REMIFENTANIL

Remifentanil should be administered only in a setting fully equipped for the monitoring and support of respiratory and cardiovascular function and by persons specifically trained in the use of anaesthetic drugs and the recognition and management of the expected adverse effects of potent opioids, including respiratory and cardiac resuscitation.

Such training must include the establishment and maintenance of a patent airway and assisted ventilation. Continuous infusions of Remifentanil must be administered by a calibrated infusion device into a fast flowing IV line or via a dedicated IV line.

6 for additional information, including tables with examples of infusion rates by body weight to help titrate Remifentanil to the patient’s anaesthetic needs). Remifentanil may also be given by target controlled infusion (TCI) with an approved infusion device incorporating the Minto pharmacokinetic model with covariates for age and lean body mass (LBM).

4). 3). 6 for storage conditions of the reconstituted/diluted product and the recommended diluents). For manually-controlled infusion Remifentanil can be diluted to concentrations of 20 to 250 micrograms/ml (50 micrograms/ml is the recommended dilution for adults and 20 to 25 micrograms/ml for paediatric patients aged 1 year and over).

For TCI the recommended dilution of Remifentanil is 20 to 50 micrograms/ml. 6 for additional information, including tables to help titrate Remifentanil to the patient's anaesthetic needs). 1 General Anaesthesia The administration of Remifentanil must be individualised based on the patient's response.

2 below. 05 to 2 When given by bolus injection at induction Remifentanil should be administered over not less than 30 seconds. At the doses recommended above, remifentanil significantly reduces the amount of hypnotic agent required to maintain anaesthesia.

Therefore, isoflurane and propofol should be administered as recommended above to avoid an increase of haemodynamic effects such as hypotension and bradycardia (see Concomitant medication below).

Induction of anaesthesia:

Remifentanil should be administered with a standard dose of an hypnotic agent, such as propofol, thiopentone, or isoflurane, for the induction of anaesthesia. Administering Remifentanil after an hypnotic agent will reduce the incidence of muscle rigidity.

5 to 1 micrograms/kg/min, with or without an initial slow bolus injection of 1 microgram/kg given over not less than 30 seconds. If endotracheal intubation is to occur more than 8 to 10 minutes after the start of the infusion of Remifentanil, then a bolus injection is not necessary.

Maintenance of anaesthesia in ventilated patients:

After endotracheal intubation, the infusion rate of Remifentanil should be decreased, according to anaesthetic technique, as indicated in the above table. Due to the fast onset and short duration of action of Remifentanil, the rate of administration during anaesthesia can be titrated upward in 25% to 100% increments or downward in 25% to 50% decrements, every 2 to 5 minutes to attain the desired level of mu- opioid response.

In response to light anaesthesia, supplemental slow bolus injections may be administered every 2 to 5 minutes. g. laryngeal mask anaesthesia): In spontaneously breathing anaesthetised patients with a secured airway respiratory depression is likely to occur.

Special care is needed to adjust the dose to the patient requirements and ventilatory support may be required. 04 micrograms/kg/min with titration to effect. 1 micrograms/kg/min has been studied. Bolus injections are not recommended in spontaneously breathing anaesthetised patients.

Remifentanil should not be used as an analgesic in procedures where patients remain conscious or do not receive any airway support during the procedure. 5). Doses of the following agents used in anaesthesia: isoflurane, thiopentone, propofol and temazepam have been reduced by up to 75% when used concurrently with remifentanil.

Guidelines for discontinuation/continuation into the immediate post- operative period: Due to the very rapid offset of action of Remifentanil no residual opioid activity will be present within 5 to 10 minutes after discontinuation.

For those patients undergoing surgical procedures where post- operative pain is anticipated, analgesics should be administered prior to […]

Summary of the safety profile The most common undesirable effects associated with remifentanil are direct extensions of mu-opioid agonist pharmacology. These adverse events resolve within minutes of discontinuing or decreasing the rate of remifentanil administration.

Tabulated list of adverse reactions The frequencies below are defined as very common (
1/10), common (
1/100 to <1/10), uncommon (
1/1,000 to <1/100), rare (
1/10,000 to <1/1,000) and very rare (<1/10,000), not known (cannot be estimated from the available data).

4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Remifentanil should be administered only in a setting fully equipped for the monitoring and support of respiratory and cardiovascular function, and by persons specifically trained in the use of anaesthetic drugs and the recognition and management of the expected adverse effects of potent opioids, including respiratory and cardiac resuscitation.

Such training must include the establishment and maintenance of a patent airway and assisted ventilation. The use of Remifentanil in mechanically ventilated intensive care patients is not recommended for a duration of treatment greater than 3 days.

Patients with a known hypersensitivity to opioids of a different class may exhibit a hypersensitivity reaction following administration of Remifentanil. Caution should be exercised before using Remifentanil in these patients. Rapid offset of action /Transition to alternative analgesia Due to the very rapid offset of action of Remifentanil, no residual opioid activity will be present within 5 to 10 minutes after the discontinuation of Remifentanil.

For those patients undergoing surgical procedures where post-operative pain is anticipated, analgesics should be administered prior to discontinuation of Remifentanil. 2). Prior to discontinuation of Remifentanil, patients must be given alternative analgesic and sedative agents.

Sufficient time must be allowed to reach the therapeutic effect of the longer acting analgesic. The choice of agent(s), the dose and the time of administration should be planned in advance and individually tailored to be appropriate for the patient’s surgical procedure and the level of post-operative care anticipated.

When other opioid agents are administered as part of the regimen for transition to alternative analgesia, the benefit of providing adequate post-operative analgesia must always be balanced against the potential risk of respiratory depression with these agents.

Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs. Concomitant use of Remifentanil and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death.

Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Remifentanil concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). Discontinuation of Treatment and withdrawal syndrome Repeated administration at short term intervals for prolonged periods may result in the development of withdrawal syndrome after cessation of therapy.

Symptoms following withdrawal of Remifentanil including tachycardia, hypertension and agitation have been reported infrequently upon abrupt cessation, particularly after prolonged administration of more than 3 days. Where reported, re-introduction and tapering of the infusion has been beneficial.

The use of Remifentanil in mechanically ventilated intensive care patients is not recommended for duration of treatment greater than 3 days. Inadvertent administration A sufficient amount of Remifentanil may be present in the dead space of the IV line and/or cannula to cause respiratory depression, apnoea and/or muscle rigidity if the line is flushed with IV fluids or other drugs.

This may be avoided by administering Remifentanil into a fast flowing IV line or via a dedicated IV line which is removed when Remifentanil is discontinued. Muscle rigidity - prevention and management At the doses recommended muscle rigidity may occur.

As with other opioids, the incidence of muscle rigidity is related to the dose and rate of administration. Therefore, bolus injections should be administered over not less than 30 seconds. Muscle rigidity induced by remifentanil must be treated in the context of the patient's clinical condition with appropriate supporting measures including ventilatory support.

Excessive muscle rigidity occurring during the induction of anaesthesia should be treated by the administration of a neuromuscular blocking agent and/or additional hypnotic agents. Muscle rigidity seen during the use of remifentanil as an analgesic may be treated by stopping or decreasing the rate of administration of remifentanil.

Resolution of muscle rigidity after discontinuing the infusion of remifentanil occurs within minutes. Alternatively an opioid antagonist may be administered, however this may reverse or attenuate the analgesic effect of remifentanil.

Respiratory depression – prevention and management As with all potent opioids, profound analgesia is accompanied by marked respiratory depression. Therefore, remifentanil should only be used in areas where facilities for monitoring and dealing with respiratory depression are available.

The appearance of respiratory depression should be managed appropriately, including decreasing the rate of infusion by 50%, or by a temporary discontinuation of the infusion. Unlike other fentanyl analogues, remifentanil has not been shown to cause recurrent respiratory depression even after prolonged administration.

However, as many factors may affect post- operative recovery it is important to ensure that full consciousness and adequate spontaneous ventilation are achieved before the patient is discharged from the recovery area. 8), which may rarely lead to asystole/cardiac arrest may be reduced by lowering the rate of […]

3 Continuation of post-operative analgesia, prior to extubation Not recommended 1 0 to 1 Induction period of anaesthesia: After administration of hypnotic to achieve loss of consciousness, Remifentanil should be administered at an initial infusion rate of 1 microgram/kg/min.

The use of bolus injections of Remifentanil during induction in cardiac surgical patients is not recommended. Endotracheal intubation should not occur until at least 5 minutes after the start of the infusion.

Maintenance period of anaesthesia:

After endotracheal intubation the infusion rate of Remifentanil can be titrated upward in 25% to 100% increments, or downward in 25% to 50% decrements, every 2 to 5 minutes according to patient need. Supplemental slow bolus doses, administered over not less than 30 seconds, may also be given every 2 to 5 minutes as required.

5 micrograms/kg. 2).

Concomitant medication:

At the doses recommended above, remifentanil significantly reduces the amount of hypnotic agent required to maintain anaesthesia. Therefore, isoflurane and propofol should be administered as recommended above to avoid excessive depth of anaesthesia.

1 Adults - Concomitant medication). Guidelines for post-operative patient management Continuation of Remifentanil post-operatively to provide analgesia prior to weaning for extubation: It is recommended that the infusion of Remifentanil should be maintained at the final intra-operative rate during transfer of patients to the post-operative care area.

3 for further information on management of intensive care patients).

Establishment of alternative analgesia prior to discontinuation of Remifentanil:

Due to the very rapid offset of action of Remifentanil, no residual opioid activity will be present within 5 to 10 minutes after discontinuation. Prior to discontinuation of Remifentanil, patients must be given alternative analgesic and sedative agents at a sufficient time in advance to allow the therapeutic effects of these agents to become established.

It is therefore recommended that the choice of agent(s), the dose and the time of administration are planned, before weaning the patient from the ventilator. 8). To minimise the risk of these occurring, adequate alternative analgesia must be established (as described above), before the Remifentanil infusion is discontinued.

The infusion rate should be reduced by 25% decrements in at least 10-minute intervals until the infusion is discontinued. During weaning from the ventilator the Remifentanil infusion should not be increased and only down titration should occur, supplemented as required with alternative analgesics.

Haemodynamic changes such as hypertension and tachycardia should be treated with alternative agents as appropriate. When other opioid agents are administered as part of the regimen for transition to alternative analgesia, the patient must be carefully monitored.

The benefit of providing adequate post-operative analgesia must always be balanced against the potential risk of respiratory depression with these agents. 2). In association with these agents, adequate analgesia for cardiac surgery is generally achieved at the higher end of the range of target blood remifentanil concentrations used for general surgical procedures.

Following titration of remifentanil to individual patient response, blood concentrations as high as 20 nanograms/ml have been used in clinical studies. At the doses recommended above, remifentanil significantly reduces the amount of hypnotic agent required to maintain anaesthesia.

2). For information on blood remifentanil concentrations achieved with manually- controlled infusion see Table 6. Guidelines for discontinuation/continuation into the immediate post- operative period: At the end of surgery when the TCI infusion is stopped or the target concentration reduced, spontaneous respiration is likely to return at calculated remifentanil concentrations in the region of 1 to 2 nanograms/ml.

) As there are insufficient data, the administration of Remifentanil by TCI for the management of post-operative analgesia is not recommended. 3 Use in Intensive Care Remifentanil can be used for the provision of analgesia in mechanically ventilated intensive care patients.

Sedative agents should be added as appropriate. Remifentanil has been studied in mechanically […]