Amiokordin

Package Leaflet: Information for the Patient

Amiokordin, 50 mg/ml, Solution for Injection

Amiodarone Hydrochloride

Read All of This Leaflet Carefully Before Using This Medicine.

• Keep This Leaflet. You May Need to Read It Again.
• If You Have Any Further Questions, Ask Your Doctor or Nurse.
• This Medicine Has Been Prescribed for You. Do Not Pass It on to Others. It May Harm Them, Even if Their Symptoms Are the Same as Yours.
• If You Experience Any Side Effects, Tell Your Doctor or Nurse. See Section 4.

Contents of the Package Leaflet:

• 1. What Amiokordin Is and What It Is Used For
• 2. Important Information Before Using Amiokordin
• 3. How to Use Amiokordin
• 4. Possible Side Effects
• 5. How to Store Amiokordin
• 6. Contents of the Package and Other Information

1. What Amiokordin Is and What It Is Used For

Amiokordin Is a Solution for Injection Containing the Active Substance Amiodarone Hydrochloride. Amiodarone Is a Potent Anti-Arrhythmic Drug Used to Treat Irregular Heartbeats.

• Treatment of Arrhythmias in Wolff-Parkinson-White Syndrome
• Atrial Fibrillation and Atrial Flutter, Paroxysmal Supraventricular Tachycardias: Supraventricular Tachycardias and Nodal Tachycardias, If Other Medicines Cannot Be Used
• Ventricular Arrhythmias (Ventricular Tachycardia, Ventricular Fibrillation), If Other Anti-Arrhythmic Medicines Are Ineffective

2. Important Information Before Using Amiokordin

When Not to Use Amiokordin:

• If You Are Allergic to Iodine, Amiodarone, or Any of the Other Ingredients of This Medicine
• In Patients with Heart Diseases: Sick Sinus Syndrome, Sinoatrial Block, and Sinoatrial Dysfunction Syndrome, Except in Patients with a Pacemaker
• In Patients with Atrioventricular Block of Second or Third Degree, Except in Patients with a Pacemaker
• In Patients with a Bifascicular or Trifascicular Block, Except in Patients with a Pacemaker or a Temporary Pacing System
• Concomitantly with Medicines That May Cause Life-Threatening Arrhythmias (Torsades de Pointes Type)
• If You Have Thyroid Disease
• If You Are Pregnant or Breastfeeding
• In Case of Cardiogenic Shock, Severe Hypotension
• In Case of Severe Respiratory Failure
• In Patients with Cardiomyopathy or Heart Failure
• In Newborns (Including Premature Infants), Infants, and Children Under 3 Years of Age

The Above Contraindications Do Not Apply If Amiodarone Is Used in the Intensive Care Unit for Resuscitation of Cardiac Arrest Due to Ventricular Fibrillation, If Defibrillation Is Not Effective.

Warnings and Precautions

Amiokordin Should Be Administered Intravenously Only in an Intensive Care Unit, Where the Patient's Clinical Condition Is Continuously Monitored (ECG Recording, Blood Pressure Values).

• Amiokordin May Cause Changes in the ECG - This Does Not Indicate Overdose.
• Amiokordin May Cause Arrhythmias or Worsen Existing Arrhythmias, Especially as a Result of Interactions with Certain Medicines (See Section "Amiokordin and Other Medicines" and Section 4) and/or in Case of Electrolyte Disturbances (Decreased Potassium and/or Magnesium Levels in the Blood).
• It Is Not Recommended to Use Amiokordin Concomitantly with the Following Medicines: Beta-Adrenergic Blocking Agents, Calcium Channel Blockers That Slow the Heart Rate (Verapamil, Diltiazem), Laxatives That May Cause Hypokalemia (See Section "Amiokordin and Other Medicines").

Tell Your Doctor ImmediatelyIf You Are Taking a Medicine Containing Sofosbuvir, Used to Treat Hepatitis C Virus Infection, If You Experience:

• Slow or Irregular Heartbeat, or Arrhythmias
• Shortness of Breath or Worsening of Existing Shortness of Breath
• Chest Pain
• Dizziness
• Palpitations
• Near Fainting or Fainting

Amiokordin and Other Medicines

Tell Your Doctor About All Medicines You Are Taking or Have Recently Taken, as Well as Any Medicines You Plan to Take.

• Medicines Used to Treat Arrhythmias (Irregular Heartbeats): Quinidine, Dizopiramid, Procainamide, Sotalol, Bretylium, Bepridil
• Intravenous Erythromycin (Antibiotic), Cotrimoxazole (Anti-Infective Medicine), or the Antiprotozoal Medicine Pentamidine
• Antipsychotic Medicines, Such as Chlorpromazine, Thioridazine, Fluphenazine, Pimozide, Haloperidol, Amisulpride, Sertindol

Do Not Use Amiokordin Concomitantly with:

• Fluoroquinolones - Anti-Infective Medicines: Ciprofloxacin, Ofloxacin, Levofloxacin
• Beta-Adrenergic Blocking Agents - Medicines Used to Treat Heart Diseases, Such as Propranolol
• Calcium Channel Blockers That Slow the Heart Rate - Medicines Used to Treat Angina (Heart Disease) or High Blood Pressure: Verapamil, Diltiazem
• Sofosbuvir, Used to Treat Hepatitis C Virus Infection
• Certain Laxatives (Used to Treat Constipation) That May Cause Low Potassium Levels in the Blood: Bisacodyl, Senna
• Cholesterol-Lowering Medicines - Statins, Such as Simvastatin, Atorvastatin, Lovastatin

Use Amiokordin with Caution When Taking:

• Diuretics, Such as Furosemide
• Corticosteroids Used Systemically

Amiokordin with Food and Drink

It Is Recommended to Avoid Consuming Grapefruit Juice During Treatment with Amiokordin.

Pregnancy, Breastfeeding, and Fertility

If You Are Pregnant or Breastfeeding, Think You May Be Pregnant, or Are Planning to Have a Baby, Ask Your Doctor for Advice Before Taking This Medicine.

Driving and Using Machines

Based on the Safety Data of Amiodarone, the Medicine Does Not Affect the Ability to Drive and Use Machines.

Amiokordin Contains Benzyl Alcohol

This Medicine Contains 20.2 Mg of Benzyl Alcohol in Each Ml of Solution. 3 Ml of Solution (1 Ampoule) Contains 60.6 Mg of Benzyl Alcohol.

3. How to Use Amiokordin

The Medicine Is Administered by a Doctor or Nurse According to the Doctor's Prescription. If You Have Any Questions, Ask Your Doctor or Nurse.

Administration

Amiokordin Is Administered Intravenously, Under Constant Control of the Patient's Condition (ECG Recording, Blood Pressure Values).

The Doctor Will Determine the Appropriate Dose for Each Patient, Based on Body Weight and Depending on the Disease Being Treated.

Usual Dosage:

Adults:

Intravenous Infusion

Loading Dose: 5 Mg/Kg Body Weight, Administered in 250 Ml of 5% Glucose Solution Over 20 Minutes to 2 Hours. The Infusion Can Be Repeated 2 to 3 Times a Day.

Maintenance Dose: 10-20 Mg/Kg Body Weight/Day (Usually 600 to 800 Mg/24 Hours, Up to 1200 Mg/24 Hours) in 250 Ml of 5% Glucose Solution for Several Days.

Special Warnings

Amiokordin Should Be Used with Caution in Elderly Patients.

Use in Children

The Safety and Efficacy of Amiodarone in Children Have Not Been Established. Therefore, the Use of Amiokordin Is Not Recommended in Children.

Overdose

Since the Medicine Will Be Administered to You in a Hospital, It Is Unlikely That You Will Receive Too Much or Too Little of the Medicine. However, If You Have Any Concerns, Inform Your Doctor or Nurse.

Missed Dose

This Medicine Is Used in a Hospital Setting.

Stopping Treatment

If You Have Any Further Questions About Using This Medicine, Ask Your Doctor or Nurse.

4. Possible Side Effects

Like All Medicines, Amiokordin Can Cause Side Effects, Although Not Everybody Gets Them.

• Anaphylactic Shock (Severe Drop in Blood Pressure, Leading to Inadequate Blood Flow to Vital Organs and Tissues, Caused by a Severe Allergic Reaction)
• Dizziness, Fatigue, and Shortness of Breath - May Be Symptoms of Severe Bradycardia, Sick Sinus Syndrome, and/or New or Worsening Arrhythmias, Sometimes with Cardiac Arrest
• Jaundice and Liver Failure (Severe Liver Damage)
• Shortness of Breath and Cough Without Expectoration - May Be Symptoms of Life-Threatening Interstitial Pneumonia or Pulmonary Fibrosis
• Headache Worsening in the Morning or After Exertion, Nausea, Seizures, Fainting, Vision Disturbances, or Disorientation - May Be Symptoms of Increased Intracranial Pressure (Pseudotumor Cerebri)

Frequent (Occurs in Less Than 1 in 10 Patients)

• Bradycardia, Usually Moderate
• Reactions at the Injection Site, Such as Pain, Redness, Swelling, Necrosis, Hematoma, Infiltration, Inflammation, Induration, Phlebitis, Thrombophlebitis, Infection, Skin Discoloration
• Hypotension, Usually Moderate and Transient, Manifested by Dizziness, Disorientation, and Fainting (Reports of Severe Hypotension or Vasovagal Shock After Overdose or Too Rapid Administration)
• Pruritic Red Rash (Exanthema)
• Decreased Libido

Rare (Occurs in Less Than 1 in 10,000 Patients)

• Malaise, Disorientation, or Weakness, Nausea, Loss of Appetite, Irritability - May Be Symptoms of the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
• Nausea
• Increased Transaminase Activity (Detected in Blood Tests), Usually Moderate (1.5 to 3 Times the Upper Limit of Normal) and Occurs at the Beginning of Treatment - These Abnormalities May Return to Normal After Dose Reduction or Spontaneously
• Headache
• Excessive Sweating
• Sudden Flushing of the Face

Frequency Not Known (Cannot Be Estimated from the Available Data)

• Back Pain
• Urticaria
• Hyperthyroidism Manifested by Agitation, Weight Loss, Increased Sweating
• Pancreatitis or Acute Pancreatitis
• Delirium (Including Confusion), Hallucinations
• Life-Threatening Complication After Heart Transplantation (Primary Graft Dysfunction), in Which the Transplanted Heart Fails to Function Properly (See Section 2. Warnings and Precautions)

Reporting Side Effects

If You Experience Any Side Effects, Tell Your Doctor or Nurse. Side Effects Can Be Reported Directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products

5. How to Store Amiokordin

Keep This Medicine Out of the Sight and Reach of Children.

Do Not Use This Medicine After the Expiration Date Stated on the Carton. The Expiration Date Refers to the Last Day of the Month Stated.

Do Not Store Above 25°C.

Store in the Original Package to Protect from Light.

Medicines Should Not Be Disposed of via Wastewater or Household Waste. Ask Your Pharmacist How to Dispose of Medicines No Longer Required. This Will Help Protect the Environment.

6. Contents of the Package and Other Information

What Amiokordin Contains

• The Active Substance Is Amiodarone Hydrochloride. 1 Ml of Solution Contains 50 Mg of Amiodarone Hydrochloride, Which Corresponds to 47.33 Mg of Amiodarone. 3 Ml of Solution (1 Ampoule) Contains 150 Mg of Amiodarone Hydrochloride, Which Corresponds to 141.98 Mg of Amiodarone.
• The Other Ingredients Are Benzyl Alcohol, Polysorbate 80, Water for Injections. See Section 2. "Amiokordin Contains Benzyl Alcohol".

What Amiokordin Looks Like and Contents of the Package

The Solution for Injection Is a Clear, Slightly Yellowish Solution.

Ampoules Made of Colorless Glass with a Red Ring, in a Cardboard Box.

Packaging:5 Ampoules of 3 Ml Each

Marketing Authorization Holder and Manufacturer

KRKA, D.D., Novo Mesto, Šmarješka Cesta 6, 8501 Novo Mesto, Slovenia

Date of Last Revision of the Leaflet:

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Information Intended for Healthcare Professionals Only:

To Obtain Full Information About the Medicinal Product, Please Consult the Summary of Product Characteristics (SPC).

Dosage and Administration

Amiokordin, Solution for Injection, Should Be Used Only in Intensive Care Units Equipped with Cardiological Monitoring, Defibrillation, and Cardiac Stimulation. The Medicine Should Be Administered Intravenously.

Special warnings and precautions for use

Amiodarone may be administered intravenously only in an intensive care unit where the patient's clinical condition is constantly monitored (ECG recording, arterial blood pressure values).
Whenever possible, intravenous amiodarone should be administered through a central venous line to avoid adverse reactions at the injection site (see section 4.8 of the SmPC).
Attention should be paid to any symptoms of hypotension, severe respiratory failure, uncontrolled or severe heart failure.
Detailed information on intravenous injections
Due to the risk of hemodynamic disorders (severe hypotension, circulatory collapse), intravenous injection is not routinely recommended. Whenever possible, intravenous infusion is preferred.
Amiodarone may be administered by intravenous injection only in emergency situations when other medications are ineffective, exclusively in an intensive care unit where the patient's condition is constantly monitored (ECG recording, arterial blood pressure values).
The dose is approximately 5 mg per kilogram of body weight. Amiodarone should be administered by intravenous injection lasting at least 3 minutes, except in cases of cardiopulmonary resuscitation associated with ventricular fibrillation when defibrillation is not effective. The next injection can be repeated no earlier than 15 minutes later, even if only a solution from one ampoule (150 mg) was administered in the first injection, due to the risk of irreversible circulatory collapse.
If further doses of amiodarone are necessary, they should be administered by intravenous infusion.
Other medications should not be mixed with amiodarone in the same syringe. Other medications should not be injected through the same venous access.
Heart function disorders (see section 4.8 of the SmPC)
The pharmacological action of amiodarone causes changes in the ECG: prolongation of the QT interval (related to the prolongation of the repolarization period), with possible formation of a U wave. However, these changes do not indicate amiodarone poisoning.
There have been reports of the occurrence of a new type of heart rhythm disorder or worsening of treated heart rhythm disorders, sometimes leading to death. It is important, but difficult to distinguish, whether this is due to the lack of efficacy of the medication, which has a proarrhythmic effect, or is related to the exacerbation of heart rhythm disorders. Proarrhythmic effects of amiodarone are less frequently reported than with other antiarrhythmic medications. The proarrhythmic effect of amiodarone occurs especially as a result of interactions with medications that prolong the QT interval and (or) in the case of electrolyte disorders (see sections 4.5 and 4.8 of the SmPC). Regardless of the prolongation of the QT interval, amiodarone has little activity inducing heart rhythm disorders of the torsade de pointestype.
Severe bradycardia and heart block (see section 4.5 of the SmPC)
During the use of regimens containing sofosbuvir in combination with amiodarone, life-threatening cases of bradycardia and heart block have been observed.
Bradycardia usually occurred within a few hours to days, but cases have also been observed where this time was longer, most often up to 2 weeks after the start of HCV treatment.
Patients using a regimen containing sofosbuvir should be administered amiodarone only when the use of other alternative antiarrhythmic medications is contraindicated or not tolerated.
If concurrent use of amiodarone is necessary, it is recommended to monitor heart function in patients in a hospital setting for the first 48 hours after the start of concurrent administration; and then the heart rate should be monitored in an outpatient setting or by the patient themselves, daily for at least the first 2 weeks of treatment.
Due to the long half-life of amiodarone, heart function should also be monitored in the manner described above in patients who have discontinued amiodarone use within the last few months and are about to start a regimen containing sofosbuvir.
All patients taking amiodarone in combination with a regimen containing sofosbuvir should be informed of the risk of symptoms of bradycardia and heart block and the need for immediate medical attention in case of their occurrence.
Respiratory system disorders (see section 4.8 of the SmPC)
The occurrence of dyspnea and non-productive cough may be related to toxic effects on the lungs, such as the occurrence of interstitial pneumonia. Very rare cases of interstitial pneumonia have been reported after intravenous administration of amiodarone. In case of suspected diagnosis in a patient who has developed exertional dyspnea, both as the only symptom and associated with worsening of the patient's general condition (fatigue, weight loss, fever), a radiological examination of the chest should be performed. In such a case, the justification for further treatment with amiodarone should be reassessed, as interstitial pneumonia is usually reversible after early discontinuation of amiodarone (clinical symptoms usually resolve within 3 to 4 weeks, with subsequent gradual improvement in radiological examination results and lung function tests, over a period of several months). The initiation of corticosteroid therapy should also be considered.
A few very rare cases of severe respiratory complications, sometimes leading to death, have been reported, usually occurring immediately after surgical procedures (adult respiratory distress syndrome). This may be related to the interaction of high concentrations of oxygen (see sections 4.5 and 4.8 of the SmPC).
Anesthesia (see sections 4.5 and 4.8 of the SmPC)
Before surgery, the anesthesiologist should be informed about the patient's use of amiodarone.
Liver function disorders (see section 4.8 of the SmPC)
Regular, close monitoring of liver function (determination of aminotransferase activity) is recommended during treatment with amiodarone, starting from the beginning of treatment.
The dose of amiodarone should be reduced or treatment discontinued in case of a three-fold increase in aminotransferase activity above the upper limit of normal, which may indicate the occurrence of acute, severe liver function disorders (including severe liver cell failure or liver failure, sometimes leading to death) or chronic liver function disorders. They may occur both during oral and intravenous administration and within 24 hours after intravenous administration of amiodarone. Clinical and biological symptoms of chronic liver function disorders may have mild severity (possible liver enlargement, increase in aminotransferase activity 1.5 to 5 times above the upper limit of normal). These abnormalities usually resolve after discontinuation of amiodarone. However, cases resulting in death have been reported.
Severe skin reactions
Treatment with amiodarone should be discontinued immediately if skin reactions occur that may indicate the occurrence of Stevens-Johnson syndrome (SJS - Stevens-Johnson syndrome) (progressive rash with blisters or changes in mucous membranes, fever, and joint pain) or toxic epidermal necrolysis (TEN - Toxic Epidermal Necrolysis) (severe, rapidly progressing disease, characterized by bursting giant subepidermal blisters, extensive skin erosion, peeling of large skin flakes, and fever), or bullous dermatitis and drug reaction with eosinophilia and systemic symptoms (DRESS). These symptoms may be life-threatening and even lead to death.
Eye disorders (see section 4.8 of the SmPC)
In case of blurred vision or worsening vision, a complete ophthalmological examination, including an ophthalmoscopic examination of the fundus, should be performed immediately.
Detection of optic neuropathy and (or) optic neuritis requires discontinuation of amiodarone treatment due to the possibility of progression to vision loss.
Interactions with other medications (see section 4.5 of the SmPC)
Concomitant use of amiodarone with the following medications is not recommended: beta-adrenergic blockers, calcium channel blockers that slow the heart rate (verapamil, diltiazem), irritating laxatives that may cause hypokalemia.
Concomitant administration of amiodarone with regimens containing sofosbuvir may lead to serious, symptomatic bradycardia.
If their concurrent use cannot be avoided, careful monitoring of the patient's heart function is recommended (see section 4.4).
Heart transplant
Retropective studies have shown that the use of amiodarone before heart transplantation in the recipient increases the risk of primary graft dysfunction (PGD, Primary Graft Dysfunction).
Primary graft dysfunction (PGD) is a life-threatening complication of heart transplantation, characterized by left ventricular, right ventricular, or biventricular dysfunction, occurring within the first 24 hours after transplantation, for which no identifiable secondary cause can be found (see section 4.8 of the SmPC). Severe PGD may be irreversible.
In patients on the waiting list for heart transplantation, the use of an alternative antiarrhythmic medication should be considered as early as possible before transplantation.
Children and adolescents
The safety and efficacy of amiodarone have not been established in children. Therefore, the use of this medication is not recommended in these patients. Available data are described in sections 5.1 and 5.2 of the SmPC.
The Amiokordin product in the form of a solution for injection contains 20 mg of benzyl alcohol per ml (see section 6.1 of the SmPC). Since benzyl alcohol can cause toxic and allergic reactions in newborns, infants, and children up to 3 years of age, intravenous administration of the product is contraindicated in these age groups. After intravenous administration of solutions containing this preservative, cases of "gasping syndrome" have been reported, resulting in death in newborns (children before the end of the first month of life). Symptoms include sudden onset of "gasping syndrome", hypotension, bradycardia, and cardiocirculatory collapse.
Special warnings regarding certain components of the medication
Amiokordin, solution for injection, contains 20.2 mg of benzyl alcohol in each ml of solution. 3 ml of solution (1 ampoule) contains 60.6 mg of benzyl alcohol.
Benzyl alcohol may cause allergic reactions.
Intravenous administration of benzyl alcohol to newborns is associated with a risk of severe adverse reactions and death (so-called "gasping syndrome"). The minimum amount of benzyl alcohol at which toxicity symptoms may occur is unknown.
In small children, there is an increased risk due to accumulation. Additional information can be found above in the subsection "Children and adolescents" (see also section 4.4 of the SmPC).
Large volumes of benzyl alcohol should be administered with caution and only when necessary, especially in patients with impaired renal or liver function, due to the risk of accumulation and toxicity (metabolic acidosis).
Pregnant or breastfeeding women should consult a doctor before using the medicinal product, as a large amount of benzyl alcohol may accumulate in their body and cause adverse reactions (so-called metabolic acidosis).

Overdose

There are no available data on overdose of amiodarone administered intravenously.
There are few reports of overdose of amiodarone administered orally.
Bradycardia, atrioventricular block, ventricular tachycardia, heart rhythm disorders of the torsade de pointestype, circulatory failure, as well as decreased blood pressure and liver damage may occur.
Both amiodarone and its metabolites are not removed during dialysis.
Overdose of the medication requires professional medical assistance, and treatment is symptomatic.