Bupivacaine Hcl 0,5 % Injection

BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS is used as a peripheral nerve block, caudal or epidural block.

Posology
The area and vascularity of the tissue, the amount of neuronal segments to be blocked, the technique of anaesthesia as well as personal tolerance to BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS are factors that need to be taken into account when administering BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS. When the correct dose of BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS is administered, complete sensory blockage will occur; however, motor blockade depends on the dose of BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS administered. The duration of anaesthesia is such that in most cases, a single dose will be sufficient. The following dosages are recommended as a guide for use and have generally proved satisfactory in the average adult:

• Procedure Dose Additional Info
• ml mg
• Trigeminal block 0,5 u2013 4 2,5 - 20
• Axillary block 15 u2013 30 75 u2013 150
• Intercostal block 3 u2013 5 15 u2013 25 Dose indicated for every segment
• Epidural anaesthesia 10 - 20 50 u2013 100
• Continuous epidural anaesthesia Starting dose of 10 ml followed by 3 ml u2013 5 ml u2013 8 ml every 4 u2013 6 hours. The dose depends on the number of segments to be rendered analgesic and the patientu2019s age.
• Caudal anaesthesia 15 - 30 75 - 150

The maximum recommended dose of BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS in a single injection is 150 mg and should not be exceeded unless there are special considerations present. Where dosage is calculated on the patientu2019s mass, this should not exceed 2 mg/kg body mass up to a maximum of 150 mg.

Special populations
Patients treated with antidysrhythmic medicines class III (e.g., amiodarone) should be under close surveillance and ECG monitoring, since cardiac effects may be additive (see section 4.5).
Elderly population
Doses should be reduced in elderly or debilitated patients (refer to section 4.4).
Paediatric population
BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS is not recommended for children younger than 12 years.

Method of administration
Injection. The utmost care should be taken to prevent an accidental intravascular injection, always including careful aspiration.

• Hypersensitivity to bupivacaine or to any of the excipients (see section 6.1).
• Known hypersensitivity to local anaesthetic medicines of the amide type.
• Intravenous regional anaesthesia (Bieru2019s block).
• Epidural anaesthesia, regardless of the local anaesthetic used, has its own general contraindications 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.

DURING LOCAL ANAESTHESIA RESUSCITATIVE MEDICINES AND EQUIPMENT MUST BE PRESENT AT ALL TIMES. Before any nerve block is attempted, intravenous access for resuscitation purposes should be established. Medical practitioners should have received adequate and appropriate training in the procedure to be performed and should be familiar with the diagnosis and treatment of side effects, systemic toxicity or other complications (see section 4.9).

Paracervical block with amide-type local anaesthetics, such as BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS, during labour often precedes foetal bradycardia and may be associated with foetal acidosis. The risk increases with premature birth, toxaemia of pregnancy, and foetal distress. Paracervical block using BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS is not recommended.

There have been reports of cardiac arrest during the use of bupivacaine, as in BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS, for epidural anaesthesia or peripheral nerve blockade where resuscitative efforts have been difficult and were required to be prolonged before the patient responded.

BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS may cause acute toxicity effects on the central nervous and cardiovascular systems if utilised for local anaesthetic procedures resulting in high blood concentrations of bupivacaine. This is especially the case after unintentional intravascular administration. Ventricular dysrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death have been reported in connection with high systemic concentrations of bupivacaine.

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 HCl 0,5 % (10 ml) FRESENIUS may cause significant increases in blood levels with each repeated dose due to accumulation of bupivacaine. Tolerance varies with the status of the patient.

Patients at risk and risks associated with certain anaesthesia techniques:

• Debilitated, elderly or acutely ill patients should be given reduced doses to commensurate with their physical status.
• Patients with partial or complete heart block u2013 due to the fact that local anaesthetics may depress myocardial conduction.
• Patients with advanced liver disease or severe renal dysfunction.
• Patients in the late stages of pregnancy.
• Caution is advised for co-administration of BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS and anti-dysrhythmic medicines class III, e.g. amiodarone (see section 4.5).
• Patients allergic to ester-type local anaesthetic medicines (procaine, tetracaine, benzocaine, etc.) have not shown cross-sensitivity to medicines of the amide-type such as bupivacaine.
• Local anaesthetics such as BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS should be used with caution for epidural anaesthesia in patients with impaired cardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of AV conduction produced by these medicines.
• The physiological effects generated by a central neural blockade are more pronounced in the presence of hypotension. Patients with hypovolaemia due to any cause can develop sudden and severe hypotension during epidural anaesthesia. Epidural anaesthesia should therefore be avoided or used with caution in patients with untreated hypovolaemia or significantly impaired venous return.
• Retrobulbar injections may reach the cranial subarachnoid space causing serious/severe reactions, including temporary blindness, cardiovascular collapse, apnoea and convulsions.
• Retro- and peribulbar injections of local anaesthetics carry a low risk of persistent ocular muscle dysfunction. The primary causes include trauma and/or local toxic effects on muscles and/or nerves. The severity of such tissue reactions is related to the degree of trauma, the concentration of the local anaesthetic and the duration of exposure of the tissue to the local anaesthetic. For this reason, as with all local anaesthetics, the lowest effective concentration and dose of local anaesthetic should be used.
• Vasoconstrictors may aggravate tissue reactions and should be used only when indicated.
• Small doses of local anaesthetics injected into the head and neck, including retrobulbar, dental and stellate ganglion blocks, may produce systemic toxicity due to inadvertent intra-arterial injection.
• There have been post-marketing reports of chondrolysis in patients receiving post-operative intra-articular continuous infusion of local anaesthetics. The majority of reported cases of chondrolysis have involved the shoulder joint. Due to multiple contributing factors and inconsistency in the scientific literature regarding mechanism of action, causality has not been established. Intra-articular continuous infusion is not an approved indication for BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS.
• Epidural anaesthesia can cause intercostal paralysis and patients with pleural effusions may suffer respiratory distress.
• Epidural anaesthesia with BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS can cause hypotension and bradycardia which should be anticipated and appropriate precautions taken. These may include pre-loading the circulation with crystalloid or colloid solution. If hypotension develops it should be treated with a suitable vasopressor intravenously. Severe hypotension may result from hypovolaemia due to haemorrhage or dehydration, or aorto-caval occlusion in patients with massive ascites, large abdominal tumours or late pregnancy. Marked hypotension should be avoided in patients with cardiac decompensation.

BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS should be used with caution in patients receiving other local anaesthetics or medicines structurally related to amide-type local anaesthetics, e.g. certain antidysrhythmics, such as lidocaine (lignocaine), since systemic toxic effects are additive (see section 4.2). Specific interaction studies with bupivacaine and antidysrhythmic medicines class III (e.g., amiodarone) have not been performed, but caution should be advised (see also section 4.4). Propranolol may reduce the clearance of BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS. There is a risk of increased bupivacaine toxicity when these medicines are used concomitantly. There is a possible risk that the adverse effects of BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS on the heart may be enhanced in patients taking calcium-channel blockers. Interactions between BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS and histamine H2-antagonists, such as cimetidine and ranitidine, resulted in a decreased clearance of bupivacaine and an increased plasma concentration, respectively, but had no significant clinical effects.

Pregnancy
Safe use in pregnancy and lactation, other than for use in labour, has not yet been established (see section 4.5).
Breastfeeding
Bupivacaine, the active ingredient of BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS, is distributed into breast milk.

Besides the direct anaesthetic effect on sensory and motive functioning, BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS may have an effect on mental function and co-ordination even in the absence of overt CNS toxicity, and may temporarily impair locomotion and alertness.

a) Summary of the safety profile
Severe systemic side effects may occur when BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS is accidentally injected intravascularly.

b) Tabulated summary of adverse reactions

MedDRA system organ class Frequency Adverse reactions

Immune system disorders Less frequent Allergic reactions, anaphylactic reaction/shock.

Psychiatric disorders Less frequent Excitation, depression, nervousness.

Nervous system disorders Frequent Paraesthesia, dizziness. Less frequent Convulsions, circumoral paraesthesia, numbness of the tongue, hyperacusis, visual disturbances, loss of consciousness, tremors, light-headedness, dysarthria, muscle twitching, chills, fever, drowsiness, neurological damage, neuropathy, peripheral nerve injury, arachnoiditis, paresis and paraplegia.

Eye disorders Less frequent Constriction of the pupils, diplopia, blurred vision.

Ear and labyrinth disorders Less frequent Tinnitus.

Cardiac disorders Frequent Bradycardia. Less frequent Myocardial depression, arrhythmia, cardiac arrest, oedema, ventricular dysrhythmias.

Vascular disorders Frequent Changes in blood pressure (usually hypotension), hypertension.

Respiratory, thoracic and mediastinal disorders Less frequent Respiratory depression.

Gastrointestinal disorders Frequent Nausea, vomiting.

Hepato-biliary disorders Less frequent Hepatic dysfunction, with reversible increase of liver enzymes and bilirubin.

Skin and subcutaneous tissue disorders Less frequent Pruritus, urticaria, skin rash.

Renal and urinary disorders Frequent Urinary retention.

General disorders and administration site conditions Less frequent Skin or intravenous reaction may occur at the site of injection if the patient shows sensitivity to BUPIVACAINE HCl 0,5 % (10 ml) FRESENIUS. Accidental sub-arachnoid injection can lead to very high spinal anaesthesia possibly with apnoea and severe hypotension.

Accidental intravascular injections of local anaesthetics may cause immediate (within seconds to a few minutes) systemic toxic reactions. In the event of overdose, systemic toxicity appears later (15 u2013 60 minutes after injection) due to the slower increase in local anaesthetic blood concentration.

Treatment of overdose:
Maintenance of the airways and ventilation with oxygen of the patient during respiratory distress. Treatment of milder symptoms of systemic toxicity may not be required but if convulsions occur, they can be controlled with oxygen and by rapid intravenous administration of a suitable benzodiazepine or a short-acting barbiturate e.g. thiopentone 100 mg u2013 200 mg or diazepam 5 mg u2013 10 mg. During circulatory distress intravenous fluids, and when necessary, vasopressors can be administered.