Consumer medicine information

Bupivacaine-Claris

Bupivacaine hydrochloride

BRAND INFORMATION

Brand name

Bupivacaine-Baxter

Active ingredient

Bupivacaine hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Bupivacaine-Claris.

What is in this leaflet

This leaflet answers some of the common questions people ask about Bupivacaine-Claris. It does not contain all the information that is known about Bupivacaine-Claris. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor will have weighed the risks of you taking Bupivacaine-Claris against the benefits they expect it will have for you.

This medicine is likely to be used while you are at the clinic or in hospital. If possible, please read this leaflet carefully before this medicine is given to you. In some cases this leaflet may be given to you after the medicine has been used.

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

Keep this leaflet. You may need to read it again.

What Bupivacaine-Claris is used for

Bupivacaine-Claris is used to prevent or relieve pain, but it will not put you to sleep.

Bupivacaine-Claris is also used after surgery to relieve pain. It can also be used to make childbirth less painful.

Bupivacaine-Claris belongs to a group of medicines called local anaesthetics.

When injected, it makes the nerves nearby unable to pass messages to the brain and will therefore prevent or relieve pain.

Depending on the amount used, Bupivacaine-Claris 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-Claris 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.

Your doctor may prescribe this medicine for uses other than those listed above. Ask your doctor if you want more information.

Bupivacaine-Claris is not addictive

Before you are given it

When you must not be given it:

Ask your doctor about the risks and benefits of being given Bupivacaine-Claris while you are pregnant or breastfeeding. 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 baby can take in very small amounts of Bupivacaine-Claris from breast milk if you are breastfeeding, but it is unlikely that the amount available to the baby will do any harm.

Bupivacaine-Claris 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. It may have no effect at all, or worse, an entirely unexpected effect if you are given Bupivacaine-Claris after the expiry date.

Before you are given it

You must tell your doctor if:

  1. you have any allergies to
  • any ingredients listed at the end of this leaflet
  • other local anaesthetics e.g. lignocaine
  • any other substances
If you have an allergic reaction, you may get a skin rash, hayfever, have difficulty breathing or feel faint.
  1. you have any of these medical conditions:
  • problems with your blood pressure or circulation
  • blood poisoning
  • problems with the clotting of your blood
  • acidosis, or too much acid in the blood.
  • epilepsy
  • nerve problems
  • heart, liver or kidney problems
  • disease of the brain or spine
  • thyrotoxicosis
  • diabetes
  • muscle disease or weakness (e.g. myasthenia gravis)
It may not be safe for you to take Bupivacaine-Claris if you have any of these conditions.

Taking other medicines

Tell your doctor if you are taking any other medicines, including

  • medicines that control your heart beat
  • medicines used to thin the blood, including aspirin
  • low molecular weight heparin or other medicines used to prevent blood clots
  • medicines for depression
  • medicines that you buy at the chemist, supermarket or health food shop.

These medicines may affect the way Bupivacaine-Claris works.

Your doctor or pharmacist can tell you what to do if you are taking any of these medicines.

If you have not told your doctor about any of these things, tell them before you are given any Bupivacaine-Claris

How Bupivacaine-Claris is given

Bupivacaine-Claris will be injected by your doctor into the skin, near a single nerve, or into an area which contains a large number of nerves. This will result in an area of numbness at the site of injection, near the site of injection or in an area that may seem unrelated to the site of injection. The last will be the case if you are given an EPIDURAL injection (an injection around the spinal cord) which will result in a feeling of numbness in your lower body.

If you are receiving an EPIDURAL INFUSION it will be injected by your doctor into the epidural space, near your spinal cord, through a space between vertebrae in your lower back. A thin tube will be inserted so a continuous dose can be given over a period of time.

Bupivacaine-Claris should not be injected directly into the blood.

The dosage you will be given will depend on your body size, age and the type of pain relief required.

Your doctor will have had a lot of experience injecting Bupivacaine-Claris or other local anaesthetics and will choose the best dose for you. They will be willing to discuss this decision with you.

Overdose

The doctor giving you Bupivacaine-Claris will be experienced in the use of local anaesthetics, so it is unlikely that you will be given an overdose. However, if you are particularly sensitive to Bupivacaine-Claris, or the dose is accidentally injected directly into your blood, you may develop problems for a short time with your sight or hearing. You may get a numb feeling in or around the mouth, feel dizzy or stiff, or have twitchy muscles.

Whenever you are given Bupivacaine-Claris, equipment will be available to revive you if an overdose happens.

While you are being given Bupivacaine-Claris

Things to be careful of

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

Do not drink alcohol while you are being given Bupivacaine-Claris. If you drink alcohol while you are being given Bupivacaine-Claris 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.

Side Effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are being given Bupivacaine-Claris.

Bupivacaine-Claris will help relieve pain in most people, but it may have unwanted side-effects.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment 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 immediately if you notice any of the following:

  • nervousness
  • dizziness
  • blurred vision
  • a tingling feeling ("pins and needles")
  • ringing in the ears
  • numbness
  • feeling strange (disoriented)
  • nausea (feeling sick), vomiting

These are all mild side effects of Bupivacaine-Claris.

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

If Bupivacaine-Claris is given wrongly, or you are very sensitive to it, it sometimes causes

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

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

Some people may get other side effects while being given Bupivacaine-Claris. Tell your doctor if you notice anything that is making you feel unwell.

After using Bupivacaine-Claris

Storage

Bupivacaine-Claris will be stored by your doctor or pharmacist under the recommended conditions. Bupivacaine-Claris should be kept in a cool dry place where the temperature stays below 30 °C.

Any Bupivacaine-Claris which is not used, and which is left in the container, will be disposed of in a safe manner by your doctor or pharmacist.

Product Description

Bupivacaine-Claris is a clear colourless solution. It is available as:

50 mg/20 mL, glass vial, packs of 1 and 5 vials AUST R 223236
50 mg/10 mL, glass vial, packs of 5 and 10 vials AUST R 223237
100 mg/20 mL, glass vial, packs of 1 and 5 vials AUST R 223238

Ingredients

Bupivacaine-Claris contains bupivacaine hydrochloride 0.25% and 0.5% as the active ingredient. It also contains sodium chloride, sodium hydroxide and/or hydrochloric acid to adjust the pH and water for injections.

Sponsor

Australia
Claris Lifesciences (Australia) Pty Ltd
Suite 1, Level 1,
127-133 Burwood Road
Burwood
NSW 2134

Date of Preparation

28 July 2016

Published by MIMS August 2017

BRAND INFORMATION

Brand name

Bupivacaine-Baxter

Active ingredient

Bupivacaine hydrochloride

Schedule

S4

 

1 Name of Medicine

Bupivacaine hydrochloride (as monohydrate).

2 Qualitative and Quantitative Composition

Bupivacaine hydrochloride (as monohydrate) 2.5 mg/mL or 5 mg/mL, solution for injection.
Bupivacaine-Baxter is a clear, colourless, sterile, isotonic, preservative-free solution containing bupivacaine hydrochloride (as monohydrate) 2.5 or 5 mg/mL.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Bupivacaine-Baxter is indicated for the production of local or regional anaesthesia and analgesia in individuals as follows.

Surgical anaesthesia.

Epidural block for surgery.
Field block (minor and major nerve blocks and infiltration).

Analgesia.

Continuous epidural infusion or intermittent bolus epidural administration for analgesia in postoperative pain or labour pain.
Field block (minor nerve block and infiltration).
The choice of 2 strengths, 0.25% and 0.5%, makes it possible to vary the degree of motor blockade.

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. The volume of the drug used will affect the extent of spread of anaesthesia.
The presentations of Bupivacaine-Baxter are intended for single use only. Any solution remaining from an opened container should be discarded.
Tables 1 and 2 are a guide to dosage. The clinician's experience and knowledge of the patient's physical status are of importance in deciding the dose. Experience to date indicates that 400 mg administered over 24 hours is well tolerated in average adults.
The normal recommended dose of plain bupivacaine injections for various anaesthetic procedures in the average, healthy 70 kg adult patient are as follows.

Notes.

Recommended doses.

Tolerability varies widely between patients and toxic effects may occur after any local anaesthetic procedure. Careful observation of the patient must therefore be maintained. It is recommended that the dose of bupivacaine at any time should not exceed 2 mg/kg. However, the dose administered must be tailored to the individual patient and procedure, and the maximum dose quoted here should be used as a guide only.

Injection.

Injection of repeated doses of bupivacaine may cause significant increase in blood levels with each repeated dose, due to accumulation of the drug or its metabolites, or due to slow metabolic degradation.
The rapid injection of a large volume of local anaesthetic solution should be avoided and fractional doses should be used when feasible. For most indications the duration of bupivacaine is such that a single dose is sufficient.

Hypotension.

During thoracic, lumbar and caudal epidural anaesthesia, a marked fall in blood pressure and/or intercostal paralysis may occur, possibly due to the use of excessive doses, improper positioning of the patient or accidental disposition of the anaesthetic within the subarachnoid space. Hypotension and bradycardia may occur as a result of sympathetic blockade.

Test dose.

For epidural anaesthesia, a 3 to 5 mL test dose of local anaesthetic solution, preferably containing up to 15 microgram adrenaline, should be administered. Verbal contact and repeated monitoring of the heart rate and blood pressure should be maintained for 5 minutes after the test dose after which, in the absence of signs of subarachnoid or intravascular injection, the main dose may be given.
Use of a test dose containing adrenaline may have further advantages in that an intravascular injection of adrenaline will be quickly recognised by an increase in heart rate, usually within about 40 seconds. To detect this, the heart rate and rhythm should be monitored with an electrocardiogram.
An accidental intrathecal injection may be recognised by signs of a spinal block.
Before administration of the total dose, aspiration should be repeated. The main dose should be injected slowly at a rate of 25 to 50 mg/min, while closely observing the patient's vital functions and maintaining verbal contact. If toxic symptoms or signs occur, the injection should be stopped immediately.

Prolonged blocks.

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.
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 solutions and metal surfaces, such as metal bowls, cannulae and syringes with metal parts.
Solutions showing discolouration and unused portions of solutions from vials should be discarded.

Use in children.

Experience with bupivacaine in children under the age of 12 is limited. The dosage in children should be calculated on a weight basis up to 2 mg/kg.

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.

Debilitated or elderly patients, including those with partial or complete heart block, advanced liver disease or severe renal dysfunction should be given a reduced dosage commensurate with their physical condition (see Section 4.4 Special Warnings and Precautions for Use).

4.3 Contraindications

1. Known hypersensitivity to local anaesthetics of the amide type. Detection of suspected hypersensitivity by skin testing is of limited value.
2. Local anaesthetic techniques must not be used when there is infection in the region of the proposed injection and/or in the presence of septicaemia.
3. Obstetrical paracervical block, intravenous regional anaesthesia (Bier's block) and all intravenous infusions.
4. Epidural and spinal anaesthesia in patients with uncorrected hypotension.
5. General contraindications related to epidural anaesthesia, regardless of the local anaesthetic used, should be taken into account.

4.4 Special Warnings and Precautions for Use

1. During administration of bupivacaine, it is mandatory to have emergency resuscitative equipment (including oxygen) and drugs immediately available 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 form any cause and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and death.
The safety and effectiveness of bupivacaine depend upon proper dosage, correct technique and adequate precautions. Standard textbooks should be consulted for specific techniques and precautions for various regional anaesthetic procedures.
2. Injections should always be made slowly with frequent aspirations to avoid inadvertent intravascular injection which can produce toxic effects (see Section 4.2 Dose and Method of Administration, Test dose).
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 CNS toxicity.
4. The use of local anaesthetics for major peripheral nerve block may involve the administration of large volumes in highly vascularised areas, often close to large blood vessels. As such there is an increased risk of intravascular injection and/or systemic absorption which can lead to high plasma concentrations. There have been reports of cardiac arrest or death during the use of bupivacaine for epidural anaesthesia or peripheral nerve blockade. In some instances, resuscitation has been difficult or impossible despite apparently adequate preparation and management.
5. Central nerve blocks may cause cardiovascular depression, especially in the presence of hypovolaemia. Epidural anaesthesia should be used with caution in patients with impaired cardiovascular function. Epidural anaesthesia may lead to hypotension and bradycardia.
6. Low molecular weight heparins and heparinoids (spinal/ epidural haematomas) - when neuraxial anaesthesia (epidural/ spinal anaesthesia) is employed, patients anticoagulated or scheduled to be anticoagulated with low molecular weight heparins or heparinoids are at risk of developing an epidural or spinal haematoma which can result in long-term or permanent paralysis. The risk of these events is increased by the use of indwelling epidural catheters, traumatic or repeated epidural/ spinal puncture, and the concomitant use of drugs affecting haemostasis such as NSAID, platelet inhibitors or other anticoagulants. Patients should be frequently monitored for signs and symptoms of neurological impairment.
7. The lowest dosage that results in effective anaesthesia should be used (see Section 4.2 Dose and Method of Administration). Repeated injection of Bupivacaine-Baxter 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.
Caution should be used when administering bupivacaine to children under 12 years of age.
8. 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.
9. Bupivacaine should be given with caution to patients with epilepsy, impaired cardiac conduction, bradycardia, severe shock or digitalis intoxication. It should also be administered with caution to patients with impaired cardiovascular function as they may be less able to compensate for functional changes associated with the prolongation of A-V conduction produced by bupivacaine. Patients being treated with antiarrhythmic drugs class III (e.g. amiodarone) should be under close surveillance and ECG monitoring since cardiac effects.
In patients with Stokes-Adams syndrome or Wolff-Parkinson-White syndrome extreme care should be taken to avoid accidental arteriovenous injection.
10. Local anaesthetics should be given with great caution (if at all) to patients with pre-existing neurological or neuromuscular disease e.g. myasthenia gravis. Use with extreme caution in epidural, caudal and 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.
11. Patients with hyperthyroidism are also more susceptible to toxicity with bupivacaine.
12. Inadvertent intravascular or subarachnoid injection of small doses of local anaesthetics injected into the head and neck area, including retrobulbar, dental and stellate ganglion blocks, may produce adverse reactions similar to systemic toxicity seen with unintentional intravascular injections of larger doses. Injections made inadvertently into an artery may cause immediate cerebral symptoms even at low doses.
Clinicians who perform retrobulbar blocks should be aware that there have been reports of cardiovascular collapse and apnoea following the use of local anaesthetic injections for retrobulbar block. Prior to retrobulbar block, necessary equipment, drugs and personnel should be immediately available as with all other regional procedures. Retrobulbar injections may very occasionally reach the subarachnoid space, causing temporary blindness, cardiovascular collapse, apnoea, convulsions, etc. These must be diagnosed and treated promptly.
Retro- and peribulbar injections carry a low risk of persistent ocular muscle dysfunction. The primary causes include trauma and/or local toxic effects on muscles 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.
13. Foetal bradycardia/ tachycardia frequently follows paracervical block with some amide type local anaesthetics and may be associated with foetal acidosis and hypoxia. Added risk appears to be present in prematurity, toxaemia of pregnancy, and foetal distress. Careful monitoring of the foetal heart rate is necessary (see Section 4.3 Contraindications).
14. Bupivacaine should be used with caution in patients with known drug sensitivities.

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.

Use in the elderly.

See Section 4.2, Use in debilitated or elderly patients.

Paediatric use.

See Section 4.2, Use in children.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Antiarrhythmic 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 lignocaine, since potentiation of cardiac effects may occur. Specific interaction studies with bupivacaine and antiarrhythmic 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.

Effects on fertility have not been determined.
(Category A)
It should be noted that the dose should be reduced in patients in the late stages of pregnancy.
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.
Bupivacaine has been effectively used for obstetrical analgesia and adverse effects on the course of labour or delivery are rare. It has been suggested that blood glucose levels should be checked in newborns after obstetric regional anaesthesia.
Foetal adverse effects due to bupivacaine, such as foetal bradycardia, seem to be most apparent in paracervical block anaesthesia. Such effects may be due to high concentrations of anaesthetic reaching the foetus (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).
The safe use of bupivacaine during pregnancy, other than labour, has not been established. It is known that local anaesthetics cross the placenta rapidly. 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.
 Bupivacaine passes into breast milk. The amount of bupivacaine appearing in breast milk from a breastfeeding mother receiving parenteral bupivacaine is unlikely to lead to a significant accumulation of the parent drug in the breastfed 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 possibility of an idiosyncratic or allergic reaction in the breastfed 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 rare in the absence of overdosage, exceptionally rapid absorption or inadvertent intravascular injection. These adverse reactions are similar in character to those observed with other amide type local anaesthetics and pertain mainly to the central nervous system and the cardiovascular system. Adverse reactions to bupivacaine are, in general, dose related and may result from high plasma levels caused by excessive dosage, rapid absorption, delayed elimination, altered metabolism, inadvertent intravascular injection or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient.
Serious adverse experiences are generally systemic in nature. Ventricular arrhythmias, ventricular fibrillation, sudden cardiovascular collapse and death have been reported when bupivacaine has been utilised for local anaesthetic procedures that may result in high systemic concentrations of bupivacaine (see Section 4.4 Special Warnings and Precautions for Use).
Pronounced acidosis, hyperkalaemia, hypocalcaemia or hypoxia in the patient may increase the risk and severity of toxic reactions.

Central nervous system.

CNS manifestations are excitatory and/or depressant and may be characterised by lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred vision, diplopia, nausea, vomiting, sensations of heat, cold or numbness, urinary retention, paraesthesia circumoral, paraesthesia, hyperacusis, twitching, tremors, convulsions, unconsciousness, respiratory depression and/or arrest, agitation, numbness of the tongue, 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).

Cardiovascular.

Cardiovascular manifestations following inadvertent intravascular injection are usually depressant and are characterised by bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest (see Section 4.9 Overdose).

Haemodynamic.

Regional anaesthesia may lead to maternal hypotension.

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.
In the practice of caudal or lumbar epidural block, occasional unintentional penetration of the subarachnoid space by the catheter may occur. Subsequent adverse effects may depend partially on the amount of drug administered subdurally.
These 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 when caudal or lumbar epidural block has been attempted. Backache and headache have also been noted following use of these anaesthetic procedures.
Paresis, paraplegia, neuropathy, peripheral nerve injury and arachnoiditis have been observed.
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 may lead to CNS depression, respiratory arrest and cardiovascular collapse.

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.

Musculoskeletal.

Although intra-articular continuous infusions of local anaesthetics following arthroscopic and other surgical procedures is an unapproved use, there have been postmarketing reports of chondrolysis in patients receiving such infusions. Symptoms include joint pain, stiffness and loss of motion.
Currently, there is no effective treatment for chondrolysis. Patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement. Therefore, bupivacaine should not be used for postoperative intra-articular continuous infusion.

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 www.tga.gov.au/reporting-problems.

4.9 Overdose

Acute emergencies associated with the use of local anaesthetics are generally related to high plasma levels, or to unintended subarachnoid injection of the local anaesthetic solution (see Section 4.8 Adverse Effects (Undesirable Effects); Section 4.4 Special Warnings and Precautions for Use).
With accidental intravascular injections of local anaesthetics, the toxic effects will be obvious within 1 to 3 minutes. With overdosage, peak plasma concentrations may not be reached for 20 to 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, lightheadedness, 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.
Signs of cardiovascular toxicity indicate a more severe situation. Hypotension, bradycardia, decreased cardiac output, heart block, arrhythmia and even ventricular arrhythmias, ventricular fibrillation and 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 then 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 ultrashort 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 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.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

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. 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 the cardiovascular system.
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 lignocaine and mepivacaine. Its potency and toxicity is approximately four times that of lignocaine.
In concentrations of 5 mg/mL it has a long duration of action, from 2-5 hours following a single epidural injection and up to 12 hours after peripheral nerve blocks. The onset of the blockade is slower than with lignocaine, especially when anaesthetising large nerves.
When used in low concentrations (2.5 mg/mL or less) there is less effect on motor nerve fibres and the duration of action is shorter. Low concentrations may, however, be used with advantage for prolonged pain relief, e.g. in labour or postoperatively.
The plasma concentration of bupivacaine depends upon the dose, the route of administration and the vascularity of the injection site. The addition of a vasoconstrictor such as adrenaline may decrease the rate of absorption and prolong the duration of action.

Absorption.

Following injection of bupivacaine solutions for caudal, epidural or peripheral nerve block, peak plasma levels of bupivacaine are reached within 30 to 45 minutes and decline to insignificant concentrations during the next 3 to 6 hours. Intercostal blocks give the highest peak plasma concentration due to rapid absorption (maximum plasma concentrations in the order of 1-4 mg/L after a 400 mg dose), while subcutaneous abdominal injections give the lowest plasma concentrations. Epidural and major plexus blocks are intermediate. In children rapid absorption (plasma concentrations are in the order of 1-1.5 mg/L after a dose of 3 mg/kg) is seen with caudal block. Absorption may be slowed by the addition of adrenaline.

Distribution.

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 (range 1.5-5.5 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 (range 8.1-14.0 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%.
Absorption of bupivacaine from the epidural space occurs in 2 phases; the first phase is in the order of 7 minutes and the second is in 6 hours. The slow absorption is rate limiting in the elimination of bupivacaine, which explains why the apparent elimination half-life after epidural administration is longer than after intravenous administration.
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.

Metabolism.

Bupivacaine is eliminated primarily by hepatic metabolism (see Section 4.4, Use in hepatic impairment).

Excretion.

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 (PPX) 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, presence or absence of adrenaline in the solution and certain concomitant medication.

5.3 Preclinical Safety Data

Genotoxicity.

Formal studies of mutagenic potential have not been carried out.

Carcinogenicity.

Long-term studies in animals of most local anaesthetics, including bupivacaine, to evaluate the carcinogenic potential have not been conducted.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium chloride, sodium hydroxide and/or hydrochloric acid as pH adjusters and water for injections.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.
Bupivacaine-Baxter does not contain any anti-microbial agent. Bupivacaine-Baxter is for single use in one patient only.

6.5 Nature and Contents of Container

Bupivacaine-Baxter, solution for injection, is available as:
50 mg/20 mL. Glass vial. Packs of 1 and 5 vials. AUST R 223236.
50 mg/10 mL. Glass vial. Packs of 5 and 10 vials. AUST R 223237.
100 mg/20 mL. Glass vial. Packs of 1 and 5 vials. AUST R 223238.

6.6 Special Precautions for Disposal

Discard any unused solution.
In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

The chemical name of 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 lignocaine.
Bupivacaine hydrochloride monohydrate is a white, crystalline powder or colourless crystals that are soluble in water, freely soluble in alcohol and slightly soluble in chloroform and ether.
The empirical formula is C18H28N2O.HCl.H2O.
The molecular weight is 342.9.

Chemical structure.


CAS number.

The CAS number is 14252-80-3.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes