Amiodar

Patient Information Leaflet

Amiodar 150 mg/3 ml intravenous solution for injection

amiodarone hydrochloride
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

1. What Amiodar is and what it is used for
2. What you need to know before using Amiodar
3. How to use Amiodar
4. Possible side effects
5. How to store Amiodar
6. Contents of the pack and other information

1. What Amiodar is and what it is used for

Amiodar contains the active substance amiodarone. Amiodar is an antiarrhythmic medicine, meaning it is used to treat and prevent heart rhythm disorders such as:

• Fast heartbeat (paroxysmal and non-paroxysmal supraventricular tachycardias) or irregular heartbeat (atrial extrasystoles, atrial flutter and fibrillation, ventricular extrasystoles and tachycardias).
• Fast heartbeat, sometimes occurring as paroxysmal reciprocating tachycardia, for example in a condition called Wolff-Parkinson-White syndrome.

Amiodar can be used to treat irregular heartbeat when other medicines have not worked or cannot be used.
Amiodar intravenous solution should be used when a rapid response is required or when oral administration is not possible.

2. What you should know before using Amiodar

Do not use Amiodar

• If you are allergic to amiodarone, iodine, or any of the other ingredients of this medicine (listed in section 6).
• If you have heart rhythm disorders such as: slow heartbeat (sinus bradycardia) or a condition called “sinoatrial block”; or if you have any other heart rhythm problems and do not have a pacemaker implanted (e.g. atrioventricular blocks, bi- or trifascicular blocks), except when used in specialized units and with an electrostimulator.
• If you have a condition called “sinoatrial disease” and do not have a pacemaker implanted (risk of sinus arrest).
• If you have severe heart problems (cardiomyopathy or heart failure).
• If you are experiencing cardiocirculatory collapse.
• If you have very low blood pressure.
• If you are taking medicines that may cause a heart disorder known as "torsade de pointes" (twisting of the points, accelerated heartbeat—ventricular tachycardia) (see section “Other medicines and Amiodar”).
• If you have or have had thyroid problems. If in doubt, a thyroid function test should be performed before starting treatment.
• If you are pregnant or suspect you may be pregnant, except in exceptional cases (see section “Pregnancy and breastfeeding”).
• If you are breastfeeding (see section “Pregnancy and breastfeeding”).
• If the patient is a newborn, infant, or child up to 3 years of age, due to the presence of benzyl alcohol in the formulation.
• If you have severe respiratory problems.

Warnings and precautions
Talk to your doctor or nurse before using Amiodar.
Lung problems
Amiodarone may cause lung toxicity. You are particularly at risk if you have heart disease.
Contact your doctor if you notice any of the following symptoms, which may occur even weeks after stopping treatment:

• Inflammation of the alveoli (pulmonary alveolitis), lung inflammation (pneumonia), and other lung problems (interstitial pneumonia, pulmonary fibrosis)
• Breathing difficulty due to narrowing of the bronchi (bronchial asthma)
• Dry cough
• Difficulty breathing (dyspnea)
• Fever
• Fatigue
• Weight loss

Your doctor may prescribe a chest X-ray, appropriate therapy, and/or discontinuation of Amiodar treatment.
Skin problems
Skin disorders (skin reactions), including very severe and potentially fatal conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis (see section “Possible side effects”), may occur. These manifest as progressive skin redness (skin rash), often accompanied by blisters and sores, and may also affect mucous membranes. In such cases, stop treatment with amiodarone immediately and contact your doctor without delay.
Heart function abnormalities
If you develop severe heart problems, new arrhythmias, or worsening of existing arrhythmias, your doctor will assess whether treatment with Amiodar should be discontinued.
Liver problems
Do not use Amiodar if you currently have liver disease.
During treatment with amiodarone, acute (including severe, sometimes fatal) and chronic liver disorders may occur within the first 24 hours after intravenous administration, as well as liver enlargement or disorders affecting bile or the gallbladder.
In all such cases, your doctor will decide whether to discontinue or reduce the dose of the medicine.
Eye problems
If you experience blurred vision or decreased visual acuity, inform your doctor immediately. Your doctor will arrange a complete ophthalmological examination without delay.
If optic nerve damage occurs, your doctor will instruct you to stop treatment with Amiodar to avoid the risk of vision loss.
Surgery
Before undergoing surgery, inform your doctor or anesthesiologist that you are taking Amiodar.
Heart transplant
Inform your doctor immediately if you are on a waiting list for a heart transplant, as your doctor may adjust your treatment. This is because amiodarone use prior to heart transplantation has been associated with an increased risk of potentially life-threatening complications (primary graft dysfunction), in which the transplanted heart fails to function properly within the first 24 hours after surgery.
Children and adolescents
The safety and efficacy of amiodarone in children and adolescents have not been established. Amiodar is not recommended for use in these patients.
Amiodar injectable contains benzyl alcohol as a preservative and must not be used in children up to 3 years of age.
Other medicines and Amiodar
Inform your doctor or nurse if you are currently using, have recently used, or might use any other medicines.
Do not use Amiodar together with the following medicines, as serious, potentially fatal side effects may occur:

• Antiarrhythmics (medicines used to treat heart rhythm disorders), e.g. sotalol, bepridil
• Vincamine (a medicine used for cerebral ischemia)
• Certain psychotropic drugs including sultopride
• Cisapride (a medicine used for stomach disorders)
• Intravenous erythromycin or pentamidine (for non-oral administration) (antibiotics)
• Fluoroquinolones (antibiotics)
• Medicines for high blood pressure (beta-blockers and calcium channel blockers)
• Verapamil, diltiazem (medicines that reduce heart rate), as they may cause slow heartbeat (bradycardia)
• Stimulant laxatives, as they may reduce potassium levels in the blood
• Medicines for chronic hepatitis C (sofosbuvir and/or daclatasvir, sofosbuvir/ledipasvir)

Inform your doctor if you are taking one or more of the following medicines, as you will be monitored closely during treatment with Amiodar:

• Medicines that increase urine production (diuretics, used to reduce fluid retention and lower high blood pressure), alone or in combination
• Glucocorticoid and mineralocorticoid medicines (corticosteroids) taken orally or by injection
• Tetracosactide (a hormone)
• Amphotericin B (a medicine for fungal infections) given intravenously
• Digitalis (a heart medicine)
• Medicines that reduce blood clotting, e.g. dabigatran, warfarin
• Phenytoin (a medicine for epilepsy)
• Flecainide (a medicine for heart rhythm disorders)
• Statins (medicines to lower cholesterol)
• Cyclosporine, tacrolimus, and sirolimus (used to help prevent transplant rejection)
• Fentanyl (a painkiller)
• Lidocaine (a local anesthetic)
• Sildenafil (a medicine for erectile dysfunction)
• Midazolam and triazolam (tranquilizers)
• Colchicine (a medicine for gout)
• Dihydroergotamine, ergotamine (medicines for circulatory disorders)

Interactions between Amiodar and other medicines may persist for several months after stopping treatment.
If you have any doubts, consult your doctor or nurse.
Amiodar with food and drink
The effect and toxicity of Amiodar may increase if grapefruit fruit or juice is consumed at the same time.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or nurse before using this medicine.
Amiodar must not be used during pregnancy except in cases where the benefit to the mother outweighs the risk to the fetus, due to its effects on fetal thyroid function.
Amiodar must not be used by breastfeeding mothers, as it passes into breast milk.
Driving and using machines
Based on the safety data of amiodarone, no influence on the ability to drive or operate machinery has been observed.
Amiodar injectable contains benzyl alcohol
Amiodar injectable contains 60.6 mg of benzyl alcohol per vial.
Benzyl alcohol may cause allergic reactions.
Benzyl alcohol has been associated with a risk of serious adverse effects, including respiratory problems (gasping syndrome), in young children. Do not administer to newborns up to 4 weeks of age and do not use for more than one week in young children (less than 3 years of age) unless otherwise directed by your doctor or pharmacist.
Consult your doctor or pharmacist if you are pregnant or breastfeeding. This is because large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (such as metabolic acidosis).
Consult your doctor or pharmacist if you have liver or kidney disease. This is because large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (such as metabolic acidosis).

3. How to use Amiodar

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or nurse.
Amiodarone produces highly variable effects from person to person; therefore, your doctor will determine the route of administration, initial dose, and maintenance dose based on the severity of the condition and your response.

Use in children and adolescents
The safety and efficacy of amiodarone in children and adolescents has not been established. Amiodar is not recommended for these patients. Due to the presence of benzyl alcohol in the formulation, intravenous administration of amiodarone is contraindicated in neonates, infants, and children up to 3 years of age.

If you use more Amiodar than you should
If you administer an excessive dose of Amiodar, inform your doctor immediately or go to the nearest hospital.
If you have any doubts about the use of Amiodar, consult your doctor or nurse.
There is limited information available regarding overdose with intravenous amiodarone.
Cases of sinus bradycardia (slowed heartbeat), cardiac arrest, ventricular tachycardia (rapid heartbeat), "torsade de pointes" (disturbances in the heart's electrical activity), circulatory problems, and liver damage have been reported.

If you forget to use Amiodar
Do not take a double dose to make up for the forgotten dose.

If you stop using Amiodar
If you have any doubts about using this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them and their severity may vary.
The side effects observed most frequently do not usually require discontinuation of treatment.
However, serious side effects have been reported, particularly affecting the lungs or liver.
In any case, your doctor will evaluate whether to reduce the dose or discontinue treatment depending on both the potential severity of the adverse reaction and the seriousness of the disease.

Common side effects (may affect up to 1 in 10 people)

• Slowing of the heartbeat (bradycardia)

• Reactions at the injection site such as pain, redness (erythema), swelling, cell death (necrosis), bleeding from blood vessels, infiltration, inflammation, hardening, presence of blood clots in veins (thrombophlebitis, phlebitis), cellulitis, infection, skin discoloration

• Decrease in blood pressure

• Itching, red skin rash (eczema)

• Decreased sexual desire

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

• Increased levels of transaminases in the blood (indicating liver damage)
• Acute liver injury, with elevated blood levels of transaminases and/or yellowing of the skin, mucous membranes, and eyes (jaundice), sometimes accompanied by liver failure, occasionally fatal
• Slowing of the heartbeat (marked bradycardia) or sinus arrest
• Onset or worsening of rhythm disorders, sometimes followed by cardiac arrest
• Anaphylactic shock
• Inflammation of the lungs (interstitial pneumonia) or fibrosis, sometimes fatal
• Severe respiratory complications, occasionally fatal (adult respiratory distress syndrome)
• Difficult and rapid breathing, accompanied by wheezing and/or apnea in cases of severe respiratory failure, especially in asthmatic patients
• Sweating
• Hot flushes
• Benign increased pressure inside the skull (pseudotumor cerebri)
• Headache
• Nausea
• Feeling unwell, confusion or weakness, nausea, loss of appetite, feeling irritable. This could be due to a condition called "syndrome of inappropriate antidiuretic hormone secretion" (SIADH)

Side effects with unknown frequency (frequency cannot be estimated from the available data)

• Disorders of the heart's electrical activity (torsade de pointes)
• Severe, life-threatening skin reactions characterized by rash, blistering, skin peeling, and pain (toxic epidermal necrolysis (TEN)), Stevens-Johnson syndrome (SJS), bullous dermatitis, drug reaction with eosinophilia and systemic symptoms (DRESS)
• Swelling due to fluid accumulation (edema), especially in the lower limbs and face (angioneurotic edema)
• 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, increasing the likelihood of infections (agranulocytosis)
• Overactivity of the thyroid gland
• Sudden-onset inflammation of the pancreas (acute pancreatitis)
• Confusion (delirium), seeing, hearing, or sensing things that are not there (hallucinations)
• Reduced sexual desire (libido)
• Back pain
• Hives
• Reduced blood flow and inflammation of the optic nerve (optic neuropathy and optic neuritis), up to vision loss (see "Warnings and precautions")

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Amiodar

Keep this medicine out of the sight and reach of children.
Do not store above 25°C.
Do not use this medicine after the expiry date stated on the packaging after "Exp.".
The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Amiodar contains

• The active substance is amiodarone hydrochloride. Each vial contains 150 mg of amiodarone hydrochloride.
• The other components are benzyl alcohol, polysorbate 80, water for injections.

Description of the appearance of Amiodar and contents of the pack
Each pack contains 5 vials of injectable solution for intravenous use.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Alfasigma S.p.A. - Via Ragazzi del ’99, n. 5 – 40133 Bologna (BO)
Manufacturer
Alfasigma S.p.A. - Via Pontina km 30,400 - 00071 Pomezia (RM)
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The following information is intended exclusively for physicians or healthcare professionals:
Warnings and precautions
Intravenous administration of amiodarone must be performed only in specialized hospital units and under continuous monitoring (ECG, blood pressure).
To avoid injection site reactions, amiodarone should be administered, whenever possible, through a central venous line.
Regarding intravenous injection:

• Intravenous bolus injection is generally not recommended due to hemodynamic risks (severe hypotension, cardiocirculatory collapse); therefore, intravenous infusion is preferred whenever possible.
• Intravenous bolus injection should be limited to emergency situations and when alternative therapies have failed, and must be used only in cardiac intensive care units under continuous monitoring (ECG, blood pressure).
• The dosage is approximately 5 mg/kg body weight administered over no less than 3 minutes. Intravenous bolus injection must not be repeated within 15 minutes following the first injection, even if the initial dose consisted of only 1 vial (risk of irreversible collapse).
• Do not add any other product to the same syringe. Do not inject other products into the same infusion line. If treatment needs to continue, intravenous infusion should be used (see "Dosage, method and duration of administration").
• The product is incompatible with aminophylline, heparin, and sodium chloride solutions.
• The use of medical equipment and devices containing plasticizers such as DEHP (di-2-ethylhexyl phthalate) may result in the release of DEHP in the presence of amiodarone. To minimize patient exposure to DEHP, the final diluted amiodarone solution for infusion should preferably be administered using DEHP-free containers and administration sets.

Dosage and method of administration
Due to its pharmaceutical characteristics, concentrations lower than 600 mg/L must not be used.
Use only 5% isotonic dextrose solution (glucose solution). Do not add any other product to the infusion solution.

• Intravenous infusion:
  o Loading dose: The usual dosage is 5 mg/kg administered exclusively in 250 ml of 5% dextrose solution (glucose solution), infused over a period of 20 minutes to 2 hours. This dose may be repeated 2 to 3 times within 24 hours. The infusion rate should be adjusted according to clinical response. The therapeutic effect appears within the first few minutes and then gradually decreases; therefore, subsequent infusions are required.
  o Maintenance dose: 10 to 20 mg/kg per 24 hours (generally 600–800 mg/24 hours, up to 1200 mg/24 hours) in 250 ml of 5% dextrose solution (glucose solution) for a few days. As soon as possible, switch from parenteral treatment to oral therapy.

• Intravenous bolus injection: The dosage is 5 mg/kg, administered over no less than 3 minutes. Do not add any other product to the syringe.