Cordarone

Package Leaflet: Information for the Patient

Cordarone

200 mg, tablets
Amiodarone hydrochloride
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Read the package leaflet carefully before taking the medicine, as it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

• 1. What Cordarone is and what it is used for
• 2. Important information 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 is available in tablet form and contains the active substance amiodarone hydrochloride. Amiodarone is a powerful anti-arrhythmic medication used to treat irregular heartbeat.

It is used to treat life-threatening heart rhythm disorders:

• arrhythmias in Wolff-Parkinson-White syndrome;
• atrial fibrillation and atrial flutter, paroxysmal supraventricular tachycardias: supraventricular tachycardias and nodal tachycardias, when other medications cannot be used;
• ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation), when other anti-arrhythmic medications are ineffective.

2. Important information before taking Cordarone

When not to take Cordarone:

• if you are allergic to iodine, amiodarone, or any of the other ingredients of this medicine (listed in section 6); In case of allergic symptoms such as itching rash, difficulty swallowing and breathing or swelling of the lips, face, throat, and tongue, you should contact your doctor immediately;
• in patients with heart disease: sinus bradycardia, sinoatrial block, sick sinus syndrome, unless they have a pacemaker;
• in patients with atrioventricular block of second or third degree, unless they have a pacemaker;
• with medications that can cause life-threatening heart rhythm disorders - type torsade de pointes(see: Cordarone and other medications);
• if you have thyroid disease;
• if you are pregnant or breastfeeding.

Warnings and precautions

Before starting treatment with amiodarone, it is recommended to perform ECG, TSH hormone level, and potassium level in serum (decreased potassium levels in the blood increase the risk of heart rhythm disorders).
The pharmacological action of amiodarone causes changes in the ECG: prolongation of the QT interval (related to the prolongation of the repolarization period) with possible formation of a U wave.
However, these changes do not cause toxic effects.
Heart function may decrease significantly in elderly patients.
In case of second or third degree atrioventricular block, sinoatrial block, or bifascicular block, treatment with Cordarone should be discontinued.
Cordarone has a pro-arrhythmic effect. There have been reports of new types of heart rhythm disorders or worsening of treated heart rhythm disorders, sometimes leading to death. Pro-arrhythmic effects of amiodarone occur especially as a result of interactions with medications that prolong the QT interval and (or) in case of electrolyte disorders (see subsection Cordarone and other medications and section 4). Regardless of the prolongation of the QT interval, Cordarone has low activity causing heart rhythm disorders of the torsade de pointestype.
Amiodarone may affect the effectiveness of pacemaker or implantable cardioverter-defibrillator function, especially with long-term use of anti-arrhythmic medications.
It is recommended to monitor its function before and during treatment with amiodarone.
Cordarone taken orally is not contraindicated in patients with heart failure, but caution should be exercised during treatment, as it may worsen it. In such cases, Cordarone may be used in combination with other medications.
Before starting to take Cordarone, you should discuss it with your doctor or pharmacist if you are currently taking a medication containing sofosbuvir, used to treat hepatitis C virus infection, as it may cause life-threatening slowing of heart rate. The doctor may consider alternative treatment methods. If treatment with amiodarone and sofosbuvir is necessary, additional monitoring of heart rate may be required.
You should immediately inform your doctorif you are taking a medication containing sofosbuvir, used to treat hepatitis C virus infection, and if the following symptoms occur during treatment:

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

Cordarone may cause hypothyroidism or hyperthyroidism, especially in patients with a history of thyroid disorders.
Clinical and biological (including TSH) monitoring is recommended before starting treatment in all patients. Monitoring should be performed during treatment, every 6 months, and for several months after treatment is completed. This is especially important in elderly patients.
In patients with a history of increased risk of thyroid disorders, regular monitoring of thyroid function is recommended.
During treatment or up to several months after completion of treatment with amiodarone, hyperthyroidism may occur. Clinical symptoms, usually mild, such as weight loss, heart rhythm disorders, shortness of breath, congestive heart failure, should alert the doctor. The diagnosis is based on a significant decrease in TSH hormone activity in serum.
Then, Cordarone should be discontinued. The disappearance of symptoms usually occurs after several months after stopping treatment with Cordarone; clinical improvement is preceded by normal laboratory test results of thyroid function. Severe cases of hyperthyroidism, sometimes leading to death, require immediate therapeutic intervention. Treatment should be individualized for each patient: anti-thyroid medications (which are not always effective), corticosteroids, beta-adrenergic blockers.
The occurrence of shortness of breath and non-productive cough may be related to toxic effects on the lungs, such as the occurrence of interstitial pneumonia. In patients who have developed shortness of breath, both as the only symptom and in relation to worsening of the patient's general condition (fatigue, weight loss, fever), a radiological examination of the chest should be performed. Further treatment with Cordarone should be considered, as interstitial pneumonia is usually reversible if therapy is discontinued quickly (clinical symptoms usually resolve within 3 to 4 weeks, radiological changes and improvement of lung function occur within several months). The use of corticosteroids should be considered.
Periodic monitoring of liver function (determination of aminotransferase activity) is recommended during treatment with Cordarone. The dosage of Cordarone should be reduced or treatment discontinued in case of a threefold increase in aminotransferase activity above normal values, which may indicate the occurrence of acute or chronic liver function disorders.
Clinical symptoms of chronic liver function disorders may be mild (possible liver enlargement, increased aminotransferase activity 1.5 to 5 times above normal values). These abnormalities usually resolve after discontinuation of Cordarone; however, there have been reports of deaths.
Treatment with Cordarone should be discontinued immediately if severe skin reactions occur (e.g., progressive rash with blisters or changes on mucous membranes, fever, and joint pain, severe rapidly progressing disease characterized by large subcutaneous blisters, extensive skin erosions, and fever - see also section 4). These symptoms can be life-threatening for the patient.
Cordarone may cause sensory-motor peripheral neuropathy and (or) myopathy. The disappearance of symptoms usually occurs within several months after discontinuation of Cordarone, but sometimes some symptoms may persist.
In case of blurred vision or worsening of vision, a complete ophthalmological examination, including a fundus examination, should be performed immediately. Detection of optic nerve damage and (or) inflammation requires discontinuation of Cordarone due to the risk of vision loss.
Concomitant use of amiodarone with the following medications is not recommended: beta-adrenergic blockers, calcium channel antagonists that slow heart rate (verapamil, diltiazem), laxatives that can cause hypokalemia.

• beta-adrenergic blockers, calcium channel antagonists that slow heart rate (verapamil, diltiazem), laxatives that can cause hypokalemia;

Caution should be exercised when using the following medications concomitantly with Cordarone:

• diuretics, e.g., furosemide,
• systemic corticosteroids, e.g., hydrocortisone, prednisolone,
• tetracosactide - a medication used to test certain hormonal disorders,
• amphotericin B - an antifungal medication administered intravenously,
• anesthetics used in general anesthesia or high concentrations of oxygen administered during surgical procedures (see Warnings and precautions in section 2 and section 4). Before surgery, you should inform the anesthesiologist about the use of Cordarone;
• phenytoin - used to treat epileptic seizures: close monitoring of the patient is required, and the dose of phenytoin should be reduced and its serum concentration determined in case of symptoms of overdose;
• digoxin - used to treat heart conditions: the doctor will order determination of digoxin serum concentration and ECG, and adjust the dose of digoxin; the patient should be monitored for signs of digoxin toxicity;
• anticoagulant medications - warfarin, dabigatran: regular monitoring of blood coagulation is required to adjust the oral doses of anticoagulant medications, both during and after treatment with Cordarone; dose adjustment of dabigatran may be necessary;
• medications to prevent transplant rejection - cyclosporine, tacrolimus, and sirolimus;
• flecainide - used to treat arrhythmias: treatment will be carried out under close medical supervision; the doctor will adjust the dose of flecainide;
• fentanyl - a strong pain medication;
• lidocaine - an anesthetic;
• sildenafil - used to treat impotence;
• midazolam - used to treat anxiety and for sedation before surgical procedures;
• triazolam - used to treat insomnia;
• dihydroergotamine and ergotamine - medications used to treat migraines;
• colchicine - used to treat acute gout attacks.

Pregnancy, breastfeeding, and fertility

In pregnancy, during breastfeeding, or if you are planning to become pregnant, you should consult your doctor before taking this medication.
Due to the effect of Cordarone on the fetal thyroid, the use of this medication during pregnancy is contraindicated, unless the doctor recommends otherwise. Before taking the medication, you should consult your doctor.
The use of Cordarone during breastfeeding is contraindicated.
There is no data on the effect of amiodarone on fertility in humans.

Driving and using machines

Based on safety data, amiodarone does not affect the ability to drive vehicles and operate machinery.

Cordarone contains lactose

Patients with hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome should not take this medication.

3. How to take Cordarone

This medication should always be taken as directed by your doctor. If you are unsure, consult your doctor.
Treatment with Cordarone should be started in a hospital and then continued under the supervision of a specialist.
Loading dose:
usually 600 mg per day (3 times 200 mg) for one week.
Maintenance dose:
the minimum effective dose should be used (allowing control of arrhythmias); depending on individual sensitivity, the dose is 100 to 200 mg per day.
Cordarone can be taken every other day in a dose of 200 mg per day or daily in a dose of 100 mg per day; it is also possible to take breaks in taking the medication (two days a week).

Use in children

The safety and efficacy of Cordarone in children have not been established. Therefore, the use of this medication in these patients is not recommended.

Use in elderly patients

As with all patients, the minimum effective dose should be used.
There is no evidence that elderly patients may require dose adjustment.
However, elderly patients may be more prone to bradycardia and conduction disorders when taking high doses. Particular attention should be paid to thyroid function.
If you feel that the effect of Cordarone is too strong or too weak, you should consult your doctor.

Overdose of Cordarone

There are few reports of amiodarone overdose. Slow heart rate or ventricular tachycardia, heart rhythm disorders of the torsade de pointestype, as well as low blood pressure and liver damage, may occur.
Overdose requires professional medical help; treatment is symptomatic.
Both amiodarone and its metabolites are not removed during dialysis.
In case of taking a higher dose of the medication than recommended, you should immediately consult your doctor or pharmacist.

Missed dose of Cordarone

In case of missing one dose, you should take it as soon as possible, unless the next dose is near. Do not take two doses of the medication at the same time or at short intervals.
In case of doubts, consult your doctor.

Discontinuation of Cordarone

In case of any further doubts about taking this medication, you should consult your doctor or nurse.

4. Possible side effects

Like all medications, Cordarone can cause side effects, although not everybody gets them.
You should stop taking Cordarone and seek medical advice immediately if you experience:

• anaphylactic shock (a set of clinical symptoms when the body's autoregulatory mechanisms are unable to ensure proper blood flow to vital organs and tissues, caused by a severe allergic reaction) manifested by confusion, weakness, fainting;

and

• anaphylactic reactions - severe allergic reactions affecting several organs, usually: cardiovascular, respiratory, and skin, occurring immediately after contact with the allergen;
• Quincke's edema - a severe allergic reaction causing swelling in the face, difficulty breathing, or dizziness;
• life-threatening skin reactions characterized by rash, blisters, skin peeling, and pain [toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), bullous dermatitis, drug rash with eosinophilia and systemic symptoms (DRESS)], changes in mucous membranes (see also "Warnings and precautions" in section 2). These symptoms can be life-threatening for the patient and even lead to death;
• irregular heartbeat, which may be a symptom of life-threatening arrhythmia of the torsade de pointestype (see Warnings and precautions and Cordarone and other medications in section 2);
• coughing up blood as a symptom of pulmonary hemorrhage;
• abdominal pain and constipation, which may be symptoms of acute pancreatitis;
• seeing, hearing, or feeling things that are not there (hallucinations);
• an increased number of infections may occur. This may be due to a decrease in the number of white blood cells (neutropenia);
• a significant decrease in the number of white blood cells, which increases the likelihood of infections (agranulocytosis). Common (may occur in up to 1 in 10 patients)
• yellowing of the eyes and skin (jaundice), abdominal pain, loss of appetite, fatigue, fever, high aminotransferase activity in blood tests; these are symptoms of life-threatening acute liver failure or liver failure;
• shortness of breath and cough without expectoration; these may be symptoms of life-threatening interstitial pneumonia or pulmonary fibrosis, pleuritis, bronchiolitis obliterans with pneumonia (see Warnings and precautions in section 2) or the occurrence of bronchospasm and (or) apnea in case of severe respiratory failure, especially in patients with asthma.

Other side effects of Cordarone may occur with the following frequency:
Very common (occurring in at least 1 in 10 patients):

• microdeposits in the cornea, forming just below the pupil. They may be accompanied by colored halos around objects when looking at bright light or blurred vision. They consist of complex lipid deposits and disappear after discontinuation of amiodarone treatment;
• mild gastrointestinal disorders (nausea, vomiting, taste disorders) usually occurring during the loading dose of Cordarone and resolving after dose reduction;
• increased aminotransferase activity in blood tests, which is usually moderate (1.5 to 3 times above the upper limit of normal), occurring at the beginning of treatment. These abnormalities may return to normal after dose reduction or on their own;
• photosensitivity.

Common (may occur in up to 1 in 10 patients)

• bradycardia (usually moderate and dose-dependent);
• hypothyroidism (manifested by severe fatigue, weight gain, constipation, and muscle pain), hyperthyroidism (manifested by agitation and restlessness, weight loss, increased sweating), sometimes ending in death;
• extrapyramidal tremors, nightmares, sleep disorders;
• blue-gray or bluish discoloration of the skin during long-term use of high doses of amiodarone, which resolves slowly after discontinuation of the medication;
• constipation;
• pruritic rash.

Uncommon (may occur in up to 1 in 100 patients)

• dry mouth. Rare (may occur in up to 1 in 10,000 patients)
• hemolytic anemia, aplastic anemia (anemia manifested by pallor of the skin and mucous membranes, fatigue, weakness, and dizziness), thrombocytopenia (decreased platelet count, manifested by bruising and bleeding);
• syndrome of inappropriate antidiuretic hormone secretion (SIADH) manifested by malaise, weakness, disorientation, nausea, loss of appetite, irritability;
• chronic liver diseases (pseudoalcoholic hepatitis, liver cirrhosis), sometimes ending in death;
• increased creatinine levels in the blood;
• headache;
• epididymitis, impotence;
• bronchospasm in patients with severe respiratory failure, especially in patients with asthma, acute respiratory distress syndrome, sometimes ending in death, especially immediately after surgery (possible interaction with high concentrations of oxygen) (see Warnings and precautions and Cordarone and other medications in section 2);
• radiation-induced dermatitis, skin rashes, usually non-specific, exfoliative dermatitis, alopecia.

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

• urticaria;
• neutropenia, agranulocytosis;
• pancreatitis, acute pancreatitis, dry mouth, constipation;
• granuloma, including granuloma of the bone marrow;
• stiffness; tremor and restlessness (parkinsonism); abnormal movements;
• abnormal sense of smell (parosmia);
• decreased appetite;
• decreased libido;
• confusion (including disorientation), hallucinations;
• lupus-like syndrome (a disease in which the immune system damages various parts of the body, leading to pain, stiffness, and swelling of the joints, as well as skin rash, sometimes in the shape of butterfly wings on the face);
• life-threatening complication after heart transplantation (primary graft dysfunction), in which the transplanted heart stops working properly (see Warnings and precautions in section 2).

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products,
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309,
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder or its representative in Poland.
By reporting side effects, you can help provide more information on the safety of this medication.

5. How to store Cordarone

Store in a temperature below 30°C.
The medication should be stored out of sight and reach of children.
Do not use this medication after the expiration date stated on the package after: "EXP". The expiration date refers to the last day of the month stated.

6. Contents of the pack and other information

What Cordarone contains

• The active substance of the medication is amiodarone hydrochloride. 1 tablet contains 200 mg of amiodarone hydrochloride.
• Other ingredients are: cornstarch, lactose monohydrate 200 mesh, magnesium stearate, povidone K90 F, colloidal silica anhydrous.

What Cordarone looks like and contents of the pack

White tablets with a dividing line on one side.
1 package contains 30 tablets in AI/PCV film blisters, in a cardboard box.

Marketing authorization holder:

Sanofi Winthrop Industrie
82, Avenue Raspail
94250 Gentilly
France

Manufacturer:

Sanofi-Winthrop Industrie
1 rue de la Vierge
33440 Ambares France
Opella Healthcare Hungary Limited Liability Company
2112 Veresegyhaz
Levai u. 5. Hungary
To obtain more detailed information, you should contact the representative of the marketing authorization holder in Poland:
Sanofi Sp. z o.o.
ul. Marcina Kasprzaka 6
01-211 Warsaw
Tel.: +48 22 280 00 00

Date of last revision of the leaflet: