FORTIVA Solution for injection Ref.[51236] Active ingredients: Remifentanil

FORTIVA is not recommended for use as the sole medicine in general anaesthesia.

FORTIVA should be administered only by persons specifically trained in the use of anaesthetics and the recognition and management of the expected adverse effects of potent opioids, including respiratory and cardiac resuscitation such as the establishment and maintenance of a patent airway and assisted ventilation.

Inadvertent administration: A sufficient amount of FORTIVA 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 medicines. This may be avoided by administering FORTIVA into a fast-flowing IV line or via a dedicated IV line, which is adequately cleared of residual medicine or which is removed upon discontinuation of FORTIVA.

FORTIVA may produce dependency.

The safety profile of FORTIVA during labour or delivery has not been demonstrated. There are insufficient data to recommend FORTIVA for use during labour and caesarean section.

Remifentanil, as contained in FORTIVA, crosses the placental barrier and fentanyl analogues can cause respiratory depression in the baby.

Rapid offset of action: Due to the very rapid offset of action of FORTIVA no residual opioid activity will be present within 5 to 10 minutes after discontinuation of FORTIVA. For those patients undergoing surgical procedures where post-operative pain is anticipated, analgesics should be administered prior to or immediately following discontinuation of FORTIVA. Sufficient time must be allowed to reach the maximum effect of the longer-acting analgesic. The choice of analgesic should be appropriate for the patient’s surgical procedure and the level of postoperative care.

Muscle rigidity – prevention and management: At the doses recommended muscle rigidity may occur. The incidence is related to the dose and rate of administration. Therefore, bolus infusions should be administered over not less than 30 seconds.

Muscle rigidity induced by FORTIVA must be treated in the context of the patient’s clinical condition with appropriate supporting measures.

Excessive muscle rigidity occurring during the induction of anaesthesia should be treated by the administration of a neuromuscular blocking medicine and/or additional hypnotic medicines.

Muscle rigidity seen during the use of FORTIVA as an analgesic may be treated by stopping or decreasing the rate of administration of FORTIVA. Resolution of muscle rigidity after discontinuing the infusion of FORTIVA occurs within minutes.

Respiratory depression – management: Analgesia is accompanied by marked respiratory depression. Therefore, FORTIVA 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 a discontinuation of the infusion. Remifentanil, as contained in FORTIVA, 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.

Cardiovascular effects: Hypotension and bradycardia may be managed by reducing the rate of infusion of FORTIVA or the dose of concurrent anaesthetics or by using IV fluids, vasopressor or anticholinergic medicines as appropriate.

Debilitated, hypovolaemic and elderly patients are more sensitive to the cardiovascular effects of remifentanil, as contained in FORTIVA.

Remifentanil, as contained in FORTIVA, is not metabolised by plasmacholinesterase and therefore interactions with medication metabolised by this enzyme are not anticipated.

If doses of concomitantly administered CNS depressant medicines are not reduced, patients may experience an increased incidence of adverse effects associated with these medicines.

The cardiovascular effects of FORTIVA (hypotension and bradycardia), may be exacerbated in patients receiving concomitant cardiac depressant medicines, such as beta-blockers and calcium channel blocking medicines.

Safety in pregnancy and lactation has not been established.

Placental and milk transfer: Remifentanil crosses the placenta and appears in breast milk (see PHARMACOLOGICAL ACTION).

If an early discharge is envisaged following treatment using anaesthetic medicines, patients should be advised not to drive or operate machinery.

The most common adverse events associated with FORTIVA are direct extensions of µ-opioid agonist pharmacology.

The overall reporting incidence, as determined from all phases of controlled anaesthesia studies at recommended doses, is as follows:

Very common (≥10%) Nausea, vomiting, hypotension, skeletal muscle rigidity.
Common (Frequent) (≥1% and <10%) Post-operative shivering, bradycardia, acute respiratory depression, apnoea, post-operative hypertension, pruritus.
Uncommon (Infrequent) (≥0,1% and <1%) Hypoxia, constipation, post-operative aches.
Rare (<0,1%) Sedation (during recovery from general anaesthesia).

These adverse events resolve within minutes of discontinuing or decreasing the rate of remifentanil, as contained in FORTIVA, administration.

The following adverse events and reporting frequencies have been determined from postmarketing reporting:

• Allergic reactions including anaphylaxis have been reported in patients receiving FORTIVA in conjunction with one or more anaesthetic medicines.
• Cases of cardiac arrest, asystole usually preceded by bradycardia, have been reported in patients receiving FORTIVA in conjunction with other anaesthetic medicines.

Patients with severe hepatic impairment are more sensitive to the respiratory depressant effects.