PACKAGE LEAFLET: INFORMATION FOR THE USER

Cordarone 150 mg/3 ml solution for injection

Amiodarone hydrochloride

Read all of this leaflet carefully before you start taking this medicine
because it contains important information for you.
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor, pharmacist or
nurse.
 This medicine has been prescribed for you only. Do not pass it on to
others. It may harm them, even if their signs of illness are the same as
yours.
 If you get any side effects talk to your doctor, pharmacist or nurse.
This includes any possible side effects not listed in this leaflet (see
section 4).

What is in this leaflet

1. What Cordaron 150 mg/3ml is and what it is used for

2. What you need to know before you use Cordaron 150 mg/3ml
3. How to use Cordaron 150 mg/3ml
4. Possible side effects
5. How to store Cordaron 150 mg/3ml
6. Contents of the pack and other information

1. What Cordaron 150 mg/3ml is and what it is used for

This medicinal product is indicated for the treatment of certain heart rhythm
disorders.
Solution for injection for intravenous infusion. Class III antiarrhythmics (C:
Cardiovascular system).

2. What you need to know before you use Cordaron 150 mg/3ml
Do not use Cordaron 150 mg/3ml

This medicinal product should not be used in the following situations:

 if you are allergic to iodine, amiodarone, or any of the other
ingredients of this medicine;
 if you have hyperthyroidism (overactive thyroid gland);
 if you have certain heart rhythm and/or heart conduction disorders;
 if you suffer from sudden malaise with decrease in blood pressure;
 if you have marked low blood pressure;
 if you have very low heart rate;
 if you are pregnant (except in emergency situations);
 if you are breastfeeding;
 in combination with other medicinal products that can cause serious
heart rhythm disturbances (see Drug interactions);
 if you have atrioventricular block or other severe atrioventricular
conduction disorders (disturbance in the transmission of an impulse
from the atria to the ventricles);
 in cases of severe arterial hypotension, circulatory collapse;
 intravenous injection is contraindicated in cases of low blood
pressure, severe respiratory failure, cardiomyopathy or heart failure
(increased risk of worsening of these conditions).

Contraindications do not apply when amiodarone is used in the emergency

treatment of cardiopulmonary resuscitation of shock (defibrillator) resistant
ventricular fibrillation.

Warnings and precautions

Cordaron 150 mg/3ml is administered only intravenously, only in emergency
cases in a special care unit under continuous monitoring (ECG and blood
pressure). It must only be diluted using isotonic glucose solution.
The standard dose is 5 mg/kg body weight given by intravenous infusion
over a period of at least 3 minutes. It should not be mixed with any
medication in the same syringe.

The recommended dose for ventricular fibrillation/pulseless ventricular

tachycardia resistant to defibrillation is 300 mg (or 5 mg/kg body-weight)
diluted in 20 ml 5% glucose and rapidly injected intravenously. An
additional 150 mg (or 2.5 mg/kg body-weight) IV dose may be considered if
ventricular fibrillation persists.

The standard recommended starting dose is 5 mg/kg body weight given by

intravenous infusion over a period of 20 to 120 minutes. This should be
administered as a dilute solution in 250 mL 5% glucose. The infusion may
be repeated 2 to 3 times over a 24-hour period. The rate of infusion should be
adjusted on the basis of clinical response.

The therapeutic effect is visible in the first minutes, then decreased

gradually, and should be followed by a maintenance infusion.

Maintenance dose: 10 to 20 mg/kg/day in 250 ml of 5% glucose solution

every 24 hours (on average 600 to 800 mg/ 24 hours up to a maximum of
1200 mg/ 24 hours) for a few days.

Transition to oral therapy: Oral treatment is started from the first day of
infusion.

The use of administration equipment or devices containing plasticizers such

as DEHP (di-2-ethylhexylphthalate) in the presence of amiodarone may
result in leaching out of DEHP. In order to minimize patient exposure to
DEHP, the final amiodarone dilution for infusion should preferably be
administered through non DEHP-containing sets, such as PVC (DEHP-free),
polyolefins (polyethylene, polypropylene), glass, etc.

Caution should be exercised in cases of hypotension (low blood pressure),

severe respiratory failure (condition in which lungs have a hard time
supplying the blood with oxygen or removing carbon dioxide) and
decompensated or severe heart failure (complaints of heart failure despite
ongoing treatment adherence or due to insufficient treatment).
Cases of severe, potentially life-threatening bradycardia (slow heart rate) and
heart block have been observed when amiodarone is used in combination
with sofosbuvir alone or in combination with another hepatitis C virus
(HCV) direct acting antiviral drugs (DAA), such as daclatasvir, simeprevir or
ledipasvir. Therefore, co-administration of these agents with amiodarone is
not recommended. If concomitant use with amiodarone cannot be avoided, it
is recommended that patients are closely monitored when initiating
sofosbuvir alone or in combination with other DAAs. Patients who are
identified as being at high risk of bradyarrhythmia should be continuously
monitored for at least 48 hours in an appropriate clinical setting after
initiation of the concomitant treatment with sofosbuvir.
Patients receiving these hepatitis C medicines with amiodarone, with or
without other medicines that lower heart rate, should be warned of the
symptoms of bradycardia and heart block (abnormal conduction of impulses
within the heart leading to cardiac arrest) and should be advised to seek
urgent medical advice if they experience them.

Eye disorders

If blurred or decreased vision occurs, complete ophthalmologic examination

including fundoscopy should be promptly performed. Appearance of optic
neuropathy and/or optic neuritis requires amiodarone withdrawal due to the
potential progression to blindness.

If you are on a heart transplant waiting list, your doctor may change your
treatment. This is because taking amiodarone before heart transplantation has
shown an increased risk of a life-threatening complication (primary graft
dysfunction) in which the transplanted heart stops working properly within
the first 24 hours after surgery.

Precautions

This medicinal product should be used cautiously in patients with electrolyte

disturbances, especially in patients with low potassium levels.
It is important to inform the anesthesiologist prior to surgery that you are
being treated with amiodarone.
Safety and effectiveness of this medicine have not been established in
pediatric patients therefore it should not be given to children.
Amiodarone injection contains benzyl alcohol. Intravenous administration of
benzyl alcohol has been associated with serious adverse events and death in
neonates (a child under 1 month of age) - “Gasping Syndrome” (symptoms
include a striking onset of gasping syndrome, hypotension, bradycardia and
cardiovascular collapse).
Ask your doctor or pharmacist for advice before using this medicine if:
 You currently take a medicine containing sofosbuvir for the treatment
of hepatitis C as it may result in a life-threatening slowing of your
heartbeat. Your doctor may consider alternative treatments. If
treatment with amiodarone and sofosbuvir is needed, you may require
additional heart monitoring.
Cordaron 150 mg/3 ml solution for injection may increase the effect of the
following medicines: Cyclosporine, tacrolimus and sirolimus - used to help
prevent rejection of transplants.
Tell your doctor immediately if you are taking a medicine containing
sofosbuvir for the treatment of hepatitis C and during treatment you
experience:
 Slow or irregular heartbeat or heart rhythm problems
 Shortness of breath or worsening of existing shortness of breath
 Chest pain
 Light-headedness
 Palpitations
 Near-fainting or fainting.
Cordaron 150 mg/3ml contains benzyl alcohol.
This medicine contains 60 mg benzyl alcohol in each 3 ml ampoule which is
equivalent to 20 mg/ml.

Benzyl alcohol may cause allergic reactions.

Benzyl alcohol has been linked with the risk of severe side effects including
breathing problems (called “gasping syndrome”) in young children. This
medicine should not be used in newborn babies (up to 4 weeks old), unless
recommended by your doctor.
This medicine should not be used for more than a week in young children
(less than 3 years old), unless advised by your doctor or pharmacist.
Ask your doctor or pharmacist for advice if you are pregnant or breast-
feeding. This is because large amounts of benzyl alcohol can build-up in
your body and may cause side effects (called “metabolic acidosis”).
Ask your doctor or pharmacist for advice if you have a liver or kidney
disease. This is because large amounts of benzyl alcohol can build-up in your
body and may cause side effects (called “metabolic acidosis”).
Other medicines and Cordaron 150 mg/3 ml
Tell your doctor or pharmacist if you are taking, have recently taken or might
take any other medicines.
Tell your doctor, if you are taking any of the following medicines:
 Sofosbuvir, used for the treatment of hepatitis C.
Talk to your doctor or pharmacist before taking sofosbuvir if:
 if you are taking a medicine containing sofosbuvir for the treatment
of hepatitis C as it may result in a life-threatening slowing of your
heartbeat. Your doctor may consider alternative treatments. If
treatment with amiodarone and sofosbuvir is needed, you may require
additional heart monitoring.
Tell your doctor immediately if you are taking a medicine containing
sofosbuvir for the treatment of hepatitis C and during treatment you
experience:
 Slow or irregular heartbeat or heart rhythm problems
 Shortness of breath or worsening of existing shortness of breath
 Chest pain
 Light-headedness
 Palpitations
 Near-fainting or fainting.
The combination of amiodarone with the following drugs that may induce
torsades de pointes (serious heart rhythm disturbance) is contra-indicated:
class Ia antiarrhythmics, sotalol, bepridil.
Amiodarone is also contraindicated in combination with certain Non-
antiarrhythmic drugs such as: vincamine, some neuroleptic agents, cisapride,
erythromycin IV, pentamidine (when administered parenterally), as there is
an increased risk of potentially lethal ‘torsades de pointes’.

Cordaron 150 mg/3 ml is not recommended to be used with the following

drugs:
 Beta-blockers and heart rate-lowering calcium channel blockers
(verapamil, diltiazem);
 Stimulating laxative agents that can cause hypokalemia.

Co-administration of amiodarone with drugs known to prolong the QT

interval (measured on an electrocardiogram) must be based on a careful
assessment of the potential risks and benefits for each patient since the risk
of torsade de pointes may increase and patients should be monitored for QT
prolongation.
Concomitant use of amiodarone with fluoroquinolones should be avoided.

Caution should be exercised when Cordaron 150 mg/3 ml is used with the
following drugs:
 drugs that prolong QT interval;
 potassium-lowering diuretics (used alone or in combination);
 systemic corticosteroids (glucocorticoids, mineralocorticoids),
tetracosactide;
 amphotericin B (intravenous);
 general anesthetics.
Cordaron 150 mg/3 ml may affect the following medicinal products:
 digitalis medicines (used to reduce heart rate);
 dabigatran (a new oral anticoagulant);
 warfarin (an anticoagulant) due to increased risk of bleeding;
  phenytoin (used in the treatment of epilepsy) - if used together, the
level of this drug in the blood may increase leading to neurological
symptoms;
 flecainide (antiarrhythmic medicine).
Concomitant use of amiodarone with the following medicinal products may
increase their toxicity: cyclosporine (immunosuppressant); fentanyl (used for
pain relief); statins (cholesterol-lowering agents); lidocaine (anesthetic);
tacrolimus (used after transplantation); sildenafil, midazolam (hypnotic),
triazolam (hypnotic), dihydroergotamine (used to treat migraine), ergotamine
(used to treat migraine), colchicine (used to treat gout).
Other interactions
Amiodarone is not recommended in combination with sofosbuvir or another
hepatitis C virus (HCV) direct acting antiviral (DAA) drugs (such as
daclatasvir, simeprevir, or ledipasvir) as it may result in severe symptomatic
bradycardia. The cause of bradycardia is not known. If co-administration
cannot be avoided, close cardiac monitoring is recommended.
Cordaron 150 mg/3 ml with food and drink
It is recommended to avoid the consumption of grapefruit juice during
treatment with amiodarone.

Pregnancy and breastfeeding

Because of its effects on the fetal thyroid gland, amiodarone is
contraindicated during pregnancy unless the benefit outweighs the risk.
Breast-feeding is contraindicated during treatment with this medicinal
product.
If you are pregnant or breast-feeding, think you may be pregnant or are
planning to have a baby, ask your doctor or pharmacist for advice before
taking this medicine.
Driving and using machines

Cordaron 150 mg/3 ml does not affect your ability to drive or use machinery.

3. How to use Cordaron 150 mg/3ml

Cordarone 150 mg/3 ml solution for injection is only used in the hospital,
under medical supervision.
The usual starting dose is 5 mg/kg body weight. The infusion may be
repeated 2 to 3 times over a 24-hour period.
Maintenance treatment: the maintenance dose is 10 to 20 mg/kg per day for
several days.
In extreme clinical emergency such as cardiopulmonary resuscitation of
shock-resistant ventricular fibrillation: 300 mg (or 5 mg / kg) amiodarone as
the first dose is diluted in 20 ml of 5% glucose solution i.v. It can be
administered by bolus injection. If ventricular fibrillation continues, an
additional 150 mg (or 2.5 mg / kg) i.v. dose administration can be
considered. Cordaron 150 mg tablets can also be prescribed on the first day
of the infusion (3 tablets per day). If necessary, this can be increased to 4 to 5
tablets per day.
There are only limited data on the efficacy and safety of this medicine in
children. The doctor will decide how much should be given.
Use in children and adolescents
Medicines administered intravenously containing benzyl alcohol should be
used with caution in children younger 3 years old (see also "Cordaron 150
mg/3ml contains benzyl alcohol").
Method of administration
To open the ampoule:
Hold the ampoule firmly, the colored point facing you (figure 1). Hold the
top of the ampoule between your thumb and forefinger (with your thumb on
the colored point), then press back (figures 2 and 3).
To avoid reactions at the injection site, if possible, Cordaron 150 mg/3 ml
should be administered through a central venous catheter. This medicinal
product should be administered as an intravenous infusion with 5% isotonic
glucose solution. Other preparations should not be mixed into the infusion
solution.
The use of administration equipment or devices containing plasticizers such
as DEHP (di-2-ethylhexylphthalate) in the presence of amiodarone may
result in leaching out of DEHP. In order to minimize patient exposure to
DEHP, the final amiodarone dilution for infusion should preferably be
administered through non DEHP-containing sets, such as PVC (DEHP-free),
polyolefins (polyethylene, polypropylene), glass, etc.

Frequency of administration
During initial treatment, amiodarone may be administered 2 or 3 times a day.

4. Possible side effects

Like all medicines, Cordarone 150 mg/3 ml solution for injection can cause
side effects, although not everybody gets them.
Common (may affect up to 1 in 10 people):
 decrease in blood pressure, usually moderate and transient. Cases of
hypotension or collapse have been reported following overdosage or
a too rapid injection;
 slow heart rate (bradycardia);
  injection site reactions such as pain, erythema, oedema, induration,
inflammation (phlebitis), cellulitis, infection, pigmentation changes;
 Decrease in sex drive.

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

 acute liver disorders with high serum transaminases (liver enzymes)
and/or jaundice, including hepatic failure, sometimes fatal;
 isolated increase in serum transaminases, which is usually moderate
(1.5 to 3 times normal range) at the beginning of therapy. They may
return to normal with dose reduction or even spontaneously;
 hot flashes, sweating;
 nausea;
 in rare cases, the following adverse effects have been observed after
direct intravenous administration: anaphylactic shock, benign
intracranial hypertension (increased intracranial pressure), headache,
respiratory disorders (inflammation or fibrosis of the lung, sometimes
fatal), severe respiratory complications (acute respiratory distress
syndrome in adults, sometimes fatal), bronchospasm (difficulty
breathing or wheezing) and/or shortness of breath in case of severe
respiratory failure, and especially in asthmatic patients;
 marked bradycardia, sinus arrest requiring discontinuation of
amiodarone, especially in patients with sinus node dysfunction and/or
in elderly patients;
 onset of worsening of arrhythmia, sometimes followed by cardiac
arrest;
 Feeling unwell, confused or weak, nausea, loss of appetite, feeling
irritable. This could be an illness called ‘syndrome of inappropriate
antidiuretic hormone secretion’ (SIADH).
Not known (frequency cannot be estimated from the available data):
 angioedema - a severe allergic reaction that causes swelling of the
face or throat;
 eczema, urticaria, severe skin reactions (sometimes fatal), including
epidermal necrolysis/Stevens-Johnson syndrome (severe reactions
with blistering of the skin, mouth, eyes and genitals), bullous
 dermatitis and drug reaction with eosinophilia and systemic
symptoms;
 hyperthyroidism (increased function of the thyroid gland, which can
cause increased appetite, weight loss or sweating, insomnia,
nervousness, etc.);
 back pain;
 "torsades de pointes" (life-threatening heart rhythm disorder);
 optic neuropathy/neuritis which can lead to blindness (see section 2);
 inflammation of the pancreas, which causes severe pain in the
abdomen and back;
 confusion/delirium;
 life-threatening complication after a heart transplant (primary graft
dysfunction) in which the transplanted heart stops working properly
within the first 24 hours after surgery (see section 2 "Warnings and
precautions");
 Seeing, hearing or feeling things that are not there (hallucinations);
 You may get more infections than usual. This could be caused by a
decrease in the number of white blood cells (neutropenia);
 Severe reduction in the number of white blood cells which makes
infections more likely (agranulocytosis).

Reporting side effects

If you get any side effects, talk to your doctor or pharmacist. This includes
any possible side effects not listed in this leaflet. You can also report side
effects directly to Bulgaria Drug Agency: str. "Damyan Gruev" № 8 1303
Sofia.
By reporting side effects, you can help provide more information on the
safety of this medicine

5. How to store Cordaron 150 mg/3ml

Do not use this medicine after the expiry date which is stated on the carton.
Cordaron 150 mg/3ml should be stored below 25°C and protected from light.
Keep out of the reach and sight of children.
6. Contents of the pack and other information

What Cordaron 150 mg/3 ml contains

The active substance is: amiodarone hydrochloride 150 mg. The other
ingredients are: polysorbate 80, benzyl alcohol, water for injections up to 3
ml.

Cordaron 150mg/3ml is available Packs with 6 ampoules.

Marketing Authorisation Holder

Sanofi-aventis groupe, France

Manufacturer
SANOFI WINTHROP INDUSTRIE, France
and/or
SANOFI-AVENTIS Zrt, Hungary
and/or
Delpharm Dijon, France

This leaflet was last revised in: January 2022

INFORMATION ON THE OUTER PACKAGING

CARTON BOX

1. NAME OF THE MEDICAL PRODUCT

Cordarone 150 mg/3 ml solution for injection

Amiodarone hydrochloride

2. ACTIVE SUBSTANCE

Each 3 ml ampoule contains 150 mg amiodarone hydrochloride (50 mg/ml).

3. BACKGROUND MATERIAL LIST

Benzyl alcohol, polysorbate 80 and water for injections.

4. PHARMACEUTICAL FORMS AND CONTENTS

6 ampoules x 3ml

5. METHODS AND ROUTE (S)

IV use.
Before use read the package leaflet.
Administered only as an intravenous infusion with 5% isotonic glucose
solution.
6. SPECIAL WARNING THAT THE MEDICAL PRODUCT MUST
BE STORED OUT OF THE RICH AND SIGHT OF CHILDREN

Keep out of the reach and sight of children.

7. EXPIRY DATE

EXP:

8. OTHER SPECIAL WARNINGS

For hospital use.

Strictly adhere to the prescribed dose.

9. SPECIAL STORAGE CONDITIONS

This medicine should be stored below 25°C and protected from light.

10. MARKETING AUTHOSIZATION HOLDER NAME AND

ADDRESS

Sanofi-aventis groupe, France

54 rue La Boetie
75008 Paris
France

11. MARKETING AUTHOTIZATION NUMBER

Reg. N: 20000427

12. BATCH NUMBER

Batch number:

13. SALES (LICENSING) ORDER

Obtained with medical prescription.

14. OTHER INFORMATION

Information in Braille
PC:
SN:
2D bar-code

INFORMATION ON THE INTERNAL PACKAGEING

AMPOULE

1. NAME OF THE MEDICAL PRODUCT

Cordarone 150 mg/3 ml solution for injection

Amiodarone hydrochloride

2. PHARMACEUTICAL FORM

6 ampoules x 3ml
50 mg/ml

3. METHODS AND ROUTE (S)

IV use.

4. EXPIRY DATE

EXP:

5. BATCH NUMBER

Batch number:

6. MARKETING AUTHORIZATION HOLDER LOGO

Sanofi