RAPIBLOC Powder for solution for infusion Ref.[9871] Active ingredients: Landiolol

Posology

Landiolol is intended for intravenous use in a monitored setting. Only a well-qualified health care professional should administer landiolol. The dosage of landiololshould be titrated individually.

Initiate the intravenous infusion by a loading dose of 100 micrograms/kg body weight (BW) for 1 min, followed by continuous intravenous infusion of 10-40 micrograms/kg BW/min. If no rapid onset of the bradycardic effect (within 2 to 4 min) is required, starting the infusion with the maintenance infusion rate of 10-40 micrograms/kg BW/min will establish the effect within 10-20 min.

Maximum dose: Should the desired therapeutic response not be achieved with this dosing regimen, the maintenance dose may be increased up to 80 micrograms/kg BW/min, if the cardiovascular status of the patient requires and allows such an increase of the dose.

Conversion table for the initial intravenous infusion from micrograms/kg/min to ml/h (Rapibloc 300 mg/50 ml = 6 mg/ml strength):

Conversion table for continuous intravenous infusion: micrograms /kg/min to ml/h (Rapibloc 300 mg/50 ml = 6 mg/ml strength):

Conversion table for the initial intravenous infusion from micrograms/kg/min to ml/h (Rapibloc 600 mg/50 ml = 12 mg/ml strength):

Conversion table for continuous intravenous infusion: micrograms/kg/min to ml/h (Rapibloc 600 mg/50 ml = 12 mg/ml strength):

The maximum recommended daily dose of landiolol is 8,064 mg/subject/day (based on 80 micrograms/kg BW/min for a 70 kg patient and a maximum infusion duration of 24 hours). There is limited experience with landiolol infusion durations beyond 24 hours.

In case of an adverse reaction (see section 4.8), the dose of landiolol should be reduced or the infusion be discontinued, and patients should receive appropriate medical management if needed. In the event of hypotension or bradycardia, administration of landiolol can be restarted at a lower dose after the blood pressure or heart rate have returned to an acceptable level. In patients with a low systolic blood pressure extra caution is needed when adjusting the dosage and during the maintenance infusion.

Transition to an alternative drug: After achieving adequate control of the heart rate and a stable clinical status, transition to alternative medicinal products (such as oral antiarrhythmics) may be accomplished.

When landiolol is replaced by alternative medicinal products, the physician should carefully consider the labelling and dosage of the alternative drug, and the dosage of landiolol can be reduced as follows:

• Within the first hour after the first dose of the alternative medicinal product has been administered, the infusion rate of landiolol should be reduced by one-half (50%).
• After administration of the second dose of the alternative medicinal product, the patient’s response should be supervised and if satisfactory control is maintained for a least one hour, the landiolol infusion can be discontinued.

Special populations

Elderly population (≥ 65 years)

No dose adjustment is necessary.

Renal impairment

No dose adjustment is necessary (see section 4.4 and 5.2).

Hepatic impairment

Data regarding the treatment in patients with hepatic impairment is limited (see section 5.2). Careful dosing starting with the lowest dose is recommended in patients with all degrees of hepatic impairment.

Cardiac dysfunction

In patients with impaired left ventricular function (LEVF <40%, CI <2.5 L/min/m², NYHA 3-4) e.g. after cardiac surgery, during ischemia or in septic states, lower doses starting from 1 microgram/kg BW/min and increased in a stepwise fashion under close blood pressure monitoring up to 10 micrograms/kg BW/min have been used to achieve heart rate control.

Paediatric population

The safety and efficacy of landiolol in children aged 0 to 18 years have not yet been established. Currently available data are described in section 5.2, but no recommendation on posology can be made.

Method of administration

Rapibloc must be reconstituted before administration (for instructions see section 6.6) and used immediately after opening (see sections 4.4 and 6.3).

Rapibloc must not be mixed with other medicinal products except those listed in section 6.6.

Landiolol should be administered intravenously via a central line or a peripheral line and should not be administered through the same intravenous line as other medicinal products (see section 6.6).

Contrary to other beta-blockers, landiolol did not show withdrawal tachycardia in response to abrupt termination after 24 h continuous infusion. Nevertheless, patients should be closely monitored when administration of landiolol is to be discontinued.

In case of overdose the following symptoms can occur: Severe hypotension, severe bradycardia, AV block, heart insufficiency, cardiogenic shock, cardiac arrest, bronchospasm, respiratory insufficiency, loss of consciousness to coma, convulsions, nausea, vomiting, hypoglycaemia, hyperkalaemia.

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

The time taken for symptoms to disappear following overdosing will depend on the amount of landiolol administered. Although landiolol’s heart rate reducing effect decreases rapidly after the end of administration, this may take longer than 30 minutes as seen with discontinuation at therapeutic dose levels.

Artificial respiration may be necessary. Based on the observed clinical effects, the following general measures should be considered:

Bradycardia: atropine or another anticholinergic medicinal product should be given intravenously and then a beta-1-stimulant (dobutamine, etc.). If bradycardia cannot be treated sufficiently, a pacemaker may be necessary.

Bronchospasm: nebulized beta-2-sympathomimetics should be given. If this treatment is not sufficient, intravenous beta-2-sympathomimetics or aminophylline can be considered.

Symptomatic hypotension: fluids and/or pressor agents should be given intravenously.

Cardiovascular depression or cardiac shock: diuretics (in case of lung oedema) or sympathomimetics can be administered. The dose of sympathomimetics (depending on the symptoms e.g. dobutamine, dopamine, noradrenaline, adrenaline, etc.) depends on the therapeutic effect. In case further treatment is necessary, the following agents can be given intravenously: atropine, inotropic agents, calcium ions.

Shelf life: 3 years.

Chemical and physical in-use stability after reconstitution has been demonstrated for 24 hours at 25°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and condition prior to use are the responsibility of the user. Do not freeze.

This medicinal product does not require any special storage conditions.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

Colourless glass (Type 1) 50 ml vial with a bromobutyl rubber stopper and an aluminium flip-off seal.

Pack size of 1 vial includes 300 mg (the colour code of the flip-off seal is yellow) or 600 mg (the colour code of the flip-off seal is red) powder for solution for infusion.

Not all pack sizes may be marketed.

Rapibloc must not be administered without reconstitution.

Instructions for use

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

• NaCl 9 mg/ml (0.9%) solution
• Glucose 50 mg/ml (5%) solution
• Ringer’s solution
• Ringer-lactate solution

Information on the pH and osmolality of the landiolol solutions ready for administration:

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

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.