BUPIVACAINE HYDROCHLORIDE

Posology Adults and children above 12 years of age The following table is a guide to dosage for the more commonly used techniques in the average adult. The figures reflect the expected average dose range needed. Standard textbooks should be consulted for factors affecting specific block techniques and for individual patient requirements.

B. When prolonged blocks are used, either by continuous infusion or by repeated bolus administration, the risks of reaching a toxic plasma concentration or inducing a local neural injury must be considered. The clinician's experience and knowledge of the patient's physical status is important in calculating the required dose.

The lowest dose required for adequate anaesthesia should be used. Individual variations in onset and duration occur. g. g. g. g. g. 5 ≤60 ≤150 1-3 3-4 1) Dose includes test dose 2) The dose for a major nerve block must be adjusted according to site of administration and patient status.

4. 3) In total ≤400 mg/24 h. 4) This solution is often used for epidural administration in combination with a suitable opioid for pain management. In total ≤400 mg/24 h. 5) If additional bupivacaine is used by any other techniques in the same patient, an overall dose limit of 150 mg should not be exceeded.

6) There have been post-marketing reports of chondrolysis in patients receiving post- operative intra-articular continuous infusion of local anaesthetics. 4). 7) Bupivacaine without adrenaline. g. epidural administration) requires the use of higher concentrations and doses.

g. in the relief of labour pain), the use of a lower concentration is indicated. The volume of drug used will affect the extent of spread of anaesthesia. In order to avoid intravascular injection, aspiration should be repeated prior to and during administration of the main dose, which should be injected slowly or in incremental doses, at a rate of 25-50 mg/min, while closely observing the patient’s vital functions and maintaining verbal contact.

An inadvertent intravascular injection may be recognised by a temporary increase in heart rate and an accidental intrathecal injection by signs of a spinal block. If toxic symptoms occur, the injection should be stopped immediately.

1) Experience to date indicates that 400 mg administered over 24 hours is well tolerated in the average adult. Paediatric population 1 to 12 years of age Paediatric regional anaesthetic procedures should be performed by qualified clinicians who are familiar with this population and the technique.

Accidental sub-arachnoid injection can lead to very high spinal anaesthesia possibly with apnoea and severe hypotension. The adverse reaction profile for bupivacaine is similar to those for other long acting local anaesthetics. g. g. g.

epidural abscess) by needle puncture. Neurological damage is a rare but well recognised consequence of regional and particularly epidural and spinal anaesthesia. g. direct injury to the spinal cord or spinal nerves, anterior spinal artery syndrome, injection of an irritant substance, or an injection of a non- sterile solution.

These may result in localised areas of paraesthesia or anaesthesia, motor weakness, loss of sphincter control and paraplegia. Occasionally these are permanent. Tabulated list of adverse reactions The adverse reactions considered at least possibly related to treatment with bupivacaine from clinical trials with related products and post-marketing experience are listed below by body system organ class and absolute frequency.

Frequencies 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), very rare (<1/10,000) or not known (cannot be estimated from the available data). 5) Respiratory, thoracic and mediastinal disorders Rare Respiratory depression Gastrointestinal disorders Very Common Nausea Common Vomiting Renal and urinary disorders Common Urinary retention Hepatic dysfunction, with reversible increases of SGOT, SGPT, alkaline phosphates and bilirubin, has been observed following repeated injections or long-term infusions of bupivacaine.

If signs of hepatic dysfunction are observed during treatment with bupivacaine, the drug should be discontinued. 1 Acute systemic toxicity Systemic toxic reactions primarily involve the central nervous system (CNS) and the cardiovascular system.

4). CNS reactions are similar for all amide local anaesthetics, while cardiac reactions are more dependent on the drug, both quantitatively and qualitatively. Central nervous system toxicity is a graded response with symptoms and signs of escalating severity.

There have been reports of cardiac arrest during the use of bupivacaine for epidural anaesthesia or peripheral nerve blockade where resuscitative efforts have been difficult, and were required to be prolonged before the patient responded.

However, in some instances resuscitation has proven impossible despite apparently adequate preparation and appropriate management. Like all local anaesthetic drugs, bupivacaine may cause acute toxicity effects on the central nervous and cardiovascular systems if utilised for local anaesthetic procedures resulting in high blood concentrations of the drug.

This is especially the case after unintentional intravascular administration or injection into highly vascular areas. Ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death have been reported in connection with high systemic concentrations of bupivacaine.

Adequate resuscitation equipment should be available whenever local or general anaesthesia is administered. 2). Before any nerve block is attempted, intravenous access for resuscitation purposes should be established. 8). Major peripheral nerve blocks may require the administration of a large volume of local anaesthetic in areas of high vascularity, often close to large vessels where there is an increased risk of intravascular injection and/or systemic absorption.

This may lead to high plasma concentrations. Overdosage or accidental intravenous injection may give rise to toxic reactions. Injection of repeated doses of bupivacaine hydrochloride may cause significant increases in blood levels with each repeated dose due to slow accumulation of the drug.

Tolerance varies with the status of the patient. Although regional anaesthesia is frequently the optimal anaesthetic technique, some patients require special attention in order to reduce the risk of dangerous side effects: • The elderly and patients in poor general condition should be given reduced doses commensurate with their physical status.

1. Bupivacaine hydrochloride solutions are contra-indicated in patients with hypersensitivity to local anaesthetic agents of the amide type. Solutions of bupivacaine hydrochloride are contra-indicated for intravenous regional anaesthesia (Bier's-block).

Epidural anaesthesia, regardless of the local anaesthetic used, has its own contra- indications which include: Active disease of the central nervous system such as meningitis, poliomyelitis, intracranial haemorrhage, sub-acute combined degeneration of the cord due to pernicious anaemia and cerebral and spinal tumours; tuberculosis of the spine; pyogenic infection of the skin at or adjacent to the site of lumbar puncture; cardiogenic or hypovolaemic shock; coagulation disorders or ongoing anticoagulation treatment.