Consumer medicine information

Bupivacaine Spinal Heavy BNM

Bupivacaine hydrochloride; Glucose monohydrate

BRAND INFORMATION

Brand name

Bupivacaine Spinal Heavy BNM

Active ingredient

Bupivacaine hydrochloride; Glucose monohydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Bupivacaine Spinal Heavy BNM.

What is in this leaflet

Please read this leaflet carefully before you are given Bupivacaine spinal heavy BNM.

This leaflet answers some common questions about Bupivacaine spinal heavy BNM. It does not contain all the available information. The most up-to-date Consumer Medicine Information can be downloaded from www.ebs.tga.gov.au.

Reading this leaflet does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks associated with giving you Bupivacaine spinal heavy BNM against the benefits this medicine is expected to have for you.

If you have any concerns about being given this medicine, ask your doctor, pharmacist or nurse.

Keep this leaflet with the medicine. You may want to read it again.

What Bupivacaine spinal heavy BNM is used for

Bupivacaine spinal heavy BNM contains bupivacaine hydrochloride monohydrate.

Bupivacaine spinal heavy BNM is used to prevent or relieve pain before surgery of the lower abdomen and lower limbs. They will not put you to sleep.

Bupivacaine spinal heavy BNM can also be used to make childbirth less painful.

Bupivacaine spinal heavy BNM belongs to a group of medicines called spinal local anaesthetics. They are injected into the spinal fluid where they make the nerves unable to pass messages to the brain.

Depending on the amount used, Bupivacaine spinal heavy BNM will either totally stop pain or will cause a partial loss of feeling.

Your doctor will have explained why you are being treated with Bupivacaine spinal heavy BNM and told you what dose you will be given.

Follow all directions given to you by your doctor carefully. They may differ from the information contained in this leaflet.

Ask your doctor if you have any questions about why it has been prescribed for you.

Bupivacaine spinal heavy BNM is only available with a doctor's prescription.

Bupivacaine spinal heavy BNM is not addictive.

Before you are given Bupivacaine spinal heavy BNM

When you must not be given it

Bupivacaine is for injection into the spinal canal. It is not for intravenous administration.

You must not be given Bupivacaine spinal heavy BNM if you are allergic to:

  • Bupivacaine hydrochloride.
  • other local anaesthetics e.g. lidocaine (lignocaine).
  • any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include:

  • shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

You must not be given Bupivacaine spinal heavy BNM if you have any of the following medical conditions:

  • problems with your blood pressure or circulation
  • blood poisoning
  • problems with the clotting of your blood
  • nerve or heart problems
  • diseases of the brain or spine
  • some types of back problems

It may not be safe for you to be given Bupivacaine spinal heavy BNM if you have any of these conditions.

Bupivacaine spinal heavy BNM will only be used if the solution is clear, the package is undamaged and the use by (expiry) date marked on the pack has not been passed. If you are given Bupivacaine spinal heavy BNM after the expiry date it may have no effect at all, or an entirely unexpected effect.

If you are not sure whether you should be given Bupivacaine spinal heavy BNM, talk to your doctor.

Before you are given it

Tell your doctor or pharmacist if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • problems with your blood pressure or circulation
  • blood poisoning
  • problems with the clotting of your blood
  • nerve or heart problems
  • neurological problems including multiple sclerosis and myasthenia gravis
  • thyroid problems
  • epilepsy
  • liver or kidney problems
  • malignant hyperthermia
  • diseases of the brain or spine including meningitis
  • some types of back problems
  • low blood pressure

It may not be safe for you to be given Bupivacaine spinal heavy BNM if you have any of these conditions.

Tell your doctor if you are pregnant or intend to become pregnant. We do not know if it is safe for you to be given it while you are pregnant. It may affect your baby if you take it early in pregnancy or in the last weeks before your baby is due. However, it can be used during childbirth.

Your doctor will discuss the risks and benefits of being given Bupivacaine spinal heavy BNM during pregnancy or childbirth.

Tell your doctor if you are breast-feeding or plan to breastfeed. Your baby can take in very small amounts of Bupivacaine spinal heavy BNM from breast milk if breastfeeding.

Your doctor will discuss the risks and benefits of being given Bupivacaine spinal heavy BNM when breastfeeding.

If you have not told your doctor or nurse about any of the above, tell them before you are given Bupivacaine spinal heavy BNM.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Bupivacaine spinal heavy BNM may interfere with each other. These include:

  • local anaesthetic agents including mexiletine or lidocaine (lignocaine).
  • medicines to treat abnormal rhythms of the heart, such as amiodarone.

The above medicines may be affected by Bupivacaine spinal heavy BNM, or may affect how well it works. You may need different amounts of your medicines or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while being given Bupivacaine spinal heavy BNM.

How Bupivacaine spinal heavy BNM is given

How it is given

Bupivacaine spinal heavy BNM will be injected by your doctor into the spinal canal through a space between the bones in your lower back. This is called a SPINAL injection and it will result in a feeling of numbness in your lower body, in an area that may seem unrelated to the site of injection.

Bupivacaine spinal heavy BNM must not be injected directly into the blood.

How much will be given

The dose you will be given will depend on your body size, age and the type of pain relief required. Your doctor will determine the best dose for you. They will be willing to discuss this decision with you.

Talk to your doctor if you are not sure about the dose of Bupivacaine spinal heavy BNM you will be given.

While you are being given Bupivacaine spinal heavy BNM

Things to be careful of

Be careful driving or operating machinery after you have been given Bupivacaine spinal heavy BNM. You may be drowsy and your reflexes may be slow.

Do not drink alcohol while you are being given Bupivacaine spinal heavy BNM. If you drink alcohol while you are being given Bupivacaine spinal heavy BNM your blood pressure may drop, making you feel dizzy and faint.

Please talk to your doctor or pharmacist about these possibilities if you think they may bother you.

In case of overdose

If you are given too much (overdose)

As Bupivacaine spinal heavy BNM is given to you in hospital by your doctor, it is very unlikely that you will receive too much.

Immediately tell your doctor or nurse if you think that you or anyone else has taken or been given too much Bupivacaine spinal heavy BNM.

If you are not in a hospital, immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26 in Australia) or (telephone 0800 POISON or 0800 764 766 in New Zealand), or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have been given too much Bupivacaine spinal heavy BNM.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include problems with your sight or hearing, numbness in or around the mouth, dizziness, stiffness, twitchy muscles, convulsions, low blood pressure, and problems with the rhythm of the heart.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are being given or after receiving Bupivacaine spinal heavy BNM.

Like all medicines, Bupivacaine spinal heavy BNM may occasionally cause side effects in some people. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

Tell your doctor or nurse if you notice any of the following and they worry you:

  • nervousness
  • dizziness
  • blurred vision
  • drowsiness
  • ringing in the ears
  • numbness
  • feeling strange (disoriented)
  • nausea
  • vomiting

These are mild side effects.

After a spinal injection you may develop a headache or backache which is not always related to the medicine used. These can, on rare occasions, last for some months after the injection is given.

Tell your doctor immediately if you notice any of the following:

  • fits
  • unconsciousness
  • breathing problems
  • low blood pressure
  • slow heart beat
  • collapse

You may experience these side effects if Bupivacaine spinal heavy BNM is given wrongly, or you are very sensitive to it.

These are serious side effects. You may need urgent medical attention.

Tell your doctor or nurse if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some patients.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After receiving Bupivacaine spinal heavy BNM

Storage

Bupivacaine spinal heavy BNM should only be given to you in hospital.

It should be stored in a cool dry place where the temperature stays below 25°C.

This is not all the information available on Bupivacaine spinal heavy BNM.

If you have any more questions or are not sure about anything, ask your doctor of pharmacist.

Product description

What it looks like

Bupivacaine spinal heavy BNM is a clear colourless sterile solution in a glass ampoule.

It is available as 4 mL glass ampoules in a sterile pack, in a box of 10 ampoules.

Ingredients

Active ingredient:

  • Bupivacaine hydrochloride monohydrate

Inactive ingredients:

  • glucose 8% w/v (80mg/mL)
  • sodium hydroxide for pH adjustment
  • water for injections.

The solution is preservative free and sulfite free.

Sponsor details

Boucher & Muir Pty Ltd
Level 9, 76 Berry Street
North Sydney NSW 2060

Distributed in NZ by:

BNM Group
39 Anzac Road
Browns Bay, Auckland 0753

AUST R 297613

Date of preparation

This leaflet was prepared in September 2019.

Published by MIMS January 2020

BRAND INFORMATION

Brand name

Bupivacaine Spinal Heavy BNM

Active ingredient

Bupivacaine hydrochloride; Glucose monohydrate

Schedule

S4

 

1 Name of Medicine

Bupivacaine hydrochloride monohydrate.

2 Qualitative and Quantitative Composition

Bupivacaine Spinal Heavy BNM solution for injection is a sterile, hyperbaric, isotonic aqueous solution containing bupivacaine hydrochloride monohydrate equivalent to bupivacaine hydrochloride 5 mg/mL (0.5% w/v) in water for injections.
It also contains glucose monohydrate equivalent to glucose 80 mg per mL of solution (8% w/v). It has a specific gravity of 1.03 g/mL at 20°C. The pH of the solution is adjusted with sodium hydroxide to remain between 4.0 and 6.0 during the approved shelf-life.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Clear and colourless solution for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Bupivacaine Spinal Heavy BNM is indicated for the production of spinal anaesthesia.
Bupivacaine Spinal Heavy BNM is suitable for abdominal surgery lasting 45 - 60 minutes and urological and lower limb surgery lasting 2 - 3 hours.

4.2 Dose and Method of Administration

As with all local anaesthetics, the dosage varies and depends upon the area to be anaesthetised, the vascularity of the tissues, the number of neuronal segments to be blocked, the depth of anaesthesia and degree of muscle relaxation required, individual tolerance, the technique of anaesthesia, and the physical condition of the patient.
The lowest dosage that results in effective anaesthesia should be used. In general, surgical anaesthesia requires the use of higher concentrations and doses than those required for analgesia.
Bupivacaine Spinal Heavy BNM is for use in one patient on one occasion only. Any solution remaining from an opened container should be discarded.
The following dosage recommendations should be regarded as a guide only for use in normal, healthy adults:

Spinal anaesthesia for surgery.

The spread of anaesthesia obtained with Bupivacaine Spinal Heavy BNM is dependent on several factors, the most important being volume of solution injected, position of patient and rate of injection.
Dosage. 2 - 4 mL Bupivacaine Spinal Heavy BNM (10 - 20 mg bupivacaine hydrochloride).
When 3 mL bupivacaine hydrochloride solution was injected into the L3 - L4 interspace and patients were kept in the sitting position for 2 minutes before being placed supine, blockade spread to the T7 - T10 segment. When a similar injection was made in patients in the lateral position who were then immediately placed supine, blockade spread to the T4 - T7 segment.
The effects of injections of bupivacaine hydrochloride solution exceeding 4 mL have not yet been studied and such volumes, therefore, cannot be recommended.

Note.

Hypotension.

During spinal anaesthesia, a marked fall in blood pressure and/or intercostal paralysis may be seen, possibly due to the use of excessive doses or improper positioning of the patient. Hypotension and bradycardia may occur as a result of sympathetic blockade.
Standard textbooks should be consulted with respect to techniques for administration of Bupivacaine Spinal Heavy BNM for spinal anaesthesia.

Use in children.

The use of spinal anaesthesia in children requires a thorough knowledge of the differences between adults and children to enable the administration of adequate doses of the drug. Since a relatively high CSF volume is found in infants and neonates, proportionately larger doses per kg are required to produce the same level of block. In small children the nerves are less myelinated, allowing easier diffusion of the drug and a more rapid onset of anaesthesia, hence lower concentrations are needed to block nerve conduction. The hypotension usually seen following spinal block in adults is uncommon in children below the age of 8.
The following doses of Bupivacaine Spinal Heavy BNM are recommended for use in children:
0.4 - 0.5 mg/kg for infants up to 5 kg;
0.3 - 0.4 mg/kg for children weighing between 5 and 15 kg;
0.25 - 0.3 mg/kg for children weighing more than 15 kg.
The onset of anaesthesia is slower than with lidocaine (lignocaine) and lasts for 60 - 120 minutes.

Use in pregnancy.

It should be noted that the dose should be reduced in patients in the late stages of pregnancy.

Use in debilitated or elderly patients.

The dose should be reduced in the elderly.

4.3 Contraindications

1. Allergy or hypersensitivity to amide type local anaesthetics. Detection of suspected sensitivity by skin testing is of limited value.
2. Intravenous administration.
3. Diseases of the cerebrospinal system such as meningitis, tumours (primary or secondary), poliomyelitis, subacute combined degeneration of the spinal cord, cranial haemorrhage, demyelinating disease and raised intracranial pressure.
4. Certain conditions of the bones of the vertebral column such as tuberculosis, tumours and osteomyelitis.
5. Arthritis, spondylitis, spinal stenosis and other diseases of the vertebral column, or recent trauma due to fracture, rendering spinal puncture impossible.
6. Local anaesthetics are contraindicated for epidural and spinal anaesthesia in patients with uncorrected hypotension or coagulation disorders or in patients receiving anti-coagulant treatment.
7. Local anaesthetic techniques must not be used when there is inflammation and/or sepsis in the region of the proposed injection or in the presence of septicaemia.
8. Pernicious anaemia with subacute combined degeneration of the spinal cord.
9. Cardiogenic or hypovolaemic shock.

4.4 Special Warnings and Precautions for Use

1. When any local anaesthetic agent is used, resuscitative equipment and drugs, including oxygen, should be immediately available in order to manage possible adverse reactions involving the cardiovascular, respiratory or central nervous systems.
Because of the possibility of hypotension and bradycardia following major blocks, an IV cannula should be inserted before the local anaesthetic is injected.
Delay in proper management of dose-related toxicity, under-ventilation from any cause and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and death.
2. Injection should always be made slowly with frequent aspirations to avoid inadvertent intravascular injection which may produce toxic effects.
3. Careful and constant monitoring of cardiovascular and respiratory vital signs and the patient's state of consciousness should be accomplished after each local anaesthetic injection. It should be kept in mind that at such times restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression or drowsiness may be early warning signs of Central Nervous System (CNS) toxicity.
4. Local anaesthetics should be given with great caution (if at all) to patients with pre-existing abnormal neurological pathology, e.g. myasthenia gravis. Use with extreme caution in spinal anaesthesia when there are serious diseases of the CNS or of the spinal cord, e.g. meningitis, spinal fluid block, cranial or spinal haemorrhage, tumours, poliomyelitis, syphilis, tuberculosis or metastatic lesions of the spinal cord.
5. Neurological disorders, such as multiple sclerosis, hemiplegia, paraplegia and neuromuscular disorders are not thought to be adversely affected by intrathecal anaesthesia, but call for caution. Before treatment is instituted, consideration should be taken if the benefits outweigh the possible risks for the patient.
6. Patients with hypovolaemia can develop sudden and severe hypotension during intrathecal anaesthesia.
7. A rare, though severe, adverse reaction following spinal anaesthesia is high or total spinal blockade resulting in cardiovascular and respiratory depression. The cardiovascular depression is caused by extensive sympathetic blockade which may result in profound hypotension and bradycardia, or even cardiac arrest. Respiratory depression may be caused by blockade of the innervation of the respiratory muscles, including the diaphragm.
8. Neurological injury is a rare consequence of intrathecal anaesthesia and may result in paraesthesia, anaesthesia, motor weakness and paralysis. Occasionally these are permanent.
9. There is an increased risk for high or total spinal blockade in the elderly and in patients in the late stages of pregnancy. The dose should therefore be reduced in these patients.
10. The safety and effectiveness of Bupivacaine Spinal Heavy BNM depend on proper dosage, correct technique and adequate precautions. Standard textbooks should be consulted for specific techniques and precautions for spinal anaesthetic procedures.
11. The lowest dosage that results in effective anaesthesia should be used (see Section 4.2 Dose and Method of Administration). Repeated injections of Bupivacaine Spinal Heavy BNM may cause accumulation of bupivacaine or its metabolites and result in toxic effects.
Tolerance to elevated blood levels varies with the status of the patient. Elderly, young or debilitated patients, including those with partial or complete conduction block, advanced liver disease or severe renal impairment, should be given reduced doses commensurate with their age and physical condition.
12. 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. Ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death have been reported in connection with high systemic concentrations of bupivacaine. However, high systemic concentrations are not expected with doses normally used for intrathecal anaesthesia.
13. Bupivacaine should be given with great caution to patients with epilepsy, impaired cardiac conduction, bradycardia, severe shock or digitalis intoxication. Bupivacaine should also be administered with great caution to patients with impaired cardiovascular function as they may be less able to compensate for functional changes associated with the prolongation of AV conduction produced by these drugs. Patients being treated with anti-arrhythmic drugs class III (e.g. amiodarone) should be under close surveillance and ECG monitoring since cardiac effects may be additive.
In patients with Stokes-Adams syndrome or Wolff-Parkinson-White syndrome extreme care should be taken to avoid accidental arterio-venous injection.
14. Bupivacaine should be used with caution in patients with known drug sensitivities.
15. Bupivacaine should be used with caution in patients with genetic predisposition to malignant hyperthermia as the safety of amide local anaesthetic agents in these patients has not been fully established. A standard protocol for the management of malignant hyperthermia should be available.
16. Intrathecal anaesthesia may lead to hypotension and bradycardia. Hypotension should be treated promptly.
17. Hepatic dysfunction, with reversible increases of alanine aminotransferase (ALT), alkaline phosphates (AlkP) and bilirubin, has been observed following repeated injections or long-term infusions of bupivacaine. Association between bupivacaine use and the development of drug-induced liver injury (DILI) has been reported in a small number of literature reports especially with prolonged use. While the pathophysiology of this reaction remains unclear, immediate withdrawal of bupivacaine has shown rapid clinical improvement. If signs of hepatic dysfunction are observed during administration with bupivacaine, the medicinal product should be discontinued.

Use in hepatic impairment.

Bupivacaine is eliminated primarily by hepatic metabolism and changes in hepatic function may have significant consequences. Bupivacaine has an intermediate clearance which depends on its unbound fraction and intrinsic metabolic clearance. Bupivacaine should therefore be used with caution in patients with severe hepatic disease.

Use in renal impairment.

Bupivacaine should be used with caution in patients with severe renal dysfunction because acidosis and reduced plasma protein concentration, which are frequently seen in these patients, may increase the risk of systemic toxicity. Patients with hyperthyroidism are also more susceptible to toxicity with bupivacaine.

Use in the elderly.

Please see Section 4.2 Dose and Method of Administration, Use in debilitated or elderly patients.

Paediatric use.

Caution should be used when administering bupivacaine to children under 12 years of age.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Bupivacaine should be used with caution in patients receiving other local anaesthetics or agents structurally related to amide-type local anaesthetics, since the systemic toxic effects are additive.

Anti-arrhythmic drugs.

Local anaesthetics of the amide type, such as bupivacaine, should be used with caution in patients receiving other local anaesthetics or agents structurally related to amide-type local anaesthetics e.g. certain antiarrhythmic drugs such as mexiletine and lidocaine (lignocaine), since potentiation of cardiac effects may occur. Specific interaction studies with bupivacaine and anti-arrhythmic drugs class III (e.g. amiodarone) have not been performed, but caution should be advised (see Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The effect on fertility has not been determined. There is no evidence from human data that bupivacaine may impair fertility.
(Category A)
The safe use of bupivacaine during pregnancy has not been established. Although bupivacaine has been used extensively for surgical procedures during pregnancy with no reports of ill effects to mother or foetus, there are no adequate and well-controlled studies in pregnant women of the effect of bupivacaine on the developing foetus. It should therefore be used cautiously during pregnancy, other than labour, with the dose being reduced in patients in the late stages of pregnancy.
Bupivacaine has been effectively used for obstetrical analgesia and adverse effects on the course of labour or delivery are rare. After epidural administration of bupivacaine to women in labour, bupivacaine crosses the placental barrier. However, concentrations in umbilical veins are lower than those found in the maternal circulation. It has been suggested that blood glucose levels should be checked in newborns after obstetric regional anaesthesia.
 Bupivacaine passes into breast milk. The amount of bupivacaine appearing in breast milk from a nursing mother receiving parenteral bupivacaine is unlikely to lead to a significant accumulation of the parent drug in the breast-fed infant.
At maternal serum levels of up to 0.45 microgram/mL produced by the epidural use of bupivacaine for vaginal delivery, bupivacaine could not be detected in breast milk during the first 24 hours after delivery (detection limit 0.02 microgram/mL).
The remote possibility of an idiosyncratic or allergic reaction in the breast-fed infant from bupivacaine remains to be determined.

4.7 Effects on Ability to Drive and Use Machines

Depending on the dosage, local anaesthetics may have a mild effect on mental function and coordination and may temporarily impair locomotion and coordination.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions to bupivacaine are similar in nature to those observed with other amide local anaesthetics. These adverse reactions are, in general, dose-related and may result from high plasma levels caused by excessive dosage or rapid absorption, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient.
A rare, though severe, adverse reaction following spinal bupivacaine is extensive (total) spinal blockade. Total spinal blockade will result in cardiovascular and respiratory depression. The cardiovascular depression is caused by an extensive sympathetic blockade which may result in profound hypotension and bradycardia, or even cardiac arrest. Ventilatory depression is caused by blockade of respiratory muscles including the diaphragm.
In view of the low dosage employed, systemic adverse reactions are rarely associated with spinal anaesthesia. The following types are those most commonly reported:

Central nervous system.

CNS manifestations are excitatory and/or depressant and may be characterised by light-headedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred vision, nausea, vomiting, sensations of heat, cold or numbness, urinary retention, paraesthesia, dysaesthesia, twitching, tremors, convulsions, unconsciousness, respiratory depression and/or arrest, agitation, difficulty swallowing and slurred speech.
The excitatory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest. Drowsiness following administration of bupivacaine is usually an early sign of a high blood level of the drug and may occur as a result of rapid absorption. In unconscious patients, circulatory collapse should be watched as CNS effects may not be apparent as an early manifestation of toxicity may in some cases progress to frank convulsions and ultimately lead to respiratory depression and/or arrest. It is crucial to have resuscitative equipment and anticonvulsant drugs available to manage such patients (see Section 4.9 Overdose, Treatment of overdosage).

Cardiovascular.

Cardiovascular manifestations are usually depressant and are characterised by bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest.

Musculoskeletal, connective tissue and bone disorders.

Muscle weakness, back pain.

Haemodynamic.

Regional anaesthesia may lead to maternal hypotension.

Allergic.

Allergic reactions are characterised by cutaneous lesions, urticaria, oedema or anaphylactoid reactions.
Allergy to amide type local anaesthetics is rare. If such a reaction occurs, it should be managed by conventional means.
The detection of sensitivity by skin testing is of doubtful value.

Neurologic.

The incidences of adverse reactions associated with the use of local anaesthetics may be related to the total dose of local anaesthetic administered and are also dependent on the particular drug used, the route of administration and the physical status of the patient.
Adverse effects experienced subsequent to spinal administration of local anaesthetic may include spinal block of varying magnitude (including total spinal block), hypotension secondary to spinal block, loss of bladder and bowel control and loss of perineal sensation and sexual function. Persistent motor, sensory and/or autonomic (sphincter control) deficit of some lower spinal segments with slow recovery (several months) or incomplete recovery have been reported in rare instances. Backache and headache have also been noted following use of this anaesthetic procedure.
Paresis, paraplegia, paralysis, neuropathy and arachnoiditis have been observed.
Pronounced acidosis, hyperkalaemia, hypocalcaemia or hypoxia in the patient may increase the risk and severity of toxic reactions.
The effects of systemic overdose and unintentional intravascular injection may involve the central nervous system and/or the cardiovascular system (see Section 4.9 Overdose). Inadvertent subarachnoid injection of high doses of local anaesthetic may lead to CNS depression, respiratory arrest and cardiovascular collapse.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems (Australia) or https://nzphvc.otago.ac.nz/reporting/ (New Zealand).

4.9 Overdose

Acute emergencies associated with the use of local anaesthetics are generally related to high plasma levels (see Section 4.8 Adverse Effects (Undesirable Effects); Section 4.4 Special Warnings and Precautions for Use). Since the dose required for spinal anaesthesia is so small (20% or less than that required for epidural anaesthesia), acute systemic toxicity is extremely unlikely and has not been reported.
With accidental intravascular injections of local anaesthetics, the toxic effects will be obvious within 1 - 3 minutes. With overdosage, peak plasma concentrations may not be reached for 20 - 30 minutes, depending on the site of injection and toxic signs will be delayed. Toxic reactions mainly involve the central nervous and cardiovascular systems.

Symptoms of acute toxicity.

Central nervous system toxicity is a graded response with symptoms and signs of escalating severity. The first symptoms are circumoral paraesthesia, numbness of the tongue, light-headedness, hyperacusis and tinnitus. Visual disturbances and muscular tremors are more serious and precede the onset of generalised convulsions. These signs must not be mistaken for neurotic behaviour.
Unconsciousness and grand mal convulsions may follow. These may last from a few seconds to several minutes. Hypoxia and hypercapnia occur rapidly following convulsions due to increased muscular activity, together with the interference with normal respiration and loss of the airway. In severe cases, apnoea may occur. Acidosis, hyperkalaemia, hypocalcaemia and hypoxia increase and extend the toxic effects of local anaesthetics.
Recovery is due to redistribution of the local anaesthetic drug from the central nervous system and metabolism. Recovery may be rapid unless large amounts of the drug have been injected.
Cardiovascular toxicity indicates a more severe situation. Hypotension, bradycardia, arrhythmia and even cardiac arrest may occur as a result of high systemic concentrations of local anaesthetics.
Cardiovascular toxic effects are generally preceded by signs of toxicity in the central nervous system, unless the patient is receiving a general anaesthetic or is heavily sedated with drugs such as benzodiazepines or barbiturates.

Treatment of overdosage.

If signs of acute systemic toxicity appear, injection of the local anaesthetic should be immediately stopped.
If convulsions occur, immediate attention is required for the maintenance of patent airway and assisted or controlled ventilation with oxygen, via a positive airway pressure delivery system mask. Adequacy of the circulation should then be evaluated, bearing in mind that drugs used to treat convulsions depress the circulation when administered intravenously.
Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, appropriate anticonvulsant medication such as an ultra-short acting barbiturate (e.g. thiopentone) or a benzodiazepine (e.g. diazepam) may be administered IV. The clinician should be familiar with these anticonvulsant drugs prior to use of local anaesthetics.
Suxamethonium will stop the muscle convulsions rapidly but will require tracheal intubation and controlled ventilation, and should only be used by those familiar with these procedures.
If cardiovascular depression occurs (hypotension, bradycardia), appropriate treatment with intravenous fluids, vasopressor, inotropic agents and/or lipid emulsion should be considered. Children should be given doses commensurate with age and weight.
If ventricular fibrillation or cardiac arrest occurs, effective cardiovascular resuscitation treatment must be instituted and maintained for a prolonged period if necessary. Optimal oxygenation and ventilation, and circulatory support as well as treatment of acidosis are of vital importance.
To counteract the pressor effects of adrenaline, use rapidly acting vasodilators, for instance nitrates or α-blocking agents.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia) or 0800 POISON (0800 764766) (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Bupivacaine, like other local anaesthetics, causes a reversible blockade of impulse propagation along nerve fibres by preventing the inward movement of sodium ions through the nerve membrane. Bupivacaine is classed as a membrane stabilising agent and is a local anaesthetic of the amide type. Local anaesthetics of the amide type are thought to act within the sodium channels of the nerve membrane.
Local anaesthetic drugs may have similar effects on excitable membranes in the brain and myocardium. If excessive amounts of drug reach the systemic circulation rapidly, symptoms and signs of toxicity will appear, emanating mainly from the central nervous system and cardiovascular systems.
Central nervous system toxicity usually precedes the cardiovascular effects as it occurs at lower plasma concentrations. Direct effects of local anaesthetics on the heart include slow conduction, negative inotropism and eventually cardiac arrest.
Indirect cardiovascular effects, e.g. hypotension and bradycardia, may occur after epidural or spinal administration depending on the extent of the concomitant sympathetic block.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Bupivacaine is a long-acting, amide-type local anaesthetic chemically related to lidocaine (lignocaine) and mepivacaine. It is approximately four times as potent as lidocaine (lignocaine). The onset of the blockade is slower than with lidocaine (lignocaine), especially when anaesthetising large nerves.
Bupivacaine has a total plasma clearance of 0.58 L/min, a volume of distribution at steady-state of 73 L, an elimination half-life of 2.7 hours and an intermediate hepatic extraction ratio of 0.40 following experimental IV administration in adults. The terminal elimination half-life is prolonged in the newborn to approximately 8 hours. In children aged over 3 months the elimination half-life is similar to that in adults. Bupivacaine is mainly bound to α1-acid glycoprotein in plasma with a plasma binding of 96%.
Bupivacaine Spinal Heavy BNM has a rapid onset and long duration of action. The duration of analgesia from the hyperbaric solution is between 2 - 3 hours in the T10 - T12 segments.
Bupivacaine Spinal Heavy BNM produces moderate muscle relaxation in the lower extremities lasting 2 - 3 hours. Motor blockade of the abdominal muscles makes the solution suitable for performance of abdominal surgery lasting 45 - 60 minutes. The duration of motor blockade does not exceed the duration of analgesia.
An increase in α1-acid glycoprotein, which occurs postoperatively after major surgery, may cause an increase in the total plasma concentration of bupivacaine. The level of free drug will remain the same. This explains why total plasma concentrations above the apparent toxic threshold level of 2.6 - 3.0 mg/L are apparently well tolerated in this situation.
Following IV administration, bupivacaine is excreted in the urine principally as metabolites with about 6% as unchanged drug. Following epidural administration, the urinary recovery of unchanged bupivacaine is about 0.2%, of pipecolylxylidine about 1% and of 4-hydroxy-bupivacaine about 0.1% of the administered dose.
Various pharmacokinetic parameters can be significantly altered by a number of factors including the presence of hepatic and renal disease, route of administration, age of the patient and certain concomitant medication.

5.3 Preclinical Safety Data

Genotoxicity.

Mutagenic potential has not been determined. There is no evidence from human data that bupivacaine may be mutagenic.

Carcinogenicity.

Long-term studies in animals of most local anaesthetics, including bupivacaine, to evaluate the carcinogenic potential have not been conducted. There is no evidence from human data that bupivacaine may be carcinogenic.

6 Pharmaceutical Particulars

6.1 List of Excipients

Bupivacaine Spinal Heavy BNM contains glucose (8% w/v), sodium hydroxide and water for injections.

6.2 Incompatibilities

Local anaesthetics react with certain metals and cause the release of their respective ions which, if injected, may cause severe local irritation. Adequate precautions should be taken to avoid prolonged contact between Bupivacaine Spinal Heavy BNM and metal surfaces such as metal bowls, cannulae and syringes with metal parts.

6.3 Shelf Life

3 years.
Solutions showing discolouration and unused portions of solutions should be discarded. The solution should be used immediately after opening the ampoule. Bupivacaine Spinal Heavy BNM solutions contain no antimicrobial agent and should be used only once and any residue discarded.
Autoclaving causes decomposition of glucose which may result in a decreased duration of anaesthesia of the hyperbaric solution. It is advisable not to re-autoclave ampoules of Bupivacaine Spinal Heavy BNM.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

4 mL glass ampoule in a sterile pack, in packs of 10.

6.6 Special Precautions for Disposal

Any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

The chemical name for bupivacaine hydrochloride monohydrate is (2RS)-1-Butyl-N-(2,6-dimethylphenyl) piperidine-2-carboxamide hydrochloride monohydrate.
Bupivacaine has a pKa of 8.1 and is more lipid soluble than lidocaine (lignocaine).

Chemical structure.


CAS number.

The CAS number for bupivacaine hydrochloride monohydrate is 73360-54-0.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes