Package Insert: Information for the User

Rytmonorm 300 mg Coated Tablets

Hydrochloride of Propafenone

Read this package insert carefully before starting to take the medicine, as it contains important information for you.

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

6. Contents of the pack and additional information

Rytmonorm is a medication used for various heart rhythm disorders. It belongs to a group of medications called class 1C antiarrhythmics according to Vaughan Williams.

Rytmonorm is used for the treatment and prevention of paroxysmal supraventricular tachycardia, including atrial fibrillation and paroxysmal atrial flutter and paroxysmal tachycardia due to re-entry phenomena affecting the atrioventricular node or accessory pathways (Wolff-Parkinson-White syndrome). For the treatment and prevention of ventricular arrhythmias, including symptomatic ventricular extrasystoles and/or sustained and nonsustained ventricular tachycardia.

Do not take Rytmonorm

• If you are allergic to the active ingredient or any of the other components of this medication (including those listed in section 6).
• If you have a history of Brugada syndrome (a hereditary disease characterized by an abnormality in the electrocardiogram (ECG) and an increased risk of sudden death). (see Warnings and precautions).
• If you have had a myocardial infarction in the 3 months prior to starting treatment.
• If you have a significant heart disease such as:

- congestive heart failure.

- cardiogenic shock, unless the cause is an arrhythmia.

- severe bradycardia.

- if you have a dysfunction of the sinoatrial node, atrial conduction defects, second-degree or higher atrioventricular block, or branch or distal block in the absence of an artificial pacemaker.

- if you have a severe drop in blood pressure.

• If you have an alteration in the balance of salts in the blood (e.g. alterations in potassium metabolism).
• If you have severe chronic obstructive pulmonary disease.
• If you have myasthenia gravis.
• If you are taking ritonavir (an antiretroviral used in the treatment of HIV infection, see Taking Rytmonorm with other medications).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Rytmonorm.

• It is essential that each patient receiving propafenone be clinically evaluated and with an electrocardiogram before and during treatment with Rytmonorm to determine if the response to propafenone justifies continued treatment.
• After treatment with this medication, your doctor should rule out Brugada syndrome that may have been present without previous symptoms.
• If you have a pacemaker, the treatment may affect it, so it should be controlled and, if necessary, reprogrammed.
• If you have atrial fibrillation, Rytmonorm may lead to the appearance of a more serious arrhythmia; see Possible adverse effects).

• If you have severe heart disease, you may be predisposed to severe adverse reactions and treatment with this medication may be contraindicated.
• If you have asthma or other chronic obstructive respiratory disease.

Children

Only interaction studies have been conducted in adults, so it is unknown if they are similar in children.

Older patients

Rytmonorm should be used with extreme caution in older patients.

Taking Rytmonorm with other medications

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

More adverse effects may appear with Rytmonorm if administered with local anesthetics (e.g. for the implantation of a pacemaker, surgical or dental interventions), as well as with other medications that have an inhibitory effect on the heart, such as beta-blockers (for hypertension) or some antidepressants.

Inform your doctor if you are taking any of the following medications, as they may increase your blood levels:

• venlafaxine (for depression)
• propranolol (for hypertension and angina pectoris)
• metoprolol (for hypertension)
• desipramine (for depression)

• ciclosporin (to reduce the body's defenses)

• theophylline (for asthma)
• digoxin (for heart problems)

If signs of overdose are observed, reduce the doses of these medications, as indicated by your doctor.

Inform your doctor if you are taking any of the following medications, as they may increase your hydrochloride propafenone levels in the blood, so you may need to be monitored and your dose adjusted:

• ketoconazole (against fungi)
• cimetidine (for stomach ulcers)
• quinidine (for heart arrhythmia or against malaria)
• erythromycin (antibiotic)
• fluoxetine (for depression)
• paroxetine (for depression)

There is also an increase in hydrochloride propafenone levels with orange juice.

The concomitant use of Rytmonorm and amiodarone may cause alterations in the heart. It may be necessary to adjust the dose of the two medications.

The concomitant use of propafenone and lidocaine increases the risk of lidocaine's central nervous system effects.

Inform your doctor if you are taking any of the following medications, as they may reduce the effectiveness of Rytmonorm:

• rifampicin (antibiotic)
• phenobarbital (sedative and antiepileptic)
• phenytoin (antiepileptic)
• carbamazepine

In the case of chronic treatment with these medications and Rytmonorm, the response to Rytmonorm treatment should be monitored.

Inform your doctor if you are receiving medications to prevent blood clotting (e.g. acenocoumarol or warfarin) because Rytmonorm may increase the effectiveness of these medications, increasing the risk of bleeding. You may need to reduce the dose of the anticoagulant.

Taking Rytmonorm with food and drinks

Due to its bitter taste and the anesthetic effect of hydrochloride propafenone on the surface, Rytmonorm tablets should be taken without chewing or sucking, accompanied by some liquid.

Pregnancy, breastfeeding, and fertility

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

No adequate and well-controlled studies have been conducted in pregnant women. Rytmonorm should not be used during pregnancy unless the expected benefit justifies the potential risk to the fetus. Hydrochloride propafenone crosses the placental barrier.

No studies have been conducted on the excretion of hydrochloride propafenone in breast milk. Limited data suggest that hydrochloride propafenone may pass into breast milk, so it should be used with caution in breastfeeding women.

Driving and operating machinery

During treatment, blurred vision, dizziness, fatigue, or a drop in blood pressure may appear, so if you notice these symptoms, you should not drive or operate hazardous machinery.

Rytmonorm contains sodium

This medication contains less than 23 mg of sodium (1 mmol) per coated tablet; that is, it is essentially "sodium-free".

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, ask your doctor or pharmacist.

Rytmonorm is administered orally.

Adults

Your doctor will determine your individual maintenance dose through heart monitoring, that is, with several electrocardiographic and blood pressure controls (adjustment phase). For the adjustment phase and maintenance therapy, a total daily dose of 450 mg to 600 mg is recommended, divided into two or three daily doses (1 Rytmonorm tablet 150 mg three times a day or 1 Rytmonorm tablet 300 mg two times a day) in patients weighing around70 kg.

It may sometimes be necessary to increase the daily dose to 900 mg (1 Rytmonorm tablet 300 mg three times a day).

For patients weighing less than70 kg, the daily dose should be reduced appropriately, starting with 150 mg two times a day. Dose increases should not be made until the patient has received treatment for 3-4 days.

If you are an elderly patient or have heart damage, Rytmonorm 300 mg, like other antiarrhythmics, will be administered in the adjustment phase with great care, starting with a dose of 150 mg once a day, so it is more advisable for your doctor to prescribe the Rytmonorm 150 mg presentation, and you can then gradually increase your dose. The maintenance dose for each person should be calculated with heart function controls and repeatedly measuring blood pressure (adjustment phase). Any dose increase that is needed should not be made until after 5 to 8 days of treatment.

The same applies to maintenance therapy. Any dose increase that is needed should not be made until after 5 to 8 days of treatment.

Patients with liver and/or kidney insufficiency

If you have liver or kidney problems, your doctor will start treatment with a dose of 150 mg once a day (with Rytmonorm 150 mg tablets) and will adjust your dose according to your response to treatment.

Use in children and adolescents

In children, the average daily dose is10 to 20 mg of propafenone hydrochloride per kilogram of body weight, divided into3 to 4 daily doses in the initial dose adjustment phase and in maintenance therapy.

Dose increases should not be made until the patient has received treatment for 3-4 days.

The maintenance dose should be calculated for each person with heart function controls and repeatedly measuring blood pressure (adjustment phase).

Your doctor will indicate the duration of your treatment. Do not stop treatment before, as although you may already be feeling better, your disease could worsen or come back.

Remember to take your medication. Take the tablets at the same time every day.

If you estimate that the action of Rytmonorm is too strong or too weak, inform your doctor or pharmacist.

If you take more Rytmonorm than you should

If you take more doses than prescribed, contact your doctor immediately so that you can receive medical attention quickly. Severe symptoms may occur.If you have taken more Rytmonorm than you should, you may notice heart effects and low blood pressure, which in severe cases can cause cardiovascular shock. Often, headache, dizziness, blurred vision, tingling or numbness of the skin, tremors, nausea, constipation, and dry mouth occur. In severe cases of poisoning, convulsions, tingling or numbness of the skin, drowsiness, coma, and respiratory arrest are observed. There have been cases of death.

Monitor the patient in an intensive care unit if this occurs.

If you have taken more Rytmonorm than you should, consult your doctor, pharmacist, or call the Toxicology Information Service, phone 91.562.04.20, indicating the medication and the amount ingested.

If you forget to take Rytmonorm

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

In case of forgetting a dose, take the medication as soon as possible and continue treatment as prescribed. However, if the next dose is near, it is better not to take the missed dose and wait for the next one.

If you interrupt treatment withRytmonorm

If you have any other doubts about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Side effects are classified as very common (may affect more than 1 in 10 people), common (may affect up to 1 in 10 people), uncommon (may affect up to 1 in 100 people), and of unknown frequency (cannot be estimated from available data).

The very common side effects related to treatment with propafenone are dizziness, cardiac conduction disorders (heart alterations), and palpitations.

Within each group, side effects are presented in order of decreasing severity, from most severe to least severe, when the severity that it posed to the patient could be determined.

The following side effects have been reported:

Blood and lymphatic system disorders

• Uncommon: decreased platelets (blood cells involved in clotting).
• Unknown frequency: decreased white blood cells (blood cells that act to defend the body against infections or foreign substances, may manifest as frequent infections with fever, chills, or sore throat), decreased granulocytes (a type of white blood cell that may predispose to infections), severe reduction of granulocytes or neutrophils (agranulocytosis, a condition in which the person is more prone to infections).

Immune system disorders

• Unknown frequency: hypersensitivity1.

1May manifest as cholestasis (bile flow detention towards the duodenum), blood alterations, and skin rash.

Metabolism and nutrition disorders

• Uncommon: decreased appetite.

Mental and behavioral disorders

• Common: anxiety, sleep disorders.
• Uncommon: nightmares.
• Unknown frequency: confusion.

Nervous system disorders

• Very common: dizziness2.
• Common: headache, altered taste perception.
• Uncommon: brief loss of consciousness (syncope), abnormal coordination, sensation of tingling, numbness, or aching in any part of the body but more frequently in feet, hands, arms, or legs (paresthesia).
• Unknown frequency: seizures, extrapyramidal symptoms (involuntary movements), restlessness.

2Excluding vertigo

Eye disorders

• Common: blurred vision.

Ear and labyrinth disorders

• Uncommon: vertigo.

Cardiac disorders

• Very common: cardiac conduction disorders3(heart alterations), palpitations
• Common: sinus bradycardia (slow heart rate), reduced heartbeats (bradycardia), tachycardia (increased heartbeats), atrial flutter (abnormal heart rhythm occurring in the atrium).
• PUncommon: ventricular tachycardia (increased heartbeats originating in the ventricles and with more than 100 beats per minute), arrhythmia4(alteration of heart rate that may increase, decrease, or become irregular).
• Unknown frequency: ventricular fibrillation, heart failure5, reduced heart rate.

3Including sinoatrial block, atrioventricular block, and intraventricular block

4Propafenone may be associated with proarrhythmic effects that manifest as an increase in heart rate (tachycardia) or ventricular fibrillation. Some of these arrhythmias may pose a life-threatening risk and may require resuscitation to prevent a potentially fatal outcome.

5A pre-existing heart failure may worsen

Vascular disorders

• Uncommon: hypotension (decreased blood pressure).
• Unknown frequency: orthostatic hypotension (decreased blood pressure while standing or standing for a long time).

Respiratory, thoracic, and mediastinal disorders

• Common: dyspnea (shortness of breath or difficulty breathing).

Gastrointestinal disorders

• Common: abdominal pain, vomiting, nausea, diarrhea, constipation, dry mouth.
• Uncommon: abdominal distension (abdominal swelling), flatulence (gas).
• Unknown frequency: hiccups, gastrointestinal discomfort.

Hepatobiliary disorders

• Common: abnormal liver function6
• Unknown frequency: liver damage, bile flow obstruction from the liver (cholestasis), hepatitis, jaundice (yellow skin and eyes)

Investigations

• Common: abnormal liver function tests detected in blood analyses such as increased aspartate aminotransferase, increased alanine aminotransferase, increased gamma-glutamyl transferase, and increased alkaline phosphatase.

Skin and subcutaneous tissue disorders

• Uncommon: urticaria, pruritus, skin rash, erythema (redness of the skin).

Musculoskeletal and connective tissue disorders

• Unknown frequency: lupus-like syndrome (autoimmune disease).

Reproductive and breast disorders

• Uncommon: erectile dysfunction (impotence).
• Unknown frequency: decreased sperm count7

7The decrease in sperm count is reversible upon discontinuing propafenone administration.

General disorders and administration site conditions

• Common: chest pain, asthenia (sensation of fatigue), fatigue, fever.

Reporting of side effects

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

Keep this medication out of the sight and reach of children.

This medication does not require special storage conditions.

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 disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. Ask your pharmacist how to dispose of packaging and medications you no longer need. This will help protect the environment.

Composition of Rytmonorm

• The active ingredient is hydrochloride of propafenone. Each tablet contains 300 mg of hydrochloride of propafenone.

• The other components (excipients) are: microcrystalline cellulose, sodium croscarmellose, magnesium stearate, cornstarch, hydroxypropylmethylcellulose, macrogol 400, macrogol 6000, titanium dioxide (E 171) and purified water.

Appearance of the product and contents of the package

Rytmonorm 300 mg coated tablets are round white tablets with "300" printed on one side.

Each package contains 60 coated tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder

Teva B.V.,

Swensweg 5, 2031GA Haarlem,

Netherlands

Responsible for manufacturing

ITC Production s.r.l.

Via Pontina km 29

00071 Pomezia (RM)

Italy

Local representative :

Teva Pharma, S.L.U.

C/ Anabel Segura, 11, Edificio Albatros B, 1st floor

Alcobendas 28108 Madrid

Spain

Last review date of this prospectus: March 2019

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

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This information is intended solely for healthcare professionals:

Treatment of overdose

In addition to general emergency measures, monitoring and correction of the patient's vital parameters (as necessary) in an intensive care unit are required.

Defibrillation, as well as the infusion of dopamine and isoprenaline, have been effective in controlling the rhythm and blood pressure. Convulsions have been alleviated with intravenous diazepam. General supportive measures such as mechanical ventilation and external cardiac massage may be necessary.

Attempts at elimination by hemoperfusion are ineffective.

Hemodialysis has no effect due to the high binding of propafenone to proteins (> 95%) and the large volume of distribution.

Other presentations

Rytmonorm 150 mg coated tablets. Packages with 60 coated tablets.

Rytmonorm 3.5 mg/ml injectable solution. Packages with 5 ampoules of 20 ml.