RAPIBLOC 300 MG POWDER FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Rapibloc 300 mg powder for solution for infusion

landiolol 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 or nurse.
• If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

1. What is Rapibloc and what is it used for
2. What you need to know before you take Rapibloc
3. How to take Rapibloc
4. Possible side effects
5. Storage of Rapibloc
6. Contents of the pack and other information

1. What is Rapibloc and what is it used for

Rapibloc contains the active substance landiolol hydrochloride. It belongs to a group of medicines called «beta-blockers». It works by converting irregular or rapid heartbeats into normal heartbeats.

This medicine is used in adults to treat heart rhythm problems, when the heart beats too quickly.

It is used during or immediately after surgery or in other situations where it is necessary to control heartbeats.

2. What you need to know before you take Rapibloc

Your doctor will NOT give you Rapibloc if:

• You are allergic to landiolol or any of the other ingredients of this medicine (listed in section 6).
• You have a very slow heart rate (less than 50 beats per minute).
• You have a fast or irregular heart rate (a condition called «sick sinus syndrome»).
• You have a condition called «severe heart block». Heart block is a problem with the electrical messages that control heartbeats.
• You have a problem with blood supply to the heart (a condition called «cardiogenic shock»).
• You have very low blood pressure.
• You have severe symptoms of heart failure.
• You have high blood pressure in the lungs (pulmonary hypertension).
• You have a disease of the glands called pheochromocytoma that has not been treated. Pheochromocytoma arises from the adrenal gland and can cause a sudden increase in blood pressure, severe headache, sweating, and increased heart rate.
• You have symptoms of asthma that worsen rapidly.
• You have very high levels of acid in the body (severe metabolic acidosis) that cannot be corrected.

Warnings and precautions

• Talk to your doctor or nurse before you start taking this medicine.
• Rapibloc is a powder and must be dissolved by your doctor or nurse before it is given to you.
• Usually, your heartbeats, blood pressure, and heart electrical activity will be continuously monitored while you are being treated with this medicine.

Your doctor will be particularly careful with this medicine if:

• You have diabetes or low blood sugar levels. Landiolol may mask the symptoms of low blood sugar.
• You have low blood pressure.
• You have a condition called «pre-excitation syndrome» in combination with an irregular and rapid heart rate (atrial fibrillation).
• • You have problems with the electrical messages that control heartbeats (heart block).
• You have problems with the progression of electrical impulses through the heart and are taking verapamil or diltiazem.
• • You have a particular type of chest pain (angina) called «Prinzmetal's angina».
  • You have or have had heart problems (such as congestive heart failure). Your doctor will closely monitor you for any cardiac symptoms. If necessary, treatment will be discontinued, the dose will be reduced, or special treatment will be initiated.
• You have certain heart rhythm disorders called supraventricular arrhythmias and:
• • you have other heart problems or
  • you are taking other heart medicines
  • You have kidney problems.
  • You have a disease of the glands called pheochromocytoma that has been treated with medicines called alpha-receptor blockers.
• You have narrowing of the airways or wheezing, such as in asthma.
• You have circulatory problems, such as pale fingers (Raynaud's disease) or pain, tiredness, and sometimes burning in the legs.
• You have allergies or are at risk of having anaphylactic reactions (severe allergic reactions). Rapibloc may make allergies worse and more difficult to treat.

If any of the above applies to you (or you are not sure), talk to your doctor or nurse before you are given this medicine.

Other medicines and Rapibloc

Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines. This includes medicines that you have obtained yourself, without a prescription, including herbal medicines and natural products. Your doctor will check that any other medicine you are taking will not affect the way Rapibloc works.

In particular, tell your doctor or nurse if you are taking any of the following:

• Medicines used to treat heart rhythm problems (such as diltiazem, verapamil, propafenone, disopyramide, amiodarone, and digitalis preparations) and high blood pressure (such as nifedipine).
• Medicines used to treat diabetes, including insulin and oral medicines.
• Medicines used normally during surgery to relax muscles (such as suxamethonium) or medicines used to reverse the effect of muscle relaxants called cholinesterase inhibitors (such as neostigmine, distigmine, and edrophonium). Your doctor will also be particularly careful when using landiolol during surgery, when you are given anesthesia and other treatments.
• Medicines known as ganglion blockers (such as trimethaphan).
• Medicines used as painkillers, such as non-steroidal anti-inflammatory drugs (NSAIDs).
• Floctafenine, which is a painkiller.
• Amisulpride, a medicine used to treat mental problems.
• Tricyclic antidepressants (such as imipramine and amitriptyline).
• Barbiturates (such as phenobarbital, used to treat epilepsy).
• Phenothiazines (such as chlorpromazine, used to treat mental disorders).
• Medicines used to treat asthma.
• Medicines that can lower blood pressure (such as reserpine and clonidine).
• Epinephrine, used to treat allergic reactions.
• Heparin, used to thin the blood.

If you are not sure if any of the above applies to you, talk to your doctor or nurse before you start taking Rapibloc.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, ask your doctor for advice before taking this medicine.

There is limited experience with the use of landiolol during pregnancy. Due to the lack of experience, the use of this medicine during pregnancy is not recommended.

Tell your doctor if you are breastfeeding. Landiolol may pass into breast milk, so you should not be given this medicine if you are breastfeeding.

Rapibloc contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e., it is essentially «sodium-free».

3. How to take Rapibloc

• Landiolol is a powder and must be dissolved by your doctor or nurse. It is given as an infusion through a needle in a vein.
• The dose will be adjusted individually. An initial dose may be given before the maintenance dose. Your doctor will determine the dosing schedule and adjust the dose as necessary.
• The duration of treatment depends on the effect and possible side effects. Your doctor will determine the duration of treatment.
• While you are being given landiolol, your heartbeats, blood pressure, and heart electrical activity will be monitored.
• After a stable state is reached, you may be given another heart medicine while your landiolol dose is reduced.

It is usually not necessary to change the dose of this medicine if you are elderly.

If you have kidney problems, your doctor will take the necessary precautions.

Liver impairment

If you have liver problems, your doctor will start treatment with a lower dose.

Use in children and adolescents

There is limited experience with the use of landiolol in children and adolescents. Your doctor will decide on treatment with landiolol.

If you take more Rapibloc than you should

If you think you have received too much landiolol, tell your doctor or nurse immediately.

Your doctor will take the necessary measures (your treatment may be stopped immediately and you may receive supportive therapy).

If you have received too much of this medicine, you may experience the following symptoms:

• Severe decrease in blood pressure (you may feel dizzy or faint).
• Very slow heartbeats
• Decreased heart function
• Shock due to decreased heart function
• Breathing problems
• Loss of consciousness that can lead to coma
• Seizures (convulsions)
• Nausea
• Vomiting
• Low blood sugar levels
• High potassium levels in the blood (hyperkalemia)

In case of overdose or accidental ingestion, contact the Toxicology Information Service (telephone 91 562 04 20) or talk to your doctor or pharmacist.

If you stop taking Rapibloc

Sudden stopping of treatment with Rapibloc usually does not cause the return of tachycardia symptoms. Your doctor will closely monitor you if treatment with this medicine is stopped.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most side effects disappear within 30 minutes of stopping treatment with landiolol. Tell your doctor or nurse immediately if you notice any of the following side effects, which can be serious.

It may be necessary to stop the infusion if your doctor observes any serious changes in:

• Your heart rate
• Your blood pressure
• The electrical activity of your heart

Common (may affect up to 1 in 10 people):

• Slow heartbeats
• Low blood pressure

Uncommon (may affect up to 1 in 100 people):

• Lung infection (pneumonia)
• Abnormally low number of blood clotting cells (decreased platelet count)
• Low sodium levels in the blood
• Reduced blood supply to the brain, headache
• Heart attack, failure of normal blood circulation (cardiac arrest), fast and/or irregular heart rate
• High blood pressure
• Asthma
• Vomiting, nausea
• Liver disease

• Cold sweating
• Redness of the skin

• Kidney failure
• Fever
• Changes in blood tests

Rare (may affect up to 1 in 1,000 people):

• Inflammation of the chest tissue

• High blood sugar levels
• Stroke
• Heart rhythm disorders, decreased heart function, certain types of heart rate problems (such as a brief pause in normal heart activity or absence of heartbeats; sensation that the heart is beating (palpitations))
• Shock, hot flashes
• Breathing problems (difficulty breathing), abnormally low oxygen levels in the blood.
• Abdominal discomfort, oral secretion, bad breath
• Abnormally high levels of bilirubin (a pigment produced by the breakdown of red blood cells) in the blood
• Kidney damage, decreased urine volume
• Chills, chest discomfort, pain at the injection site
• Increased pressure in the pulmonary vessels

• Sugar (glucose) in the urine
• Abnormal readings (ECG, medical ultrasound) of the heart

• Abnormal urine tests (protein in the urine, increased urea in the urine)
• Pain at the injection site
• Changes in the skin at the injection site
• Feeling of pressure at the injection site

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are 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 Rapibloc

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and vial after EXP. The expiry date is the last day of the month stated.
• This medicine does not require any special storage conditions. Do not freeze.
• Landiolol must be dissolved before use. The diluted medicine is stable for 24 hours at 25°C. However, it must be used immediately after dilution.
• Do not use this medicine if you notice particles or discoloration of the solution.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Rapibloc Composition

The active ingredient is landiolol hydrochloride. One vial contains 300 mg of landiolol hydrochloride (in powder form), which is equivalent to 280 mg of landiolol. After dilution, 1 ml contains 6 mg of landiolol hydrochloride.

The other components are mannitol (E421) and sodium hydroxide (E524) (for pH adjustment).

Appearance of Rapibloc and Container Contents

Rapibloc is a white to almost white powder for solution for infusion.

The container contains a 50 ml vial with a glass body, a chlorobutyl rubber stopper, and an aluminum flip-off cap.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Orpha-Devel Handels und Vertriebs GmbH

Wintergasse 85/1b

3002, Purkersdorf

Austria

Manufacturer

AOP Orphan Pharmaceuticals GmbH

Leopold-Ungar-Platz 2

1190 Vienna

Austria

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

AOP Orphan Pharmaceuticals Iberia S.L.U.

Calle de Cólquide nº6, Edif. Prisma – Portal 2, 1º F

28231, Las Rozas, Madrid

Spain

This medicinal product is authorized in the EEA Member States under the following names:

Belgium Runrapiq 300 mg powder for solution for infusion

Ireland Rapibloc 300 mg powder for solution for infusion

Portugal Rapibloc 300 mg powder for solution for infusion

Spain Rapibloc 300 mg powder for solution for infusion

Netherlands Landiolol Hydrochloride Orpha-Devel 300 mg powder for solution for infusion

Date of Last Revision of this Leaflet:11/2024

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

This information is intended solely for healthcare professionals:

This section contains practical information related to administration. Read the leaflet for complete information on dosage and administration, contraindications, warnings, etc.

Landiolol is indicated for intravenous use in a supervised setting. Only a qualified healthcare professional should administer landiolol. The dose of landiolol should be adjusted individually.

Rapibloc should not be administered without reconstitution.

Reconstitute 1 vial with 50 ml of one of the following solutions:

• Sodium chloride 9 mg/ml (0.9%) solution
• Glucose 50 mg/ml (5%) solution
• Ringer's solution
• Ringer's lactate solution

The white to almost white powder dissolves completely after reconstitution. Mix gently until a clear solution is obtained. The reconstituted solutions should be visually inspected for visible particles and discoloration. Only clear and colorless solutions should be used.

Infusion is normally started with an infusion rate of 10 to 40 micrograms/kg/min, which will establish the effect of heart rate reduction within 10-20 minutes.

If a rapid onset of the hypotensive effect (within 2 to 4 minutes) is desired, an optional loading dose of 100 micrograms/kg/min for 1 minute may be considered, followed by a continuous intravenous infusion of 10 to 40 micrograms/kg/min.

In patients with cardiac dysfunction and septic shock, lower initial doses should be used. Dosage instructions are provided in "Special Populations" and in the integrated dosing scheme.

Maximum dose:The maintenance dose may be increased up to 80 micrograms/kg/min for a limited period of time (see section 5.2 of the leaflet), if the patient's cardiovascular status requires and tolerates such an increase in dose and does not exceed the maximum daily dose.

The recommended maximum daily dose of landiolol hydrochloride is 57.6 mg/kg/day (e.g., infusion of 40 micrograms/kg/min for 24 hours). There is limited experience with landiolol infusion durations exceeding 24 hours for doses >10 micrograms/kg/min.

Conversion formula for continuous intravenous infusion: micrograms/kg/min to ml/h

(Landiolol 300 mg/50 ml = 6 mg/ml):

Target dose (micrograms/kg/min) x body weight (kg)/100 = infusion rate (ml/h)

Conversion table (example):

Optional bolus administration for hemodynamically stable patients:

Conversion formula from 100 micrograms/kg/min to ml/h (landiolol 300 mg/50 ml = 6 mg/ml):

Loading dose infusion rate (ml/h) for 1 minute = body weight (kg)

(Example: loading dose infusion rate of 70 ml/h for 1 minute for a 70 kg patient)

In case of an adverse reaction, the dose of landiolol should be reduced or the infusion stopped, and patients should receive appropriate medical treatment if necessary. In case of hypotension or bradycardia, administration of landiolol may be restarted at a lower dose after blood pressure or heart rate has returned to an acceptable level. In patients with low systolic blood pressure, special caution is needed when adjusting the dose and during maintenance infusion.

In case of overdose, the following symptoms may occur: severe hypotension, severe bradycardia, AV block, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, respiratory failure, loss of consciousness up to coma, convulsions, nausea, vomiting, hypoglycemia, hyperkalemia.

In case of overdose, administration of landiolol should be stopped immediately.

Transition to an alternative drug:After achieving adequate control of heart rate and a stable clinical condition, transition to alternative medications (such as oral antiarrhythmics) may be possible.

When replacing landiolol with alternative medications, the physician should carefully consider the labeling and dosage of the alternative medication. If switching to an alternative medication, the dose of landiolol may be reduced as follows:

• Within the first hour after administration of the first dose of the alternative medication, the landiolol infusion rate may be reduced by half (50%).
• After administration of the second dose of the alternative medication, the patient's response should be monitored, and if satisfactory control is maintained for at least one hour, the landiolol infusion may be stopped.

Special Populations

Elderly population (≥ 65 years):No dose adjustment is necessary.

Renal impairment:No dose adjustment is necessary.

Hepatic impairment:Data on treatment in patients with hepatic impairment are limited. Careful dosing is recommended, starting with the lowest dose in patients with all degrees of hepatic impairment.

Cardiac dysfunction:In patients with impaired left ventricular function (LVEF <40%, CI <2.5 L/min/m2, NYHA 3-4), e.g., after cardiac surgery, during ischemia, or in septic states, lower doses have been used, starting from 1 microgram/kg/min and gradually increased under close monitoring of blood pressure up to 10 micrograms/kg/min to achieve heart rate control. Further dose increases may be considered under close hemodynamic monitoring if the patient's cardiovascular status requires and tolerates it.

Septic shock

In patients with septic shock receiving vasopressor therapy, lower doses have been used, starting from 1 microgram/kg/min up to a maximum of 40 micrograms/kg/min to achieve heart rate control. The dose was increased in increments of 1 microgram/kg/min with a minimum interval of 20 minutes under close monitoring of blood pressure.

Pediatric population:The safety and efficacy of landiolol in children from 0 to 18 years have not been established.

Administration

Rapibloc should be reconstituted before administration and used immediately after opening.

Rapibloc should not be mixed with other medications except those listed in section 6.6 of the Summary of Product Characteristics.

Rapibloc should be administered intravenously through a central or peripheral line and should not be administered through the same intravenous line as other medications.

Unlike other beta-blockers, landiolol did not show withdrawal tachycardia in response to abrupt interruption after 24 hours of continuous infusion. However, patients should be closely monitored when landiolol administration is to be stopped.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the Summary of Product Characteristics.
• Severe bradycardia (less than 50 beats per minute)
• Sick sinus syndrome without a pacemaker
• Severe conduction disorders (AV block of second or third degree) without a pacemaker
• Cardiogenic shock
• Severe hypotension
• Uncompensated heart failure when not related to arrhythmia
• Pulmonary hypertension
• Untreated pheochromocytoma
• Acute asthma attack

Severe and uncorrectable metabolic acidosis.