Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Remifentanil B.Braun 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 B.Braun 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 B.Braun. Caution should be exercised before using Remifentanil B.Braun in these patients.

Rapid offset of action /Transition to alternative analgesia
Due to the very rapid offset of action of Remifentanil B.Braun, no residual opioid activity will be present within 5 to 10 minutes after the discontinuation of Remifentanil B.Braun.
For those patients undergoing surgical procedures where post-operative pain is anticipated, analgesics should be administered prior to discontinuation of Remifentanil B.Braun. The possibility of tolerance, hyperalgesia and associated haemodynamic changes should be considered when used in
Intensive Care Unit. Prior to discontinuation of Remifentanil B.Braun, 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.

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 B.Braun 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 B.Braun in mechanically ventilated intensive care patients is not recommended for duration of treatment greater than 3 days.

Inadvertent administration

A sufficient amount of Remifentanil B.Braun 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 B.Braun into a fast flowing IV line or via a dedicated IV line which is removed when Remifentanil B.Braun 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 postoperative recovery it is important to ensure that full consciousness and adequate spontaneous ventilation are achieved before the patient is discharged from the recovery area.

Cardiovascular effects

The risk of cardiovascular effects such as hypotension and bradycardia (see section 4.8), which may rarely lead to asystole/cardiac arrest may be reduced by lowering the rate of infusion of Remifentanil B.Braun or the dose of concurrent anaesthetics or by using IV fluids, vasopressor or anticholinergic agents as appropriate.
Debilitated, hypovolaemic, and elderly patients may be more sensitive to the cardiovascular effects of remifentanil.

Tolerance and opioid use disorder (abuse and dependence)
Tolerance, physical and psychological dependence, and opioid use disorder (OUD) may develop upon repeated administration of opioids. Abuse or intentional misuse of opioids may result in overdose and/or death. The risk of developing OUD is increased in patients with a personal or a family history (parents or siblings) of substance use disorders (including alcohol use disorder), in current tobacco users or in patients with a personal history of other mental health disorders (e.g. major depression, anxiety and personality disorders).

Effects on Driving

4.7 Effects on ability to drive and use machines

After anaesthesia with remifentanil the patient should not drive or operate machinery. The physician should decide when these activities may be resumed. It is advisable that the patient is accompanied when returning home and that alcoholic drink is avoided.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. When prescribing this medicine, patients should be told: • The medicine is likely to affect your ability to drive
• Do not drive until you know how the medicine affects you
• It is an offence to drive while under the influence of this medicine