Package leaflet: Information for the patient

Rytmonorm, 3.5 mg/ml, solution for injection
Propafenoni hydrochloridum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

Keep this leaflet, so that you can read it again if necessary.
If you have any further questions, please consult your doctor or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or nurse. See section 4.

Table of contents of the leaflet

What Rytmonorm is and what it is used for
Important information before using Rytmonorm
How to use Rytmonorm
Possible side effects
How to store Rytmonorm
Contents of the package and other information

1. What Rytmonorm is and what it is used for

Propafenone hydrochloride – the active substance in Rytmonorm – has antiarrhythmic properties,
i.e. it restores or maintains normal heart rhythm. The mechanism of action of the drug is complex
and includes, among others, stabilization of the cell membrane and blockade of sodium channels. Propafenone
hydrochloride also exhibits weak β-adrenolytic activity.
Rytmonorm is indicated:

for symptomatic supraventricular tachyarrhythmias requiring treatment, such as: nodal tachycardia, supraventricular tachycardia in patients with Wolff-Parkinson-White (WPW) syndrome, or paroxysmal atrial fibrillation.
for severe symptomatic ventricular tachyarrhythmia, if the physician considers it life-threatening.

NOTE. Rytmonorm solution for injection is intended exclusively
for use in a hospital setting.

2. Important information before using Rytmonorm

When not to use Rytmonorm

If the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
If the patient has been diagnosed with:
Brugada syndrome,
Clinically significant structural heart disease, such as:
Myocardial infarction within the last 3 months,
Uncompensated congestive heart failure with left ventricular ejection fraction below 35%,
Cardiogenic shock, except shock caused by arrhythmia,
Symptomatic severe bradycardia,
Sinus node dysfunction, atrial conduction disorders, second- or higher-degree atrioventricular block, bundle branch block or distal block in patients without a cardiac pacemaker,
Severe hypotension.
If the patient has symptoms of water-electrolyte imbalance (e.g. disturbances in potassium metabolism).
In case of severe obstructive lung disease.
In patients with myasthenia gravis (a disease characterized by muscle weakness).
If the patient is currently taking ritonavir (a medicine used in the treatment of HIV infections).

Warnings and precautions
Before starting treatment with Rytmonorm, discuss it with your doctor.
Propafenone, like other antiarrhythmic drugs, may have a proarrhythmic effect,
i.e. it may cause new or worsen pre-existing cardiac arrhythmias (see section 4).
Before starting treatment with Rytmonorm and during treatment, your doctor will order
ECG tests and assess your clinical condition to confirm the appropriateness of treatment
and to rule out Brugada syndrome (a genetically determined heart disease).
Special caution is required:

In patients with an implanted cardiac pacemaker: the doctor will check the pacemaker function and, if necessary, reprogram it, because the drug may affect stimulation threshold and sensitivity of the implanted pacemaker;
In patients with clinically significant structural heart disease, the drug is contraindicated;
In patients with asthma.

In some patients, the drug may cause conversion of paroxysmal atrial fibrillation
into atrial flutter with associated 2:1 conduction block or 1:1 conduction.
Rytmonorm and other medicines
Tell your doctor about all medicines you are currently taking or have recently taken,
as well as any medicines you plan to take.
Concomitant use of Rytmonorm with the following medicines may increase the risk of adverse effects:

Local anesthetics (e.g. during pacemaker implantation, surgical or dental procedures),
Other medicines that reduce heart rate and/or myocardial contractility (β-blockers, tricyclic antidepressants). Increased risk of lidocaine-induced central nervous system adverse effects has been reported when lidocaine was used concomitantly with propafenone hydrochloride.

Rytmonorm may enhance the effects of the following medicines:

Medicines metabolized by the CYP2D6 isoenzyme, such as venlafaxine,
β-Blockers, such as propranolol, metoprolol,
Antidepressants, such as desipramine,
Immunosuppressive agents, such as cyclosporine,
Medicines used in the treatment of asthma, such as theophylline,
Cardiac glycosides, such as digoxin,
Oral anticoagulants, such as phenprocoumon, acenocoumarol, warfarin.

The following medicines may enhance the effect of Rytmonorm:

Antifungal agents (e.g. ketoconazole),
Medicines used in the treatment of peptic ulcer disease (e.g. cimetidine),
Antiarrhythmics (e.g. quinidine),
Antibacterial agents - antibiotics (e.g. erythromycin),
Antidepressants that are selective serotonin reuptake inhibitors (SSRIs), such as paroxetine, fluoxetine.

If these medicines are used concomitantly with Rytmonorm, your doctor will monitor cardiovascular function and, if necessary, adjust the dose of propafenone hydrochloride.
The following medicines, when used concomitantly with Rytmonorm, may reduce its effectiveness:

Phenobarbital,
Rifampicin.

When concomitant treatment with amiodarone and Rytmonorm is required, dosage adjustment of both medicines may be necessary, based on the treatment response.
Children and adolescents
Studies on the interactions between medicines have been conducted exclusively in adults.
It is not known whether the extent of these interactions in children and adolescents is similar to that in adults.
Rytmonorm and grapefruit juice
Grapefruit juice may increase blood concentrations of propafenone hydrochloride.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine.
Rytmonorm may be used during pregnancy only if the benefits to the mother outweigh the potential risks to the fetus.
Excretion of propafenone into human breast milk has not been studied. Limited data suggest that propafenone may pass into breast milk. Caution should be exercised when administering Rytmonorm to breastfeeding women.
Driving and operating machinery
Not applicable – the medicine is used only in a hospital setting.

3. How to use Rytmonorm

This medicine should always be used exactly as directed by your doctor. If in doubt, consult your doctor or nurse.
The doctor will determine the dose individually for each patient in order to achieve optimal therapeutic effect. Cardiac function should be monitored by ECG and measurement of arterial blood pressure. During infusion, the ECG trace (QRS complex, PR and QTc intervals) and haemodynamic parameters should be closely monitored.

The recommended single dose is 1 mg/kg body weight. Desired therapeutic effect is often achieved with a dose of 0.5 mg/kg body weight. If necessary, the doctor may increase the single dose up to 2 mg/kg body weight. Treatment should be initiated with the lowest possible dose, carefully observing the patient and monitoring ECG and arterial blood pressure.

Intravenous injection should be administered slowly over 3 to 5 minutes. The interval between consecutive injections should not be shorter than 90 to 120 minutes. If widening of the QRS complex or heart rate-dependent prolongation of the QT interval by more than 20% occurs, the injection should be stopped immediately.

Short-term intravenous infusion
If hydrochloride propafenone is administered as a short-term intravenous infusion lasting from 1 to 3 hours, the recommended infusion rate is 0.5 to 1 mg/min.

Slow intravenous infusion
If hydrochloride propafenone is administered as a slow intravenous infusion, the maximum recommended daily dose is 560 mg.

To prepare the infusion solution, use glucose or fructose 5% solution.
Do not use isotonic sodium chloride solution for this purpose, as precipitation of the drug from the solution may occur.

Use of a higher than recommended dose of Rytmonorm

If an overdose of Rytmonorm occurs, the patient should remain under continuous clinical observation. Appropriate symptomatic treatment should be administered.

In case of overdose, cardiac disturbances, cardiac arrest and hypotension may occur, and in severe cases, cardiogenic shock.

Metabolic acidosis (a condition involving disturbance of the body's acid-base balance), headache, dizziness, blurred vision, sensory disturbances (burning, pricking, tingling) in hands or feet, tremor, nausea, constipation, dry mouth and convulsions (seizures) may also occur.
Death has also been reported.

In severe cases of poisoning, tonic-clonic seizures (seizures with loss of consciousness and generalized muscle contractions), paresthesias (tingling sensations), somnolence, coma and respiratory arrest may additionally occur.

Treatment
In addition to standard emergency procedures, the patient's vital signs should be monitored in an intensive care setting, and normalization of these parameters should be achieved when required.

Defibrillation and administration of dopamine and isoprenaline by infusion have proven effective in controlling heart rhythm and blood pressure. Seizures may be controlled by intravenous diazepam. General supportive measures to maintain vital functions, such as mechanical ventilation and external cardiac massage, may be necessary.

Attempts at elimination via hemoperfusion have limited effectiveness.
Due to the high degree of protein binding (95%) and large volume of distribution, hemodialysis is ineffective.

Missed dose of Rytmonorm
Do not use a double dose to make up for a missed dose.

Discontinuation of Rytmonorm
The doctor will decide when to discontinue administration of Rytmonorm injection solution.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
The most commonly reported adverse effects associated with propafenone hydrochloride treatment are dizziness, conduction disturbances, and palpitations.
The adverse effects listed below have been reported in clinical trials and following the marketing of medicines containing propafenone hydrochloride.

Very common (affects at least 1 in 10 people)

Dizziness (excluding peripheral vertigo).
Impulse conduction disturbances in the heart.
Palpitations.

Common (affects 1 to 10 in 100 people)

Anxiety, sleep disturbances.
Headache, taste disturbance.
Blurred vision.
Sinus bradycardia (slow heart rate), bradycardia, tachycardia (fast heart rate), atrial flutter.
Dyspnea (shortness of breath).
Abdominal pain, vomiting, nausea, diarrhea, constipation, dry mouth.
Abnormal liver function (abnormal liver function tests, such as increased aspartate aminotransferase activity, increased alanine aminotransferase activity, increased gamma-glutamyl transferase activity, and increased alkaline phosphatase activity in blood).
Chest pain, asthenia (weakness), feeling of fatigue, fever.

Uncommon (affects 1 to 10 in 1,000 people)

Thrombocytopenia (low platelet count).
Decreased appetite, nightmares.
Fainting, ataxia (movement coordination disorders), paresthesia (numbness, tingling).
Dizziness.
Ventricular tachycardia.
Cardiac arrhythmia.
Hypotension (low blood pressure).
Increased abdominal girth, flatulence.
Urticaria, itching, rash, erythema.
Erectile dysfunction.

Frequency unknown (cannot be estimated from the available data)

Agranulocytosis (complete or almost complete absence of granulocytes in blood), leukopenia (reduced white blood cell count), granulocytopenia (reduced granulocyte count).
Hypersensitivity (may manifest as cholestasis, abnormal blood composition, and rash).
Confusional state.
Seizures, extrapyramidal symptoms, akathisia (motor restlessness).
Ventricular fibrillation, heart failure (may lead to worsening of pre-existing heart failure), decreased heart rate.
Orthostatic hypotension (sudden drop in blood pressure related to changing position from lying down to standing up).
Vomiting reflex, gastrointestinal disturbances.
Hepatocellular damage, cholestasis, hepatitis, jaundice.
Lupus-like syndrome.
Acneiform skin eruptions.
Reduced sperm count (reversible after discontinuation of propafenone).

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products at Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Rytmonorm

Keep the medicine out of sight and reach of children.
Do not store in the refrigerator or freeze.
Do not use this medicine after the expiry date stated on the packaging following the words
"Expiry date (EXP)" or "EXP". The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Rytmonorm contains
The active substance is propafenone hydrochloride. 1 ml of solution contains 3.5 mg of the active substance.
The other components are: monohydrate glucose, water for injections.

What Rytmonorm looks like and contents of the pack
Rytmonorm is packed in ampoules made of colourless glass.
Each pack (cardboard box) contains 5 ampoules of 20 ml each.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Viatris Healthcare Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw
Manufacturer
Famar Health Care Services Madrid S.A.U.
Avda. de Leganés, 62
28923 Alcorcón-Madrid
Spain

For further information, please contact the Marketing Authorisation Holder:
Viatris Healthcare Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw
Tel: 22 546 64 00