RYTMONORM 150 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Rytmonorm 150 mg Coated Tablets

Propafenone Hydrochloride

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

Contents of the pack and other information

1. What is Rytmonorm and what is it used for
2. What you need to know before you take Rytmonorm
3. How to take Rytmonorm
4. Possible side effects
5. Storage of Rytmonorm

1. Contents of the pack and other information

1. What is Rytmonorm and what is it used for

Rytmonorm is a medicine used for cardiac rhythm disorders of various origins. It belongs to a group of medicines called class 1C antiarrhythmic agents of Vaughan Williams.

Rytmonorm is used for the treatment and prevention of paroxysmal supraventricular tachycardia, including atrial fibrillation and paroxysmal flutter, and 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 non-sustained and sustained ventricular tachycardia.

2. What you need to know before you take Rytmonorm

Do not take Rytmonorm

• If you are allergic to the active substance or to any of the other ingredients of this medicine (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 the start of treatment.

• If you have or have had significant heart disease, such as:
• • congestive heart failure
  • cardiogenic shock unless the cause is an arrhythmia
  • severe bradycardia (slow heart rate)
  • if you have sinus node dysfunction, atrioventricular block of second or third degree, or bundle branch block and do not have an artificial pacemaker
  • if you have a marked decrease in blood pressure.
• If you have an electrolyte imbalance (e.g., potassium metabolism disorders).
• If you have severe 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 medicines).

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 have an electrocardiogram before and during treatment with Rytmonorm to determine if the response to propafenone justifies continued treatment.
• After treatment with this medicine, your doctor should rule out Brugada syndrome that may have been present without any prior symptoms.
• If you have a pacemaker, as treatment may affect it, and it may need to be controlled and reprogrammed if necessary.
• If you have atrial fibrillation because Rytmonorm may lead to the appearance of a more important arrhythmia; see Possible side effects.
• If you have severe heart disease because you may be predisposed to suffer from serious adverse reactions and in that case, treatment with this medicine is contraindicated.
• If you have asthma or other chronic obstructive respiratory disease.

Children

Only interaction studies have been conducted in adults, so it is not known if they are similar in children.

Elderly patients

In elderly patients, Rytmonorm should be used with great caution.

Taking Rytmonorm with other medicines

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

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

Tell your doctor if you are taking any of the following medicines because they may increase your blood levels:

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

• cyclosporin (to decrease the body's immune response)

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

If signs of overdose are observed, the doses of these medicines should be reduced, as indicated by your doctor.

Tell your doctor if you are taking any of the following medicines because they may increase your propafenone hydrochloride blood levels, and you may need to be monitored and have 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 propafenone hydrochloride levels with grapefruit juice.

The combined use of Rytmonorm and amiodarone may produce cardiac alterations. It may be necessary to adjust the dose of both medicines.

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

Tell your doctor if you are taking any of the following medicines, as they may reduce the efficacy of Rytmonorm:

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

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

Tell your doctor if you are receiving medicines to prevent blood clotting (e.g., acenocoumarol or warfarin) because Rytmonorm may increase the efficacy of these medicines, increasing the risk of bleeding. It may be necessary to reduce the dose of the anticoagulant.

Taking Rytmonorm with food and drinks

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

Pregnancy, breast-feeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

There are no adequate and well-controlled studies in pregnant women. Rytmonorm should not be used during pregnancy unless the expected benefit justifies the potential risk to the fetus. Propafenone hydrochloride crosses the placental barrier.

It has not been studied whether propafenone hydrochloride is excreted in breast milk. Limited data suggest that propafenone hydrochloride may pass into breast milk, so it should be used with caution in breast-feeding mothers.

Driving and using machines

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

Rytmonorm contains sodium

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

3. How to take Rytmonorm

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are unsure, ask your doctor or pharmacist.

Rytmonorm is administered orally.

Adults

Your doctor will determine the maintenance dose individually by monitoring your heart, i.e., with several electrocardiographic and blood pressure checks (dose adjustment phase). For the dose adjustment phase and maintenance therapy, a total daily dose of 450 mg to 600 mg divided into two or three daily doses (1 Rytmonorm 150 mg tablet 3 times a day or 1 Rytmonorm 300 mg tablet 2 times a day) is recommended in patients weighing around 70 kg.

Sometimes it may be necessary to increase the daily dose to 900 mg (2 Rytmonorm 150 mg tablets 3 times a day).

For patients weighing less than 70 kg, the daily dose should be reduced accordingly, starting with 150 mg twice 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 150 mg, like other antiarrhythmics, will be administered in the dose adjustment phase with great caution, starting with a dose of 150 mg once a day and gradually increasing the dose. The maintenance dose for each person should be calculated with heart function checks and repeated blood pressure measurements (dose 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 treatment. Any dose increase that is needed should not be made until after 5 to 8 days of treatment.

Hepatic and/or renal impairment

If you have liver or kidney disease, your doctor will start treatment with a dose of 150 mg once a day and adjust the dose according to your response to treatment.

Use in children and adolescents

In children, the average daily dose is 10 to 20 mg of propafenone hydrochloride per kilogram of body weight, divided into 3 to 4 daily doses in the initial dose adjustment phase and in maintenance treatment.

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 checks and repeated blood pressure measurements (dose adjustment phase).

Your doctor will indicate the duration of your treatment. Do not stop treatment before, as your disease could worsen or reappear.

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

If you think the effect of Rytmonorm is too strong or too weak, tell your doctor or pharmacist.

If you take more Rytmonorm than you should

If you take more than the prescribed dose, contact your doctor immediately so that you can receive medical attention as soon as possible. Serious symptoms may occur. If you have taken more Rytmonorm than you should, you may notice effects on the heart and a decrease in blood pressure, which in severe cases can cause cardiovascular shock. Often, headache, dizziness, blurred vision, tingling or numbness of the skin, tremor, nausea, constipation, and dry mouth appear.

In severe poisonings, convulsions, tingling or numbness of the skin, somnolence, coma, and respiratory arrest are observed. There have been cases of death.

If this happens, the patient should be monitored in an intensive care unit.

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

If you forget to take Rytmonorm

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

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

If you stop taking Rytmonorm

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Adverse effects are classified as 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), and of unknown frequency (cannot be estimated from available data).

The very frequent adverse reactions related to treatment with propafenone are dizziness, cardiac conduction disorders (heart alterations), and palpitations.

Within each group, adverse reactions are presented in decreasing order of severity, from most severe to least severe, when the severity for the patient could be determined.

The following adverse effects have been reported:

Blood and lymphatic system disorders:

• Infrequent: decreased platelet count (blood cells involved in coagulation).
• Frequency not known: decreased white blood cell count (blood cells that defend the body against infections or foreign substances, may manifest as frequent infections with fever, chills, or sore throat), decreased granulocyte count (a type of white blood cell that may predispose to infections), severe reduction of granulocytes or neutrophils (agranulocytosis, a disease in which the person is more prone to infections).

Immune system disorders:

• Frequency not known: hypersensitivity.

1 May manifest as cholestasis (stoppage of bile flow to the duodenum), blood alterations, and skin rash.

Metabolism and nutrition disorders:

• Infrequent: decreased appetite.

Psychiatric disorders:

• Frequent: anxiety, sleep disorders.
• Infrequent: nightmares.
• Frequency not known: confusion.

Nervous system disorders:

• Very frequent: dizziness.
• Frequent: headache, altered taste perception.
• Infrequent: brief loss of consciousness (syncope), abnormal coordination, tingling sensation, numbness, or paresthesia (tingling, numbness, or burning sensation in any part of the body, but more frequently in feet, hands, arms, or legs).
• Frequency not known: convulsions, extrapyramidal symptoms (involuntary movements), restlessness.

2 Excluding vertigo.

Eye disorders:

• Frequent: blurred vision.

Ear and labyrinth disorders:

• Infrequent: vertigo.

Cardiac disorders:

• Very frequent: cardiac conduction disorders, palpitations.
• Frequent: sinus bradycardia (slow heart rate), reduced heart rate (bradycardia), tachycardia (increased heart rate), atrial flutter (abnormal heart rhythm that occurs in the atria).
• Infrequent: ventricular tachycardia (increased heart rate that starts in the ventricles and exceeds 100 beats per minute), arrhythmia (alteration of heart rate that can increase, decrease, or become irregular).
• Frequency not known: ventricular fibrillation, heart failure, reduced heart rate.

3 Including sinoatrial block, atrioventricular block, and intraventricular block.

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

5 Worsening of pre-existing heart failure may occur.

Vascular disorders:

• Infrequent: hypotension (decreased blood pressure).
• Frequency not known: orthostatic hypotension (decreased blood pressure when standing up).

Respiratory, thoracic, and mediastinal disorders:

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

Gastrointestinal disorders:

• Frequent: abdominal pain, vomiting, nausea, diarrhea, constipation, dry mouth.
• Infrequent: abdominal distension (swelling of the abdomen), flatulence (gas).
• Frequency not known: retching, gastrointestinal discomfort.

Hepatobiliary disorders:

• Frequent: abnormal liver function.
• Frequency not known: liver damage, bile flow obstruction from the liver (cholestasis), hepatitis, jaundice (yellow skin and eyes).

Investigations:

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

Skin and subcutaneous tissue disorders:

• Infrequent: urticaria, itching, skin rash, erythema (redness of the skin).

Musculoskeletal and connective tissue disorders:

• Frequency not known: lupus-like syndrome (autoimmune disease).

Reproductive system and breast disorders:

• Infrequent: impotence (erectile dysfunction).
• Frequency not known: decreased sperm count.

7 The decrease in sperm count is reversible upon discontinuation of propafenone.

General disorders and administration site conditions:

• Frequent: chest pain, asthenia (feeling of tiredness), fatigue, fever.

Reporting of Adverse Effects

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

5. Storage of Rytmonorm

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

This medicine does not require special storage conditions.

Do not use this medicine after the expiration date stated on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and any unused medicines in the pharmacy's SIGRE point. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Rytmonorm Composition

The active ingredient is propafenone hydrochloride. Each tablet contains 150 mg of propafenone hydrochloride.

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

Product Appearance and Package Contents

Rytmonorm 150 mg coated tablets are round, white tablets with "150" printed on one side.

Each package contains 60 coated tablets.

Marketing Authorization Holder and Manufacturer

Holder:

Teva B.V.,

Swensweg 5,

2031GA Haarlem,

Netherlands

Manufacturer:

ITC Production s.r.l.

Via Pontina km 29

00071 Pomezia (RM)

Italy

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Teva Pharma, S.L.U.

C/ Anabel Segura, 11, Edificio Albatros B, 1ª planta

Alcobendas 28108 Madrid

Spain

Date of the last revision of this prospectus: March 2019

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

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This information is intended only for healthcare professionals:

Treatment of Overdose

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

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

Attempts at elimination through hemoperfusion are ineffective.

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

Other Presentations

Rytmonorm 300 mg coated tablets. Packages with 60 coated tablets.

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