Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Procedures using regional or local anaesthesia should always be performed in the vicinity of resuscitation equipment unless the procedure is very minor. An intravenous cannula should be inserted prior to large blocks, before the injection of the local anaesthetic.

Reports have been received of cardiac arrest or death following the use of bupivacaine in epidural anaesthesia or peripheral nerve block. In some cases, resuscitation was difficult or impossible despite adequate treatment.

Extensive peripheral nerve blocks can involve the administration of large volumes of local anaesthetics to highly vascularised areas, often in the vicinity of large blood vessels. In such cases there is a heightened risk of intravascular injection and/or systemic absorption, which can lead to high plasma concentrations.
Like all local anaesthetics, bupivacaine may cause acute toxic effects on the central nervous and cardiovascular systems if use results in high blood concentrations. This applies particularly after inadvertent intravascular administration or administration to highly vascularised areas.

Some regional anaesthesia techniques may be associated with severe adverse reactions as follows:
• Epidural anaesthesia may cause cardiovascular depression, particularly in the case of concomitant hypovolemia. Caution should therefore be observed in patients with impaired cardiovascular function.
• Retrobulbar injections can, in rare cases, reach the cranial subarachnoid space and cause e.g. temporary blindness, cardiovascular collapse, apnoea and convulsions. These symptoms must be treated immediately.
• Retrobulbar and peribulbar injections of local anaesthetic are associated with a certain risk of residual ocular muscle dysfunction. The primary causes are traumatic nerve injuries and/or local toxic effects on muscles and/or nerves due to injection of local anaesthetic.
The scope of the tissue damage depends on the magnitude of the trauma, the concentration of local anaesthetic and the duration of exposure of the tissue to local anaesthetic. For this reason, the lowest possible effective dose should be used.
Inadvertent intravascular injections in the head and neck regions can cause cerebral symptoms even at low doses.
• Paracervical block can sometimes cause bradycardia or tachycardia in the foetus; the foetal heart rhythm must be closely monitored.

Caution should be observed in patients with AV block II or III, as local anaesthetics may decrease myocardial transmittance. Particular attention should also be paid to the elderly and patients with severe hepatic disease or severe renal impairment, patients in the late stage of pregnancy or with poor general health.

Patients treated with antiarrhythmic class III agents (e.g. amiodarone) should be monitored closely and ECG monitoring should be considered as the cardiac effects of bupivacaine and class III antiarrhythmics may be additive.

Hepatic dysfunction, with reversible increases in aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), and bilirubin, have been observed in rare cases following repeated bupivacaine injections or bupivacaine infusions of long duration.
Immediate discontinuation of bupivacaine has led to rapid clinical improvement. If signs of hepatic dysfunction are observed during administration of bupivacaine, the medicinal product must be discontinued immediately. (See section 4.8).

Epidural anaesthesia can lead to hypotension and bradycardia. The risk of such effects can be reduced by e.g. injection of a vasopressor. Hypotension should be treated immediately with administration of an intravenous sympathomimetic and repeated if required.

There have been post-marketing reports of chondrolysis in patients receiving continuous postoperative intra-articular infusions of local anaesthetic. The majority of reported cases concerned chondrolysis in the shoulder joint. It has not been possible to establish a causal link due to several contributing factors as well inconsistencies in the scientific literature with regard to the mechanism of action. Continuous intra-articular infusion is not an approved indication for Bupivacaine Aguettant 5 mg/ml.

Paediatric population
The safety and efficacy of bupivacaine in children younger than one year of age have not been established. Only limited data are available.

The use of bupivacaine for intra-articular block in children aged 1 to 12 years has not been documented.

The use of bupivacaine for major nerve blocks in children aged 1 to 12 years has not been documented.

In epidural anaesthesia, children should be given incrementally increasing doses in proportion to their age and weight, as epidural anaesthesia at the thoracic level in particular can result in severe hypotension and impaired respiration.
This medicinal product contains 63 mg sodium per 20 ml vial, equivalent to 3.2% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Effects on Driving

4.7 Effects on ability to drive and use machines
Depending on the dose and method of administration, bupivacaine may have a transient effect on mobility and coordination.