Package Insert: Information for the Patient

Rytmonorm 3.5 mg/ml Injectable Solution

Propafenone Hydrochloride

Read the entire package insert carefully before starting to use the medication, 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 medication 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.

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 (Wolf-Parkinson-White Syndrome). Treatment and prevention of ventricular arrhythmias, including symptomatic ventricular extrasystoles and/or sustained and non-sustained ventricular tachycardia.

No use Rytmonorm

• If you are allergic to the active ingredient or to any of the other components of this medication (listed in section 6).
• If you have a history of Brugada syndrome (a hereditary condition 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 a arrhythmia.

- severe bradycardia.

- sinus node dysfunction, 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 Use of Rytmonorm with other medications).

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use 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 prior symptoms.
• If you have a pacemaker, the treatment may affect it, so it should be monitored and, if necessary, reprogrammed.
• If you have atrial fibrillation, Rytmonorm may lead to the appearance of a more serious arrhythmia; see Adverse reactions).

• 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 these interactions are similar in children.

Older patients

Rytmonorm should be used with extreme caution in older patients.

Use of Rytmonorm with other medications

Inform your doctor or pharmacist if you are using, have used recently or may need to use any other medication.

More adverse reactions 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 heart-inhibiting drugs 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 needed.

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

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

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

The concomitant use of Rytmonorm and amiodarone may cause heart abnormalities. 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 phenobarbital and/or rifampicin 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. If signs of overdose are observed, reduce the doses of these medications as needed.

Pregnancy, lactation 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. Propafenone hydrochloride crosses the placental barrier.

There are limited data on the excretion of propafenone hydrochloride in breast milk. Propafenone hydrochloride 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 low blood pressure may appear, so if you notice these symptoms, you should not drive or operate hazardous machinery.

Rytmonorm injectable is administered via intravenous route.

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

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

Adults:

Treatment should be adapted individually and determined with a control of the electrocardiogram and blood pressure.

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

Treatment should start with the lowest possible dose while keeping the patient under close observation and with close 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. In case of observed prolongation of the QRS interval or corrected QT interval by more than 20%, administration of the injection should be suspended immediately.

Short infusion

When Rytmonorm is administered in short infusion, from one to three hours, the dosing rate is 0.5 to 1 mg/minute.

Lenta intravenous infusion

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

Patients with liver insufficiency

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

Patients with renal insufficiency

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

Older patients

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

Use in children

No experience in children.

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

If you use more Rytmonorm than you should

If you receive more Rytmonorm than you should, you may experience effects on the heart and blood pressure drop, which in severe cases can cause cardiovascular shock. Often, headache, dizziness, blurred vision, numbness or tingling of the skin, tremors, nausea, constipation and dry mouth appear.

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

If this occurs, 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 Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

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 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 represented for the patient could be determined.

The following side effects have been reported:

Blood and lymphatic system disorders

-Uncommon: decrease in platelets (blood cells involved in clotting).

-Unknown frequency: decrease in 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), decrease in granulocytes (a type of white blood cell that may predispose to infections), severe reduction in 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 obstruction), blood alterations and skin rash.

Metabolism and nutrition disorders

-Uncommon: decrease in appetite.

Mental and behavioural 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: convulsions, 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 heart rate (bradycardia), tachycardia (increased heart rate), atrial flutter (abnormal heart rhythm occurring in the atrium).

-Uncommon: ventricular tachycardia (increased heart rate originating in the ventricles and with more than 100 beats per minute), arrhythmia4(abnormal heart rhythm 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 be life-threatening 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 when standing for a long time and/or when standing up).

Respiratory, thoracic and mediastinal disorders

Common: dyspnea (shortness of breath).

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 function

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 tests 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 discontinuation of propafenone.

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, 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.

Do not store above 86 °F (30 °C).

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

Appearance of the product and contents of the package

Each package contains 5 ampoules of 20 ml of a transparent and colorless solution in colorless glass.

Holder of the marketing authorization and responsible for manufacturing

Holder

Teva B.V.,

Swensweg 5, 2031GA

Haarlem, Netherlands

Responsible for manufacturing:

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 holder of the marketing authorization:

Teva Pharma, S.L.U.

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

Alcobendas 28108 Madrid

Spain

Date of the last review of thisleaflet: March 2019

The detailed information about this medication 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:

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

Treatment of overdose

Symptoms of overdose:

Cardiac symptoms:The effects of propafenone hydrochloride overdose on the myocardium manifest as alterations in the generation and conduction of cardiac stimuli, such as prolongation of the PQ interval, widening of the QRS complex, suppression of sinoatrial node automatism, AV block, ventricular tachycardia, ventricular flutter, and ventricular fibrillation. Reduction of contractility (negative inotropic effect) may cause hypotension, which in severe cases can cause cardiovascular shock.

Non-cardiac symptoms:may appear frequentlyheadache, dizziness, blurred vision, paresthesia, tremor, nausea, constipation, and dry mouth. In extremely rare cases, seizures have been reported. Death has also been reported.

In severe cases, tonic-clonic seizures, paresthesia, somnolence, coma, and respiratory arrest may appear.

Treatment:

In addition to general emergency measures, it is necessary to monitor and correct the patient's vital parameters (as needed) in an intensive care unit.

Defibrillation, as well as the infusion of dopamine and isoprenaline, have been effective in controlling rhythm and blood pressure. Diazepam intravenously has been effective in alleviating seizures. General supportive measures such as mechanical ventilation and external cardiac massage may be necessary.

Attempts at elimination by hemoperfusion are of limited effectiveness.

Hemodialysis is not effective due to the high protein binding (> 95%) and 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.