RYTMONORM 3.5 mg/ml INJECTABLE SOLUTION

1. What is Rytmonorm and what is it used for

Rytmonorm is a medicine used for heart 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 (Wolf-Parkinson-White syndrome). 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 use Rytmonorm

Do not use Rytmonorm

• If you are allergic to the active substance or 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 a significant heart disease such as:

• congestive heart failure.
• cardiogenic shock unless the cause is an arrhythmia.
• severe bradycardia (slow heart rate).
• sinus node dysfunction, atrioventricular conduction defects, second-degree or greater atrioventricular block, or bundle branch block or distal block in the absence of an artificial pacemaker.
• if you have a marked decrease in blood pressure.
• If you suffer from an electrolyte imbalance in the blood (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 Using Rytmonorm with other medicines).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting treatment with 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 medicine, your doctor must rule out a Brugada syndrome that may have been present without giving any previous symptoms.
• If you have a pacemaker, treatment may affect it, so it should be monitored and, if necessary, reprogrammed.
• 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 severe 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 unknown if such interactions are similar in children.

Elderly patients

In elderly patients, Rytmonorm should be used with caution.

Using Rytmonorm with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

More side effects may appear 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)

• cyclosporine (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 appropriate.

Tell your doctor if you are taking any of the following medicines because they may increase your propafenone hydrochloride blood levels, so 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 because they may reduce the efficacy of Rytmonorm:

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

In the case of chronic treatment with phenobarbital and/or rifampicin and Rytmonorm, the response to Rytmonorm treatment 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. If signs of overdose are observed, the doses of these medicines should be reduced accordingly.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using 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 breastfeeding mothers.

Driving and using machines

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

3. How to use Rytmonorm

Rytmonorm injectable is administered intravenously.

Follow exactly the administration instructions of this medicine indicated by your doctor, pharmacist, or nurse. If in doubt, ask your doctor, pharmacist, or nurse.

Your doctor will decide what dose of Rytmonorm is most suitable for you.

Adults:

Treatment should be individualized and determined with electrocardiogram and blood pressure control.

Normally, a single dose of 1 mg/kg body weight is administered, although the desired effect can often be achieved with doses of 0.5 mg/kg. If necessary, the single dose can be increased to 2 mg/kg body weight. However, your doctor will decide what dose of Rytmonorm is most suitable for you.

Treatment should be started with the lowest possible dose while keeping the patient under close observation and with strict monitoring of ECG and blood pressure.

Intravenous injections should be administered slowly over a period of 3 to 5 minutes, and the interval between injections should not be less than 90 to 120 minutes. If a prolongation of the QRS interval or the corrected QT interval of more than 20% is observed, the administration of the injection should be suspended immediately.

Short-term infusion

When Rytmonorm is administered as a short-term infusion, over one to three hours, the dosing rate is 0.5 to 1 mg/minute.

Slow intravenous infusion

When Rytmonorm is administered as a slow intravenous infusion, usually a maximum daily dose of 560 mg is sufficient. Glucose or fructose (5%) should be used to obtain the solution. Sodium chloride solution should not be used due to the possibility of precipitation.

Patient with hepatic impairment

No dose adjustment is recommended in patients with moderate hepatic impairment. These patients should start with the lowest recommended dose and be closely monitored. Patients with severe hepatic impairment should start with half the dose or less than the recommended dose for patients with normal hepatic function. These patients should be closely monitored, and the dose adjustment should be based on clinical symptoms.

Patient with renal impairment

No dose adjustment is required with intravenous dosing in patients with renal impairment, although propafenone should be administered with caution in this type of patient.

Elderly patients

Rytmonorm should be administered carefully, paying special attention to clinical and electrocardiographic evidence of toxicity.

Use in children

There is no experience in children.

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

If you use more Rytmonorm than you should

If you receive more Rytmonorm than you should, you may notice effects on the heart and low 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 used 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 taken.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets 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 frequency not known (cannot be estimated from the 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 decreasing order of severity, from most severe to least severe, when the severity could be determined.

The following side effects have been reported:

Blood and lymphatic system disorders

-Uncommon: decreased platelet count.

-Frequency not known: decreased white blood cell count, decreased granulocyte count, severe decrease in granulocyte or neutrophil count (agranulocytosis, a disease in which the person is more prone to infections).

Immune system disorders

-Frequency not known: hypersensitivity.

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

Metabolism and nutrition disorders

-Uncommon: decreased appetite.

Psychiatric disorders

-Common: anxiety, sleep disorders.

-Uncommon: nightmares.

-Frequency not known: confusion.

Nervous system disorders

-Very common: dizziness.

-Common: headache, altered taste perception.

-Uncommon: brief loss of consciousness (syncope), abnormal coordination, tingling, numbness, or prickling sensation in any part of the body but more frequently in feet, hands, arms, or legs (paresthesia).

-Frequency not known: convulsions, extrapyramidal symptoms (involuntary movements), restlessness.

2 Excluding vertigo

Eye disorders

Common: blurred vision.

Ear and labyrinth disorders

Uncommon: vertigo

Cardiac disorders

-Very common: cardiac conduction disorders, palpitations

-Common: sinus bradycardia (slow heart rate), reduced heart rate (bradycardia), tachycardia (increased heart rate), atrial flutter (abnormal heart rhythm that occurs in the atria).

-Uncommon: ventricular tachycardia (increased heart rate that starts in the ventricles and with more than 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, which manifest as an increase in 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 Heart failure may worsen.

Vascular disorders

-Uncommon: hypotension (low blood pressure).

-Frequency not known: orthostatic hypotension (low blood pressure when standing up and/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 (swelling of the abdomen), flatulence (gas).

-Frequency not known: retching, gastrointestinal discomfort.

Hepatobiliary disorders

-Common: abnormal liver function

-Frequency not known: liver damage, obstruction of bile flow from the liver (cholestasis), hepatitis, jaundice (yellow skin and eyes)

Investigations

Common: 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

-Uncommon: urticaria, itching, skin rash, erythema (redness of the skin).

Musculoskeletal and connective tissue disorders

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

Reproductive system and breast disorders

-Uncommon: 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

-Common: chest pain, asthenia (feeling of tiredness), fatigue, fever.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Rytmonorm

Keep this medication out of sight and reach of children.

Do not store above 30 °C.

Do not use this medication after the expiration date shown 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 medications at the pharmacy's SIGRE Point. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Rytmonorm

• The active ingredient is propafenone hydrochloride. Each 20 ml ampoule contains 70 mg of propafenone hydrochloride.
• The other components (excipients) are: glucose monohydrate and water for injectable preparations.

Appearance of the Product and Package Contents

Each package contains 5 ampoules of 20 ml of a clear, colorless solution in clear glass.

Marketing Authorization Holder and Manufacturer

Holder

Teva B.V.,

Swensweg 5, 2031GA

Haarlem, Netherlands

Manufacturer:

FAMAR HEALTH CARE SERVICES MADRID, S.A.U.

Avda. de Leganés, 62. 28923

Alcorcón-Madrid.

You can request more information about this medication 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 thisleaflet: March 2019

Detailed information about this medication 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:

For continuation of treatment by oral route and for prevention of new rhythm disorders, Rytmonorm 150 mg and 300 mg coated tablets are available.

Overdose Treatment

Overdose Symptoms:

Myocardial Symptoms:The effects of propafenone hydrochloride overdose on the myocardium are manifested as alterations in the genesis and conduction of cardiac stimuli, such as prolongation of the PQ interval, widening of the QRS complex, suppression of sinus node automatism, AV block, ventricular tachycardia, ventricular flutter, and ventricular fibrillation. The reduction of contractility (negative inotropic effect) can cause hypotension, which, in severe cases, can lead to cardiovascular shock.

Non-Cardiac Symptoms:Headache, dizziness, blurred vision, paresthesia, tremor, nausea, constipation, and dry mouth may frequently appear. In extremely rare cases, seizures have been reported with overdose. Death has also been reported.

In severe poisonings, tonic-clonic seizures, paresthesias, somnolence, coma, and respiratory arrest may occur.

Treatment:

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 dopamine and isoprenaline infusion, have been effective in controlling rhythm and blood pressure. Seizures 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 of limited efficacy.

Hemodialysis is not effective due to the high binding to proteins (> 95%) and the large volume of distribution.

Incompatibilities

Rytmonorm injectable should not be mixed with physiological saline solutions as it may precipitate.

Other Presentations

Rytmonorm 150 mg coated tablets. Packages with 30 and 60 coated tablets.

Rytmonorm 300 mg coated tablets. Packages with 20 and 60 coated tablets.