Drugs List

Therapeutic Indications

Uses

Surgical anaesthesia in adults

Major - such as epidural (including caesarean section), intrathecal, and peripheral nerve block.

Minor - such as local infiltration, peribulbar block in ophthalmic surgery.

Pain management in adults

Management of pain, especially post-operative or labour analgesia.

Children

Analgesia for ilioinguinal/iliohypogastric blocks in children.

Administration

For epidural injection or infusion, or intrathecal, peripheral nerve, or peribulbar injection in adults.

For ilioinguinal/iliohypogastric injection in children.

Before infusion, careful aspiration is recommended to prevent intravascular injection.

Epidural administration
Concentrated solutions (0.5 - 0.75%) should be administered in incremental doses of 3 - 5ml. Sufficient time should be allowed between doses to detect toxic symptoms resulting from accidental intravascular or intrathecal injection.
When a large dose is to be injected, e.g. in epidural block, a test dose of 3-5ml lidocaine with
adrenaline is recommended. An inadvertent intravascular injection may then be recognised by a temporary increase in heart rate and accidental intrathecal injection by signs of a spinal block.
Aspiration should be repeated before and during administration of each injection in continuous catheter techniques. An intravascular injection is still possible despite negative aspirations for blood. During administration of epidural anaesthesia, a test dose should be administered and effects monitored before the full dose is given.

Major regional nerve blocks
Intravenous fluids should be run via an indwelling catheter to assure a functioning intravenous pathway. The lowest effective dose should be used to avoid high plasma concentrations and serious adverse effects.
A rapid injection of a large volume should be avoided and incremental doses should be administered when feasible.

Use in head and neck area
Small doses into the head or neck area, including retrobulbar, dental and stellate ganglion blocks, can cause adverse reactions similar to those seen following accidental intravascular injection.
Reactions may be caused by intra-arterial injection with retrograde flow to the cerebral circulation. They may also be due to the puncture of the dural sheath of the optic nerve during retrobulbar block, with diffusion of the solution along the subdural space to the midbrain.
Patients receiving these blocks should be constantly observed and circulatory and respiratory function should be monitored.

Reconstitution

Inspect the solution visually prior to use. Only use clear solutions without visible particles.

Diluted product should be used immediately but chemical and physical stability has been demonstrated for 7 days at 20-22 degrees C.

Compatibilities

Incompatibilities

Levobupivacaine may precipitate from alkaline solutions. In particular, it must not be diluted or administered with sodium bicarbonate injections or infusions.

Contraindications

The general contraindications to regional anaesthesia should be respected.

Hypersensitivity to local anaesthetics of the amide type

Severe hypotension such as cardiogenic or hypovolaemic shock

Complete heart block

Intravenous regional anaesthesia (Bier's block).

Paracervical block in obstetrics

Precautions and Warnings

Levobupivacaine should be administered in well-equipped facilities. Administration should be by individuals who are trained/experienced in the required anaesthetic technique and who are able to diagnose/treat any adverse effects that may arise.

To avoid excessive dosage in obese patients, dose may need to be calculated on ideal bodyweight.

Use with caution in patients with the following conditions:
Central nervous system disorders
Impaired cardiovascular function, (e.g. cardiac arrhythmias and conduction defects)
Bradycardia
Respiratory impairment
Myasthenia gravis
Epilepsy

Epidural administration may cause hypotension and bradycardia, therefore all patients must have intravenous access established. Appropriate fluids, vasopressors, anaesthetics with anticonvulsant properties, myorelaxants, atropine, and resuscitation equipment must be immediately available.

Before infusion, careful aspiration is recommended to prevent intravascular injection. It is recommended that a test dose is given and effects monitored before the full dose is administered.

Reduced doses should be administered in elderly, debilitated or acutely ill patients depending on their physical status. These patients should be treated with caution.

Patients with existing central nervous system diseases receiving intrathecal or epidural injections/infusions may experience an exacerbation of their condition. Clinical judgement is required when considering epidural or intrathecal administration to these patients.

Small doses into the head or neck area, including retrobulbar, dental and stellate ganglion blocks, can cause adverse reactions similar to those seen following accidental intravascular injection.
Patients receiving these blocks should be constantly observed and circulatory and respiratory function should be monitored.

As levobupivacaine is metabolised in the liver it should be used with caution in patients with hepatic impairment or with reduced hepatic blood flow (e.g. alcoholics or patients with cirrhosis).

Pregnancy - see Pregnancy section

Levobupivacaine may have a major effect on a patients ability to drive and operate machinery. Patients should be warned not to attempt such tasks until all of the effects of anaesthesia and/or surgery have ceased.

Product contains 3.6mg/ml sodium which should be taken into consideration in patients on a controlled sodium diet.

Pregnancy and Lactation

Pregnancy

There is no clinical data on patients exposed to levobupivacaine during the first-trimester of pregnancy.

Animal studies do not indicate teratogenic effects but have shown embryo-foetal toxicity at systemic exposure levels similar to those obtained in clinical use. The potential risk for humans is unknown. Levobupivacaine should therefore not be given during early pregnancy unless clearly necessary.

Clinical experience with bupivacaine during obstetric surgery is extensive and has not demonstrated any foetotoxic effects. Large doses during delivery can cause neonatal respiratory depression, hypotonia and bradycardia after epidural block.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Licensed in pregnancy? - Yes as epidural in labour

Recommended for use in pregnancy? - Not during first or second trimester

Animal data - Studies in rats do not indicate teratogenic effects but have shown embryo-foetal toxicity

Lactation

Breastfeeding may resume following administration of levobupivacaine.

It is not known if levobupivacaine is excreted in human breast milk. However, levobupivacaine is likely to be poorly transmitted into breast milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - likely to be poorly transmitted into breast milk.

Considered suitable or recommended by manufacturer? - Yes

Drug substance licensed in infants? - No

Side Effects

Hypotension
Nausea
Anaemia
Vomiting
Dizziness
Headache
Pyrexia
Back pain
Allergic reaction
Anaphylaxis
Hypersensitivity reactions
Convulsions
Unconsciousness
Somnolence
Syncope
Paraesthesia
Paraplegia
Blurred vision
Atrioventricular block
Cardiac arrest
Ventricular tachyarrhythmias
Tachycardia
Bradycardia
Respiratory arrest
Laryngeal oedema
Apnoea
Sneezing
Oral hypoaesthesia
Loss of sphincter control
Angioneurotic oedema
Urticaria
Pruritus
Hyperhidrosis
Erythema
Muscle twitch
Muscle weakness
Decreased cardiac output
ECG changes
Neurological damage
Paralysis
Ptosis
Miosis
Enophthalmos
Flushing
Anhidrosis
Priapism
Bladder dysfunction

Presentation

Solution for injection or concentrate for solution for infusion containing 25mg/10ml levobupivacaine (as levobupivacaine hydrochloride)

Solution for injection or concentrate for solution for infusion containing 50mg/10ml levobupivacaine (as levobupivacaine hydrochloride)

Drugs List

Therapeutic Indications

Uses

Surgical anaesthesia in adults

Major - such as epidural (including caesarean section), intrathecal, and peripheral nerve block.

Minor - such as local infiltration, peribulbar block in ophthalmic surgery.

Pain management in adults

Management of pain, especially post-operative or labour analgesia.

Children

Analgesia for ilioinguinal/iliohypogastric blocks in children.

Dosage

Levobupivacaine should be administered in well-equipped facilities. Administration should be by individuals who are trained/experienced in the required anaesthetic technique and who are able to diagnose/treat any adverse effects that may arise.

For analgesia (e.g. epidural administration for pain management), the lower concentrations and doses are recommended. Where profound or prolonged anaesthesia is required with dense motor block (e.g. epidural or peribulbar block), the higher concentrations may be used.

The maximum dosage must be determined by evaluating the size and physical status of the patient, together with the concentration of the agent and the area and route of administration. Individual variation in onset and duration of block does occur. Experience from clinical studies shows onset of sensory block adequate for surgery in 10-15 minutes following epidural administration, with a time to regression in the range of 6-9 hours.
The recommended maximum single dose is 150mg. Where sustained motor and sensory block are required for a prolonged procedure, additional doses may be required. The maximum recommended dose during a 24-hour period is 400mg. For post-operative pain management, the dose should not exceed 18.75mg/hour.

The licensed doses stated may not be appropriate in some settings and expert advice should be sought

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For epidural injection or infusion, or intrathecal, peripheral nerve, or peribulbar injection in adults.

For ilioinguinal/iliohypogastric injection in children.

Before infusion, careful aspiration is recommended to prevent intravascular injection.

Epidural administration
Concentrated solutions (0.5 - 0.75%) should be administered in incremental doses of 3 - 5ml. Sufficient time should be allowed between doses to detect toxic symptoms resulting from accidental intravascular or intrathecal injection.
When a large dose is to be injected, e.g. in epidural block, a test dose of 3-5ml lidocaine with
adrenaline is recommended. An inadvertent intravascular injection may then be recognised by a temporary increase in heart rate and accidental intrathecal injection by signs of a spinal block.
Aspiration should be repeated before and during administration of each injection in continuous catheter techniques. An intravascular injection is still possible despite negative aspirations for blood. During administration of epidural anaesthesia, a test dose should be administered and effects monitored before the full dose is given.

Major regional nerve blocks
Intravenous fluids should be run via an indwelling catheter to assure a functioning intravenous pathway. The lowest effective dose should be used to avoid high plasma concentrations and serious adverse effects.
A rapid injection of a large volume should be avoided and incremental doses should be administered when feasible.

Use in head and neck area
Small doses into the head or neck area, including retrobulbar, dental and stellate ganglion blocks, can cause adverse reactions similar to those seen following accidental intravascular injection.
Reactions may be caused by intra-arterial injection with retrograde flow to the cerebral circulation. They may also be due to the puncture of the dural sheath of the optic nerve during retrobulbar block, with diffusion of the solution along the subdural space to the midbrain.
Patients receiving these blocks should be constantly observed and circulatory and respiratory function should be monitored.

Reconstitution

Inspect the solution visually prior to use. Only use clear solutions without visible particles.

Diluted product should be used immediately but chemical and physical stability has been demonstrated for 7 days at 20-22 degrees C.

Compatibilities

Incompatibilities

Levobupivacaine may precipitate from alkaline solutions. In particular, it must not be diluted or administered with sodium bicarbonate injections or infusions.

Contraindications

The general contraindications to regional anaesthesia should be respected.

Hypersensitivity to local anaesthetics of the amide type

Severe hypotension such as cardiogenic or hypovolaemic shock

Complete heart block

Intravenous regional anaesthesia (Bier's block).

Paracervical block in obstetrics

Precautions and Warnings

Levobupivacaine should be administered in well-equipped facilities. Administration should be by individuals who are trained/experienced in the required anaesthetic technique and who are able to diagnose/treat any adverse effects that may arise.

To avoid excessive dosage in obese patients, dose may need to be calculated on ideal bodyweight.

Use with caution in patients with the following conditions:
Central nervous system disorders
Impaired cardiovascular function, (e.g. cardiac arrhythmias and conduction defects)
Bradycardia
Respiratory impairment
Myasthenia gravis
Epilepsy

Epidural administration may cause hypotension and bradycardia, therefore all patients must have intravenous access established. Appropriate fluids, vasopressors, anaesthetics with anticonvulsant properties, myorelaxants, atropine, and resuscitation equipment must be immediately available.

Before infusion, careful aspiration is recommended to prevent intravascular injection. It is recommended that a test dose is given and effects monitored before the full dose is administered.

Reduced doses should be administered in elderly, debilitated or acutely ill patients depending on their physical status. These patients should be treated with caution.

Patients with existing central nervous system diseases receiving intrathecal or epidural injections/infusions may experience an exacerbation of their condition. Clinical judgement is required when considering epidural or intrathecal administration to these patients.

Small doses into the head or neck area, including retrobulbar, dental and stellate ganglion blocks, can cause adverse reactions similar to those seen following accidental intravascular injection.
Patients receiving these blocks should be constantly observed and circulatory and respiratory function should be monitored.

As levobupivacaine is metabolised in the liver it should be used with caution in patients with hepatic impairment or with reduced hepatic blood flow (e.g. alcoholics or patients with cirrhosis).

Pregnancy - see Pregnancy section

Levobupivacaine may have a major effect on a patients ability to drive and operate machinery. Patients should be warned not to attempt such tasks until all of the effects of anaesthesia and/or surgery have ceased.

Product contains 3.6mg/ml sodium which should be taken into consideration in patients on a controlled sodium diet.

Pregnancy and Lactation

Pregnancy

There is no clinical data on patients exposed to levobupivacaine during the first-trimester of pregnancy.

Animal studies do not indicate teratogenic effects but have shown embryo-foetal toxicity at systemic exposure levels similar to those obtained in clinical use. The potential risk for humans is unknown. Levobupivacaine should therefore not be given during early pregnancy unless clearly necessary.

Clinical experience with bupivacaine during obstetric surgery is extensive and has not demonstrated any foetotoxic effects. Large doses during delivery can cause neonatal respiratory depression, hypotonia and bradycardia after epidural block.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Licensed in pregnancy? - Yes as epidural in labour

Recommended for use in pregnancy? - Not during first or second trimester

Animal data - Studies in rats do not indicate teratogenic effects but have shown embryo-foetal toxicity

Lactation

Breastfeeding may resume following administration of levobupivacaine.

It is not known if levobupivacaine is excreted in human breast milk. However, levobupivacaine is likely to be poorly transmitted into breast milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - likely to be poorly transmitted into breast milk.

Considered suitable or recommended by manufacturer? - Yes

Drug substance licensed in infants? - No

Counselling

Levobupivacaine may have a major effect on a patients ability to drive and operate machinery. Patients should be warned not to attempt such tasks until all of the effects of anaesthesia and/or surgery have ceased.

Side Effects

Hypotension
Nausea
Anaemia
Vomiting
Dizziness
Headache
Pyrexia
Back pain
Allergic reaction
Anaphylaxis
Hypersensitivity reactions
Convulsions
Unconsciousness
Somnolence
Syncope
Paraesthesia
Paraplegia
Blurred vision
Atrioventricular block
Cardiac arrest
Ventricular tachyarrhythmias
Tachycardia
Bradycardia
Respiratory arrest
Laryngeal oedema
Apnoea
Sneezing
Oral hypoaesthesia
Loss of sphincter control
Angioneurotic oedema
Urticaria
Pruritus
Hyperhidrosis
Erythema
Muscle twitch
Muscle weakness
Decreased cardiac output
ECG changes
Neurological damage
Paralysis
Ptosis
Miosis
Enophthalmos
Flushing
Anhidrosis
Priapism
Bladder dysfunction

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Reference Sources

British National Formulary, 64th Edition (2012) Pharmaceutical Press, London.

BNF for Children (2012 - 2013) Pharmaceutical Press, London.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Chirocaine 2.5mg/ml solution for injection/concentrate for solution for infusion. Abbott Laboratories Ltd. Revised October 2011.

Summary of Product Characteristics: Chirocaine 5mg/ml solution for injection/ concentrate for solution for infusion. Abbott Laboratories Ltd. Revised October 2011.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Levobupivacaine. Last reviewed: March 31, 2010.
Last accessed: October 3, 2012.