PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Warning! Keep the leaflet. Information on the immediate packaging in a foreign language!
Cordarone (Angoron)
200 mg, tablets
Amiodarone hydrochloride
Cordarone and Angoron are different brand names for the same medicine.
Please read this leaflet carefully before using 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, please consult your doctor or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or nurse. See section 4.

Table of contents of the leaflet

What Cordarone is and what it is used for
Important information before taking Cordarone
How to take Cordarone
Possible side effects
How to store Cordarone
Contents of the package 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 heart rhythm disorders:

rhythm disorders 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 rhythm disorders (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 to 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 an implanted pacemaker (risk of sinus node inhibition);
in patients with second- or third-degree atrioventricular block, except in patients with an implanted pacemaker;
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, ECG, serum TSH level, and serum potassium concentration should be assessed (low blood potassium levels increase the risk of 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.
Heart function may significantly decrease in elderly patients.
If second- or third-degree atrioventricular block, sinoatrial block, or dual bundle branch block occurs, treatment with Cordarone should be discontinued.
Cordarone has proarrhythmic effects. Cases of new-onset arrhythmias or worsening of treated arrhythmias have been reported, sometimes leading to death.
Proarrhythmic effects of Cordarone have been reported less frequently than with other antiarrhythmic drugs. Proarrhythmic effects of amiodarone occur especially as a result of interactions with QT-prolonging drugs and/or in the presence of electrolyte disturbances (see section "Cordarone and other medicines" and section 4). Despite QT interval prolongation, Cordarone has low activity in causing torsade de pointes arrhythmias.
Amiodarone may affect the performance 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 heart failure. In such cases, Cordarone may be used in combination with other medicines.
Before starting Cordarone, discuss with a 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 slowing of heart rate. The doctor may consider alternative treatment options. If treatment with both amiodarone and sofosbuvir is necessary, additional cardiac monitoring may be required.
Contact a doctor immediately if the patient is taking a medicine containing sofosbuvir for hepatitis C and during treatment experiences:

slow or irregular heartbeat or arrhythmias,
shortness of breath or worsening of existing breathlessness,
chest pain,
dizziness,
palpitations,
near-syncope 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 treatment or several months after discontinuation of amiodarone.
Clinical symptoms, usually mild, such as weight loss, new 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 several months after stopping Cordarone; clinical improvement is preceded by normalization of laboratory thyroid function tests. Severe cases of hyperthyroidism, sometimes fatal, 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 sole 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 over several months). Consideration should be given to corticosteroid therapy.
Periodic monitoring of liver function (measurement of aminotransferase activity) is recommended during Cordarone treatment.
Dosage of Cordarone should be reduced or treatment discontinued if aminotransferase activity increases more than 3 times 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 values). These abnormalities usually resolve after discontinuation of Cordarone; however, fatal cases have been reported.
Cordarone treatment should 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 rupturing subcutaneous bullae, extensive skin erosions, sloughing 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 certain 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 that reduce heart rate (verapamil, diltiazem), and laxatives that may cause hypokalemia.
Avoid exposure to sunlight and use sun-protective measures during treatment. Cordarone causes photosensitivity, which may persist for several months after stopping treatment.
Most common symptoms are tingling, burning, and erythema on skin areas exposed to sunlight.
Phototoxic reactions and rash have been rarely observed.
Before surgery, inform the anesthesiologist that the patient is taking amiodarone; cases of severe circulatory and respiratory system 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 before 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 taken or recently taken, as well as any medicines planned for use.
Do not use Cordarone concomitantly with medicines that may cause life-threatening arrhythmias (type torsade de pointes). These include:

medicines used to treat arrhythmias (irregular heartbeat): quinidine, disopyramide, procainamide, sotalol, bretylium, bepridil,
intravenous erythromycin (antibiotic), cotrimoxazole (antimicrobial agent), or the antiprotozoal agent pentamidine,
antipsychotic medicines 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 – antimicrobial 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 to treat hepatitis C, e.g. sofosbuvir, daklatasvir, symeprevir, or ledipasvir, due to the risk of bradycardia,
certain laxatives (used to treat 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,
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 phenytoin dose should be reduced immediately if signs of overdose occur; plasma phenytoin levels should be measured,
cardiac glycoside, e.g. digoxin – used in heart diseases: the doctor will order digoxin plasma level monitoring and ECG; the patient should be monitored for signs of digoxin toxicity,
anticoagulants – warfarin, dabigatran: regular blood coagulation tests are necessary to adjust oral anticoagulant doses, both during and after Cordarone treatment; dabigatran dose adjustment may be required,
immunosuppressants to prevent transplant rejection – cyclosporine, tacrolimus, and sirolimus,
flecainide – used to treat arrhythmias: treatment will be under strict medical supervision; the doctor will adjust the flecainide dose,
fentanyl – a strong analgesic,
lidocaine – an anesthetic,
sildenafil – used to treat impotence,
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, or if pregnancy is suspected or planned, consult a doctor before using this medicine.
Due to the effect of Cordarone on the fetal thyroid, its use during pregnancy is contraindicated unless otherwise directed by a doctor. 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 rare hereditary problems of 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 as directed by the physician. If in doubt, consult your
doctor.
Treatment with Cordarone should be initiated in a hospital setting and subsequently continued under
the supervision of a specialist.
Loading dose:
typically 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; intermittent dosing schedules (two days off per week) may also be used.
Use in children
The safety and efficacy of Cordarone in children have not been established. Therefore, use 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 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.
Overdose of Cordarone
There are few reports of amiodarone overdose. Bradycardia, ventricular tachycardia,
torsade de pointes type arrhythmias, hypotension, and liver damage may occur.
Overdose requires professional medical intervention; treatment is symptomatic.
Neither amiodarone nor its metabolites are removed during dialysis.
If an overdose has been taken, seek immediate medical advice from a doctor or pharmacist.
Missed dose of Cordarone
If a dose is missed, take it as soon as possible, unless it is almost time for the next dose.
Do not take two doses at the same time or within a short interval.
If in doubt, consult your doctor.
Discontinuation of Cordarone
If you have any further questions regarding the use of this medicine, consult your doctor or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You should stop taking Cordarone and seek immediate medical advice if any of the following occur:
Frequency unknown (frequency cannot be estimated from the available data)

anaphylactic shock (a clinical syndrome in which the body's autoregulatory mechanisms fail 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 allergic reactions affecting multiple organ systems simultaneously, typically the cardiovascular, respiratory, and skin systems, occurring immediately after exposure to an allergen;
Quincke's edema (angioedema) – a severe allergic reaction causing swelling of the face, 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 be a sign of the life-threatening arrhythmia torsade de pointes (see "Warnings and precautions" and "Cordarone and other medicines" in section 2);
coughing up blood as a sign of pulmonary hemorrhage;
abdominal pain and constipation, which may indicate acute pancreatitis;
seeing, hearing, or feeling things that are not there (hallucinations);
an increased number of infections. This may be due to a reduced number of white blood cells (neutropenia);
a significant decrease in white blood cells, increasing the risk 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, and elevated aminotransferase levels in blood tests; these are symptoms of life-threatening acute liver dysfunction or liver failure;
shortness of breath and dry cough; these may be symptoms of life-threatening interstitial pneumonitis or pulmonary fibrosis, pleuritis, bronchiolitis obliterans with pneumonia (see "Warnings and precautions" in section 2), or bronchospasm and/or respiratory arrest in cases of severe respiratory failure, particularly in patients with bronchial asthma;
decreased sexual drive.
Uncommon (may occur in up to 1 in 100 patients)
cardiac arrhythmias or worsening of existing arrhythmias, sometimes leading to cardiac arrest (see "Warnings and precautions" and "Cordarone and other medicines" in section 2), conduction disturbances 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), 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 may lead to vision loss (see "Warnings and precautions" in section 2);
dizziness, fatigue, and shortness of breath; these may be symptoms of significant bradycardia, 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 motor coordination.

Other adverse reactions of 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 colored halos around objects when viewing bright light 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 reducing the amiodarone dose;
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 after dose reduction or spontaneously;
photosensitivity.
Common (may occur in up to 1 in 10 patients)
slow heartbeat (bradycardia), usually moderate and dose-dependent;
hypothyroidism (manifesting as severe fatigue, weight gain, constipation, and muscle pain), hyperthyroidism (manifesting as restlessness, motor agitation, weight loss, and increased sweating), sometimes resulting in death;
extrapyramidal tremors, nightmares, sleep disturbances;
grayish-blue skin discoloration during long-term treatment with high doses of amiodarone, which slowly resolves after discontinuation of the drug;
constipation;
itchy red rash (urticaria).
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 resulting in death;
increased blood creatinine levels;
headaches;
epididymitis, impotence;
bronchospasm in patients with severe respiratory failure and especially in patients with bronchial asthma, adult respiratory distress syndrome, sometimes resulting in death, particularly immediately after surgery (possible interaction with high concentrations of oxygen) (see "Warnings and precautions" and "Cordarone and other medicines" in section 2);
erythema during radiotherapy, skin rashes (usually nonspecific), desquamative dermatitis, alopecia.
Frequency unknown (frequency cannot be estimated from the 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;
abnormal sense of smell (parosmia);
decreased appetite;
decreased libido;
delirium (including confusion), hallucinations;
lupus-like syndrome (a disease in which the immune system attacks various parts of the body, leading to joint pain, stiffness, swelling, and skin redness, sometimes in a butterfly-shaped pattern 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 or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 4921301, fax: +48 22 4921309, website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to gather more information on the safety of this medicine.

5. How to store Cordarone

Store below 30°C. Protect from light.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Cordarone contains

The active substance is amiodarone hydrochloride. Each tablet contains 200 mg of amiodarone hydrochloride.
Other ingredients: monohydrate lactose, corn starch, povidone K 90, colloidal anhydrous silica, magnesium stearate.

What Cordarone looks like and contents of the pack
Round, biconvex tablets with a dividing score, white to off-white in colour, imprinted with a heart symbol and the number 200 on one side.
Each pack contains 30 tablets in aluminium-PVC blisters, packed in a cardboard box.
For further information, please contact the marketing authorisation holder or the parallel importer.

Marketing Authorisation Holder in Greece, country of export:
Sanofi-Aventis AEBE
L. Sygrou 348, Building A
176 74 Kallithea
Greece

Manufacturer:
Sanofi-Aventis S.A.
Ctra. La Battloria-Hostalric, km 63.09, (C-35)
17404 Riells i Viabrea (Girona)
Spain

Parallel Importer:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Poland

Repackaged in:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Poland

Marketing Authorisation number in Greece, country of export: 77642/07/04-04-08
Parallel Import Licence number: 15/20