Leaflet: information for the user

Trangorex 200 mg tablets

Amiodarone

Read this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
  If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What is Trangorex and what it is used for

2. What you need to know before starting to take Trangorex

3. How to take Trangorex

4. Possible side effects

5. Storage of Trangorex

6. Contents of the pack and additional information

Trangorex belongs to a group of medications known as antiarrhythmic agents (used to control a fast or irregular heart rhythm).

Trangorex is used to prevent or treat heart rhythm disturbances, such as:

• Wolff-Parkinson-White syndrome-related tachyarrhythmias.
• Atrial fibrillation and flutter.
• All types of paroxysmal tachyarrhythmias including: supraventricular tachycardia, nodal tachycardia, ventricular tachycardia, and ventricular fibrillation.

Do not take Trangorex

• If you are allergic to iodine, amiodarone, or any of the other components of this medication (listed in section 6)
• If you have a low heart rate (sinus bradycardia) or have other rhythm or conduction disorders (sinoatrial block, sinus node disease, severe atrioventricular conduction disorders), unless a pacemaker is implemented
• If you have any thyroid-related disease
• If you are pregnant, except in special circumstances or during breastfeeding
• In association with medications that may cause "torsades de pointes" (severe heart rhythm problems): see "Trangorex use with other medications" section.

Warnings and precautions

In case of unusual shortness of breath, cough, fatigue, or prolonged or unexplained fever, diarrhea, weight loss, or reappearance of a very fast heart rate, consult your doctor.

The decrease in heart rate may be more pronounced in older patients.

Trangorex may cause changes in the electrocardiogram, such as prolongation of the QT interval (related to prolonged repolarization), which do not reflect toxicity.

There have been cases where new arrhythmias or worsening of treated arrhythmias have occurred, with death in some cases. This usually happens when associated with other medications or electrolyte disorders (such as low calcium levels in the blood). In these cases, your doctor will evaluate the withdrawal of treatment with this medication.

Treatment with amiodarone should be discontinued in case of the onset of cardiac block (second- or third-degree atrioventricular block, sinoatrial block, or bifascicular block).

Consult your doctor or pharmacist before starting to take Trangorex if you are currently taking a medication containing sofosbuvir for the treatment of hepatitis C, as it may cause potentially fatal bradycardia. Your doctor may consider alternative treatments. If amiodarone treatment is needed and sofosbuvir is required, you may need additional cardiac monitoring.

Consult your doctor immediately if you are taking a medication containing sofosbuvir for the treatment of hepatitis C and during treatment experience:

• slow or irregular heartbeats or heart rhythm problems;
• shortness of breath or worsening of existing shortness of breath;
• chest pain;
• dizziness;
• palpitations;
• syncope or near syncope.

Trangorex contains iodine, which may interfere with radioactive iodine uptake.

Your doctor will reduce or discontinue your amiodarone treatment if your liver enzyme levels (transaminases) exceed three times the normal value due to severe liver damage.

Neuromuscular changes may occur, which usually resolve upon discontinuation of the medication.

Consult your doctor in case of visual disturbances: blurred vision, decreased vision, colored halos, or a sense of fog. If any of these problems occur, a complete eye examination should be performed.

Before starting treatment, your doctor may order tests: complete clinical examination, thyroid function determination, liver enzymes, blood potassium levels, chest X-ray, electrocardiogram.

During treatment, your doctor may order tests to monitor thyroid and liver function every 6 months. Additionally, lung function tests, chest X-ray, electrocardiogram, or eye examination may be performed if symptoms occur or worsen. If you are to undergo surgery or receive anesthesia, inform your doctor that you are taking Trangorex.

If you have a pacemaker or implantable cardioverter-defibrillator (devices used to ensure proper heart function), the administration of Trangorex may affect the effectiveness of these devices. Your doctor will perform tests before and after treatment with Trangorex to ensure that these devices function correctly.

During treatment, severe skin changes (Stevens-Johnson syndrome or toxic epidermal necrolysis) may occur, which can be life-threatening (see section 4). If symptoms or signs of Stevens-Johnson syndrome or toxic epidermal necrolysis (progressive skin rash often with blisters or mucous membrane lesions) appear, amiodarone treatment should be discontinued immediately.

Amiodarone has not been established as safe and effective in children, so it is not recommended for use in children.

Avoid exposure to sunlight or tanning beds and take protective measures throughout the treatment period.

Before starting treatment with amiodarone, if blood potassium levels are low, they must be corrected.

If you are on a heart transplant waiting list, your doctor may change your treatment. This is because taking amiodarone before heart transplantation has been shown to increase the risk of a life-threatening complication (primary graft dysfunction) where the transplanted heart fails to function correctly within the first 24 hours after surgery.

Trangorex use with other medications

This medication may alter the response to other medications; therefore, inform your doctor if you are using or have recently used other medications, even those obtained without a prescription. Your doctor will decide which medication to discontinue or modify the dose.

1- Medications that may inducetorsades de pointes(severe heart rhythm problems) or prolongation of the QT interval:

Concomitant treatment with medications that may inducetorsades de pointesis contraindicated:

• Antiarrhythmic medications of Class Ia (quinidine, hydroquinidine, disopyramide), sotalol, bepridil.
• Non-antiarrhythmic medications such as vincamine (used to treat cerebral circulation disorders), some neuroleptic medications (used to treat psychosis and agitation, such as: chlorpromazine, levomepromazine, thioridazine, trifluoperazine, haloperidol, amisulpride, sulpiride, tiapride, pimozide), cisapride (used to treat gastrointestinal disorders), intravenous erythromycin (antibiotic), pentamidine when administered parenterally (antibiotic), as there is a higher risk oftorsades de pointespotentially fatal.

- Medications that prolong the QT interval

The administration of amiodarone with medications that prolong the QT interval should be based on a careful evaluation of the risks and benefits for each patient, as the risk oftorsades de pointesmay increase. Prolongation of the QT interval should be monitored.

Additionally, the use of a type of antibiotic (fluoroquinolones) during treatment with amiodarone should be avoided.

2- Medications that reduce heart rate or produce automaticity or conduction disorders:

Concomitant treatment with the following medications is not recommended:

• Other antiarrhythmic medications or medications that may cause arrhythmia (phenothiazines, tricyclic antidepressants, terfenadine).
• Beta-blockers and calcium channel blockers that decrease heart rate (verapamil, diltiazem).
• Sofosbuvir, used to treat hepatitis C.

3- Agents that may induce hypokalemia:

Concomitant treatment with the following medications is not recommended:

• Laxatives that may induce low potassium levels in the blood and thereby increase the risk oftorsades de pointes.

Special caution should be exercised when amiodarone is combined with the following medications:

• Diuretics that decrease potassium levels in the blood alone or in combination, corticosteroids, tetracosactide (used to diagnose adrenal problems and treat ulcerative colitis), amphotericin B when administered intravenously (antibiotic).
• Oral anticoagulants (acenocoumarol, warfarin, dabigatran), as it increases the risk of bleeding.
• Digitals (used to treat heart failure), phenytoin (antiepileptic), flecainide (for arrhythmia treatment), fentanyl (for pain), lidocaine (for pain), sildenafila (for erectile dysfunction), midazolam (muscle relaxant and antiepileptic), triazolam (for anxiety), dihydroergotamine (for migraines), ergotamine (for migraines), colchicine (for gout), as it may increase blood concentrations of these medications.
• Ciclosporin, tacrolimus, and sirolimus (used to prevent transplant rejection), as it may increase the effect of these medications.
• Statins such as simvastatin, atorvastatin, and lovastatin (used to lower high levels of fats in the blood, primarily cholesterol and triglycerides), as it increases the risk of muscle toxicity (e.g., rhabdomyolysis, a disease characterized by muscle tissue breakdown).

Anesthesia

Severe complications have been observed after association with general anesthetics.

Amiodarone contains iodine and may interfere with radioactive iodine uptake. However, thyroid function tests (free T3, free T4, and TSHus) remain interpretable.

It is recommended to avoid taking grapefruit juice during treatment with amiodarone, as it may increase amiodarone levels.

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication.

Pregnancy and breastfeeding

Trangorex should not be taken during pregnancy, except in special circumstances or during breastfeeding, as it affects the fetal thyroid gland. Inform your doctor if you are pregnant or think you may be pregnant.

Trangorex should not be taken during breastfeeding, as it passes into breast milk in significant amounts.

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machinery

No specific information is available to indicate that Trangorex affects the patient's ability to drive and operate machinery.

Trangorex contains lactose

This medication contains lactose. If your doctor has indicated that you have an intolerance to certain sugars, consult with them before taking this medication.

The treatment will only begin under the supervision of a specialist doctor. For proper use of this medication, it is essential to undergo regular medical follow-up that may include analytical controls.

In case of doubt, consult your doctor again.

Trangorex must be administered orally.

The minimum effective dose should always be used according to the response of each patient. The usual dosing regimen is:

• Initial treatment: 3 tablets (600 mg) per day for 8 to 10 days. In certain cases, the attack dose may be higher than 4-5 tablets (1000 mg) per day. After the initial treatment, reduce the dose to 2 tablets (400 mg) per day for the following week.
• Maintenance treatment: from half (100 mg) to 1 tablet (200 mg) per day. It is recommended to perform rest periods (2 days a week); these are possible due to the effect of this medication. Rarely, a higher maintenance dose may be needed. The maintenance treatment should be reviewed regularly, mainly when taking more than 1 tablet per day.

In patients over 65 years old, it is recommended to start with the lowest dose taking into account the patient's heart, kidney, and liver function, as well as any other disease or medication being taken.

Use in children and adolescents

The data on safety and efficacy in children are limited. Your doctor will decide on the appropriate dose.

Follow exactly the administration instructions for Trangorex indicated by your doctor. Consult your doctor or pharmacist if you have doubts.

Your doctor will indicate the duration of your treatment with Trangorex. Do not discontinue treatment before.

If you take more Trangorex than you should

Like other medications, an overdose can be hazardous.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to take Trangorex

The best option is to take the next dose in the usual manner.

Do not take a double dose to compensate for the missed doses.

Like all medications, this medication may cause side effects, although not everyone will experience them.

The side effects observed according to their frequency of presentation,very frequent (may affect more than 1 in 10 people); frequent (may affect up to 1 in 10 people); infrequent (may affect up to 1 in 100 people); rare (may affect up to 1 in 1,000 people); very rare (may affect up to 1 in 10,000 people); unknown frequency (cannot be estimated from available data), have been:

From the blood and lymphatic system:

• Very rare: Anemia (decrease in the number of red blood cells in the blood), aplastic anemia (failure of the bone marrow to produce blood cells), reduction in the number of platelets in the blood (thrombocytopenia).
• Unknown frequency: You may have more infections than usual. This may be due to a decrease in the number of white blood cells(neutropenia). Severe reduction in the number of white blood cells that makes infections more likely (agranulocytosis).

Cardiac:

• Frequent: Moderate and dose-dependent bradycardia (slow heart rate).
• Infrequent: Initiation or worsening of arrhythmias (abnormal heart rhythms) sometimes followed by cardiac arrest. Alterations in the conduction of the heart's electrical impulse.
• Very rare: Marked bradycardia (slow heart rate) or sinoatrial block (absence of electrical stimuli in the heart), especially in patients with sinus dysfunction and/or over 65 years old.
• Unknown frequency: Torsades de pointes.

Endocrine:

• Frequent: Hypothyroidism (underactive thyroid gland); hyperthyroidism, sometimes fatal (overactive thyroid gland).
• Very rare: Increase in creatinine (substance related to kidney function) in the blood. Problems with antidiuretic hormone (hormone that regulates water elimination).

Ocular:

• Very frequent: Seeing halos of color in bright light or blurred vision, decreased vision, which disappear when treatment is stopped.
• Very rare: Inflammation of the optic nerve (optic neuritis) that may progress to blindness.

Gastrointestinal::

• Very frequent: Nausea, vomiting, altered taste, which usually disappear when the dose is reduced.
• Frequent: Constipation.
• Infrequent: Dry mouth.
• Unknown frequency: Sudden inflammation of the pancreas (acute pancreatitis).

General and at the site of administration:

• Unknown frequency: Granuloma (type of hard and reddish nodule), including granuloma in bone marrow.

Hepatobiliary::

• Very frequent: Isolated and moderate increase in transaminases (substances related to liver function), which resolves when the dose is reduced or spontaneously.
• Frequent: Acute liver damage with increased transaminases and/or jaundice (yellow discoloration of the skin). Liver insufficiency (sometimes fatal).
• Very rare: Chronic liver damage (sometimes fatal).

Immune system:

• Unknown frequency: You may experience edema (swelling due to fluid accumulation under the skin) (Quincke's edema). Severe allergic reaction (anaphylactic reaction, anaphylactic shock), includingsevere allergic reaction that may put your life at risk (shock).

Others:

• Very rare: Increase in blood creatinine.

Metabolism and nutrition:

• Unknown frequency:Decreased appetite.

Musculoskeletal:

• Unknown frequency: Syndrome similar to lupus (a disease where the immune system attacks various parts of the body, causing pain, stiffness, and swelling in joints and red skin, sometimes with butterfly-shaped rash on the face).

Nervous system:

• Frequent: Tremor, nightmares, sleep disturbances.
• Infrequent: Peripheral neuropathy (loss of sensation in limbs) and/or muscle problems (myopathies) that resolve when treatment is stopped.
• Very rare: Problems with voluntary movements (ataxia), benign intracranial hypertension, headache.
• Unknown frequency: Abnormal muscle movements, stiffness, tremor, and restlessness (parkinsonism), abnormal sense of smell (parosmia).

Psychiatric:

• Frequent:Decreased libido.
• Unknown frequency: Confusion (delirium). Seeing, hearing, or feeling things that do not exist (hallucinations).

Reproductive:

• Very rare: Inflammation of the testicles, impotence.

Respiratory:

• Frequent: Pulmonary toxicity, sometimes fatal (see section 2 "Warnings and precautions").
• Very rare: Bronchospasm (contraction of bronchial muscles) in patients with severe respiratory insufficiency and in patients with asthma. Acute respiratory distress syndrome (difficulty breathing) in adults, usually after surgery.
• Unknown frequency: Pulmonary hemorrhage.

Skin and subcutaneous tissue:

• Very frequent: Sensitivity to light (photosensitivity).
• Frequent: Pruritic erythematous rash (eczema). Gray or lilac-colored skin patches when taking high doses for a long time. They disappear when treatment is stopped, although slowly.
• Very rare: Skin patches (erythema) when associated with radiation therapy. Skin eruptions. Inflammation of the skin (dermatitis). Hair loss (alopecia).
• Unknown frequency:Urticariacharacterized by the appearance ofhives, skin irritation, and itching. Reactions threatening life characterized by skin rash, blisters, peeling, and pain (toxic epidermal necrolysis (TEN)), Stevens-Johnson syndrome (SJS), bullous dermatitis, drug reaction with eosinophilia and systemic symptoms (DRESS).

Vascular:

• Very rare: Inflammation of blood vessels (vasculitis).

Lesions, intoxications, and complications of therapeutic procedures:

• Unknown frequency:Life-threatening complication after heart transplant (primary graft dysfunction) in which the transplanted heart fails to function correctly (see section 2, Warnings and precautions).

The appearance of adverse reactions with amiodarone is frequent, particularly in the heart, lungs, and liver. In some cases, these manifestations are related to the dose and resolve after its reduction.

If you consider that any of the side effects you experience are severe or if you notice any side effect not mentioned in this leaflet, inform your doctor or pharmacist.

Reporting of adverse reactions:

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use:https://www.notificaram.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medication.

Do not store at a temperature above 25°C.

Store in the outer packaging to protect it from light.

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging after CAD.The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Trangorex

• The active ingredient is amiodarone.
• The other components are: lactose monohydrate, cornstarch, magnesium stearate, povidone, colloidal silica, and purified water.

Appearance of the product and contents of the packaging

Trangorex 200 mg are white, round, bisected, scored on one face and smooth on the other. On the scored face, “200” is engraved.

Each package contains 30 tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

Responsible for manufacturing:

sanofi-aventis, S.A.

Ctra. C-35 (La Batlloria-Hostalric, km 63,09

17404 Riells i Viabrea (Gerona)

Spain

or

Sanofi Winthrop Industrie

1, rue de la Vierge

Ambarès et Lagrave

33565 Carbon Blanc Cedex

France

Last review date of this leaflet: January 2022

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/