Landiobloc

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

LANDIOBLOC 300 mg powder for solution for infusion

landiolol hydrochloride
Please read this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4. The full name of the medicine is Landiobloc 300 mg powder for solution for infusion. The abbreviated name Landiobloc is used throughout this leaflet. Contents of this leaflet:
  1. What Landiobloc is and what it is used for
  2. What you need to know before you are given Landiobloc
  3. How Landiobloc is administered
  4. Possible side effects
  5. How to store Landiobloc
  6. Contents of the pack and other information

1. What Landiobloc is and what it is used for

Landiobloc contains the active substance landiolol hydrochloride. It belongs to a group of medicines called
"beta-blockers", which work by changing an irregular or fast heartbeat into a normal heartbeat.
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 control of the heartbeat is required.

2. What you need to know before you are given Landiobloc

Your doctor will NOT give you Landiobloc if:

• You are allergic to landiolol or to 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 heart rate or alternating fast and slow heart rate (a condition called "sinoatrial syndrome").
• You have a condition called "severe heart block". Heart block is a problem with the electrical signals that control your heartbeat.
• You have a condition affecting blood flow to the heart (a condition called cardiogenic shock).
• You have very low blood pressure.
• You have symptoms of severe heart failure.
• You have increased pressure in the lungs (pulmonary hypertension).
• You have an untreated adrenal gland disease called phaeochromocytoma. Phaeochromocytoma is an adrenal gland disorder that can cause sudden high blood pressure, severe headache, sweating, and increased heart rate.
• You have rapidly worsening asthma symptoms.
• You have a very high level of acid in your body (severe metabolic acidosis) that cannot be corrected.

Landiobloc will not be given to you if any of the conditions listed above apply to you. If you are unsure, consult your doctor or nurse before this medicine is administered.

Warnings and precautions

• Talk to your doctor or nurse before you are given this medicine.
• Landiobloc is a powder and must be dissolved by a doctor or nurse before administration.
• Normally, during treatment with this medicine, your heart rate, blood pressure, and heart's electrical activity should be continuously monitored. Your doctor will be particularly cautious 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 "ventricular pre-excitation syndrome" in combination with an irregular and rapid heartbeat (atrial fibrillation).
  • You have problems with the electrical signals controlling your heartbeat (heart block).
  • You have problems with the conduction of electrical impulses through the heart and are taking verapamil or diltiazem.
  • You have a specific type of angina (chest pain) called "Prinzmetal's angina".
  • You have or have had heart problems (such as congestive heart failure). Your doctor will closely monitor for any signs of heart-related symptoms. If necessary, treatment may need to be stopped, the dose reduced, or special treatment initiated.
  • You have certain heart rhythm disorders called supraventricular arrhythmias and:
    • You have other heart problems, or
    • You are taking other heart medications.
  • You have kidney problems.
  • You have an adrenal gland disease called phaeochromocytoma 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 (e.g., Raynaud's disease) or pain, fatigue, and sometimes burning sensations in the legs.
  • You have allergies or are at risk of anaphylactic reactions (severe allergic reactions). Landiobloc may make allergies more severe and more difficult to treat.

If any of the above conditions apply to you (or if you have any doubts), discuss this with your doctor or nurse before receiving this medicine.

For athletes: Using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.

Other medicines and Landiobloc

Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines, including those without a prescription, herbal medicines, and natural products. Your doctor will check that any other medicines you are taking do not interfere with the way Landiobloc works.

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

• Medicines used to treat heart rhythm disorders (such as diltiazem, verapamil, propafenone, disopyramide, amiodarone, digoxin, digitalis) and high blood pressure (such as nifedipine).
• Medicines used to treat diabetes, such as insulin and oral antidiabetic drugs.
• Medicines used to relax muscles, usually during surgery (such as succinylcholine), or medicines used to reverse the effect of muscle relaxants called cholinesterase inhibitors (such as neostigmine, distigmine, edrophonium). Your doctor will also be particularly cautious when using Landiobloc during surgical procedures, especially when administering anaesthetics or other treatments.
• Medicines known as ganglion blockers (e.g., trimethaphan).
• Medicines used as painkillers, such as non-steroidal anti-inflammatory drugs (NSAIDs).
• Floctafénine, a painkiller.
• Amisulpride, a medicine used to treat mental disorders.
• Tricyclic antidepressants, medicines used to treat depression (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 used to treat colds or nasal congestion, called "nasal decongestants".
• Medicines that can lower blood pressure (such as reserpine and clonidine).
• Adrenaline, used to treat allergic reactions.
• Heparin, used to thin the blood.

If you are unsure whether any of the conditions listed above apply to you, consult your doctor or nurse before receiving Landiobloc.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before this medicine is administered. Available data on the use of Landiobloc during pregnancy are limited. Due to limited experience, it is preferable to avoid using landiolol during pregnancy.

Inform your doctor if you are breastfeeding. Landiobloc may pass into breast milk; therefore, this medicine should not be administered if you are breastfeeding.

3. How Landiobloc will be administered to you

• Landiobloc is a powder and must be dissolved by a doctor or nurse before being administered to you as an intravenous infusion through a needle in the vein.
• The dosage must be individually adjusted. An initial dose may be given before the maintenance dose. Your doctor will determine and adjust the dosing regimen according to your needs.
• The duration of the infusion depends on the effect and possible side effects. Your doctor will determine how long the treatment will last. Landiobloc will not normally be administered for more than 24 hours.
• While you are receiving Landiobloc, your heart rate, blood pressure, and heart's electrical activity will be monitored.
• After a stable condition has been achieved, you may be given another heart medication, while the dose of Landiobloc is gradually reduced. Dose adjustments of this medication are usually not necessary if you are elderly. If you have kidney problems, your doctor will take appropriate precautions.

Hepatic 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 Landiobloc in children and adolescents. Your doctor will decide whether treatment with Landiobloc is appropriate.
If you are given more Landiobloc than you should have
If you feel you have been given too much Landiobloc, inform your doctor or nurse immediately. Your doctor will take appropriate measures (treatment may be stopped immediately and you may receive supportive therapy).
If you have received an excessive amount of this medicine, the following symptoms may occur:

• Severe drop in blood pressure (you may feel dizzy or confused)
• Slowed heart rate
• Reduced heart function
• Shock due to reduced heart function
• Breathing difficulties
• Loss of consciousness up to coma
• Seizures (convulsions)
• Nausea
• Vomiting
• Low blood sugar levels
• High potassium levels in the blood (hyperkalemia)

When administration of Landiobloc is stopped
Usually, abruptly stopping Landiobloc does not cause rebound symptoms such as fast heart rate (tachycardia). Your doctor will monitor you closely if treatment with this medicine is discontinued.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Most of the side effects disappear within 30 minutes after stopping treatment with Landiobloc.
Contact your doctor or nurse immediately if you notice any of the following side effects, which could be serious.
It may be necessary to stop the infusion if your doctor observes serious changes in:

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

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

• Slow heart rate
• Low blood pressure

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

• Lung infection (pneumonia)
• Low sodium levels in the blood (hyponatremia)
• Reduced blood supply to the brain, headache
• Inadequate blood circulation (cardiac arrest), rapid heartbeat
• High blood pressure
• Fluid accumulation in the lungs
• Vomiting, nausea
• Liver disorders
• Changes in blood test results
• Abnormalities in the number of blood clotting cells (platelets)
• Higher than normal levels of bilirubin (a pigment produced from the breakdown of red blood cells) in the blood

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

• Inflammation of the chest tissue
• High blood sugar levels
• Stroke, seizures
• Heart attack, heart rhythm disorders, reduced heart function
• Shock, hot flushes
• Breathing problems (lung disease associated with narrowing of the airways, making breathing difficult), pulmonary disorders, lower than normal oxygen levels in the blood
• Abdominal disorders, excessive salivation, bad breath
• Skin flushing, cold sweat
• Muscle cramps
• Kidney failure, kidney injury, reduced urine volume
• Fever, chills, chest pain, injection site pain
• Increased pressure in the blood vessels of the lungs
• Presence of sugar (glucose) in the urine
• Abnormalities in urine tests (protein in urine, increased urea in urine)
• Abnormalities in heart examinations (ECG, echocardiography)

Not known (frequency cannot be estimated from the available data):

• Skin changes at the injection site, sensation of pressure at the injection site

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, tell your doctor or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Landiobloc

• Keep the vial in the outer packaging to protect the medicine from light.
• Keep this medicine out of the sight and reach of children.
• Do not use Landiobloc after the expiry date which is stated on the carton and on the vial after "Exp". The expiry date refers to the last day of that month.
• This medicine does not require any special storage temperature.
• Landiobloc must be dissolved before use. The diluted medicine is stable for 24 hours at 25°C. However, it should be used immediately after dilution.
• This medicine must not be administered if particles or discoloration of the solution are observed. Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Landiobloc contains
The active substance is landiolol hydrochloride. One vial contains 300 mg of landiolol hydrochloride (as
powder), equivalent to 280 mg of landiolol. After dilution, 1 ml contains 6 mg of landiolol hydrochloride.
The other components are mannitol and sodium hydroxide (to ensure the correct pH).

Description of the appearance of Landiobloc and package contents
Landiobloc is a white or almost white powder for infusion solution.
The package consists of one 50 ml vial.

MARKETING AUTHORISATION HOLDER AND MANUFACTURER
Amomed Pharma GmbH
Leopold-Ungar-Platz 2
1190 Vienna
Austria

MANUFACTURER
AOP Orphan pharmaceuticals GmbH
Leopold-Ungar-Platz 2
1190 Vienna
Austria

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Austria Rapibloc 300 mg Powder for solution for infusion
Bulgaria Rapibloc 300 mg powder for infusion solution
Croatia Rapibloc 300 mg powder for infusion solution
Cyprus Rapibloc 300 mg κόνις για διάλυμα προς έγχυση
Czech Republic Rapibloc 300 mg powder for infusion solution
Denmark Rapibloc 300 mg powder for solution for infusion
Estonia Raploc 300 mg infusion powder
Germany Rapibloc 300 mg Pulver zur Herstellung einer Infusionslösung
Greece Rapibloc 300 mg κόνις για διάλυμα προς έγχυση
Finland Rapibloc 300 mg infuusiokuiva-aine, liuosta varten
France Rapibloc 300 mg poudre pour solution pour perfusion
Hungary Rapibloc 300 mg por infúziós oldathoz
Latvia Raploc 300 mg pulveris infūziju šķīduma pagatavošanai
Lithuania Raploc 300 mg milteliai infuziniam tirpalui
Netherlands Rapibloc 300 mg powder for solution for infusion
Norway Raploc 300 mg pulver til infusjonsvæske, oppløsning
Poland Runrapiq 300 mg proszek do sporządzania roztworu do infuzji
Romania Rapibloc 300 mg pulbere pentru soluţie perfuzabilă
Slovakia Rapibloc 300 mg prášok na infúzny roztok
Slovenia Rapibloc 300 mg prašek za raztopino za infundiranje
Sweden Rapibloc 300 mg pulver till infusionsvätska, lösning

The following information is intended exclusively for healthcare professionals:
This section contains practical information regarding administration. Refer to the Summary of Product Characteristics for complete information on dosage, route of administration, contraindications, warnings, etc.

Landiolol is intended for intravenous use in a monitored setting and must be administered only by qualified healthcare professionals. The dosage of landiolol must be titrated individually.
Landiobloc must not be administered without reconstitution.

Reconstitute one 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 lactate solution

The white to almost white powder dissolves completely after reconstitution. Gently mix until a clear solution is obtained. Reconstituted solutions should be inspected visually for visible particles and discoloration. Only clear, colourless solutions should be used. The infusion is generally started at a rate of 10–40 micrograms/kg/min; this will result in a reduction of heart rate within 10–20 minutes.

If a more rapid reduction in heart rate is desired (within 2–4 minutes), an optional loading dose of 100 micrograms/kg/min for 1 minute may be considered, followed by a continuous intravenous infusion of 10–40 micrograms/kg/min.

In patients with cardiac dysfunction and septic shock, lower initial doses should be used. Administration instructions are provided in the section "Special populations" and in the integrated dosing schedule.

Maximum dose: The maintenance dose may be increased up to 80 micrograms/kg/min for a limited period (see section 5.2 of the SmPC), if the patient's cardiovascular status requires and allows such dose increase and the maximum daily dose is not exceeded.
The recommended maximum daily dose of landiolol hydrochloride is 57.6 mg/kg/day (e.g., infusion at 40 micrograms/kg/min for 24 hours).
Experience with landiolol hydrochloride infusions at doses >10 micrograms/kg/min for longer than 24 hours is limited.

Conversion formula for continuous intravenous infusion: from micrograms/kg/min to ml/h
(Landiobloc 300 mg/50 ml = 6 mg/ml):
Target dose (micrograms/kg/min) × body weight (kg) / 100 = infusion rate (ml/h)

Conversion table (example):

Optional bolus administration in hemodynamically stable patients:
Conversion formula from 100 micrograms/kg/min to ml/h (Landiobloc 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 must be reduced or the infusion must be stopped, and, if necessary, patients should receive appropriate medical treatment. In cases of hypotension or bradycardia, administration of landiolol may be resumed at a lower dosage once blood pressure or heart rate have returned to an acceptable level. Particular caution should be exercised when adjusting the dosage and during maintenance infusion in patients with low systolic blood pressure.

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

In case of overdose, administration of landiolol must be immediately discontinued.

Transition to an alternative medicinal product: after adequate control of heart rate and clinical stability have been achieved in patients, transition to therapy with alternative medicinal products (e.g., oral antiarrhythmics) may be considered.

When landiolol is replaced by alternative medicinal products, the physician must carefully consider the instructions and dosage recommendations for the selected alternative medicinal product. When switching to an alternative medicinal product, the landiolol dosage may be reduced as follows:

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

Special Populations

Elderly patients (≥ 65 years)
No dose adjustment is required.

Renal impairment
No dose adjustment is required.

Hepatic impairment
Data regarding treatment of patients with hepatic impairment are limited. In patients with any degree of hepatic impairment, careful titration of the medicinal product is recommended, starting with the lowest dose.

Cardiac dysfunction
In patients with impaired left ventricular function (LVEF <40%, CI <2.5 L/min/m², NYHA 3-4), for example following cardiac surgery, during ischemia, or in septic states, reduced doses starting from 1 microgram/kg/min have been used and gradually increased up to 10 micrograms/kg/min under close monitoring of arterial pressure to achieve control of heart rate. If necessary and tolerated by the patient's cardiovascular status, further dose increases may be considered under strict hemodynamic monitoring.

Septic shock

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

Paediatric population
The safety and efficacy of landiolol in children aged 0 to 18 years have not yet been established.

Method of administration
Landiobloc must be reconstituted prior to administration and used immediately after opening.
Landiobloc must not be mixed with other medicinal products except those listed in section 6.6 of the Summary of Product Characteristics (SmPC).
Landiolol must be administered intravenously via a central or peripheral line and must not be administered through the same intravenous line used for other medicinal products.

Unlike other beta-blockers, landiolol has not shown rebound tachycardia following abrupt discontinuation after 24 hours of continuous infusion. Nevertheless, patients must be closely monitored when administration of landiolol is stopped.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SmPC.
• Severe bradycardia (heart rate less than 50 beats per minute)
• Sinus node syndrome
• Severe atrioventricular conduction disorders (in the absence of a pacemaker): second- or third-degree atrioventricular block
• Cardiogenic shock
• Severe hypotension
• Decompensated heart failure when considered unrelated to arrhythmia
• Pulmonary hypertension
• Untreated pheochromocytoma
• Acute asthma attack
• Severe metabolic acidosis unresponsive to treatment