PACKAGE LEAFLET: INFORMATION FOR THE USER

Warning! Keep the leaflet, information on the immediate packaging in a foreign language!
Cordarone
200 mg, tablets
Amiodaroni hydrochloridum
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 doubts, 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 reactions, 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 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 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 and other medicines);
if the patient has a thyroid disorder;
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 (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 a proarrhythmic effect. Cases of new-onset cardiac arrhythmias or worsening of treated arrhythmias have been reported, sometimes leading to death.
Proarrhythmic effects of Cordarone are reported less frequently than with other antiarrhythmic drugs. The proarrhythmic effect of amiodarone occurs particularly as a result of interaction with drugs prolonging the QT interval and/or in the presence of electrolyte disturbances (see section Cordarone and other medicines and section 4). Regardless of QT interval prolongation, Cordarone has low activity in inducing torsade de pointes arrhythmias.
Amiodarone may affect the function of a pacemaker or an implantable cardioverter-defibrillator, especially during long-term antiarrhythmic therapy.
Therefore, monitoring of device function is recommended before and during amiodarone treatment.
Oral Cordarone is not contraindicated in patients with heart failure, but caution is required during treatment, as it may exacerbate heart failure. In such cases, Cordarone may be used in combination with other drugs.
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, onset of 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 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 sole symptom or associated with deterioration of 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.
Regular 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 threefold 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 and joint pain, severe rapidly progressing illness with large subcutaneous blisters, extensive skin erosions, peeling of large skin areas, 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 drugs is not recommended: beta-blockers, calcium channel blockers reducing heart rate (verapamil, diltiazem), 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 discontinuation of treatment.
The most common symptoms are tingling, burning, and erythema on skin areas exposed to sunlight.
Phototoxic reactions and rash are rarely observed.
Before surgery, inform the anesthesiologist that the patient is taking amiodarone; cases of 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 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 and 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 (antimicrobial agent), or the antiprotozoal drug 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 drugs: 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 pectoris (heart disease) or hypertension (high blood pressure): verapamil, diltiazem,
antiviral drugs used in the treatment of hepatitis C, e.g. sofosbuvir, daclatasvir, symmetrel, or ledipasvir, due to the risk of bradycardia,
certain laxatives (used to treat constipation) causing low blood potassium levels: bisacodyl, senna,
cholesterol-lowering drugs – statins, e.g. simvastatin, atorvastatin, lovastatin.

Use caution when taking the following medicines concomitantly with Cordarone:

diuretics, e.g. furosemide,
anti-inflammatory drugs – systemic corticosteroids, e.g. hydrocortisone, prednisolone,
tetracosactide – a drug used to diagnose certain hormonal disorders,
antifungal drug – intravenous amphotericin B,
agents used in general anesthesia or high concentrations of oxygen 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 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 serum digoxin level tests and ECG, and may adjust the digitalis glycoside dose; the patient should be monitored for signs of digitalis 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, sirolimus,
flecainide – used to treat arrhythmias: treatment should 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 drugs,
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, 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 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 used as directed by the physician. In case of 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 applied.
Use in children
The safety and efficacy of Cordarone in children have not been established. Therefore, its use is not
recommended in these patients.
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
exposed to excessive doses. 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 few reports of amiodarone overdose. Symptoms may include
slowing of heart rate or 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 a dose is missed, take it as soon as possible,
except when the next dose is due soon. Do not take two doses
simultaneously or in close succession. In case of doubt, consult your doctor.
Stopping treatment with 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 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 fail to maintain adequate blood flow to vital organs and tissues), manifesting as confusion, weakness, or fainting;
anaphylactic reactions – severe, systemic allergic reactions affecting multiple organ systems, 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 indicate the life-threatening arrhythmia torsade de pointes (see Warnings and precautions and Cordarone and other medicines in section 2);
coughing up blood, indicating pulmonary haemorrhage;
abdominal pain and constipation, which may be symptoms of acute pancreatitis;
seeing, hearing, or feeling things that are not there (hallucinations);
increased frequency of infections, possibly due to reduced white blood cell count (neutropenia);
significant 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 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, pulmonary fibrosis, pleuritis, bronchiolitis obliterans organising pneumonia, or bronchospasm and/or respiratory arrest in cases of severe respiratory failure, especially in patients with bronchial asthma (see Warnings and precautions in section 2);
decreased sexual desire.

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 (sinuatrial 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), which are usually reversible upon discontinuation of Cordarone.

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

blurred vision or worsening of vision; these may be symptoms of optic nerve damage, which 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 (slow heart rate) or sinus node arrest, particularly in patients with sinus node dysfunction and/or elderly patients;
skin rash indicating vasculitis (inflammation of blood vessels);
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 coordination of movements.

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 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 moderately elevated (1.5 to 3 times above the upper limit of normal), occurring early in treatment. These abnormalities may return to normal 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 (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)

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 diseases (pseudo-alcoholic hepatitis, cirrhosis of the liver), sometimes leading to 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 leading to death, particularly immediately after surgery (possible interaction with high-concentration oxygen) (see Warnings and precautions and Cordarone and 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 (an autoimmune disorder 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 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 of the 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

Store below 30°C. Protect from light.
Keep the medicine in a place out of sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "EXP". The expiry date refers to the last day of the stated month.
Medicines should 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 packaging and other information

What Cordarone contains

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

What Cordarone looks like and contents of the pack
White tablets with a dividing groove on one side.
One pack contains 30 tablets in Al/PVC foil blisters, packed in a cardboard box.
For more detailed information, please contact the Marketing Authorisation Holder or the Parallel Importer.
Marketing Authorisation Holder in Bulgaria, country of export:
sanofi-aventis groupe
54 rue La Boétie
75008 Paris
France
Manufacturer:
Sanofi Winthrop Industrie
1, rue de la Vierge
Ambarès et Lagrave
33565 Carbon Blanc Cedex
France
Opella Healthcare Hungary Ltd.
2112 Veresegyház Levai utca 5
Hungary
sanofi-aventis, S.A.
Ctra. C-35 (La Batllòria-Hostalric) Km. 63.09
17404 Riells i Viabrea (Girona)
Spain
Parallel Importer:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Repackaged in:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
SHIRAZ PRODUCTIONS Sp. z o.o.
ul. Tymiankowa 24/28
95-054 Ksawerów
Marketing Authorisation Number in Bulgaria, country of export: 9800028
Parallel Import Licence Number: 251/23