Package leaflet: Information for the patient

Warning! Keep this leaflet! The packaging information in a foreign language.
Cordarone
200 mg, tablets
Amiodaroni hydrochloridum
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 the patient experiences any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or nurse immediately. See section 4.

Table of contents of the leaflet

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

1. What is Cordarone and what is it used for

Cordarone is available in the form of tablets and contains amiodarone hydrochloride as the active substance. Amiodarone is a potent antiarrhythmic medicine used to treat irregular heartbeat.
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 tachyarrhythmias: supraventricular and nodal tachycardias, when other drugs cannot be used;
ventricular rhythm disorders (ventricular tachycardia, ventricular fibrillation), when other antiarrhythmic drugs 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 inhibition);
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), possibly with appearance of U waves.
However, these changes are not toxic.
Heart rate may significantly decrease in elderly patients.
If second- or third-degree atrioventricular block, sinoatrial block, or bifascicular block occurs, treatment with Cordarone should be discontinued.
Cordarone has proarrhythmic effects. Cases of new-onset cardiac 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 particularly as a result of interaction 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 ventricular arrhythmias.
Amiodarone may affect the function of pacemakers or implantable cardioverter-defibrillators, especially during long-term antiarrhythmic therapy.
Therefore, device function should be monitored before and during amiodarone treatment.
Oral administration of Cordarone is not contraindicated in patients with heart failure, but caution is advised 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 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 your 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-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 treatment initiation in all patients. Monitoring should continue during treatment every 6 months and for several months after treatment discontinuation. This is particularly important in elderly patients.
In patients with a history suggesting 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 or worsened arrhythmias, dyspnea, or congestive heart failure, should alert the physician. Diagnosis is based on a marked decrease in serum TSH levels. Cordarone should then be discontinued. Symptoms usually resolve several months after stopping Cordarone; clinical improvement is preceded by normalization of 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. The dosage of Cordarone should be reduced or treatment discontinued if aminotransferase activity increases more than three times above normal values, which may indicate acute or chronic liver dysfunction.
Clinical symptoms of chronic liver dysfunction may be mild (possible liver enlargement, 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 therapy (e.g., progressive rash with blisters or mucosal lesions, fever, joint pain, severe rapidly progressing illness with rupturing subepidermal bullae, extensive skin erosions, sloughing of large epidermal 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 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 protection during treatment. Cordarone causes photosensitivity, which may persist for several months after treatment discontinuation.
The most common symptoms are tingling, burning, and erythema on skin areas exposed to sunlight.
Phototoxic reactions and rash are rarely observed.
Before undergoing surgery, inform the anaesthesiologist that the patient is taking amiodarone; severe circulatory and respiratory disorders (sometimes fatal) have been reported in patients undergoing general anaesthesia 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:

antiarrhythmic medicines: quinidine, disopyramide, procainamide, sotalol, bretylium, bepridil,
intravenous erythromycin (antibiotic), cotrimoxazole (antimicrobial agent), or the antiprotozoal agent pentamidine,
antipsychotics: chlorpromazine, thioridazine, fluphenazine, pimozide, haloperidol, amisulpride, sertindole,
some medicines used for other psychiatric disorders: lithium and tricyclic antidepressants, e.g. doxepin, amitriptyline,
some antihistamines used for allergies: terfenadine, astemizole, mizolastine,
antimalarial medicines: quinine, chloroquine, mefloquine, halofantrine,
vincamine – used in the treatment of cerebral circulation disorders, dizziness, tinnitus, memory and learning disorders, especially in the elderly,
neuroleptics,
cisapride – used for delayed gastric emptying.

Concomitant use of Cordarone is not recommended with:

fluoroquinolone antibiotics: 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, symeprevir, ledipasvir, due to risk of bradycardia,
certain laxatives (used for constipation) causing low potassium levels: 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 – used to diagnose certain hormonal disorders,
antifungal medicine – intravenous amphotericin B,
anaesthetics used in general anaesthesia or high oxygen concentrations during surgical procedures (see Warnings and precautions in section 2 and section 4). Inform the anaesthesiologist about Cordarone use before surgery,
phenytoin – used in seizure treatment: close monitoring is required; reduce phenytoin dose and measure plasma levels immediately if signs of overdose occur,
digitalis glycosides, e.g. digoxin – used in heart diseases: the doctor will order digoxin plasma level monitoring and ECG; monitor for signs of digitalis toxicity,
anticoagulants – warfarin, dabigatran: regular blood coagulation tests are necessary to adjust oral anticoagulant doses during and after Cordarone treatment; dabigatran dose adjustment may be needed,
immunosuppressants to prevent transplant rejection – cyclosporine, tacrolimus, sirolimus,
flecainide – used in arrhythmia treatment: treatment must be closely supervised; the doctor will adjust the flecainide dose,
fentanyl – a strong painkiller,
lidocaine – an anaesthetic,
sildenafil – used in erectile dysfunction treatment,
midazolam – used for anxiety and sedation before surgery,
triazolam – used for insomnia,
dihydroergotamine and ergotamine – antimigraine medicines,
colchicine – used in acute gout attacks.

Pregnancy, breastfeeding, and effects on fertility
During pregnancy, breastfeeding, if pregnancy is suspected, or if planning pregnancy, consult a doctor before using this medicine.
Due to Cordarone's effects on fetal thyroid function, its use during pregnancy is contraindicated unless otherwise advised 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 regarding amiodarone, the medicine does not impair the ability to drive or operate machinery.

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

3. How to use Cordarone

This medicine should always be taken as directed by the physician. In case of 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 rhythm disturbances) 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 breaks (two days per week) may also be applied.

Use in children
The safety and efficacy of Cordarone in children have not been established. Therefore, the use of this medicine 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 Cordarone than recommended
There are only a few reports of amiodarone overdose. Symptoms may include slowing of heart contractions, ventricular tachycardia, torsade de pointes-type arrhythmias, as well as 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, seek immediate medical advice from your doctor or pharmacist.

Missed dose of Cordarone
If you miss a dose, 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.
In case of doubt, consult your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Treatment with Cordarone must be discontinued and immediate medical advice sought if any of the following occur:
Frequency unknown (frequency cannot be estimated from the available data)

anaphylactic shock (a clinical syndrome of life-threatening circulatory failure due to a severe allergic reaction, in which the body's autoregulatory mechanisms are unable to maintain adequate blood flow to vital organs and tissues), 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 oedema (angioedema) – a severe allergic reaction causing swelling of the face, breathing difficulties, or dizziness;
life-threatening skin reactions characterised 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 life-threatening arrhythmia torsade de pointes (see Warnings and precautions and Cordarone with other medicines in section 2);
coughing up blood as a sign of pulmonary haemorrhage;
abdominal pain and constipation, which may indicate acute pancreatitis;
seeing, hearing, or feeling things that are not there (hallucinations);
increased susceptibility to infections, possibly due to reduced white blood cell count (neutropenia);
significant reduction in white blood cells, increasing the risk of infections (agranulocytosis).
Common (may affect up to 1 in 10 patients)
yellowing of the eyes and skin (jaundice), abdominal pain, loss of appetite, fatigue, fever, and elevated liver 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 lung disease or 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 insufficiency, particularly in those with bronchial asthma;
decreased sexual drive.
Uncommon (may affect up to 1 in 100 patients)
heart rhythm disturbances or their worsening, sometimes leading to cardiac arrest (see Warnings and precautions and Cordarone with other medicines in section 2), conduction disturbances in the heart muscle (sinoatrial block, atrioventricular block of varying degrees);
numbness, muscle weakness, tingling, and burning sensations; these may be symptoms of sensory-motor peripheral neuropathy (nerve disease) and/or myopathy (muscle disease), usually reversible after discontinuation of Cordarone.
Very rare (may affect up to 1 in 10,000 patients)
blurred or deteriorating vision; these may be symptoms of optic nerve damage that could 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 arrest, particularly in patients with sinus node dysfunction and/or elderly patients;
skin rash due to vasculitis (inflammation of blood vessels);
morning or exertion-induced headaches, nausea, seizures, fainting, visual disturbances, or disorientation; these may be symptoms of brain dysfunction due to increased intracranial pressure (pseudotumour cerebri);
impaired motor coordination.

Other adverse effects of Cordarone may occur with the following frequencies:
Very common (affects at least 1 in 10 patients):

corneal microdeposits located just beneath the pupil. These may be associated with seeing coloured 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 mild to moderate (1.5 to 3 times above the upper normal limit), occurring early in treatment. These abnormalities may normalise spontaneously or after dose reduction;
photosensitivity.

Common (may affect up to 1 in 10 patients)

abnormally slow heartbeat (bradycardia), usually moderate and dose-dependent;
hypothyroidism (manifesting as severe fatigue, weight gain, constipation, and muscle pain), hyperthyroidism (manifesting as restlessness, agitation, weight loss, and excessive sweating), sometimes leading to death;
extrapyramidal tremors, nightmares, sleep disturbances;
greyish-blue skin discoloration during long-term, high-dose amiodarone therapy, which slowly resolves after discontinuation of the drug;
constipation;
itchy red rash (exanthema).

Uncommon (may affect up to 1 in 100 patients)

dry mouth.

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

haemolytic anaemia, aplastic anaemia (anaemias 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 disease (pseudo-alcoholic hepatitis, liver cirrhosis), sometimes leading to death;
increased blood creatinine levels;
headaches;
epididymitis, impotence;
bronchospasm in patients with severe respiratory insufficiency, particularly in those with bronchial asthma, adult respiratory distress syndrome (ARDS), sometimes fatal, especially immediately after surgery (possible interaction with high concentrations of 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 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;
altered sense of smell (parosmia);
decreased appetite;
decreased libido;
delirium (including confusion), hallucinations;
lupus-like syndrome (an autoimmune disorder 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 across 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 effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or nurse. Adverse effects can 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, Poland, Tel: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl.
Reporting adverse effects helps provide 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 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 specified month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Proper disposal helps 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.
Other components are: maize starch, monohydrate lactose, magnesium stearate, povidone, colloidal anhydrous silica.

What Cordarone looks like and contents of the pack
White tablets with a dividing line on one side.
One pack contains 30 tablets in PVC/Aluminium blisters, in a cardboard box.
For more detailed information, please contact the responsible party or the parallel importer.
Marketing Authorisation Holder in Bulgaria, the country of export:
sanofi-aventis groupe
54 rue La Boétie
75008 Paris
France
Manufacturer:
Sanofi Winthrop Industrie
1, rue de la Vierge
Ambares et Lagrave
33565 Carbon Blanc Cedex
France
Opella Healthcare Hungary Ltd.
2112 Veresegyház
Lévai utca 5
Hungary
Sanofi-aventis, S.A.
Ctra. C-35 (La Ballòria-Hostalric) Km. 63.09
17404 Riells i Viabrea (Girona) – Spain
Parallel Importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Repackaged by:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Marketing Authorisation Number in Bulgaria, the country of export: 9800028
Parallel Import Licence Number: 128/23