Cordarone

Patient Information Leaflet

Warning!
Keep this leaflet. The information on the immediate packaging is in a foreign language.
Cordarone
200 mg, tablets
Amiodarone hydrochloride
Please read the entire leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of Contents

1. What Cordarone is and what it is used for
2. Important information before taking Cordarone
3. How to take Cordarone
4. Possible side effects
5. How to store Cordarone
6. Contents of the pack and other information

1. What Cordarone is and what it is used for

Cordarone is available as tablets and contains amiodarone hydrochloride as the active substance. Amiodarone is a potent antiarrhythmic medicine used to treat irregular heartbeats.
It is used to treat 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, sino-atrial block, sick sinus syndrome, except in patients with a pacemaker implanted (risk of sinus node inhibition);
• in patients with second- or third-degree atrioventricular block, except in patients with a pacemaker implanted;
• concurrently with medicines that may cause life-threatening cardiac 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 ECG: QT interval prolongation (due to prolonged repolarization period), possibly with the appearance of a U wave.
However, these changes do not cause toxic effects.
Heart rate may significantly decrease in elderly patients.
If second- or third-degree atrioventricular block, sino-atrial block, or dual AV nodal pathway 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 have been reported less frequently than with other antiarrhythmic drugs. The proarrhythmic effect of amiodarone occurs particularly as a result of interaction 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 inducing torsade de pointes-type 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 the condition. In such cases, Cordarone may be used in combination with other medicines.
Before starting Cordarone, discuss with your doctor or pharmacist if the patient is currently taking a medicine containing sofosbuvir, used in the treatment of hepatitis C virus infection, as this may cause life-threatening bradycardia. The doctor may consider alternative treatment options. If treatment with both amiodarone and sofosbuvir is necessary, additional cardiac monitoring may be required.
Contact your doctor immediately if the patient is taking a medicine containing sofosbuvir for hepatitis C and experiences any of the following during treatment:

• slow or irregular heartbeat or arrhythmias,
• shortness of breath or worsening of existing 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 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 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 treatment should be reconsidered, 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 more than three times the upper normal limit, 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 therapy (e.g., progressive rash with blisters or mucosal lesions, fever and joint pain, severe rapidly progressing illness with large subcutaneous bullae, extensive skin erosions, large epidermal sloughing, and fever – see also section 4). These symptoms may be life-threatening.
Cordarone may cause sensory-motor peripheral neuropathy and/or myopathy.
Symptoms usually resolve within several months after discontinuation of Cordarone, but sometimes some symptoms may persist.
If blurred vision or worsening of vision occurs, a complete ophthalmological examination, including fundoscopy, should be performed immediately. If optic nerve damage and/or optic neuritis is detected, Cordarone must be discontinued due to the risk of vision loss.
Concomitant use of amiodarone with the following medicines is not recommended: beta-blockers, calcium channel blockers 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 discontinuation of treatment.
The most common symptoms are tingling, burning, and erythema on 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 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 taken, recently taken, or planned for use.
Do not take Cordarone concurrently with medicines that may cause life-threatening cardiac arrhythmias (type torsade de pointes). These include:

• medicines used to treat arrhythmias (irregular heartbeat): quinidine, disopyramide, procainamide, sotalol, bretylium, bepridil;
• intravenous erythromycin (antibiotic), cotrimoxazole (antibacterial 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 – antibacterial agents: ciprofloxacin, ofloxacin, levofloxacin;
• beta-blockers – used in heart diseases, e.g. propranolol;
• calcium channel blockers that slow heart rate – used in angina (heart disease) or hypertension (high blood pressure): verapamil, diltiazem;
• antiviral medicines used in the treatment of hepatitis C, e.g. sofosbuvir, daklatasvir, symeprevir, or ledipasvir, due to the risk of bradycardia;
• certain laxatives (used to treat constipation) that cause low blood potassium levels: bisacodyl, senna;
• cholesterol-lowering medicines – statins, e.g. simvastatin, atorvastatin, lovastatin.

Use caution when taking the following medicines concurrently 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 concentrations of oxygen administered during surgical procedures (see: “Warnings and precautions” in section 2 and section 4). Inform the anesthesiologist about Cordarone use before surgery;
• phenytoin – used to treat epileptic seizures: close monitoring is required and if signs of phenytoin overdose occur, the dose should be reduced immediately and serum phenytoin levels measured;
• digitalis glycosides, e.g. digoxin – used in heart diseases: the doctor will order serum digoxin level tests and ECG, and adjust the digoxin 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, and sirolimus;
• flecainide – used to treat arrhythmias: treatment will be under strict medical supervision; the doctor will adjust the flecainide dose;
• fentanyl – a strong painkiller;
• lidocaine – an anesthetic;
• sildenafil – used to treat erectile dysfunction;
• midazolam – used for anxiety and sedation before surgical procedures;
• triazolam – used for insomnia;
• dihydroergotamine and ergotamine – antimigraine agents;
• colchicine – used to treat acute gout attacks.

Pregnancy, breastfeeding, and effects on fertility
During pregnancy, breastfeeding, or if pregnancy is suspected or planned, consult a doctor before using this medicine.
Due to Cordarone's effects on the fetal thyroid, use during pregnancy is contraindicated unless otherwise directed by a physician. Consult a doctor before use.
Use of Cordarone during breastfeeding is contraindicated.
There are no data on the effects 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. 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 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 interruptions (two days per week) may also be applied.
Use in children
The safety and efficacy of Cordarone treatment in children have not been established.
Therefore, use in this patient group 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
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.
Overdose of Cordarone
There are few reports regarding amiodarone overdose. Symptoms may include slowing of heart
contractions 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.
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, except when the next dose is due soon. 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 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 everybody gets 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 of life-threatening systemic reactions due to a severe allergic response, 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 allergic reactions affecting multiple organ systems simultaneously, usually 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 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 haemorrhage;
• abdominal pain and constipation, which may indicate acute pancreatitis;
• seeing, hearing, or sensing things that are not there (hallucinations);
• increased frequency of infections. This may be due to a reduced number of white blood cells (neutropenia);
• a marked decrease in white blood cells, increasing the risk of infections (agranulocytosis).

Frequent (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 enzyme levels in blood tests; these are symptoms of potentially life-threatening acute liver injury or liver failure;
• shortness of breath and dry cough; these may be symptoms of life-threatening interstitial lung disease, pulmonary fibrosis, pleuritis, bronchiolitis obliterans with pneumonia (see "Warnings and precautions" in section 2), or bronchospasm and/or respiratory arrest in patients with severe respiratory insufficiency, especially those with bronchial asthma;
• decreased sexual desire.

Uncommon (may affect 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), and 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 after discontinuation of Cordarone.

Very rare (may affect 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, especially 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 (pseudotumour cerebri);
• impaired coordination.

Other adverse reactions 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 reducing the amiodarone dose;
• increased liver enzyme 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.

Frequent (may affect 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 fatal;
• extrapyramidal tremors, nightmares, sleep disturbances;
• greyish-blue skin discoloration during long-term, high-dose amiodarone therapy, which slowly resolves after discontinuation;
• 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 diseases (pseudo-alcoholic hepatitis, liver cirrhosis), sometimes fatal;
• increased blood creatinine levels;
• headache;
• epididymitis, impotence;
• bronchospasm in patients with severe respiratory insufficiency, especially those with bronchial asthma, adult respiratory distress syndrome, sometimes fatal, 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), 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;
• abnormal sense of smell (parosmia);
• decreased appetite;
• reduced libido;
• delirium (including confusion), hallucinations;
• lupus-like syndrome (a condition in which the immune system attacks various parts of the body, causing joint pain, stiffness, swelling, and skin redness, sometimes in a butterfly-shaped rash on the face);
• life-threatening complication after heart transplantation (primary graft dysfunction), in which the transplanted heart fails to function properly (see "Warnings and precautions" in section 2).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at 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, in the original packaging.
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 packaging and other information

What Cordarone contains

• The active substance is amiodarone hydrochloride. One tablet contains 200 mg of amiodarone hydrochloride.
• Other ingredients are: maize starch, monohydrate lactose, magnesium stearate, povidone K 90 F, 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/Al blisters, in a cardboard box.
For more detailed information, please contact the marketing authorization holder or the parallel importer.

Marketing authorization holder in Romania, country of export:
Sanofi Romania SRL
Str. Gara Herăstrău, no. 4, Clădirea B, floors 8-9
Sector 2, Bucharest, Romania

Manufacturer:
Sanofi Winthrop Industrie
1, rue de la Vierge, Ambarès et Lagrave
33565 Carbon Blanc Cedex
France
Opella Healthcare Hungary Limited Liability Company
Lévai u. 5, 2112 Veresegyház
Hungary

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 authorization number in Romania, country of export: 11070/2018/02
Parallel import authorization number: 312/14