METHODS FOR REDUCING RISK

1 . A method of treating a patient with atrial fibrillation or atrial flutter while preventing use of dronedarone in a patient for whom treatment with dronedarone may present an unacceptable risk, said method comprising providing a medication guide to said patient receiving a sample or a prescription of dronedarone.

2 . The method according to claim 1 , wherein the medication guide comprises at least one message selected from the group consisting of:

a. dronedarone is not for people with severe heart failure;

b. dronedarone should not be taken by a patient with severe heart failure:

i. where any physical activity causes shortness of breath or the patient has shortness of breath while at rest or after a small amount of exercise; and

ii. if the patient was hospitalized with heart failure within the last month;

c. the patient's doctor should be contacted if the patient has any of the symptoms selected from the group consisting of:

i. shortness of breath or wheezing at rest;

ii. wheezing, chest tightness or coughing up frothy sputum at rest, nighttime or after minor exercise;

iii. trouble sleeping or waking up at night because of breathing problems;

iv. using more pillows to prop up at night to breath more easily;

v. gaining more than 5 pounds quickly; and

vi. increasing swelling of feet or legs.

3 . The method according to claim 1 , wherein the medication guide comprises at least one message selected from the group consisting of:

a. a patient should not take dronedarone if the patient has severe heart failure or has recently been in the hospital for heart failure;

b. a patient should not take dronedarone if the patient has severe liver problems;

c. a patient should not take dronedarone if the patient takes certain medications that can change the amount of dronedarone that gets into the patient's body;

d. a patient should not dronedarone with a medication selected from the group consisting of nefazodone, ritonavir, ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, and cyclosporine;

e. a patient should not take dronedarone if the patient takes certain medications that can lead to a dangerous abnormal heartbeat selected from the group consisting:

i. some medicines for mental illness called phenothiazines;

ii. some medicines for depression called tricyclic antidepressants;

iii. some medicines for abnormal heart rhythm or fast heartbeat; and

iv. some medicines for bacterial infection;

f. a patient should not take dronedarone if the patient is pregnant or plans to become pregnant;

g. a patient should not take dronedarone if the patient is breast-feeding or plans to breast feed.

4 . The method according to claim 1 , wherein the medication guide comprises at least one message selected from the group consisting of:

a. a patient should tell his or her doctor and pharmacist if the patient takes medicine for high blood pressure, chest pain, or other heart conditions;

b. a patient should tell his or her doctor and pharmacist if the patient takes a statin medicine to lower blood cholesterol;

c. a patient should tell his or her doctor and pharmacist if the patient takes medicine for tuberculosis;

d. a patient should tell his or her doctor and pharmacist if the patient takes medicine for seizures;

e. a patient should tell his or her doctor and pharmacist if the patient takes medicine for organ transplant;

f. a patient should tell his or her doctor and pharmacist if the patient takes an herbal supplement called St. John's wort.

5 . The method according to claim 1 , wherein the medication guide comprises at least one message to a patient selected from the group consisting of:

a. take dronedarone exactly as the doctor prescribes;

b. take dronedarone two times a day with food;

c. do not stop taking dronedarone even if you are feeling well for a long time;

d. if you miss a dose, wait and take your next dose at your regular time;

e. do not take 2 doses at the same time;

f. do not try to make up for a missed dose; and

g. do not drink grapefruit juice while you take dronedarone.

6 . An article of manufacture comprising:

a. a packaging material;

b. dronedarone or a pharmaceutically acceptable salt thereof; and

c. a medication guide.

7 . A package comprising dronedarone or a pharmaceutically acceptable salt thereof and a medication guide.

8 . The package according to claim 7 , wherein the medication guide comprises at least one message selected from the group consisting of:

a. dronedarone is not for people with severe heart failure;

b. dronedarone should not be taken by a patient with severe heart failure:

i. where any physical activity causes shortness of breath or the patient has shortness of breath while at rest or after a small amount of exercise; and

ii. if the patient was hospitalized with heart failure within the last month;

c. the patient's doctor should be contacted if the patient has any of the symptoms selected from the group consisting of:

i. shortness of breath or wheezing at rest;

ii. wheezing, chest tightness or coughing up frothy sputum at rest, nighttime or after minor exercise;

iii. trouble sleeping or waking up at night because of breathing problems;

iv. using more pillows to prop up at night to breath more easily;

v. gaining more than 5 pounds quickly; and

vi. increasing swelling of feet or legs.

9 . The package according to claim 7 , wherein the medication guide comprises at least one message selected from the group consisting of:

a. a patient should not take dronedarone if the patient has severe heart failure or has recently been in the hospital for heart failure;

b. a patient should not take dronedarone if the patient has severe liver problems;

c. a patient should not take dronedarone if the patient takes certain medications that can change the amount of dronedarone that gets into the patient's body;

d. a patient should not take dronedarone with a medication selected from the group consisting of nefazodone, ritonavir, ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, and cyclosporine;

e. a patient should not take dronedarone if the patient takes certain medications that can lead to a dangerous abnormal heartbeat selected from the group consisting:

i. some medicines for mental illness called phenothiazines;

ii. some medicines for depression called tricyclic antidepressants;

iii. some medicines for abnormal heart rhythm or fast heartbeat; and

iv. some medicines for bacterial infection;

f. a patient should not take dronedarone if the patient is pregnant or plans to become pregnant;

g. a patient should not take dronedarone if the patient is breast-feeding or plans to breast feed.

10 . The package according to claim 7 , wherein the medication guide comprises at least one message selected from the group consisting of:

a. a patient should tell his or her doctor and pharmacist if the patient takes medicine for high blood pressure, chest pain, or other heart conditions;

b. a patient should tell his or her doctor and pharmacist if the patient takes a statin medicine to lower blood cholesterol;

c. a patient should tell his or her doctor and pharmacist if the patient takes medicine for tuberculosis;

d. a patient should tell his or her doctor and pharmacist if the patient takes medicine for seizures;

e. a patient should tell his or her doctor and pharmacist if the patient takes medicine for organ transplant; and

f. a patient should tell his or her doctor and pharmacist if the patient takes an herbal supplement called St. John's wort.

11 . The package according to claim 7 , wherein the medication guide comprises at least one message to a patient selected from the group consisting of:

a. take dronedarone exactly as the doctor prescribes;

b. take dronedarone two times a day with food;

c. do not stop taking dronedarone even if you are feeling well for a long time;

d. if you miss a dose, wait and take your next dose at your regular time;

e. do not take 2 doses at the same time;

f. do not try to make up for a missed dose; and

g. do not drink grapefruit juice while you take dronedarone.

12 . A method of preventing dronedarone use in patients with NYHA Class IV heart failure or NYHA Class II-Ill heart failure with recent decompensation requiring hospitalization or referral to a specialized heart failure clinic, said method comprising educating prescribers about increased mortality when dronedarone is used in these patients.

13 . The method according to claim 12 , comprising providing healthcare professionals with a physician information sheet or a health care professional information sheet.

14 . The method according to claim 13 , wherein the physician information sheet or health care professional information sheet comprises at least one message selected from the group consisting of:

a. dronedarone is an antiarrhythmic drug indicated to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AFib) or atrial flutter (AFL), with a recent episode of AFib/AFL and associated cardiovascular risk factors (i.e., age >70, hypertension, diabetes, prior cerebrovascular accident, left atrial diameter ≧50 mm or left ventricular ejection fraction [LVEF]<40%), who are in sinus rhythm or who will be cardioverted;

b. dronedarone is contraindicated in patients with NYHA Class IV heart failure, or NYHA Class II-III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic; and

c. in a placebo-controlled study in patients with severe heart failure requiring recent hospitalization or referral to a specialized heart failure clinic for worsening symptoms (the ANDROMEDA Study), patients given dronedarone had a greater than two-fold increase in mortality; such patients should not be given dronedarone.

15 . The method according to claim 13 , wherein the physician information sheet or health care professional information sheet comprises at least one message selected from the group consisting of:

a. dronedarone is contraindicated with the coadministration of strong CYP3A4 inhibitors, medicinal products inducing Torsade de Pointes, or Class I or III antiarrhythmic agents;

b. dronedarone is contraindicated in patients with second- or third-degree atrioventricular block, sick sinus syndrome (except when used in conjunction with a functioning pacemaker), or bradycardia of <50 bpm;

c. dronedarone is contraindicated in patients having QTc Bazett ≧500 ms or PR interval >280 ms;

d. dronedarone is contraindicated in patients with severe hepatic impairment; and

e. dronedarone is contraindicated in pregnant or nursing mothers.

16 . The method according to claim 13 , wherein the physician information sheet or health care professional information sheet comprises at least one message to a healthcare professional selected from the group consisting of:

a. initiate dronedarone in appropriate patients;

i. screen patients for severity and stability of heart failure; dronedarone should not be initiated in patients with NYHA Class IV heart failure or NYHA Class II-III heart failure with recent decompensation requiring hospitalization or referral to a specialized heart failure clinic;

ii. treatment may be initiated in an outpatient or an inpatient setting;

iii. discontinue use of other Class I or Class III antiarrhythmic therapies;

iv. the dosage of certain cardiovascular medications may need to be adjusted and certain laboratory test changes may occur;

b. counsel patients to report changes in their symptoms and their medications;

i. advise patients to consult a physician if they develop signs or symptoms of worsening heart failure such as weight gain, dependent edema, and/or increasing shortness of breath;

ii. advise patients that dronedarone should not be taken with certain other medications and to consult with their physicians before starting any new drugs as the dosage of certain cardiovascular medications may need to be adjusted;

iii. refer patients to the medication guide and address any additional questions;

c. check patients for changes in their symptoms or certain lab tests;

i. observe patients regularly for signs and symptoms of heart failure that may require additional treatment and/or dronedarone discontinuation; and

ii. be aware that within a week, dronedarone causes a small change in serum creatinine that does not reflect a change in underlying renal function.