TRANGOREX 200 mg TABLETS

Introduction

Package Leaflet: Information for the User

Trangorex 200 mg Tablets

Amiodarone

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 or pharmacist.
• 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet

1. What is Trangorex and what is it used for
2. What you need to know before you take Trangorex
3. How to take Trangorex
4. Possible side effects
5. Storage of Trangorex
6. Contents of the pack and further information

1. What is Trangorex and what is it used for

Trangorex belongs to a group of medicines known as anti-arrhythmic agents (used to control rapid or irregular heart rhythm).

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

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

2. What you need to know before you take Trangorex

Do not take Trangorex

• if you are allergic to iodine, amiodarone or any of the other ingredients of this medicine (listed in section 6)
• if you have a low heart rate (sinus bradycardia) or suffer from other heart rhythm or conduction disorders (sino-atrial block, sick sinus syndrome, severe atrioventricular conduction disorders), unless a pacemaker is implanted
• if you have any thyroid-related disease
• if you are pregnant, except in special circumstances or during breastfeeding
• in combination with medicines that may cause "torsades de pointes" (serious heart rhythm problems): see section "Using Trangorex with other medicines".

Warnings and precautions

In case of unusual shortness of breath, cough, prolonged or unexplained fatigue or fever, diarrhea, weight loss, or recurrence of a very rapid heart rhythm, consult your doctor.

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

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

There have been cases where new arrhythmias or worsening of treated arrhythmias may occur, with death in some cases. This usually occurs when associated with other medications or electrolyte disturbances (such as changes in blood calcium levels). In these cases, your doctor will assess the withdrawal of treatment with this medicine.

Treatment with amiodarone should be discontinued in case of onset of heart 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 medicine that contains sofosbuvir for the treatment of hepatitis C, as it may cause a potentially fatal decrease in heart rate. Your doctor may consider alternative treatments. If treatment with amiodarone and sofosbuvir is needed, you may need additional cardiac monitoring.

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

• slow or irregular heartbeats or heart rhythm problems;
• shortness of breath or worsening of existing shortness of breath;
• chest pain;
• dizziness;
• palpitations;
• fainting or feeling like you are about to faint.

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

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

Neuromuscular disorders may occur, which usually resolve when the medicine is discontinued.

Consult your doctor if you experience vision changes: blurred vision, decreased vision, colored halos, or a sensation of fog. If any of these problems occur, a complete eye examination should be performed.

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

During treatment, your doctor may indicate the need for tests to monitor thyroid and liver function every 6 months. Additionally, lung function tests, chest X-ray, electrocardiogram, or eye exams will be performed if symptoms occur or worsen. If you are going to undergo surgery or receive treatment with anesthetics, you should inform your doctor that you are taking Trangorex.

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

During treatment, skin changes (severe bullous reactions) such as Stevens-Johnson syndrome or toxic epidermal necrolysis may occur, which can be very serious or even fatal (see section 4). If symptoms or signs of Stevens-Johnson syndrome or toxic epidermal necrolysis (progressive skin rash often with blisters or mucosal lesions) occur, treatment with amiodarone should be discontinued immediately.

The safety and efficacy of amiodarone in children have not been established, so it is not recommended to administer amiodarone to children.

You should avoid exposure to the sun or sunlamps and take protective measures during the entire duration of treatment.

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

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

Using Trangorex with other medicines

This medicine may alter the response to other medicines; therefore, inform your doctor if you are using or have recently used other medicines, including those obtained without a prescription. Your doctor will decide which medication to discontinue or whether the dose should be modified.

1- Medicines that may induce "torsades de pointes" (serious heart rhythm problems) or prolong the QT interval:

• Medicines that induce "torsades de pointes"

Concomitant treatment with medicines that may induce "torsades de pointes" is contraindicated:

• Class Ia anti-arrhythmic medicines (quinidine, hydroquinidine, disopyramide), sotalol, bepridil.
• Non-anti-arrhythmic medicines such as vincamine (used to treat blood circulation disorders in the brain), certain neuroleptics (used to treat psychosis and agitation, such as: chlorpromazine, levomepromazine, thioridazine, trifluoperazine, haloperidol, amisulpride, sulpiride, tiapride, pimozide), cisapride (used to treat stomach and intestine disorders), intravenous erythromycin (antibiotic), pentamidine when administered parenterally (antibiotic), as there is an increased risk of potentially fatal "torsades de pointes".

• Medicines that prolong the QT interval

The administration of amiodarone with medicines that prolong the QT interval should be based on a careful assessment of the risks and benefits for each patient, as the risk of "torsades de pointes" may increase. QT interval prolongation should be monitored.

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

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

Treatment with the following medicines is not recommended:

• With other anti-arrhythmics or medicines that may cause arrhythmia (phenothiazines, tricyclic antidepressants, terfenadine - antihistamine-).
• 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 medicines is not recommended:

• Stimulant laxatives that may induce decreased blood potassium levels and thus increase the risk of "torsades de pointes".

Special care should be taken when amiodarone is combined with the following medicines:

• Diuretics that decrease blood potassium levels alone or in combination, corticosteroids, tetracosactide (used to diagnose adrenal problems and to treat ulcerative colitis), intravenous amphotericin B (antibiotic).
• Oral anticoagulants (acenocoumarol, warfarin, dabigatran), as they increase the risk of bleeding.
• Digitalis (used to treat heart failure), phenytoin (antiepileptic), flecainide (used to treat heart rhythm problems), fentanyl (used to treat pain), lidocaine (used to treat pain), sildenafil (used to treat erectile dysfunction), midazolam (muscle relaxant and antiepileptic), triazolam (used to treat anxiety), dihydroergotamine (used to treat migraines), ergotamine (used to treat migraines), colchicine (used to treat gout), as increased blood levels of these medicines may occur.
• Cyclosporin, tacrolimus, and sirolimus (used to help prevent transplant rejection), as they may increase the effect of these medicines.
• Statins such as simvastatin, atorvastatin, and lovastatin (medicines used to lower high blood fat levels, mainly cholesterol and triglycerides), as they increase the risk of muscle toxicity (e.g., rhabdomyolysis, a disease characterized by muscle tissue breakdown).

General anesthesia

Potentially serious complications have been observed after combination with general anesthetics.

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

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

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Pregnancy and breastfeeding

In case of pregnancy, do not take Trangorex, unless the benefits outweigh the risks, as it affects the fetus's thyroid gland. Inform your doctor if you are pregnant or think you might be pregnant.

In case of breastfeeding, do not take Trangorex, as it passes into breast milk in significant amounts.

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

There is no specific information that indicates Trangorex affects the patient's ability to drive or use machines.

Trangorex contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Trangorex

Treatment will only be started under the supervision of a specialist doctor. For proper use of this medicine, regular medical follow-up is essential, which may involve analytical tests.

In case of doubt, consult your doctor again.

Trangorex should be taken orally.

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

• initial treatment: 3 tablets (600 mg) per day, for 8 to 10 days. In some cases, the loading dose may be higher than 4-5 tablets (1000 mg) per day. After 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 take regular breaks (2 days a week); these are possible due to the effect of this medicine. Rarely, a higher maintenance dose may be needed. Maintenance treatment should be regularly reviewed, mainly when taking more than 1 tablet per day.

In patients over 65 years of age, 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

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

Follow exactly the administration instructions of 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 stop treatment before.

If you take more Trangorex than you should

Like other medicines, an overdose can be dangerous.

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

If you forget to take Trangorex

It is recommended to take the next dose as usual.

Do not take a double dose to make up for forgotten doses.

4. Possible Adverse Effects

Like all medications, this medication can produce adverse effects, although not all people suffer from them.

The adverse 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:

Of the blood and lymphatic system:

• Very rare: Anemia (decrease in the number of red blood cells), lack of bone marrow development (aplastic anemia), reduction in the number of blood platelets (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 decrease in the number of white blood cells that makes infections more likely (agranulocytosis).

Cardiac:

• Frequent: Weak heart rhythm (bradycardia) of moderate severity and varying according to the administered dose.
• Infrequent: Onset or worsening of changes in heart rhythm (arrhythmia) sometimes followed by cardiac arrest. Alterations in the conduction of the heart's nervous impulse.
• Very rare: Weak heart rhythm (bradycardia) marked or sinus arrest (lack of electrical stimuli in the heart), especially in patients with sinus dysfunction and/or over 65 years of age.
• Unknown frequency: Torsades de pointes.

Endocrine:

• Frequent: Hypothyroidism (deficient activity of the thyroid gland); hyperthyroidism, sometimes fatal (exaggerated activity of the thyroid gland).
• Very rare: Increase in creatinine (substance related to kidney function) in the blood. Problems with the antidiuretic hormone (hormone that controls the amount of water the body eliminates).

Ocular:

• Very frequent: Vision of colored halos in very intense light or blurred vision, decreased vision, which disappear when treatment is stopped.
• Very rare: Inflammation of the optic nerve (optic neuritis) that can progress to blindness.

Gastrointestinal:

• Very frequent: Nausea, vomiting, alteration of 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 administration site:

• 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 remit when the dose is reduced or spontaneously.
• Frequent: Acute liver alterations with increased transaminases and/or jaundice (yellowing of the skin) in the blood. Liver failure (sometimes fatal).
• Very rare: Chronic liver alterations (sometimes fatal).

Immune system:

• Unknown frequency: Swelling due to fluid accumulation under the skin (Quincke's edema) may occur. Severe allergic reaction (anaphylactoid reaction, anaphylactic shock), including a severe allergic reaction that can put your life at risk (shock).

Others:

• Very rare: Increase in blood creatinine.

Metabolism and nutrition:

• Unknown frequency: Decrease in appetite.

Muscular and skeletal:

• Unknown frequency: Lupus-like syndrome (a disease where the immune system attacks several parts of the body, leading to pain, stiffness, and swelling in joints and reddened skin, sometimes with a butterfly-shaped rash on the face).

Nervous system:

• Frequent: Tremor, nightmares, sleep disturbances.
• Infrequent: Loss of sensitivity in the extremities (peripheral neuropathies) and/or muscle problems (myopathies) that cease when treatment is interrupted.
• Very rare: Problems with voluntary movement (ataxia), benign increase in cranial tension, headache.
• Unknown frequency: Abnormal muscle movements, rigidity, tremor, and restlessness (parkinsonism), abnormal sense of smell (parosmia).

Psychiatric:

• Frequent: Decrease in sexual desire.
• Unknown frequency: State of confusion (delirium). Seeing, hearing, or feeling things that do not exist (hallucinations).

Reproductive system:

• Very rare: Inflammation of the testicles, impotence.

Respiratory:

• Frequent: Toxicity in the lungs, sometimes fatal (see section 2 "Warnings and precautions").
• Very rare: Contraction of the bronchial muscles (bronchospasm) in patients with severe respiratory failure and in patients with asthma. Acute respiratory distress syndrome (difficulty breathing) in adults, usually after surgery.
• Unknown frequency: Hemorrhage in the lungs.

Skin and subcutaneous tissue:

• Very frequent: Sensitivity to light (photosensitization).
• Frequent: Pruriginous rash (eczema). Gray or lilac spots on the skin when taking high doses for a long time. They disappear when treatment is stopped, although slowly.
• Very rare: Spots on the skin (erythema) when associated with radiotherapy. Skin eruptions. Skin inflammation (dermatitis). Hair loss (alopecia).
• Unknown frequency: Urticaria characterized by the appearance of hives, irritation, and itching of the skin. Life-threatening skin reactions 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).

Traumatic lesions, poisonings, and complications of therapeutic procedures:

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

The appearance of adverse reactions with amiodarone is frequent, particularly at the level of the heart, lungs, and liver. Sometimes these manifestations are related to the dose and reverse after reduction.

If you consider that any of the adverse effects you suffer from is serious or if you notice any adverse effect not mentioned in this prospectus, inform your doctor or pharmacist.

Reporting of adverse effects:

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

5. Conservation of Trangorex

Do not store at a temperature above 25°C.

Keep in the outer packaging to protect it from light.

Keep this medication out of the 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.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

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 package contents

Trangorex 200 mg are white, round, and bisected tablets, scored on one side and smooth on the other. On the scored side, "200" is engraved.

Each package contains 30 tablets.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Manufacturer:

sanofi-aventis, S.A.

Ctra. C-35 (La Batlloria-Hostalric, km 63.09

17404 Riells i Viabrea (Girona)

Spain

or

Sanofi Winthrop Industrie

1, rue de la Vierge

Ambarès et Lagrave

33565 Carbon Blanc Cedex

France

Date of the last revision of this prospectus: January 2022

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/