Package leaflet: Information for the patient

Warning! Keep this leaflet. Information on the immediate packaging is 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 doubts, please 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 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 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 heartbeat.
It is used to treat life-threatening heart rhythm disorders:

rhythm disturbances 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 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 levels increase the risk of cardiac arrhythmias).
The pharmacological action of amiodarone causes changes in the ECG: QT interval prolongation (associated with prolonged repolarization phase) with possible appearance of U waves.
However, these changes do not indicate toxic effects.
Heart function 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 types of 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 interactions with medicines that prolong the QT interval and/or in the presence of electrolyte disturbances (see subsection "Cordarone with other medicines" and section 4). Regardless of QT interval prolongation, Cordarone shows low activity in causing torsade de pointes arrhythmias.
Amiodarone may affect the performance of a pacemaker or an implanted cardioverter-defibrillator, especially during long-term antiarrhythmic therapy. Therefore, monitoring of device function is recommended before and during amiodarone treatment.
Oral administration of 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 this 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 cardiac arrhythmias,
shortness of breath or worsening of existing shortness of breath,
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 be performed 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 an increased risk of thyroid disorders, regular monitoring of thyroid function is recommended.
Hyperthyroidism may occur during treatment or up to several months after discontinuation of amiodarone. 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 several months after stopping Cordarone; clinical improvement is preceded by normalization of thyroid function laboratory 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 toxic lung effects, 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. Consideration should be given to continuing Cordarone treatment, as interstitial pneumonitis is usually reversible if therapy 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 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 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 ruptured large subcutaneous blisters, extensive skin erosions, shedding 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 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 antagonists that reduce heart function (verapamil, diltiazem), and laxatives that may cause hypokalemia.
Avoid exposure to sunlight and use sun protection measures during treatment. Cordarone causes photosensitivity, which may persist for several months after discontinuation of treatment.
The most common symptoms are tingling, burning, and erythema affecting skin areas exposed to sunlight.
Phototoxic reactions and rash have been rarely observed.
Before undergoing surgery, inform the anesthesiologist that the patient is taking amiodarone; cases of severe cardiovascular and respiratory complications (sometimes leading to death) 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 or recently taken, as well as any medicines the patient plans to take.
Do not use Cordarone concomitantly with medicines that may cause life-threatening arrhythmias (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 – vincamine;
neuroleptic medicines;
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 pectoris (heart disease) or arterial hypertension (high blood pressure): verapamil, diltiazem;
antiviral medicines used in the treatment of hepatitis C, e.g., sofosbuvir, daclatasvir, simprevir, ledipasvir, due to the risk of bradycardia;
certain laxatives (used to treat constipation) causing low blood potassium levels: bisacodyl, sena;
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). Before surgery, inform the anesthesiologist about Cordarone use;
phenytoin – used to treat epileptic seizures: close monitoring of the patient is required, and if signs of phenytoin overdose occur, the dose should be reduced immediately and serum phenytoin concentration measured;
cardiac glycosides, e.g., digoxin – used in heart diseases: the doctor will order serum digoxin concentration tests and ECG, and adjust the glycoside dose; the patient should be monitored for signs of cardiac glycoside 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 necessary;
immunosuppressants to prevent transplant rejection – cyclosporine, tacrolimus, sirolimus;
flecainide – used to treat arrhythmias: treatment will be conducted under strict medical supervision; the doctor will adjust the flecainide dose;
fentanyl – a potent 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 medicines;
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 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 use, 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. 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:
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; 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, its use is not recommended in this patient group.

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 if 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 regarding amiodarone overdose. Symptoms may include slowing of heart rate, ventricular tachycardia, torsade de pointes arrhythmias, hypotension, and liver damage.
Overdose requires immediate medical attention; treatment is symptomatic.
Neither amiodarone nor its metabolites are removed during dialysis.
In case of ingestion of a higher than recommended dose, 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 the next scheduled dose is approaching. Do not take two doses at once or within a short interval.
If in doubt, consult your doctor.

Discontinuation of Cordarone
If you have any further questions about 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 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 allergic reactions affecting multiple organs simultaneously, typically the cardiovascular, respiratory, and skin systems, occurring immediately after exposure to an allergen;
Quincke's oedema (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 be a sign of the life-threatening arrhythmia torsade de pointes (see "Warnings and precautions" and "Cordarone with other medicines" in section 2);
coughing up blood, which may indicate pulmonary haemorrhage;
abdominal pain and constipation, which may be symptoms of acute pancreatitis or sudden onset of pancreatitis;
seeing, hearing, or feeling things that are not there (hallucinations);
increased frequency of infections, possibly 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 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 pneumonitis or pulmonary fibrosis, pleuritis, bronchiolitis obliterans organising pneumonia, or bronchospasm and (or) respiratory arrest in cases of severe respiratory failure, particularly in patients with bronchial asthma (see "Warnings and precautions" in section 2);
decreased libido.

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 with other medicines" in section 2), and disturbances in cardiac conduction (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 neuropathy, 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 or sinus node arrest, particularly in patients with sinus node dysfunction and (or) elderly patients;
skin rash as a sign of 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 (pseudotumour 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, forming 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 reduction of 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 return to normal either after dose reduction or spontaneously;
photosensitivity.

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

slow heart rate (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 increased sweating), sometimes leading to death;
extrapyramidal tremors, nightmares, sleep disturbances;
greyish-blue 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):

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 tendencies);
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 concentration;
headaches;
epididymitis, impotence;
bronchospasm in patients with severe respiratory failure and particularly in patients with bronchial asthma, adult respiratory distress syndrome, sometimes leading to death, 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 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 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 or nurse. Adverse reactions can be reported directly to the Department for Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +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

Store below 30°C. Protect from light.
Keep the medicine in a place inaccessible and out of sight 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 what to do with medicines no longer required. This will help protect the environment.

6. Contents of the pack 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, lactose monohydrate 200 mesh, magnesium stearate, povidone K90 F, colloidal anhydrous silica.

What Cordarone looks like and contents of the pack
White tablets with a score line on one side.
One pack contains 30 tablets in PVC/Al blisters, packed in a cardboard box.
For further information, please contact the marketing authorisation holder or the parallel importer.
Marketing authorisation holder in Bulgaria, the country of export:
Sanofi Winthrop Industrie
82 avenue Raspail
94250 Gentilly
France
Manufacturer:
Sanofi Winthrop Industrie
1, rue de la Vierge
Ambares et Lagrave
33565 Carbon Blanc Cedex
France
Opella Healthcare Hungary Ltd.
Lévai utca 5
2112 Veresegyház
Hungary
sanofi-aventis, S.A.
Ctra. C-35 (La Batllòria-Hostalric) Km. 63.09
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 Bulgaria, the country of export: 9800028
Parallel import authorisation number: 365/18