Amiodarone hydrochloride Bioindustria Lim: detailed information

Package leaflet: Information for the user

AMIODARONE HYDROCHLORIDE Bioindustria LIM 150 mg/3 ml solution for injection

amiodarone hydrochloride
Generic medicine
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, pharmacist, or nurse.
If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

What AMIODARONE HYDROCHLORIDE Bioindustria LIM is and what it is used for
What you need to know before using AMIODARONE HYDROCHLORIDE Bioindustria LIM
How to use AMIODARONE HYDROCHLORIDE Bioindustria LIM
Possible side effects
How to store AMIODARONE HYDROCHLORIDE Bioindustria LIM
Contents of the pack and other information

1. What AMIODARONE HYDROCHLORIDE Bioindustria LIM is and what it is used for

This medicinal product contains the active substance amiodarone hydrochloride, which belongs to a class of medicines called "class III antiarrhythmics" that work by regulating the heartbeat.
AMIODARONE HYDROCHLORIDE Bioindustria LIM is intended for intravenous injection when a rapid response is required or when oral administration is not possible.
This medicinal product is indicated for:

the treatment and prevention of serious heart rhythm disorders when other medicines have not been effective: abnormally fast heartbeat, sometimes characterized by sudden stopping and restarting (paroxysmal and non-paroxysmal supraventricular tachycardias), irregular heartbeat characterized by premature contraction of the heart muscle disrupting the regular sequence of beats (atrial extrasystoles), irregular and excessively rapid heartbeat (atrial flutter), and irregular and accelerated heartbeat (atrial fibrillation);
sudden and abrupt changes in heartbeat with increased rate (reciprocating paroxysmal supraventricular tachycardias) in patients affected by conditions such as Wolff-Parkinson-White syndrome, a disorder characterized by rapid heartbeat, dizziness, loss of consciousness, easy fatigue, and anxiety. Heart rhythm disorders involving extra beats that disrupt the normal heartbeat and may sometimes cause a sensation of missed beats in the chest area (ventricular extrasystoles), and disturbances of the heartbeat characterized by a very rapid heartbeat (ventricular tachycardias).

2. What you need to know before using AMIODARONE HYDROCHLORIDE Bioindustria LIM

Do not use AMIODARONE HYDROCHLORIDE Bioindustria LIM

if you are allergic to amiodarone or to iodine, or to any of the other ingredients of this medicine (listed in section 6);
if you have a slower than normal heart rate (sinus bradycardia), if you suffer from a condition known as sinoatrial block, characterized by delayed formation of heartbeats, or if you have sinus node disease, characterized by irregular heartbeat, and you do not have a pacemaker with risk of heart block (sinus arrest);
if you suffer from severe disorders in the formation of heartbeats and do not have a pacemaker (severe atrioventricular blocks, bi- or trifascicular blocks). In this case, AMIODARONE HYDROCHLORIDE Bioindustria LIM may be administered to you in specialized hospital units via a venous catheter reaching the heart (electrostimulator);
if you have severe reduction in blood circulation (cardiovascular collapse) or severe drop in blood pressure (severe arterial hypotension);
if you are taking medicines that can cause heart rhythm abnormalities (torsades de pointes) (see "Other medicines and AMIODARONE HYDROCHLORIDE Bioindustria LIM");
if you suffer or have suffered from thyroid function disorders (thyroid dysfunction). In doubtful cases, your doctor will perform a thyroid function test before starting treatment with this medicine;
if you are pregnant, except in exceptional cases, because this medicine may harm the fetus (see section "Pregnancy and breastfeeding");
if you are breastfeeding, because this medicine passes into breast milk;
if you have low blood pressure (hypotension) and severe heart problems (cardiomyopathy and heart failure) or if you have severe breathing difficulties, your doctor will not administer AMIODARONE HYDROCHLORIDE Bioindustria LIM intravenously, as your condition may worsen;
if the medicine is intended for a newborn or a child under 3 years of age, because the intravenous formulation contains benzyl alcohol.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using AMIODARONE HYDROCHLORIDE Bioindustria LIM:

if you have severe heart disorders (cardiomyopathies and severe coronary artery disease) and during treatment develop productive cough (with sputum), difficulty breathing, fever, or weight loss;
if you suffer from low blood pressure (hypotension), severe breathing difficulties (severe respiratory failure), or severe heart problems (severe uncompensated heart failure);
if you are scheduled for surgery under general anesthesia;
if you have liver problems; your doctor will closely monitor your liver function, both at the beginning and during treatment. In case of severe liver function abnormalities, your doctor will stop administration of the medicine and initiate appropriate therapy;
if you experience vision problems, particularly reduced blood supply or inflammation of the optic nerve (optic neuropathy and optic neuritis). In this case, your doctor will discontinue the medicine;
if you have thyroid problems;
if you are currently taking a medicine containing sofosbuvir for the treatment of hepatitis C, as it may cause a life-threatening slowing of the heartbeat. Your doctor may consider alternative treatments. If treatment with amiodarone and sofosbuvir is necessary, additional cardiac monitoring may be required;
if you are taking other medicines (see section "Other medicines and AMIODARONE HYDROCHLORIDE Bioindustria LIM").

AMIODARONE HYDROCHLORIDE Bioindustria LIM will be administered only in specialized hospital units and under continuous monitoring (electrocardiogram and blood pressure).
To avoid injection site reactions, the medicine will be administered, whenever possible, into a large vein (see also "Possible side effects").
If during treatment with AMIODARONE HYDROCHLORIDE Bioindustria LIM you develop dry cough, fever, difficulty breathing associated with severe general malaise, your doctor will perform chest X-rays and other tests to assess your lung function. This is because pulmonary toxicity may occur during treatment with AMIODARONE HYDROCHLORIDE Bioindustria LIM, which, if not diagnosed promptly, can be life-threatening.
If necessary, your doctor may reduce the dose or discontinue the medicine and initiate appropriate therapy. In some cases, lung toxicity may appear weeks after discontinuation of the medicine.
Severe and potentially fatal skin reactions (cutaneous reactions) may occur due to conditions known as Stevens-Johnson syndrome and toxic epidermal necrolysis (see "Possible side effects"), manifesting as progressive skin redness (skin rash), often accompanied by blisters and bullae, which may also affect mucous membranes. In such cases, stop treatment with amiodarone and contact your doctor immediately.
If new heart rhythm disturbances occur or existing ones worsen, your doctor will determine whether this is due to loss of efficacy of the medicine or progression of the underlying disease.
During treatment with this medicine, increased thyroid function (hyperthyroidism) may occur; in such cases, treatment must be discontinued.
During treatment with this medicine, it is recommended to avoid direct sunlight exposure.
Contact 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 rhythm disturbances;
shortness of breath or worsening of existing shortness of breath;
chest pain;
dizziness;
palpitations;
near-fainting or fainting.

If you are on a waiting list for a heart transplant, your doctor may modify your treatment. This is because amiodarone use prior to heart transplantation has been associated with an increased risk of potentially fatal complications (primary graft dysfunction), in which the transplanted heart fails to function properly within the first 24 hours after surgery.
Children
AMIODARONE HYDROCHLORIDE Bioindustria LIM must not be administered to children under 3 years of age, because the intravenous formulation contains benzyl alcohol, and is not recommended in children of any age (see also "AMIODARONE HYDROCHLORIDE Bioindustria LIM contains benzyl alcohol").
Other medicines and AMIODARONE HYDROCHLORIDE Bioindustria LIM
Inform your doctor or pharmacist if you are using, have recently used, or might use any other medicine.
The combination of AMIODARONE HYDROCHLORIDE Bioindustria LIM with the following medicines is contraindicated:

medicines that may cause a specific type of heart rhythm disturbance (torsades de pointes), such as medicines used to prevent and control heart rhythm disorders (Class IA antiarrhythmics, sotalol, bepridil), vincamine (an antibiotic), medicines for mental illnesses (such as sultopride), cisapride (a medicine used to treat gastroesophageal reflux), intravenous erythromycin (an antibiotic);
intravenous pentamidine (used for certain types of pneumonia);
antibiotics known as fluoroquinolones.

The combination of AMIODARONE HYDROCHLORIDE Bioindustria LIM with the following medicines is not recommended:

medicines that slow the heart rate (beta-blockers and calcium channel blockers) such as verapamil and diltiazem;
medicines that may cause a reduction in blood potassium levels (hypokalemia), such as stimulant laxatives (medicines that increase intestinal motility and evacuation);
sofosbuvir, a medicine used in combination with others for the treatment of chronic hepatitis C.

The combination of AMIODARONE HYDROCHLORIDE Bioindustria LIM with the following medicines requires caution:

medicines that may cause a specific type of heart rhythm disturbance known as QT prolongation;
medicines that promote urine production (diuretics), alone or in combination;
medicines for controlling inflammation and allergies (systemic glucocorticoids and mineralocorticoids);
tetracosactide, used to investigate certain hormonal disorders;
intravenous amphotericin B, used to treat fungal infections.

The effects of AMIODARONE HYDROCHLORIDE Bioindustria LIM may be influenced by, or may influence, the following medicines:

general anesthesia and high doses of oxygen during surgical procedures;
digoxin, used to increase the force of heart contraction;
dabigatran and warfarin, anticoagulants used to thin the blood;
phenytoin, a medicine for the treatment of epilepsy;
flecainide, a medicine for controlling irregular heartbeat;
statins, used to reduce blood cholesterol levels, such as simvastatin, atorvastatin, and lovastatin, whose combination increases the risk of muscle disorders (e.g., rhabdomyolysis). Your doctor will prescribe the appropriate statin to be taken with amiodarone;
cyclosporine, tacrolimus, and sirolimus, used to suppress the immune system and help prevent organ transplant rejection;
fentanyl and ergotamine, medicines for pain control;
lidocaine, used as an anesthetic;
sildenafil, used for the treatment of impotence;
midazolam and triazolam, used to treat anxiety or help relaxation;
dihydroergotamine, used to treat certain types of headache (migraine);
colchicine, used to treat joint inflammation causing pain and swelling (gout).

AMIODARONE HYDROCHLORIDE Bioindustria LIM with food and beverages
Do not drink grapefruit juice while taking this medicine, as it may increase the likelihood of side effects.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine.
Pregnancy
Do not use this medicine during pregnancy unless your doctor considers it necessary, as it may harm the fetus.
Breastfeeding
Do not use this medicine if you are breastfeeding. AMIODARONE HYDROCHLORIDE Bioindustria LIM passes into breast milk and may harm your baby.
Driving and using machines
This medicine does not impair the ability to drive or operate machinery.
AMIODARONE HYDROCHLORIDE Bioindustria LIM contains benzyl alcohol
This medicine contains 60.6 mg of benzyl alcohol per 3 ml vial.
Benzyl alcohol may cause allergic reactions.
Benzyl alcohol may cause toxic and allergic reactions in newborns and children up to 3 years of age (see section "Do not use AMIODARONE HYDROCHLORIDE Bioindustria LIM").
Benzyl alcohol has been associated with the risk of serious adverse effects, including breathing problems ("gasping syndrome") in young children.
Benzyl alcohol may cause a fatal condition (gasping syndrome) in newborns, characterized by multiple severe symptoms such as breathing difficulties and seizures.
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).
AMIODARONE HYDROCHLORIDE Bioindustria LIM contains polysorbate
This medicine contains 300.0 mg of polysorbate 80 per 3 ml vial.
Polysorbates may cause allergic reactions. Inform your doctor if you or your child has known allergies.
Polysorbates may affect the heart and blood circulation (e.g., irregular or abnormal heartbeat, low blood pressure).
Polysorbates may affect the liver. If you have liver disease, consult your doctor or pharmacist.

3. How to use AMIODARONE HYDROCHLORIDE Bioindustria LIM

Your doctor will determine the route of administration, the initial dose, and the maintenance dose based on the severity of your condition and your response to treatment.
This medicine will be administered to you by slow intravenous injection or infusion by medical or nursing staff.
Concomitant therapy with statins
If you are taking statins during treatment with AMIODARONE HYDROCHLORIDE Bioindustria LIM to reduce cholesterol levels in the blood, your doctor will prescribe a specific statin (see also “Other medicines and AMIODARONE HYDROCHLORIDE Bioindustria LIM”).
Use in Children
The use of AMIODARONE HYDROCHLORIDE Bioindustria LIM is not recommended in children.
Since AMIODARONE HYDROCHLORIDE Bioindustria LIM contains benzyl alcohol, it must not be administered to neonates and children up to 3 years of age.
If you use more AMIODARONE HYDROCHLORIDE Bioindustria LIM than you should
There are no available data regarding overdose with AMIODARONE HYDROCHLORIDE Bioindustria LIM. Possible adverse effects due to an overdose of this medicine include: slowed heartbeat (sinus bradycardia), cessation of heartbeat (cardiac arrest), rapid heartbeat (ventricular tachycardia), heart rhythm abnormalities (torsades de pointes), circulatory disturbances (circulatory failure), and liver damage (hepatic injury).
If you forget to use AMIODARONE HYDROCHLORIDE Bioindustria LIM
Since this medicine will be administered under close medical supervision, it is unlikely that a dose will be missed. However, inform your doctor if you think a dose has been missed.
Do not take a double dose to make up for a forgotten dose.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur, with the following frequencies:
Common (may affect up to 1 in 10 people):

Slow heartbeat (bradycardia). This effect is generally mild;
Reactions at the injection site such as pain, skin redness (erythema), fluid accumulation (edema), localized tissue destruction (necrosis), leakage of medicine from the blood vessel (extravasation), fluid accumulation in the skin and tissues (infiltration), inflammation, hardening of the areas where the medicine was injected, inflammation of blood vessels with or without formation of blood clots (thrombophlebitis and phlebitis), inflammation of the tissues under the skin (cellulitis), infection, skin color changes (pigmentation changes);
Reduction in blood pressure, usually mild and transient. After an excessive dose (overdose) or too rapid injection, severe reduction in blood pressure (hypotension) and sudden drop in blood pressure, rapid heartbeat, paleness, and bluish discoloration of the skin and mucous membranes (collapse) may occur;
Itching, red skin rash (eczema);
Decreased sexual desire.

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

Severe slowing of the heartbeat (marked bradycardia), which may require discontinuation of treatment, especially in patients with heart rhythm disorders and elderly patients;
Onset or worsening of heart rhythm disorders, up to complete heart block (see also “Warnings and precautions”);
Nausea;
Mild changes in specific liver function tests (transaminases), which return to normal with dose reduction or without any specific intervention;
Liver disorders (hepatopathy) with abnormal liver function tests and yellowing of the skin and whites of the eyes. These disorders can be severe (liver failure) and sometimes life-threatening, and require discontinuation of therapy;
Severe allergic reaction (anaphylactic shock);
Increased pressure inside the skull (benign intracranial hypertension, pseudotumor cerebri);
Headache;
Lung inflammation with cough and difficulty breathing (interstitial pneumonia), which resolves upon discontinuation of therapy;
Severe lung disease characterized by scarring of the tissue lining the lungs, cough, difficulty breathing, weight loss, and fatigue, sometimes life-threatening (pulmonary fibrosis);
Severe lung disease in which the lungs are unable to function properly (adult respiratory distress syndrome), sometimes life-threatening;
Bronchial narrowing and worsening of breathing difficulties (bronchospasm) in patients with breathing problems (severe respiratory insufficiency), and especially in patients with asthma;
Sweating and hot flushes;
Malaise, confusion or weakness, nausea, loss of appetite, irritability, fluid retention in the body. This group of symptoms may be related to a condition called “syndrome of inappropriate antidiuretic hormone secretion (SIADH)”.

Frequency not known (cannot be estimated from the available data):

Heart rhythm abnormalities (torsades de pointes) (see “Other medicines and AMIODARONE HYDROCHLORIDE Bioindustria LIM”);
Thyroid disorders (hyperthyroidism);
Swelling of the face, hands and feet, lips, tongue or throat (Quincke's oedema);
Back pain;
Sudden inflammation of the pancreas (pancreatitis (acute));
Confusion (delirium), hallucinations;
Itching (urticaria), life-threatening skin reactions characterized by rashes, blisters, skin peeling and pain (toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), bullous dermatitis, drug reaction with eosinophilia and systemic symptoms (DRESS));
Reduced blood supply and inflammation of the optic nerve (optic neuropathy and optic neuritis), up to vision loss (see “Warnings and precautions”);
Potentially fatal complication after heart transplantation (primary graft dysfunction), in which the transplanted heart fails to function properly (see section 2, Warnings and precautions);
Seeing, hearing or sensing things that are not there (hallucinations);
You may get more infections than usual. This could be due to 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).

Lung toxicity, sometimes life-threatening, may occur in approximately 10% of patients: lung inflammation (pneumonitis) characterized by fever, cough, chest pain and difficulty breathing; severe lung disease characterized by scarring of lung tissue, cough, difficulty breathing, weight loss and fatigue (pulmonary fibrosis); inflammation of the membrane covering the outer part of the lungs (pleuritis); inflammatory lung disease with symptoms such as fever, cough, general malaise, weight loss and difficulty breathing (bronchiolitis obliterans with organizing pneumonia). Your doctor may discontinue the treatment and initiate appropriate therapy.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at the following website: 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 AMIODARONE HYDROCHLORIDE Bioindustria LIM

Keep this medicine out of the sight and reach of children.
Store below 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 refrigerate or freeze.
Storage at low temperatures may cause the formation of a crystalline precipitate.
Vials containing a precipitate must not be used.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What AMIODARONE HYDROCHLORIDE Bioindustria LIM contains

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

Description of the appearance of AMIODARONE HYDROCHLORIDE Bioindustria LIM and contents of the
package
Packaging containing 5 vials of 3 ml solution each.
Marketing Authorization Holder and Manufacturer
Bioindustria Laboratorio Italiano Medicinali S.p.A.
(Bioindustria L.I.M. S.p.A.)
Via De Ambrosiis 2, 15067 Novi Ligure (AL) – Italy

The following information is intended exclusively for doctors or healthcare professionals

DOSAGE, METHOD AND DURATION OF ADMINISTRATION
Due to its pharmaceutical characteristics, concentrations lower than 600 mg/l must not be used. Use only 5% glucose (dextrose) solution (isotonic). Do not add any other product to the infusion solution.
Intravenous infusion:

Loading dose: the average dosage is 5 mg/kg administered exclusively in 250 ml of 5% dextrose solution, given over a period of time between 20 minutes and 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, a subsequent infusion should be administered.
Maintenance dose: 10 to 20 mg/kg over 24 hours (generally 600–800 mg/24 hours, up to 1200 mg/24 hours) in 250 ml of 5% dextrose solution for a few days. Switch to oral administration from the first day of infusion.

Intravenous injection:
(see also “Special warnings”)
The dosage is 5 mg/kg; the injection must last no less than 3 minutes. Do not add any other product to the syringe.
Paediatric population:
The safety and efficacy of amiodarone in children have not been established.
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.

PRECAUTIONS FOR USE
Intravenous administration of amiodarone must be carried out 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. Exercise caution in cases of hypotension, severe respiratory insufficiency, severe and uncompensated heart failure.
Anaesthesia. Prior to surgery, the anaesthetist must be informed that the patient is being treated with amiodarone.

SPECIAL WARNINGS

Intravenous injection is generally not recommended due to haemodynamic risks (severe hypotension, cardiocirculatory collapse); therefore, intravenous infusion is preferred whenever possible.
Intravenous 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 injection must not be repeated within 15 minutes following the first injection, even if the initial dose consisted of only one vial (risk of irreversible collapse). During treatment, direct exposure to sunlight should be avoided.
Do not add any other product to the same syringe. Do not inject other products through the same line. If treatment needs to be continued, intravenous infusion should be used.
The product is incompatible with aminophylline, heparin, and sodium chloride solutions.
The use of medical equipment and devices containing plasticizing agents such as DEHP (di-2-ethylhexyl phthalate) may result in their release 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 materials.

For further information, please consult the Summary of Product Characteristics.