Cordarone

Leaflet accompanying the packaging: patient information

Warning! The leaflet should be kept. Information on the immediate packaging in a foreign language.

Cordarone (Angoron)

200 mg, tablets
Amiodarone hydrochloride
Cordarone and Angoron are different trade names for the same drug.

You should carefully read the contents of the leaflet before using the drug, as it contains important information for the patient.

• You should keep this leaflet so that you can read it again if necessary.
• In case of any doubts, you should consult a doctor or nurse.
• This drug has been prescribed to a specific person. It should not be given to others. The drug may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is Cordarone and what is it used for
• 2. Important information before taking Cordarone
• 3. How to take Cordarone
• 4. Possible side effects
• 5. How to store Cordarone
• 6. Package contents and other information

1. What is Cordarone and what is it used for

Cordarone is available in tablet form and contains amiodarone hydrochloride as the active substance. Amiodarone is a powerful anti-arrhythmic drug used to treat irregular heartbeats.
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 drugs cannot be used;
• ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation), when other anti-arrhythmic drugs are ineffective.

2. Important information before taking Cordarone

When not to take Cordarone:

• if the patient is allergic to iodine, amiodarone, or any of the other ingredients of this drug (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, the doctor should be contacted immediately.
• in patients with heart diseases: sinus bradycardia, sinoatrial block, sick sinus syndrome, except for patients with a pacemaker (risk of inhibition of sinus node activity);
• in patients with atrioventricular block of second or third degree, except for patients with a pacemaker;
• concomitantly with drugs that may cause life-threatening arrhythmias - type torsade de pointes(see: "Cordarone and other drugs");
• if the patient has thyroid disease;
• if the patient is 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 level in the blood increases the risk of arrhythmias).
The pharmacological effect 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 arrhythmias or worsening of treated arrhythmias, sometimes leading to death.
Pro-arrhythmic effects of amiodarone are less common than with other anti-arrhythmic drugs.
Pro-arrhythmic effects of amiodarone occur especially as a result of interactions with drugs that prolong the QT interval and (or) in case of electrolyte disorders (see subsection "Cordarone and other drugs" and section 4). Regardless of the prolongation of the QT interval, Cordarone has a low activity of causing arrhythmias of the torsade de pointestype.
Amiodarone may affect the effectiveness of a pacemaker or implantable cardioverter-defibrillator, especially in the case of long-term use of anti-arrhythmic drugs.
Therefore, 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 drugs.
Before starting treatment with Cordarone, the patient should discuss it with their doctor or pharmacist if they are currently taking a drug containing sofosbuvir, used to treat viral hepatitis C, as it may cause life-threatening bradycardia.
The doctor may consider alternative treatment methods.
If treatment with amiodarone and sofosbuvir is necessary, additional monitoring of heart function may be required.
The doctor should be informed immediatelyif the patient is taking a drug containing sofosbuvir, used to treat viral hepatitis C, and if any of the following symptoms occur during treatment:

• slow or irregular heartbeat or arrhythmias,
• 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 the end of treatment.
This is especially important in elderly patients.
In patients with a history of thyroid disorders, regular monitoring of thyroid function is recommended.
During treatment or up to several months after the end of treatment with amiodarone, hyperthyroidism may occur.
Clinical symptoms, usually mild, such as weight loss, arrhythmias, shortness of breath, congestive heart failure, should alert the doctor.
Diagnosis is based on a significant decrease in TSH hormone activity in serum.
Then, Cordarone should be discontinued.
Resolution of symptoms usually occurs within a few months after the end of 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 drugs (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 development 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).
Corticosteroids should be considered.
Periodic monitoring of liver function (determination of aminotransferase activity) is recommended during treatment with Cordarone.
The dose of Cordarone should be reduced or treatment discontinued in case of increased aminotransferase activity 3 times above normal values, which may indicate acute or chronic liver dysfunction.
Clinical symptoms of chronic liver dysfunction 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, cases of death have been reported.
Treatment with Cordarone should be discontinued immediately if severe skin reactions occur (e.g., progressive rash with blisters or mucous membrane changes, fever, and joint pain, severe rapidly progressing disease characterized by large subcutaneous blisters, extensive skin erosions, and fever - see also section 4).
These symptoms may be life-threatening.
Cordarone may cause sensory-motor peripheral neuropathy and (or) myopathy.
Resolution of symptoms usually occurs within a few 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 drugs is not recommended:

• beta-adrenergic blockers, calcium channel antagonists that reduce heart rate (verapamil, diltiazem), laxatives that may cause hypokalemia;
• drugs that may cause life-threatening arrhythmias (type torsade de pointes);

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

• diuretics, e.g., furosemide;
• systemic corticosteroids, e.g., hydrocortisone, prednisolone;
• tetracosactide - a drug used to test certain hormonal disorders;
• amphotericin B - an antifungal drug administered intravenously;
• general anesthetics or high oxygen concentrations administered during surgical procedures (see "Warnings and precautions" in section 2 and section 4).
  Before surgery, the anesthesiologist should be informed about the patient's use of amiodarone; there have been reports of severe cardiovascular and respiratory disorders (sometimes leading to death) in patients undergoing general anesthesia and oxygen therapy;
• phenytoin - used to treat epileptic seizures: close monitoring of the patient is necessary, and the dose of phenytoin should be reduced and its serum concentration measured in case of symptoms of overdose;
• digitalis glycosides, e.g., digoxin - used to treat heart diseases: the doctor will order measurements of digoxin serum concentration and perform an ECG, and adjust the dose of digitalis glycosides; the patient should be monitored for signs of digitalis glycoside toxicity;
• anticoagulant drugs - warfarin, dabigatran: regular monitoring of blood coagulation is necessary to adjust the oral doses of anticoagulant drugs, both during and after treatment with Cordarone; the dose of dabigatran may need to be adjusted;
• drugs 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 reliever;
• lidocaine - a local anesthetic;
• sildenafil - used to treat impotence;
• midazolam - used to treat anxiety and to sedate before surgical procedures;
• triazolam - used to treat insomnia;
• dihydroergotamine and ergotamine - anti-migraine drugs;
• colchicine - used to treat acute gout attacks.

Pregnancy and breastfeeding and fertility

In pregnancy and during breastfeeding, or if pregnancy is suspected, or if the patient is planning to become pregnant, the patient should consult their doctor before taking this drug.
Due to the effect of Cordarone on the fetal thyroid, the use of the drug during pregnancy is contraindicated, unless the doctor recommends otherwise.
Before taking the drug, the patient should consult their doctor.
The use of Cordarone during breastfeeding is contraindicated.
There are no data on the effect of amiodarone on human fertility.

Driving and using machines

In light of the safety data on amiodarone, the drug does not limit the ability to drive vehicles and operate machines.

Cordarone contains lactose monohydrate

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

3. How to take Cordarone

This drug should always be taken according to the doctor's instructions.
In case of doubts, the patient should consult their 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 a 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 may 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 drug (two days a week).

Use in children

The safety and efficacy of Cordarone in children have not been established.
Therefore, the use of the drug 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 the patient feels that the effect of Cordarone is too strong or too weak, they should consult their doctor.

Overdose of Cordarone

There are few reports of amiodarone overdose.
Bradycardia or ventricular tachycardia, arrhythmias of the torsade de pointestype, as well as hypotension 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 drug than recommended, the patient should immediately consult their doctor or pharmacist.

Missed dose of Cordarone

In case of missing a dose, the patient should take it as soon as possible, unless it is close to the time of the next dose.
The patient should not take two doses of the drug at the same time or at short intervals.
In case of doubts, the patient should consult their doctor.

Discontinuation of Cordarone

In case of any further doubts about the use of this drug, the patient should consult their doctor or nurse.

4. Possible side effects

Like all drugs, Cordarone can cause side effects, although not everybody gets them.
The patient should stop taking Cordarone and seek medical advice immediately if they 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;
• anaphylactic reactions - severe allergic reactions affecting several organs, usually: cardiovascular, respiratory, and skin, occurring immediately after contact with the allergen;
• angioedema - a severe allergic reaction causing swelling in the face, difficulty breathing, or dizziness;
• life-threatening skin reactions characterized by rash, blisters, and skin peeling, and pain [toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), bullous dermatitis, drug rash with eosinophilia and systemic symptoms (DRESS)], and mucous membrane changes (see also "Warnings and precautions" in section 2). These symptoms may be life-threatening 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 drugs" in section 2),
• 2);
• hemoptysis as a symptom of pulmonary hemorrhage;
• abdominal pain and constipation, which may be symptoms of acute pancreatitis or pancreatitis.
• hallucinations, hearing or seeing things that are not there;
• 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 risk of infections (agranulocytosis).

Frequent (may occur in up to 1 in 10 patients):

• jaundice and skin discoloration, abdominal pain, loss of appetite, fatigue, fever, elevated aminotransferase activity in blood tests; these are symptoms of life-threatening acute liver dysfunction 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 pulmonary pneumonia (see "Warnings and precautions" in section 2) or bronchospasm and (or) respiratory failure in case of severe respiratory failure and especially in patients with asthma.
• decreased libido.

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

• arrhythmias or their exacerbation, sometimes with cardiac arrest (see "Warnings and precautions" and "Cordarone and other drugs" in section 2), conduction disorders in the heart muscle (sinoatrial block, atrioventricular block of various degrees);
• numbness, muscle weakness, tingling, and burning; these may be symptoms of sensory-motor peripheral neuropathy (nerve disease) and (or) myopathy (muscle disease), usually reversible after discontinuation of Cordarone.

Rare (may occur in up to 1 in 10,000 patients):

• blurred vision or worsening of vision; these may be symptoms of optic nerve damage, which can lead to vision loss (see "Warnings and precautions" in section 2);
• dizziness, fatigue, and shortness of breath; these may be symptoms of significant bradycardia, sinoatrial arrest, especially in patients with sick sinus syndrome and (or) elderly patients;
• skin rash as a symptom of vasculitis;
• headache worsening in the morning or after exertion, nausea, seizures, fainting, vision disturbances, or disorientation; these may be symptoms of cerebral dysfunction due to increased intracranial pressure (pseudotumor cerebri);
• coordination disorders.

Very common (occurring in at least 1 in 10 patients):

• corneal microdeposits 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 are reversible after discontinuation of amiodarone treatment;
• mild gastrointestinal disorders (nausea, vomiting, taste disturbances) usually occurring during the loading dose of Cordarone and resolving after dose reduction of amiodarone;
• 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 discontinuation of the drug;
• photosensitivity.

Frequent (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 fatal;
• extrapyramidal tremors, nightmares, sleep disturbances;
• blue-gray or dark skin discoloration during long-term use of high doses of amiodarone, which resolves slowly after discontinuation of the drug;
• 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, 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 fatal;
• increased creatinine levels in the blood;
• headache;
• epididymitis, impotence;
• bronchospasm in patients with severe respiratory failure and especially in patients with asthma, acute respiratory distress syndrome, sometimes fatal, especially immediately after surgery (possible interaction with high oxygen concentrations) (see "Warnings and precautions" and "Cordarone and other drugs" in section 2);
• radiation recall, skin rash, usually non-specific, exfoliative dermatitis.

Frequency not known (frequency cannot be estimated from the 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 confusion), 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 a butterfly 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 side effects occur, including any side effects not listed in the leaflet, the patient should inform their doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Drug Safety, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych, Al. Jerozolimskie 181C, 02-222 Warszawa, tel.: +48 (22) 49 21 301, fax: +48 (22) 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting side effects can help gather more information on the safety of the drug.

5. How to store Cordarone

Do not store above 30°C.
The drug should be stored out of sight and reach of children.
Do not use this drug after the expiry date stated on the packaging.
The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste.
The patient should ask their pharmacist how to dispose of medicines that are no longer needed.
This will help protect the environment.

6. Package contents and other information

What Cordarone contains

• The active substance of the drug is amiodarone hydrochloride. 1 tablet contains 200 mg of amiodarone hydrochloride.
• Other ingredients are: cornstarch, lactose monohydrate, magnesium stearate, povidone K 90, anhydrous colloidal silica.

What Cordarone looks like and contents of the pack

Round tablet, white or off-white, with a score line and a heart-shaped imprint and "200" on one side.
1 package contains 30 tablets in Al/PVC blisters in a cardboard box.
For more detailed information, the patient should contact the marketing authorization holder or parallel importer.

Marketing authorization holder in Greece, country of export:

Sanofi-aventis AEBE
Syngrou Avenue 348, Building A
176 74 Kallithea
Greece

Manufacturer:

Sanofi-aventis SA
Ctra. La Battloria-Hostalric, km 63,09
(C-35) 17404 Riells I Viabrea (Girona)
Spain

Parallel importer:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź

Repackaged by:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Marketing authorization number in Greece, country of export: 77642/07/04-04-2008

Parallel import authorization number: 100/17 Date of leaflet approval: 21.03.2022

[Information about the trademark]