Cordarone

Package leaflet: Information for the patient

Cordarone 150 mg/3 ml concentrate for solution for infusion

amiodarone hydrochloride
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What Cordarone is and what it is used for
2. What you need to know before taking Cordarone
3. How to take Cordarone
4. Possible side effects
5. How to store Cordarone
6. Contents of the pack and other information

1. What Cordarone is and what it is used for

Cordarone contains the active substance amiodarone hydrochloride, which belongs to a class of medicines called "class III antiarrhythmics" that work by regulating the heartbeat.
Cordarone for intravenous use, i.e. administered into a vein, is used when a rapid response is required or when oral administration is not possible.
Cordarone is indicated for:

• the treatment and prevention of serious heart rhythm disorders when other medicines have not worked: abnormally fast heartbeat, sometimes characterized by sudden stops and starts (paroxysmal and non-paroxysmal supraventricular tachycardias), irregular heartbeat characterized by premature contractions of the heart muscle that disrupt the regular sequence of beats (atrial extrasystoles), irregular and excessively rapid heartbeat (atrial flutter), and irregular and accelerated heartbeat (atrial fibrillation);
• sudden and abrupt changes in heartbeat with increased rate (reciprocating paroxysmal supraventricular tachycardias) in patients affected by conditions such as Wolff-Parkinson-White syndrome, a condition characterized by rapid heartbeat, dizziness, loss of consciousness, easy fatigability, and anxiety.
  Heart rhythm disorders involving extra beats that disrupt the normal heartbeat and may sometimes cause the sensation of having missed a beat at the chest level (ventricular extrasystoles), and disorders characterized by a very rapid heartbeat (ventricular tachycardias).

2. What you should know before taking Cordarone

Do not take Cordarone:

• if you are allergic to amiodarone or iodine, or to any of the other ingredients of this medicine (listed in section 6);
• if you have a slower than normal heart rate (sinus bradycardia), if you suffer from a condition known as sinoatrial block, characterized by delayed formation of heartbeats, or if you have sinus node disease, characterized by irregular heartbeat, and do not have a pacemaker with risk of heart block (sinus arrest);
• if you suffer from severe disorders in heart rhythm generation and do not have a pacemaker (severe atrioventricular blocks, bi- or trifascicular blocks). In this case, injectable Cordarone may be administered in specialized hospital units via a venous catheter reaching the heart (electrostimulating device);
• if you have severe reduction in blood circulation (cardiovascular collapse) or severe drop in blood pressure (severe arterial hypotension);
• if you are taking medicines that can cause heart rhythm abnormalities (torsades de pointes) (see "Other medicines and Cordarone");
• if you currently have or have previously had thyroid function disorders (thyroid dysfunction). In doubtful cases, your doctor will perform a thyroid function test before starting treatment with this medicine;
• if you are pregnant, except in exceptional cases, because this medicine may harm the fetus (see "Pregnancy and breastfeeding");
• if you are breastfeeding, because this medicine passes into breast milk;
• if you have low blood pressure (hypotension) and severe heart problems (cardiomyopathy and heart failure), or if you have severe breathing difficulties, your doctor will not administer Cordarone intravenously, as your condition may worsen.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Cordarone:

• if you have severe heart disorders (cardiomyopathies and severe coronary artery disease) and during treatment develop productive cough (with phlegm), breathing difficulties, fever, or weight loss;
• if you suffer from low blood pressure (hypotension), severe breathing difficulties (severe respiratory insufficiency), or severe heart problems (severe uncompensated heart failure);
• if you are scheduled for surgery under general anesthesia;
• if you have liver problems; your doctor will closely monitor liver function, both at the beginning and during treatment. If severe liver function abnormalities occur, your doctor will discontinue the medicine and initiate appropriate therapy;
• if you have vision problems, particularly reduced blood supply or inflammation of the optic nerve (optic neuropathy and optic neuritis). In such cases, your doctor will discontinue the medicine;
• if you have thyroid problems;
• if you are currently taking a medicine containing sofosbuvir for the treatment of hepatitis C, as this combination may cause a life-threatening slowing of the heart rate. Your doctor may consider alternative treatments. If treatment with amiodarone and sofosbuvir is necessary, additional cardiac monitoring may be required;
• if you are taking other medicines (see section "Other medicines and Cordarone").

Intravenous Cordarone will only be administered in specialized hospital units and under continuous monitoring (electrocardiogram and blood pressure).
To avoid injection site reactions, the medicine will be administered, whenever possible, into a large vein (see also "Possible side effects").
If during Cordarone treatment you develop dry cough, fever, breathing difficulties associated with severe general malaise, your doctor will perform a chest X-ray and other tests to assess your lung function. This is because pulmonary toxicity may occur during Cordarone treatment, which, if not diagnosed promptly, can be life-threatening. If necessary, your doctor may reduce the dose or discontinue the medicine and initiate appropriate therapy. In some cases, lung toxicity may appear weeks after stopping the medicine.
Severe and potentially fatal skin disorders (skin reactions) may occur, due to conditions known as Stevens-Johnson syndrome and toxic epidermal necrolysis (see: Possible side effects), manifesting as progressive skin redness (rash), often accompanied by blisters and sores, which may also affect mucous membranes. In such cases, stop taking amiodarone immediately and contact your doctor without delay.
If new heart rhythm disturbances occur or existing ones worsen, your doctor will determine whether this is due to loss of efficacy of the medicine or worsening of the underlying condition.
Contact your doctor immediately if you are taking a medicine containing sofosbuvir for the treatment of hepatitis C and during treatment you experience:

• slow or irregular heartbeat, or heart rhythm disturbances;
• shortness of breath or worsening of existing shortness of breath;
• chest pain;
• dizziness;
• palpitations;
• near-fainting or fainting.

If you are on a waiting list for a heart transplant, your doctor may modify your treatment. This is because taking amiodarone before a heart transplant has been associated with an increased risk of potentially fatal complications (primary graft dysfunction), in which the transplanted heart fails to function properly within the first 24 hours after surgery.
Children
Cordarone should be administered with caution in children up to 3 years of age, as the intravenous formulation contains benzyl alcohol, and is not recommended even in older children (see also "Cordarone contains benzyl alcohol").
Other medicines and Cordarone
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The combination of Cordarone with the following medicines is contraindicated:

• medicines that may cause a specific type of heart rhythm disturbance (torsades de pointes), such as medicines used to prevent and control heart rhythm disorders (Class IA antiarrhythmics, sotalol, bepridil), vincamine (an antibiotic), medicines for mental illnesses (e.g. sultopride), cisapride (a medicine used to treat gastroesophageal reflux), intravenous erythromycin (an antibiotic), intravenous pentamidine (used for certain types of pneumonia);
• antibiotics known as fluoroquinolones.

The combination of Cordarone with the following medicines is not recommended:

• medicines that slow the heart rate (beta-blockers and calcium channel blockers) such as verapamil and diltiazem;
• medicines that may cause low blood potassium levels (hypokalemia), such as stimulant laxatives (medicines that increase intestinal motility and evacuation);
• sofosbuvir, a medicine used in combination with others for the treatment of chronic hepatitis C.

The combination of Cordarone with the following medicines requires caution:

• medicines that may cause a specific type of heart rhythm disturbance known as QT prolongation;
• medicines that promote urine production (diuretics), alone or in combination;
• medicines for controlling inflammation and allergies (systemic glucocorticoids and mineralocorticoids);
• tetracosactide, used to investigate certain hormonal disorders;
• intravenous amphotericin B, used to treat fungal infections.

The effects of Cordarone may be influenced by, or may influence, the following medicines:

• general anesthesia and high doses of oxygen during surgery;
• digoxin, used to increase the force of heart contraction;
• dabigatran and warfarin, anticoagulants used to thin the blood;
• phenytoin, a medicine used to treat epilepsy;
• flecainide, a medicine used to control irregular heartbeat;
• statins, used to lower blood cholesterol levels, such as simvastatin, atorvastatin, and lovastatin; their combination increases the risk of muscle disorders (e.g. rhabdomyolysis). Your doctor will prescribe the appropriate statin to be taken with amiodarone;
• cyclosporine, tacrolimus, and sirolimus, used to suppress the immune system and help prevent transplant rejection;
• fentanyl and ergotamine, medicines used to control pain;
• lidocaine, used as an anesthetic;
• sildenafil, used to treat erectile dysfunction;
• midazolam and triazolam, used to treat anxiety or help relaxation;
• dihydroergotamine, used to treat certain types of headache (migraine);
• colchicine, used to treat joint inflammation causing pain and swelling (gout).

Cordarone with food and drinks
Do not drink grapefruit juice while taking this medicine, as it may increase the likelihood of side effects.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not take Cordarone during pregnancy unless your doctor considers it necessary, as it may harm the fetus.
Breastfeeding
Do not take Cordarone if you are breastfeeding. Cordarone passes into breast milk and may harm your baby.
Driving and using machines
Not applicable.
Cordarone contains benzyl alcohol
This medicine contains 60 mg of benzyl alcohol per 3 ml vial.
Benzyl alcohol may cause allergic reactions.
Benzyl alcohol has been associated with a risk of serious adverse reactions, including breathing problems ("gasping syndrome"), in young children.
This medicine must not be administered to neonates up to 4 weeks of age unless otherwise recommended by a doctor.
This medicine should not be used for more than one week in young children (under 3 years of age) unless otherwise recommended by a doctor or pharmacist.
Consult your doctor or pharmacist if you are pregnant or breastfeeding. This is because large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (such as metabolic acidosis).
Consult your doctor or pharmacist if you have liver or kidney disease. This is because large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (such as metabolic acidosis).

3. How to take Cordarone

Your doctor will determine the route of administration, the initial dose, and the maintenance dose based on the severity of your condition and your response to treatment.
The medicine will be administered to you by slow intravenous injection or infusion by medical or nursing staff.
Concomitant therapy with statins
If you are taking statins during Cordarone treatment to reduce cholesterol levels in the blood, your doctor will prescribe a specific statin (see also “Other medicines and Cordarone”).
Use in children
The use of Cordarone is not recommended in children.
Medicinal products administered intravenously containing benzyl alcohol must be administered with caution in children up to 3 years of age (see also “Cordarone contains benzyl alcohol”).
If you take more Cordarone than you should
There are no available data regarding overdose with Cordarone. Possible adverse effects due to an overdose of this medicine include: slowed heartbeat (sinus bradycardia), cessation of heartbeat (cardiac arrest), rapid heartbeat (ventricular tachycardia), disturbances in heart rhythm (torsades de pointes), circulatory problems (circulatory failure), and liver damage (hepatic injury).
If you forget to take Cordarone
Do not take a double dose to make up for the missed dose.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur, according to the following frequency:

Common (may affect up to 1 in 10 people):

• Slow heart rate (bradycardia). This effect is generally mild;
• Reactions at the injection site such as pain, skin redness (erythema), fluid accumulation (edema), localized tissue damage (necrosis), leakage of medicine from the blood vessel (extravasation), accumulation of fluid in the skin and tissues (infiltration), inflammation, hardening of the areas where the medicine was injected, inflammation of blood vessels with or without formation of blood clots (thrombophlebitis and phlebitis), inflammation of the tissues beneath the skin (cellulitis), infection, skin discoloration (pigmentation changes);
• Reduction in blood pressure, usually mild and transient. After an excessive dose (overdose) or too rapid injection, severe reduction in blood pressure (hypotension) and sudden drop in blood pressure, rapid heartbeat, paleness, and bluish discoloration of the skin and mucous membranes (collapse) may occur;
• Itching, red-colored skin rash (eczema);
• Decreased sexual desire.

Very rare (may affect up to 1 in 10,000 people):

• Severe slowing of the heart rate (marked bradycardia) which may require discontinuation of treatment, especially in patients with heart rhythm disorders and in elderly patients;
• Onset or worsening of heart rhythm disturbances, up to complete heart block (see also “Warnings and precautions”);
• Nausea;
• Mild abnormalities in specific liver function tests (transaminases), which return to normal with dose reduction or without any specific intervention;
• Liver disorders (hepatopathy) with abnormalities in liver function tests and yellowing of the skin and whites of the eyes (jaundice). These disorders can be severe (liver failure) and sometimes life-threatening, and require discontinuation of therapy;
• Severe allergic reaction (anaphylactic shock);
• Increased pressure inside the head (benign intracranial hypertension, pseudotumor cerebri);
• Headache;
• Lung inflammation with cough and difficulty breathing (interstitial pneumonia), which resolves upon discontinuation of therapy;
• Severe lung disease characterized by scarring of the tissue lining the lungs, cough, difficulty breathing, weight loss, and fatigue, sometimes life-threatening (pulmonary fibrosis);
• Severe lung disease in which the lungs are unable to function properly (acute respiratory distress syndrome in adults), sometimes life-threatening;
• Bronchial narrowing and worsening of breathing difficulties (bronchospasm) in patients with respiratory difficulties (severe respiratory insufficiency), and especially in patients with asthma;
• Sweating and hot flushes;
• Excessive secretion of antidiuretic hormone (syndrome of inappropriate antidiuretic hormone secretion, SIADH), with fluid retention in the body.

Frequency not known (frequency cannot be estimated from the available data):

• Heart rhythm abnormalities (torsade de pointes) (see “Other medicines and Cordarone”);
• Thyroid disorders (hyperthyroidism);
• Swelling of the face, hands and feet, lips, tongue, or throat (Quincke’s edema);
• Back pain;
• Sudden inflammation of the pancreas (pancreatitis (acute));
• Confusion (delirium);
• Itching (urticaria), life-threatening skin reactions characterized by rashes, blisters, skin peeling, and pain (toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), bullous dermatitis, drug reaction with eosinophilia and systemic symptoms (DRESS));
• Reduced blood flow and inflammation of the optic nerve (optic neuropathy and optic neuritis), leading to vision loss (see “Warnings and precautions”);
• Potentially fatal complication after heart transplantation (primary graft dysfunction), in which the transplanted heart fails to function properly (see section 2, Warnings and precautions);
• Seeing, hearing, or perceiving things that are not there (hallucinations);
• You may get more infections than usual. This could be due to a decrease in the number of white blood cells (neutropenia);
• Severe reduction in the number of white blood cells, increasing the risk of infections (agranulocytosis).

Lung toxicity, sometimes life-threatening, may occur in approximately 10% of patients: lung inflammation (pneumonitis) characterized by fever, cough, chest pain, and difficulty breathing; severe lung disease with scarring of lung tissue, cough, difficulty breathing, weight loss, and fatigue (pulmonary fibrosis); inflammation of the membrane covering the outer part of the lungs (pleuritis); inflammatory lung disease with symptoms such as fever, cough, general malaise, weight loss, and difficulty breathing (bronchiolitis obliterans with organizing pneumonia). Your doctor may discontinue the treatment and initiate appropriate therapy.

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at the website
http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cordarone

Keep this medicine out of the sight and reach of children.
Do not store above 25°C.
Do not use this medicine after the expiry date stated on the carton and blister after Exp. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Cordarone contains
The active substance is amiodarone hydrochloride. Each vial of Cordarone contains 150 mg of amiodarone hydrochloride.
The other components are: benzyl alcohol, polysorbate and water for injections.

Description of the appearance of Cordarone and contents of the pack
Cordarone is a solution for injection.

• Box containing 5 vials of 150 mg/3 ml
• Box containing 6 vials of 150 mg/3 ml

Marketing Authorization Holder
Sanofi S.r.l. - Viale L. Bodio, 37/B – Milan
Manufacturer
SANOFI WINTHROP INDUSTRIE - 1, rue de la Vierge - Ambarès & Lagrave F - 33565 Carbon Blanc Cedex - France
Delpharm Dijon – 6 Boulevard de L’Europe – 21800 Quétigny – France

The following information is intended exclusively for doctors or healthcare professionals

DOSAGE, METHOD AND DURATION OF ADMINISTRATION
Due to its pharmaceutical characteristics, concentrations lower than 600 mg/l must not be used. Use only 5% isotonic dextrose solution (glucose solution). Do not add any other product to the infusion solution.
Intravenous infusion:

• Loading dose: the average dosage is 5 mg/kg administered exclusively in 250 ml of 5% dextrose solution (glucose solution), infused over a period of 20 minutes to 2 hours; this dose may be repeated 2 to 3 times within 24 hours. The infusion rate should be adjusted according to clinical response.
  The therapeutic effect appears within the first few minutes and then progressively decreases; therefore, a subsequent infusion should be administered.

• Maintenance dose: 10 to 20 mg/kg over 24 hours (generally 600–800 mg/24 hours, up to 1200 mg/24 hours) in 250 ml of 5% dextrose solution (glucose solution) for a few days. Switch to oral administration from the first day of infusion.

Intravenous injection
(see also “Special warnings”)
The dosage is 5 mg/kg; the injection must last no less than 3 minutes. Do not add any other product to the syringe.
Paediatric population
The safety and efficacy of amiodarone in children have not been established.
Due to the presence of benzyl alcohol in the formulation, intravenous administration of amiodarone must be used with caution in children up to 3 years of age.
PRECAUTIONS FOR USE
Intravenous administration of amiodarone must be performed only in specialized hospital units and under continuous monitoring (ECG, blood pressure).
To avoid injection site reactions, amiodarone should be administered, whenever possible, through a central venous line.
Use with caution in cases of hypotension, severe respiratory failure, and severe uncompensated heart failure.
Anaesthesia. Prior to surgery, the anaesthetist must be informed that the patient is being treated with amiodarone.
SPECIAL WARNINGS

• Intravenous injection is generally not recommended due to haemodynamic risks (severe hypotension, cardiocirculatory collapse); therefore, intravenous infusion is preferred whenever possible.
• Intravenous injection should be reserved for emergency situations and when alternative therapies have failed, and must be used only in cardiac intensive care units under continuous monitoring (ECG, blood pressure).
• The dosage is approximately 5 mg/kg body weight, administered over no less than 3 minutes. Intravenous injection must not be repeated within 15 minutes after the first injection, even if the initial dose consisted of only one vial (risk of irreversible collapse).
• Do not add any other product to the same syringe. Do not inject other products through the same line. If treatment needs to continue, intravenous infusion should be used.
• The product is incompatible with aminophylline, heparin, and sodium chloride solutions.
• The use of medical equipment and devices containing plasticizing substances such as DEHP (di-2-ethylhexyl phthalate) may result in their release in the presence of amiodarone. To minimize patient exposure to DEHP, the final diluted amiodarone solution for infusion should preferably be administered using DEHP-free materials.

Patient information leaflet: information for the patient

Cordarone 200 mg tablets

amiodarone hydrochloride
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, because it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Cordarone is and what it is used for
2. What you need to know before taking Cordarone
3. How to take Cordarone
4. Possible side effects
5. How to store Cordarone
6. Contents of the pack and other information

1. What Cordarone is and what it is used for

Cordarone contains the active substance amiodarone hydrochloride, which belongs to a class of medicines called "class III antiarrhythmics" that work by regulating the heartbeat.
Cordarone is indicated for:

• the treatment and prevention of serious heart rhythm disorders when other medicines have not worked: excessive increase in heart rate, sometimes characterized by sudden stops and starts (paroxysmal and non-paroxysmal supraventricular tachycardias), alteration of the heartbeat characterized by premature contraction of the heart muscle disrupting the regular sequence of beats (atrial extrasystoles), alteration of the heartbeat becoming irregular and excessively rapid (atrial flutter), and alteration of the heartbeat characterized by irregular and accelerated rhythm (atrial fibrillation);

• sudden and abrupt changes in heartbeat with increased frequency (reciprocating paroxysmal supraventricular tachycardias) in patients affected by conditions such as Wolff-Parkinson-White Syndrome, a disorder characterized by rapid heartbeat, dizziness, loss of consciousness, easy fatigue, and anxiety. Heart rhythm disturbances in which extra beats disrupt the normal heartbeat and may sometimes cause a sensation of having missed a beat in the chest area (ventricular extrasystoles), and alterations of the heartbeat characterized by a very rapid heartbeat (ventricular tachycardias);

• the preventive treatment of angina pectoris attacks, a heart disease caused by reduced blood flow to the heart, mainly manifested by chest pain.

2. What you need to know before taking Cordarone

Do not take Cordarone

• if you are allergic to amiodarone or iodine, or to any of the other ingredients of this medicine (listed in section 6);
• if you have a slower than normal heart rate (sinus bradycardia) or a condition known as sinoatrial block, characterized by delayed formation of heartbeats;
• if you suffer from severe disorders in the formation of heartbeats and do not have a pacemaker (severe atrioventricular blocks, bi- or trifascicular blocks);
• if you suffer from a condition affecting heart rhythm and do not have a pacemaker, with risk of abnormal heartbeats (sinus arrest);
• if you are taking medicines that can cause heart rhythm abnormalities (torsades de pointes) (see "Other medicines and Cordarone");
• if you currently have or have previously had thyroid disorders (thyroid dysfunction). In doubtful cases (uncertain previous history, family history of thyroid disorders), your doctor will perform a thyroid function test before starting treatment with this medicine;
• if you are pregnant, except in exceptional cases where your doctor prescribes it (see "Pregnancy and breastfeeding"); if you are breastfeeding (see "Pregnancy and breastfeeding").

Warnings and precautions
Talk to your doctor or pharmacist before taking Cordarone:

• if you have a pacemaker or an implanted cardioverter defibrillator. In such cases, your doctor will check that the device is functioning properly before and during treatment;

• if you are elderly. Your doctor will monitor you more closely;

• if you have severe heart problems (cardiomyopathies and severe coronary artery disease) and during treatment develop productive cough (with sputum), difficulty breathing, fever, or weight loss;

• if you are scheduled for surgery under general anesthesia;

• if you have liver problems; your doctor will perform careful monitoring of liver function, both at the start of therapy and during treatment. In case of severe liver function abnormalities, your doctor will discontinue the medicine and initiate appropriate therapy;

• if you have vision problems, particularly reduced blood supply or inflammation of the optic nerve (optic neuropathy and optic neuritis). In this case, your doctor will discontinue the medicine;

• if you have muscle problems;

• if you have thyroid problems;

• if you are currently taking a medicine containing sofosbuvir for the treatment of hepatitis C, as this combination may cause a life-threatening slowing of the heart rate. Your doctor may consider alternative treatments. If treatment with amiodarone and sofosbuvir is necessary, additional cardiac monitoring may be required;

• if you are taking other medicines (see "Other medicines and Cordarone").

Cordarone will only be administered after your doctor has carefully evaluated your health status. Your doctor will closely monitor you during treatment.
Before starting treatment with Cordarone, your doctor will perform an electrocardiogram (ECG), a test that analyzes heart activity, and check your blood potassium levels. During treatment with this medicine, you will undergo periodic blood tests for liver function (transaminases) and ECGs.
Since the risk of adverse effects (see "Possible side effects") increases with higher doses (dose-dependent), your doctor will prescribe the lowest effective dose to control your heart rhythm. If your heart rhythm disturbances worsen or new ones appear, your doctor will determine whether this is due to loss of effectiveness of the medicine or progression of the underlying disease.
Contact your doctor immediately if you are taking a medicine containing sofosbuvir for the treatment of hepatitis C and experience any of the following during treatment:

• slow or irregular heartbeat, or heart rhythm disturbances;
• shortness of breath or worsening of existing shortness of breath;
• chest pain;
• dizziness;
• palpitations;
• near-fainting or fainting.

If you are on a waiting list for a heart transplant, your doctor may modify your treatment. This is because taking amiodarone before heart transplantation has been associated with an increased risk of potentially fatal complications (primary graft dysfunction), in which the transplanted heart fails to function properly within the first 24 hours after surgery.
During treatment with Cordarone, or even long after stopping treatment, you may develop increased thyroid function with symptoms such as weight loss, heart rhythm disturbances, and chest pain. Your doctor will perform careful monitoring and, if necessary, discontinue the medicine.
Cordarone may cause serious muscle problems (sensory-motor peripheral neuropathy and myopathy). In such cases, your doctor will discontinue the medicine.
Skin disorders (skin reactions), including severe and potentially fatal conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis (see: Possible side effects), may occur. These are characterized by progressive skin redness (rash), often accompanied by blisters and sores, which may also affect mucous membranes. In such cases, stop taking amiodarone and contact your doctor immediately.
If during treatment with Cordarone you develop a dry cough, fever, difficulty breathing associated with severe general malaise, your doctor will perform a chest X-ray and other tests to evaluate your lung function. This is because pulmonary toxicity may occur during treatment with Cordarone, which, if not diagnosed promptly, can be life-threatening. If necessary, your doctor may reduce the dose or discontinue the medicine and initiate appropriate therapy.
Avoid exposure to sunlight and use protective measures (apply a high-protection sunscreen, wear a hat, and wear clothing covering arms and legs) during treatment with this medicine (see "Possible side effects").
Children
The use of Cordarone is not recommended in children.
Other medicines and Cordarone
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The combination of Cordarone with the following medicines is contraindicated:

• medicines that may cause a specific type of heart rhythm disturbance (torsades de pointes), such as medicines used to prevent and control heart rhythm disorders (Class IA antiarrhythmics, sotalol, bepridil), vincamine (an antibiotic), medicines for mental illnesses (e.g., sultopride), cisapride (a medicine used to treat gastroesophageal reflux, i.e., stomach contents rising into the esophagus), intravenous erythromycin (an antibiotic), intravenous pentamidine (used for certain types of pneumonia);
• antibiotics known as fluoroquinolones;
• medicines used to treat depression (MAO inhibitors).

The combination of Cordarone with the following medicines is not recommended:

• medicines that slow the heart rate (beta-blockers and calcium antagonists) such as verapamil and diltiazem;
• medicines that may cause low blood potassium levels (hypokalemia), such as stimulant laxatives (medicines that increase intestinal motility and evacuation);
• sofosbuvir, a medicine used in combination with others for the treatment of chronic hepatitis C.

Combining Cordarone with the following medicines requires caution:

• medicines that may cause a specific heart rhythm alteration known as QT prolongation;
• medicines that promote urine production (diuretics), alone or in combination;
• medicines used to control inflammation and allergies (systemic glucocorticoids and mineralocorticoids);
• tetracosactide, used to investigate certain hormonal disorders;
• intravenous amphotericin B, used to treat fungal infections.

The effects of Cordarone may be influenced by, or may influence, the following medicines:

• general anesthesia and high doses of oxygen during surgery;
• digoxin, used to increase the strength of heart contractions;
• dabigatran and warfarin, anticoagulants used to thin the blood;
• phenytoin, a medicine used to treat epilepsy;
• flecainide, a medicine used to control heart rhythm;
• statins, used to reduce blood cholesterol levels, such as simvastatin, atorvastatin, and lovastatin; their combination increases the risk of muscle disorders (e.g., rhabdomyolysis). Your doctor will prescribe the appropriate statin to take with amiodarone;
• cyclosporine, tacrolimus, and sirolimus, used to suppress the immune system and help prevent transplant rejection;
• fentanyl and ergotamine, medicines used to control pain;
• lidocaine, used as an anesthetic;
• sildenafil, used to treat erectile dysfunction;
• midazolam and triazolam, used to treat anxiety or help relaxation;
• dihydroergotamine, used to treat certain types of headache (migraine);
• colchicine, used to treat joint inflammation causing pain and swelling (gout).

Cordarone with food and drinks
Do not drink grapefruit juice while taking this medicine, as it may increase the likelihood of side effects.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not take Cordarone during pregnancy unless your doctor considers it necessary, as it may harm the fetus.
Breastfeeding
Do not take Cordarone if you are breastfeeding. Cordarone passes into breast milk and may harm your baby.
Driving and using machines
Cordarone does not impair your ability to drive or operate machinery.
Cordarone contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take Cordarone

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Your doctor will determine the route of administration, the initial dose, and the maintenance dose based on the severity of your condition and your response to treatment.
The recommended doses are:
For the treatment of heart rhythm disorders
The initial dose is 600 mg (3 tablets) daily for at least two weeks. Afterwards, your doctor will reduce the dose until establishing a maintenance dose of 100–400 mg daily (½ to 2 tablets) or until establishing an intermittent therapy (e.g., taking Cordarone for 2 or 3 weeks per month or for 5 days per week).
For preventive treatment of episodes of heart pain
Initial dose: 600 mg (3 tablets) daily for approximately 7 days.
Maintenance dose: 100–400 mg daily (½ to 2 tablets daily) or intermittent therapy (5 days per week or 2 or 3 weeks per month).
Concomitant therapy with statins
If you are taking statins during Cordarone treatment to reduce cholesterol levels in the blood, your doctor will prescribe a specific statin (see also “Other medicines and Cordarone”).
Use in children
The use of Cordarone is not recommended in children.
If you take more Cordarone than you should
There is no available data regarding overdose with Cordarone. Possible adverse effects due to overdose may include: slowed heartbeat (sinus bradycardia), cardiac arrest (cardiac arrest), rapid heartbeat (ventricular tachycardia), heart rhythm abnormalities (torsades de pointes), circulatory disturbances (circulatory failure), and liver damage (hepatic damage).
In case of accidental ingestion/overdose of Cordarone, contact your doctor immediately or go to the nearest hospital.
If you forget to take Cordarone
Do not take a double dose to make up for the forgotten tablet.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur with the following frequency:
Very common (may affect more than 1 in 10 people):

• Vision disorders such as blurred vision or seeing coloured halos around lights due to small deposits of fat in the eye; this side effect resolves upon discontinuation of treatment;
• Allergic reactions to light (photosensitisation). See also “Warnings and precautions”;
• At the beginning of therapy, changes in specific blood tests used to monitor liver function (increase in transaminases) may occur. These test results usually return to normal with dose reduction or spontaneously, i.e. without any specific intervention;
• Nausea, vomiting and altered sense of taste (dysgeusia), which generally resolve with dose reduction.

Common (may affect up to 1 in 10 people):

• Slow heart rate (bradycardia); this side effect is generally mild and caused by increasing the dose;
• Grey or bluish skin discoloration, particularly after prolonged treatment or with high daily doses. These side effects resolve upon discontinuation of treatment;
• Thyroid disorders (hypothyroidism and hyperthyroidism), sometimes life-threatening;
• Liver disorders with abnormal liver function tests and yellowing of the skin and whites of the eyes (jaundice). These disorders can be serious (liver failure) and sometimes life-threatening;
• Sleep disturbances and nightmares;
• Hand tremor;
• Constipation (stipsis);
• Itching, red skin rash (eczema);
• Pulmonary toxicity: lung inflammation (pneumonitis) characterised by fever, cough, chest pain and difficulty breathing; serious lung disease characterised by scarring of the tissue lining the lungs, cough, difficulty breathing, weight loss and fatigue (pulmonary fibrosis); inflammation of the membrane covering the outer surface of the lungs (pleuritis); inflammatory lung disease with symptoms such as fever, cough, general malaise, loss of appetite, weight loss and difficulty breathing (bronchiolitis obliterans with organising pneumonia);
• Decreased sexual desire.

Uncommon (may affect up to 1 in 100 people):

• Severe heart rhythm disorders (sinoatrial block, A-V block of various degrees) (see also “Warnings and precautions”);
• Onset or worsening of heart rhythm disorders, up to cardiac arrest (see also “Warnings and precautions” and “Other medicines and Cordarone”);
• Deterioration or malfunction of peripheral nerves, manifesting as: tingling, prickling sensations, reduced ability to feel pain, and numbness in hands and feet (sensory-motor peripheral neuropathy) and/or muscle disorders with symptoms such as loss of strength, fatigue, pain, cramps and muscle stiffness (myopathy), which generally resolve upon discontinuation of the medicine (“Warnings and precautions”);
• Dry mouth.

Very rare (may affect up to 1 in 10,000 people):

• Breakdown of red blood cells (haemolytic anaemia);
• Reduced ability of the bone marrow to produce red blood cells (aplastic anaemia);
• Reduced number of blood platelets (thrombocytopenia);
• Severe slowing of the heart rate, especially in elderly patients (bradycardia);
• Reduced blood flow and inflammation of the optic nerve (optic neuropathy and optic neuritis), up to vision loss (see “Warnings and precautions”);
• Redness and irritation of the skin following radiotherapy;
• Skin irritations;
• Skin inflammation with peeling (exfoliative dermatitis);
• Hair loss (alopecia);
• Prolonged liver disorders (chronic hepatopathies such as pseudo-alcoholic hepatitis and cirrhosis), sometimes life-threatening;
• Constriction of the bronchi and worsening of breathing difficulties (bronchospasm) in patients with breathing difficulties (severe respiratory failure) and particularly in patients with asthma or severe lung disease where the lungs are unable to function properly (acute respiratory distress syndrome in adults), sometimes life-threatening, usually observed shortly after surgery (possible interaction with high oxygen concentration) (see “Warnings and precautions”);
• Increased blood creatinine levels (a blood test);
• Brain disorders such as loss of balance, tremor, difficulty controlling limb and eye movements, difficulty speaking and writing (cerebellar ataxia);
• Increased pressure inside the skull (benign intracranial hypertension, pseudotumour cerebri);
• Headache;
• Inflammation of the epididymis, the tube located behind the testicles that stores and transports sperm (epididymitis);
• Inability of a male to achieve and/or maintain an erection sufficient for satisfactory sexual intercourse (impotence);
• Inflammation of blood vessels (vasculitis);
• Excessive secretion of antidiuretic hormone (syndrome of inappropriate antidiuretic hormone secretion, SIADH), with fluid retention in the body.

Frequency not known (frequency cannot be estimated from the available data):

• Bone marrow abnormalities (granulomas);
• Heart rhythm abnormalities (torsades de pointes) (see also “Other medicines and Cordarone”);
• Liver abnormalities (granulomas);
• Severe bleeding in the lungs (pulmonary haemorrhage);
• Swelling of the face, hands and feet, lips, tongue or throat (Quincke’s oedema);
• Itching (urticaria), life-threatening skin reactions characterised by rashes, blisters, skin peeling and pain (toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), bullous dermatitis, drug reaction with eosinophilia and systemic symptoms (DRESS));
• Severe allergic reaction (anaphylactic reaction/shock);
• Decreased appetite;
• Sudden inflammation of the pancreas (pancreatitis (acute));
• Unusual muscle movements, stiffness, restlessness and agitation (parkinsonism);
• Altered sense of smell (parosmia);
• Confusion (delirium);
• Lupus-like syndrome (a disease in which the immune system attacks various parts of the body, causing pain, stiffness and swelling of the joints and redness of the skin, sometimes in a butterfly-shaped rash on the face);
• Potentially fatal complication after heart transplant (primary graft dysfunction), in which the transplanted heart fails to function properly (see section 2, Warnings and precautions);
• Seeing, hearing or sensing things that are not there (hallucinations);
• You may get more infections than usual. This could be due to a decrease in the number of white blood cells (neutropenia);
• Severe reduction in the number of white blood cells, increasing the likelihood of infections (agranulocytosis).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the website
http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cordarone

Keep this medicine out of the sight and reach of children.
This medicine requires no special storage conditions.
Do not use this medicine after the expiry date stated on the carton and blister pack after "Exp". The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Cordarone contains
The active substance is amiodarone hydrochloride. 1 tablet of Cordarone contains 200 mg of
amiodarone hydrochloride.
The other components are: monohydrate lactose, maize starch, povidone, anhydrous colloidal silicon dioxide, magnesium stearate.
Description of the appearance of Cordarone and contents of the pack
Cordarone is available in tablet form.

• Box containing 2 blisters of 10 tablets of 200 mg each
• Box containing 1 blister of 20 tablets of 200 mg.

Marketing Authorization Holder
Sanofi S.r.l. - Viale L. Bodio, 37/B – Milan
Manufacturer
SANOFI WINTHROP Industrie, 1-rue de la Vierge - Ambares (France)
SANOFI-AVENTIS S.A. – Riells Y Viabrea – Girona (Spain)
Opella Healthcare Hungary Limited Liability Company (Opella Healthcare Hungary Ltd.) - Lévai
u.5 2112 Veresegyház (Hungary)
Sanofi S.r.l. - S.S. n. 17, km. 22 – 67019 Scoppito (AQ)