, amiodarone should be reserved for patients who are intolerant of or unresponsive to beta-blockers with or without digoxin. When acute heart rate control is necessary, the use of intravenous amiodarone (or intravenous digoxin) is preferred.

Atrial fibrillation in patients with hypertrophic cardiomyopathy

Based on the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for the management of patients with atrial fibrillation, the use of amiodarone for rate control of atrial fibrillation in patients with hypertrophic cardiomyopathy is an effective and recommended treatment option for this condition.

Atrial fibrillation in critically ill patients without preexcitation who require heart rate control

Based on the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for the management of patients with atrial fibrillation, the use of intravenous amiodarone for rate control in critically ill patients with AF without preexcitation is effective and recommended for this condition.

Maintenance of sinus rhythm after cardioversion of atrial fibrillation

Based on the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for the management of patients with atrial fibrillation, amiodarone may be used to maintain sinus rhythm. However, amiodarone should only be used after considering the risk of therapy and when other agents have failed or are contraindicated.

Pharmacologic conversion of atrial fibrillation to and maintenance of normal sinus rhythm

Based on the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for the management of patients with atrial fibrillation, the use of amiodarone for pharmacologic conversion of atrial fibrillation to and maintenance of normal sinus rhythm is effective and recommended for this condition.

Prevention of postoperative atrial fibrillation and atrial flutter associated with cardiothoracic surgery

Based on the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for the management of patients with atrial fibrillation and the American College of Cardiology Foundation/American Heart Association guideline for coronary artery bypass graft surgery, the use of amiodarone for prevention of postoperative atrial fibrillation associated with cardiothoracic surgery for patients in whom beta-blockers are contraindicated is effective and recommended for this condition. The American College of Chest Physicians has recommended that amiodarone should be considered in patients undergoing cardiac surgery when beta-blockers are contraindicated [ACCP [Bradley 2005]].

Supraventricular tachycardia (eg, AV nodal reentrant tachycardia [AVNRT], AV reentrant tachycardia [AVRT], focal atrial tachycardia [AT]) (adults)

Based on the American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines for the management of patients with supraventricular arrhythmias, amiodarone may be considered in the ongoing management of symptomatic supraventricular tachycardia (AVNRT or AVRT) or in the acute and ongoing management of focal atrial tachycardias; however, safety risks limit its therapeutic use. In many cases, amiodarone is reserved for use in patients in whom other therapies have failed or are contraindicated (eg, patients with structural or ischemic heart disease).

Supraventricular tachycardia (infants/children/adolescents)

Amiodarone is an effective therapeutic option with a variety of potential uses in the management of SVT; however, safety risks limit its therapeutic use. In many cases, amiodarone is reserved for use in patients who have failed other therapies or who have structural heart disease, including left ventricular dysfunction.

Additional Off-Label Uses

Adjunct to ICD therapy to suppress symptomatic ventricular tachyarrhythmias in otherwise optimally-treated patients with heart failure (ACC/AHA/ESC Practice Guidelines); Paroxysmal supraventricular tachycardia (SVT) (not initial drug of choice); Cardiac arrest with pulseless VT or VF unresponsive to CPR, defibrillation, and vasopressor administration have failed (ACLS/PALS guidelines); Control of hemodynamically-stable monomorphic VT, polymorphic VT with a normal baseline QT interval, or wide-complex tachycardia of uncertain origin (ACLS/PALS guidelines); Control of rapid ventricular rate due to accessory pathway conduction in pre-excited atrial arrhythmias (ACLS guidelines) or stable narrow-complex tachycardia (ACLS guidelines)

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

Ventricular arrhythmias:

Prevention of recurrent life-threatening ventricular arrhythmias (eg, VF or hemodynamically unstable VT): Oral: 800 to 1600 mg daily in 1 to 2 doses for 1 to 3 weeks, then when adequate arrhythmia control is achieved, decrease to 600 to 800 mg daily in 1 to 2 doses for 1 month; usual maintenance: 400 mg daily (some patients may require lower or higher dosages up to 600 mg daily).

Pulseless VT or VF (ACLS 2010; ACLS 2015): IV push, I.O.: Initial: 300 mg rapid bolus; if pulseless VT or VF continues after subsequent defibrillation attempt or recurs, administer supplemental dose of 150 mg. Note: In this setting, administering undiluted is preferred (Dager 2006; Skrifvars 2004). The Handbook of Emergency Cardiovascular Care (Hazinski 2015) and the ACLS guidelines do not make any specific recommendations regarding dilution of amiodarone in this setting. Experience limited with I.O. administration of amiodarone. Maximum recommended total daily dose is 2.2 g (ACLS 2010).

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

Stable VT: IV: 150 mg over 10 minutes, then 1 mg/minute for 6 hours, followed by 0.5 mg/minute; continue this rate for at least 18 hours (total infusion duration: 24 hours) or until complete transition to oral (see Recommendations for conversion to oral amiodarone after IV administration).

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

Supraventricular arrhythmias:

Atrial fibrillation:

Pharmacologic cardioversion (off-label use):

Oral: 600 to 800 mg daily in divided doses until 10 g total, then 200 mg daily as maintenance (AHA/ACC/HRS [January 2014]). Although not supported by clinical evidence, a maintenance dose of 100 mg daily is commonly used especially for the elderly or patients with low body mass (Zimetbaum 2007). Note: Other regimens have been described and may be used clinically:

800 mg daily for 14 days, followed by 600 mg daily for the next 14 days, then 300 mg daily for the remainder of the first year, then 200 mg daily thereafter (Singh 2005)

or

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

IV: 150 mg over 10 minutes, then 1 mg/minute for 6 hours, then 0.5 mg/minute for 18 hours or change to oral maintenance dosing (eg, 100 to 200 mg once daily) (AHA/ACC/HRS [January 2014]).

Maintenance of sinus rhythm (off-label use): Oral: 400 to 600 mg daily in divided doses for 2 to 4 weeks followed by a maintenance dose of 100 to 200 mg once daily (AHA/ACC/HRS [January 2014])

Prevention of postoperative atrial fibrillation and atrial flutter associated with cardiothoracic surgery (off-label use): Note: A variety of regimens have been used in clinical trials, including oral and intravenous regimens:

Oral: 200 mg 3 times daily for 7 days prior to surgery, followed by 200 mg daily until hospital discharge (Daoud, 1997).

IV:

Preoperative regimen: 150 mg loading dose, followed by 0.4 mg/kg/hour (~0.5 mg/minute for a 70 kg patient) for 3 days prior to surgery and for 5 days postoperative (Lee 2000).

Postoperative regimen: Starting at postop recovery, 1000 mg infused over 24 hours for 2 days (Guarnieri, 1999).

Rate control (off-label use): IV: 300 mg over 1 hour, then 10 to 50 mg/hour over 24 hours followed by an oral maintenance dose; usual maintenance dose: 100 to 200 mg once daily. Note: Amiodarone requires a longer time to achieve rate control as compared to nondihydropyridine calcium channel blockers (eg, diltiazem) (7 hours vs 3 hours, respectively) (AHA/ACC/HRS [January 2014])

Supraventricular tachycardia (eg, AVNRT, AVRT, focal AT) (off-label use): Note: Amiodarone is usually reserved for use when other therapies have failed or are contraindicated. In general, most patients do not require chronic long-term treatment with antiarrhythmic therapy.

Pharmacologic cardioversion:

Oral:

Loading dose: 400 to 600 mg daily in divided doses for 2 to 4 weeks; in an inpatient monitoring setting, loading doses up to 1,200 mg daily may be considered (ACC/AHA/HRS [Page 2015])

Maintenance dose: 100 to 200 mg daily (maximum maintenance dose: 200 mg daily) (ACC/AHA/HRS [Page 2015])

IV: 150 mg over 10 minutes, then 1 mg/minute for 6 hours, then 0.5 mg/minute for 18 hours or may change to oral dosing (ACC/AHA/HRS [Page 2015])

Recommendations for conversion to oral amiodarone after IV administration: Use the following as a guide:

<1-week IV infusion: 800 to 1600 mg daily

1- to 3-week IV infusion: 600 to 800 mg daily

>3-week IV infusion: 400 mg

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

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

No dosage adjustment necessary.

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

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

A 5 mg/mL oral suspension may be made with tablets and either a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus® adjusted to a pH between 6-7 using a sodium bicarbonate solution (5 g/100 mL of distilled water). Crush five 200 mg tablets in a mortar and reduce to a fine powder. Add small portions of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 200 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 200 mL. Label “shake well” and “protect from light”. Stable for 42 days at room temperature or 91 days refrigerated (preferred) (Nahata, 2004).

Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended. You will receive your first few doses in a hospital setting, where your heart rhythm can be monitored.

If you have been taking another heart rhythm medicine, you may need to gradually stop taking it when you start using amiodarone. Follow your doctor's dosing instructions very carefully.

You may take amiodarone with or without food, but take it the same way each time.

It may take up to 2 weeks before your heart rhythm improves. Keep using the medicine as directed even if you feel well.

While using amiodarone, you will need frequent medical tests and chest x-rays to check your thyroid, vision, lungs, and liver function. Amiodarone can have long lasting effects on your body. You may need medical tests for several months after you stop using this medicine.

If you need surgery (including laser eye surgery), tell the surgeon ahead of time that you are using amiodarone. You may need to stop using the medicine for a short time.

Amiodarone can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using amiodarone.

Store at room temperature away from moisture, heat, and light.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.