Patient Information Leaflet

Warning! Keep this leaflet. The information on the immediate packaging is in a foreign language.
Cordarone (Angoron)
200 mg, tablets
Amiodaroni hydrochloridum
Cordarone and Angoron are different brand names for the same medicinal product.
Please read this leaflet carefully before taking the medicine, as it contains important information for the patient.

Keep this leaflet so that you can read it again if necessary.
If you have any questions, consult your doctor or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents:

What Cordarone is and what it is used for
What you need to know before taking Cordarone
How to take Cordarone
Possible side effects
How to store Cordarone
Contents of the pack and other information

1. What Cordarone is and what it is used for

Cordarone is available as tablets and contains amiodarone hydrochloride as the active substance. Amiodarone is a potent antiarrhythmic medicine used to treat irregular heartbeats.
It is used in the treatment of life-threatening cardiac arrhythmias:

arrhythmias associated with Wolff-Parkinson-White syndrome;
atrial fibrillation and atrial flutter, paroxysmal supraventricular tachycardias: supraventricular and nodal tachycardias, when other medicines cannot be used;
ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation), when other antiarrhythmic medicines are ineffective.

2. Important information before using Cordarone

When not to use Cordarone:

if the patient is allergic to iodine, amiodarone, or any of the other ingredients of this medicine (listed in section 6). If symptoms of allergy occur, such as itchy rash, difficulty swallowing or breathing, or swelling of the lips, face, throat, or tongue, contact a doctor immediately.
in patients with heart diseases: sinus bradycardia, sinoatrial block, sick sinus syndrome, except in patients with implanted pacemakers (risk of sinus node suppression);
in patients with second- or third-degree atrioventricular block, except in patients with implanted pacemakers;
concomitantly with medicines that may cause life-threatening arrhythmias – torsade de pointes (see: “Cordarone with other medicines”);
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 serum potassium concentration tests (low blood potassium increases the risk of cardiac arrhythmias).
The pharmacological action of amiodarone causes changes in ECG: QT interval prolongation (due to prolonged repolarization phase) with possible appearance of U waves.
However, these changes are not toxic in nature.
Heart rate may significantly decrease in elderly patients.
If second- or third-degree atrioventricular block, sinoatrial block, or dual AV nodal pathway block occurs, treatment with Cordarone should be discontinued.
Cordarone has proarrhythmic effects. New types of cardiac arrhythmias or worsening of existing arrhythmias have been reported, sometimes leading to death.
Proarrhythmic effects of Cordarone are reported less frequently than with other antiarrhythmic drugs. Proarrhythmia associated with amiodarone occurs particularly as a result of interactions with QT-prolonging drugs and/or in the presence of electrolyte disturbances (see subsection “Cordarone with other medicines” and section 4). Despite QT interval prolongation, Cordarone has low activity in inducing torsade de pointes-type arrhythmias.
Amiodarone may affect the function of a pacemaker or implanted cardioverter-defibrillator, especially during long-term antiarrhythmic therapy. Therefore, device function should be monitored before and during amiodarone treatment.
Oral Cordarone is not contraindicated in patients with heart failure, but caution is advised during treatment, as it may exacerbate the condition. In such cases, Cordarone may be used in combination with other medicines.
Before starting Cordarone, discuss with your doctor or pharmacist if the patient is currently taking a medicine containing sofosbuvir, used in the treatment of hepatitis C virus infection, as this may cause life-threatening bradycardia. The doctor may consider alternative treatment options. If treatment with both amiodarone and sofosbuvir is necessary, additional cardiac monitoring may be required.
Contact your doctor immediately if the patient is taking a medicine containing sofosbuvir for hepatitis C and experiences any of the following during treatment:

slow or irregular heartbeat or arrhythmias,
shortness of breath or worsening of existing dyspnea,
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 monitoring (including TSH levels) is recommended before starting treatment in all patients. Monitoring should continue during treatment every 6 months and for several months after treatment ends. This is particularly important in elderly patients.
In patients with a history indicating increased risk of thyroid disorders, regular monitoring of thyroid function is recommended.
Hyperthyroidism may occur during or several months after amiodarone treatment. Clinical symptoms, usually mild, such as weight loss, new or worsening arrhythmias, dyspnea, or congestive heart failure, should alert the physician. Diagnosis is based on a marked decrease in serum TSH levels. In such cases, Cordarone should be discontinued. Symptoms usually resolve within several months after stopping Cordarone; clinical improvement is preceded by normalization of thyroid function tests. Severe cases of hyperthyroidism, sometimes leading to death, require immediate appropriate therapeutic intervention. Treatment should be individually tailored: antithyroid drugs (which are not always effective), corticosteroids, beta-blockers.
The onset of dyspnea and non-productive cough may be related to pulmonary toxicity, such as interstitial pneumonitis. In patients who develop exertional dyspnea, either as the only symptom or associated with worsening general condition (fatigue, weight loss, fever), a chest X-ray should be performed. Continuing Cordarone therapy should be reconsidered, as interstitial pneumonitis is usually reversible if treatment is promptly discontinued (clinical symptoms usually resolve within 3 to 4 weeks, radiological changes and lung function improvement occur within several months). Consideration should be given to corticosteroid therapy.
Periodic monitoring of liver function (measurement of aminotransferase activity) is recommended during Cordarone treatment. The dose of Cordarone should be reduced or treatment discontinued if aminotransferase activity increases threefold above normal values, which may indicate acute or chronic liver dysfunction.
Clinical symptoms of chronic liver dysfunction may be mild (possible hepatomegaly, aminotransferase activity increased 1.5 to 5 times above normal). These abnormalities usually resolve after discontinuation of Cordarone; however, fatal cases have been reported.
Cordarone treatment must be immediately discontinued if severe skin reactions occur during its use (e.g. progressive rash with blisters or mucosal lesions, fever and joint pain, severe rapidly progressing disease with ruptured subcutaneous bullae, extensive skin erosions, peeling of large skin sheets, and fever – see also section 4). These symptoms may be life-threatening.
Cordarone may cause sensory-motor peripheral neuropathy and/or myopathy.
Symptoms usually resolve within several months after discontinuation of Cordarone, but sometimes some symptoms may persist.
If blurred vision or worsening of vision occurs, a complete ophthalmological examination, including fundoscopy, should be performed immediately. If optic nerve damage and/or optic neuritis is detected, Cordarone must be discontinued due to the risk of vision loss.
Concomitant use of amiodarone with the following medicines is not recommended: beta-blockers, calcium channel blockers reducing heart rate (verapamil, diltiazem), and laxatives that may cause hypokalemia.
Avoid exposure to sunlight and use sun protection during treatment. Cordarone causes photosensitivity, which may persist for several months after treatment ends.
The most common symptoms are tingling, burning, and erythema affecting skin areas exposed to sunlight.
Phototoxic reactions and rash are rarely observed.
Before surgery, inform the anesthesiologist that the patient is taking amiodarone; severe circulatory and respiratory disorders (sometimes fatal) have been reported in patients undergoing general anesthesia and oxygen therapy.
If the patient is on a heart transplant waiting list, the treating physician may change the treatment regimen before transplantation. This is because amiodarone use prior to heart transplantation increases the risk of a life-threatening complication (primary graft dysfunction), in which the transplanted heart fails to function properly within the first 24 hours after surgery.

Cordarone with other medicines
Inform your doctor about all medicines currently or recently taken, as well as any medicines planned for use.
Do not use Cordarone concomitantly with medicines that may cause life-threatening cardiac arrhythmias (type torsade de pointes). These include:

medicines used to treat arrhythmias (irregular heartbeat): quinidine, disopyramide, procainamide, sotalol, bretylium, bepridil;
intravenous erythromycin (antibiotic), cotrimoxazole (antibacterial), or the antiprotozoal agent pentamidine;
antipsychotics such as: chlorpromazine, thioridazine, fluphenazine, pimozide, haloperidol, amisulpride, sertindole;
some medicines used for other psychiatric disorders: lithium preparations and tricyclic antidepressants, e.g. doxepin, amitriptyline;
some antihistamines used to treat allergies: terfenadine, astemizole, mizolastine;
antimalarial medicines: quinine, chloroquine, mefloquine, halofantrine;
a medicine used to treat cerebral circulation disorders, dizziness, tinnitus, memory and learning disorders, especially in the elderly – vinpocetine;
neuroleptics;
a medicine used to treat delayed gastric emptying – cisapride.

Concomitant use of Cordarone is not recommended with:

fluoroquinolones – antibacterial agents: ciprofloxacin, ofloxacin, levofloxacin;
beta-blockers – used in heart diseases, e.g. propranolol;
calcium channel blockers that slow heart rate – used in angina (heart disease) or hypertension (high blood pressure): verapamil, diltiazem;
antiviral medicines used in hepatitis C treatment, e.g. sofosbuvir, daclatasvir, simprevir, ledipasvir, due to risk of bradycardia;
certain laxatives (used for constipation) causing low blood potassium: bisacodyl, senna;
cholesterol-lowering medicines – statins, e.g. simvastatin, atorvastatin, lovastatin.

Use caution when using the following medicines concomitantly with Cordarone:

diuretics, e.g. furosemide;
anti-inflammatory medicines – systemic corticosteroids, e.g. hydrocortisone, prednisolone;
tetracosactide – a medicine used to diagnose certain hormonal disorders;
the antifungal medicine – intravenous amphotericin B;
agents used in general anesthesia or high oxygen concentrations administered during surgical procedures (see “Warnings and precautions” in section 2 and section 4). Inform the anesthesiologist about Cordarone use before surgery;
phenytoin – used to treat epileptic seizures: close monitoring is required and if signs of phenytoin overdose occur, the dose should be reduced immediately and plasma phenytoin levels measured;
digitalis glycosides, e.g. digoxin – used in heart diseases: the doctor will order blood digoxin level tests and ECG, and adjust the digitalis glycoside dose; the patient should be monitored for signs of digitalis toxicity;
anticoagulants – warfarin, dabigatran: regular blood coagulation tests are required to adjust oral anticoagulant doses, both during and after Cordarone treatment; dabigatran dose adjustment may be necessary;
immunosuppressants to prevent transplant rejection – cyclosporine, tacrolimus, sirolimus;
flecainide – used to treat arrhythmias: treatment will be under strict medical supervision; the doctor will adjust the flecainide dose;
fentanyl – a strong painkiller;
lidocaine – an anesthetic;
sildenafil – used to treat erectile dysfunction;
midazolam – used for anxiety and sedation before surgical procedures;
triazolam – used for insomnia;
dihydroergotamine and ergotamine – antimigraine agents;
colchicine – used to treat acute gout attacks.

Pregnancy, breastfeeding, and effects on fertility
During pregnancy, breastfeeding, if pregnancy is suspected, or when planning pregnancy, consult a doctor before using this medicine.
Due to the effect of Cordarone on the fetal thyroid, use during pregnancy is contraindicated unless otherwise directed by a physician. Consult a doctor before use.
Use of Cordarone during breastfeeding is contraindicated.
There are no data on the effect of amiodarone on human fertility.

Driving and operating machinery
Based on safety data for amiodarone, the medicine does not impair the ability to drive or operate machinery.

Cordarone contains monohydrate lactose
Patients with hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

3. How to use Cordarone

This medicine should always be used exactly as directed by your doctor. If in doubt, consult your doctor.
Treatment with Cordarone should be initiated in a hospital setting and continued under the supervision of a specialist.

Loading dose:
Usually 600 mg per day (three times 200 mg) for one week.

Maintenance dose:
The minimum effective dose (allowing control of arrhythmias) should be used; depending on individual sensitivity, the dose ranges from 100 to 200 mg per day.
Cordarone may be administered every other day at a dose of 200 mg per day or daily at a dose of 100 mg per day; treatment interruptions (two days per week) may also be considered.

Use in children
The safety and efficacy of Cordarone in children have not been established.
Therefore, use in pediatric 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 require dose adjustment.
However, elderly patients may be more susceptible to bradycardia and conduction disturbances when excessive doses are administered. Particular attention should be paid to thyroid gland function.

If you feel that the effect of Cordarone is too strong or too weak, consult your doctor.

Taking more than the recommended dose of Cordarone
There are few reports of amiodarone overdose. Possible effects include slowing of heart rate, ventricular tachycardia, torsade de pointes arrhythmias, hypotension, and liver damage.
Overdose requires professional medical assistance; treatment is symptomatic.
Neither amiodarone nor its metabolites are removed during dialysis.
If you have taken more than the recommended dose, contact your doctor or pharmacist immediately.

Missed dose of Cordarone
If you miss a dose, take it as soon as possible, unless the next scheduled dose is approaching. Do not take two doses at the same time or in rapid succession.
If in doubt, consult your doctor.

Stopping Cordarone
If you have any further questions about using this medicine, consult your doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.

Stop taking Cordarone and seek immediate medical advice if any of the following occur:

Frequency unknown (frequency cannot be determined from available data):

Anaphylactic shock (a clinical syndrome in which the body's autoregulatory mechanisms are unable to maintain adequate blood flow to vital organs and tissues, caused by a severe allergic reaction), manifesting as confusion, weakness, or fainting;
Anaphylactic reactions – severe, immediate allergic reactions affecting multiple organ systems, typically the cardiovascular, respiratory, and skin systems, occurring immediately after exposure to an allergen;
Quincke's edema (angioedema) – a severe allergic reaction causing facial swelling, breathing difficulties, 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 reaction with eosinophilia and systemic symptoms (DRESS)], and mucosal lesions (see also "Warnings and precautions" in section 2). These symptoms may be life-threatening and may even lead to death;
Irregular heartbeat, which may indicate the potentially life-threatening arrhythmia torsade de pointes (see "Warnings and precautions" and "Cordarone with other medicines" in section 2);
Coughing up blood, which may be a sign of pulmonary hemorrhage;
Abdominal pain and constipation, which may indicate acute pancreatitis;
Experiencing sights, sounds, or sensations that are not real (hallucinations);
Increased frequency of infections, possibly due to reduced white blood cell count (neutropenia);
Marked reduction in white blood cells, increasing the risk of infections (agranulocytosis).

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

Yellowing of the eyes and skin (jaundice), abdominal pain, loss of appetite, fatigue, fever, and elevated liver aminotransferase activity in blood tests; these are symptoms of potentially life-threatening acute liver dysfunction or liver failure;
Shortness of breath and dry cough; these may be symptoms of life-threatening interstitial lung disease, pulmonary fibrosis, pleuritis, bronchiolitis obliterans with pneumonia (see "Warnings and precautions" in section 2), or bronchospasm and/or respiratory arrest in patients with severe respiratory failure, particularly those with bronchial asthma;
Decreased sexual drive.

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

Heart rhythm disturbances or worsening of existing arrhythmias, sometimes leading to cardiac arrest (see "Warnings and precautions" and "Cordarone with other medicines" in section 2), conduction disorders in the heart muscle (sinus node block, atrioventricular block of varying degrees);
Numbness, muscle weakness, tingling, and burning sensations; these may be symptoms of sensorimotor peripheral neuropathy (nerve disease) and/or myopathy (muscle disease), which are usually reversible upon discontinuation of Cordarone.

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

Blurred or worsening 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 marked slowing of heart rate or sinus node arrest, particularly in patients with sinus node dysfunction and/or elderly patients;
Skin rash indicating vasculitis;
Headache worsening in the morning or after exertion, nausea, seizures, fainting, visual disturbances, or disorientation; these may be symptoms of brain dysfunction due to increased intracranial pressure (pseudotumor cerebri);
Impaired coordination of movement.

Other adverse reactions associated with Cordarone may occur with the following frequencies:

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

Corneal microdeposits, located just beneath the pupil. These may be associated with seeing colored halos around objects when looking at bright lights or blurred vision. These deposits consist of complex lipid accumulations and usually resolve after discontinuation of amiodarone therapy;
Mild gastrointestinal disturbances (nausea, vomiting, taste disturbances), usually occurring during the loading dose phase and resolving after dose reduction of amiodarone;
Increased aminotransferase activity detected in blood tests, usually moderately elevated (1.5 to 3 times above the upper normal limit), occurring early in treatment. These abnormalities may normalize spontaneously or after dose reduction;
Photosensitivity.

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

Slow heart rate (bradycardia), usually moderate and dose-dependent;
Hypothyroidism (manifesting as profound fatigue, weight gain, constipation, and muscle pain), hyperthyroidism (manifesting as restlessness, agitation, weight loss, and increased sweating), sometimes leading to death;
Extrapyramidal tremors, nightmares, sleep disturbances;
Bluish-gray skin discoloration during long-term treatment with high doses of amiodarone, which slowly resolves after discontinuation of the drug;
Constipation;
Itchy red rash (exanthema).

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

Dry mouth.

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

Hemolytic anemia, aplastic anemia (anemias manifesting as pallor of the skin and mucous membranes, fatigue, weakness, and dizziness), thrombocytopenia (reduced platelet count, manifesting as increased bruising and bleeding);
Syndrome of inappropriate antidiuretic hormone secretion (SIADH), manifesting as malaise, weakness, disorientation, nausea, loss of appetite, and nervousness;
Chronic liver diseases (pseudoalcoholic hepatitis, liver cirrhosis), sometimes leading to death;
Increased blood creatinine levels;
Headaches;
Epididymitis, impotence;
Bronchospasm in patients with severe respiratory failure, particularly those with bronchial asthma, adult respiratory distress syndrome, sometimes leading to death, especially immediately after surgery (possible interaction with high-concentration oxygen) (see "Warnings and precautions" and "Cordarone with other medicines" in section 2);
Erythema during radiotherapy, skin rashes (usually nonspecific), exfoliative dermatitis, alopecia.

Frequency unknown (frequency cannot be determined from available data):

Urticaria;
Neutropenia, agranulocytosis;
Pancreatitis, acute pancreatitis, dry mouth, constipation;
Granuloma, including bone marrow granuloma;
Stiffness; tremor and motor restlessness (parkinsonism); unusual muscle movements;
Distorted sense of smell (parosmia);
Decreased appetite;
Decreased libido;
Delirium (including confusion), hallucinations;
Lupus-like syndrome (a condition in which the immune system attacks various parts of the body, causing joint pain, stiffness, swelling, and skin redness, sometimes in a butterfly-shaped rash on the face);
Life-threatening complication after heart transplantation (primary graft dysfunction), in which the transplanted heart fails to function properly (see "Warnings and precautions" in section 2).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can also be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration 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
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Cordarone

Do not store at temperatures above 30°C.
Keep the medicine in a place invisible and inaccessible to children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month indicated.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the packaging and other information

What Cordarone contains

The active substance is amiodarone hydrochloride. One tablet contains 200 mg of amiodarone hydrochloride.
The other ingredients are: maize starch, monohydrate lactose, magnesium stearate, povidone K 90, colloidal anhydrous silicon dioxide.

What Cordarone looks like and contents of the pack
White or off-white, round tablet with a central groove, printed with a heart symbol and "200" on one side.
One pack contains 30 tablets in Al/PVC blisters, packed in a cardboard box.
For further information, please contact the Marketing Authorisation Holder or Parallel Importer.
Marketing Authorisation 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 in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Marketing Authorisation number in Greece, country of export: 77642/07/04-04-2008
Parallel Import Licence number: 100/17