Bupivacaine is an active pharmaceutical ingredient in the Amides group (N01BB). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised September 9, 2024[1]
Bupivacaine Heavy 5mg/ml Solution for Injection is indicated in adults and children of all ages for intrathecal (subarachnoid) spinal anaesthesia for surgery (urological and lower limb surgery lasting 2–3 hours, abdominal surgery lasting 45–60 minutes).
Bupivacaine is a long-acting anaesthetic agent of the amide type. Bupivacaine injection has a rapid onset of action and long duration. The duration of analgesia in the T10–T12 segments is 2–3 hours. 5 hours. The motor blockade of the abdominal muscles makes the solution suitable for performance of abdominal surgery lasting 45–60 minutes.
The duration of the motor blockade does not exceed the duration of analgesia. The cardiovascular effects of Bupivacaine injection are similar or less than those seen with other spinal agents. Bupivacaine Heavy 5mg/ml Solution for Injection is exceptionally well tolerated by all tissues with which it comes in contact.
CACanada· Health Canada
14 products
Uses
CAOfficial regulatory label· revised March 22, 2025[2]
Bupivacaine Injection BP (bupivacaine hydrochloride) is indicated for the production of local or regional anaesthesia or analgesia with the following procedures: Local infiltration Peripheral minor or major nerve blocks Epidural block for surgery Epidural block by continuous infusion or intermittent bolus for postoperative or labour pain relief Standard procedures for local infiltration, minor and major nerve blocks, retrobulbar block or epidural block should be observed.
1 Pediatrics Pediatrics (< 2 years of age): No data are available to Health Canada; therefore, Bupivacaine Injection BP is not recommended for use. 2 Geriatrics Geriatrics (> 65 years of age): Elderly patients should be given reduced doses commensurate with their age and physical condition.
USUnited States· FDA
6 products
Uses
USOfficial regulatory label· revised March 9, 2026[3]
1 INDICATIONS AND USAGE Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is indicated in adults for the production of local or regional anesthesia or analgesia for surgery, dental and oral surgery procedures, diagnostic and therapeutic procedures, and for obstetrical procedures.
2) ]. Bupivacaine Hydrochloride Injection contains bupivacaine, an amide local anesthetic, and Bupivacaine Hydrochloride and Epinephrine Injection is a combination of bupivacaine, an amide local anesthetic, and epinephrine, an alpha and beta-adrenergic agonist.
Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is indicated in adults for the production of local or regional anesthesia or analgesia for surgery, dental and oral surgery procedures, diagnostic and therapeutic procedures, and for obstetrical procedures.
For each type of block indicated to produce local or regional anesthesia or analgesia, specific concentrations and presentations are recommended. 2 ) Limitations of Use Not all blocks are indicated for use with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection given clinically significant risks associated with use.
EUEuropean Union· EMA
1 product
Uses
EUOfficial regulatory label· revised August 13, 2025[4]
1): • in adults as a brachial plexus block or femoral nerve block for treatment of post-operative pain; • in adults and children aged 6 years or older as a field block for treatment of somatic post- operative pain from small- to medium-sized surgical wounds.
How to take
EU
Drug interactions
Known interactions involving Bupivacaine. Select one for details. This list is informational and not a complete interaction checker.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[1]MHRA (UK) · PL298310761 · revised September 9, 2024
[2]Health Canada (DPD) · 02443686 · revised March 22, 2025
[3]FDA DailyMed · 02a845c3-4521-49… · revised March 9, 2026 [PDF]
[4]European Medicines Agency · EMEA/H/C/004586 · revised August 13, 2025
[5]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
How to take
GBOfficial regulatory label· revised September 9, 2024[1]
Adults and children above 12 years of age The doses recommended below should be regarded as a guide for use in the average adult. The figures reflect the expected average dose range needed. Standard textbooks should be consulted for factors affecting specific block techniques and for individual patient requirements.
The clinician’s experience and knowledge of the patient’s physical status are of importance in calculating the required dose. The lowest dose required for adequate anaesthesia should be used. Individual variations in onset and duration occur, and the extent of the spread of anaesthesia may be difficult to predict, but will be affected by the volume of the drug used, especially with the isobaric (plain) solution.
Dosage recommendations Intrathecal anaesthesia for surgery: 2-4 ml (10-20 mg bupivacaine hydrochloride). The dose should be reduced in the elderly and in patients in the late stages of pregnancy, see Section
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised September 9, 2024[1]
Tabulated list of adverse reactions The adverse reaction profile for Bupivacaine injection is similar to those for other long acting local anaesthetics used for intrathecal anaesthesia. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to<1/1,000), very rare (<1/10,000) or not known (cannot be estimated from the available data).
g. g. g. g. postdural puncture headache). Acute systemic toxicity Bupivacaine injection, used as recommended, is not likely to cause blood levels high enough to cause systemic toxicity. However, if other local anaesthetics are concomitantly administered, toxic effects are additive and may cause systemic toxic reactions.
Systemic toxicity is rarely associated with spinal anaesthesia but might occur after accidental intravascular injection. Systemic adverse reactions are characterised by numbness of the tongue, light-headedness, dizziness and tremors, followed by convulsions and cardiovascular disorders.
Treatment of acute systemic toxicity No treatment is required for milder symptoms of systemic toxicity but if convulsions occur then it is important to ensure adequate oxygenation and to arrest the convulsions if they last more than 15–30 seconds.
Oxygen should be given by face mask and the respiration assisted or controlled if necessary. Convulsions can be arrested by injection of thiopental 100–150 mg intravenously or with diazepam 5– 10 mg intravenously. Alternatively, succinylcholine 50–100 mg intravenously may be given but only if the clinician has the ability to perform endotracheal intubation and to manage a totally paralysed patient.
High or total spinal blockade causing respiratory paralysis should be treated by ensuring and maintaining a patent airway and giving oxygen by assisted or controlled ventilation. g. ephedrine 10–15 mg intravenously and repeated until the desired level of arterial pressure is reached.
Intravenous fluids, both electrolytes and colloids, given rapidly can also reverse hypotension. Paediatric population Adverse drug reactions in children are similar to those in adults, however, in children, early signs of local anaesthetic toxicity may be difficult to detect in cases where the block is given during sedation or general anaesthesia.
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme.
uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
GBOfficial regulatory label· Warnings and precautions· revised September 9, 2024[1]
4. Neonates, infants and children up to 40 kg Bupivacaine injection may be used in children. One of the differences between small children and adults is a relatively high CSF volume in infants and neonates, requiring a relatively larger dose/kg to produce the same level of block as compared to adults.
Paediatric regional anaesthesia procedures should be performed by qualified clinicians who are familiar with this population and the techniques. The doses in the table should be regarded as guidelines for use in paediatric patients.
Individual variations occur. Standard textbooks should be consulted for factors affecting specific block technique and for individual patient requirements. The lowest dose required for adequate anaesthesia should be used. 30 mg/kg The spread of anaesthesia obtained with Bupivacaine injection depends on several factors including the volume of solution and the position of the patient during and following the injection.
When injected at the L3–L4 intervertebral space, with the patient in the sitting position, 3 ml of Bupivacaine injection spreads to the T7–T10 spinal segments. With the patient receiving the injection in the horizontal position and then turned supine, the blockade spreads to T4–T7 spinal segments.
It should be understood that the level of spinal anaesthesia achieved with any local anaesthetic can be unpredictable in a given patient. The recommended site of injection is below L3. The effects of injections of Bupivacaine injection exceeding 4 ml have not yet been studied and such volumes can therefore not be recommended.
Method of administration Route of administration:
For intrathecal injection. 1. Hypersensitivity to local anaesthetics of the amide type. Intrathecal anaesthesia, regardless of the local anaesthetic used, has its own contraindications, which include: • Active disease of the central nervous system such as meningitis, poliomyelitis, intracranial haemorrhage, sub-acute combined degeneration of the cord due to pernicious anaemia and cerebral and spinal tumours.
g. g. fracture) in the vertebral column. • Septicaemia. • Pyogenic infection of the skin at or adjacent to the site of lumbar puncture. • Cardiogenic or hypovolaemic shock. • Coagulation disorders or ongoing anticoagulation treatment. 4 Special warnings and precautions for use Intrathecal anaesthesia should only be undertaken by clinicians with the necessary knowledge and experience.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised September 9, 2024[1]
1. Hypersensitivity to local anaesthetics of the amide type. Intrathecal anaesthesia, regardless of the local anaesthetic used, has its own contraindications, which include: • Active disease of the central nervous system such as meningitis, poliomyelitis, intracranial haemorrhage, sub-acute combined degeneration of the cord due to pernicious anaemia and cerebral and spinal tumours.
g. g. fracture) in the vertebral column. • Septicaemia. • Pyogenic infection of the skin at or adjacent to the site of lumbar puncture. • Cardiogenic or hypovolaemic shock. • Coagulation disorders or ongoing anticoagulation treatment.
This is not medical advice. Consult a qualified healthcare professional.
How to take
CAOfficial regulatory label· revised March 22, 2025[2]
2 Geriatrics Geriatrics (> 65 years of age): Elderly patients should be given reduced doses commensurate with their age and physical condition. 2 CONTRAINDICATIONS Bupivacaine Injection BP (bupivacaine hydrochloride) is contraindicated: In patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[2]
and 7 WARNINGS AND PRECAUTIONS). Central nervous system reactions are similar for all amide local anaesthetics, while cardiac reactions are more dependent on the drug, both quantitatively and qualitatively. Symptoms Accidental intravascular injections of local anaesthetics may cause immediate (within seconds to a few minutes) systemic toxic reactions.
In the event of overdose, systemic toxicity appears later (15-60 minutes after injection) due to the slower increase in local anaesthetic blood concentration. Central nervous system toxicity is a graded response with symptoms and signs of escalating severity.
The first symptoms are usually circumoral paresthesia, numbness of the tongue, light-headedness, hyperacousis, tinnitus and visual disturbances. Dysarthria, muscular twitching or tremors are more serious and precede the onset of generalized convulsions.
These signs must not be mistaken for a neurotic behaviour. Unconsciousness and grand mal convulsions may follow which may last from a few seconds to several minutes. Hypoxia and hypercarbia occur rapidly following convulsions due to the 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 and subsequent metabolism and excretion of the local anaesthetic drug.
Recovery may be rapid unless large amounts of the drug have been BUPIVACAINE INJECTION BP Page 10 of 33 administered. Cardiovascular system toxicity may be seen in severe cases and is generally preceded by signs of toxicity in the central nervous system.
In patients under heavy sedation or receiving a general anaesthetic, prodromal CNS symptoms may be absent. Hypotension, bradycardia, arrhythmia and even cardiac arrest may occur as a result of high systemic concentrations of local anaesthetics, but in rare cases cardiac arrest has occurred without prodromal CNS effects.
Cardiovascular toxic reactions are usually related to depression of the conduction system of the heart and myocardium, leading to decreased cardiac output, hypotension, heart block, bradycardia and sometimes ventricular arrhythmias, including ventricular tachycardia, ventricular fibrillation and cardiac arrest.
In children, early signs of local anaesthetic toxicity may be difficult to detect in cases where the block is given during general anaesthesia. Treatment The first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient’s state of consciousness after each local anaesthetic injection.
If signs of acute systemic toxicity appear, injection of the local anaesthetic should be immediately stopped. The first step in the management of systemic toxic reactions, as well as underventilation or apnoea due to unintentional subarachnoid injection of drug solution, consists of immediate attention to the establishment and maintenance of a patent airway and assisted or controlled ventilation with 100% oxygen and a delivery system capable of permitting immediate positive airway pressure by mask or endotracheal intubation.
This may prevent convulsions if they have not already occurred. CNS symptoms (convulsion, CNS depression) must promptly be treated with appropriate airway/ respiratory support and the administration of anticonvulsant drugs. If cardiovascular depression occurs (hypotension, bradycardia), appropriate treatment with intravenous fluids, vasopressors and/or inotropic agents should be considered as per standard practice guidance.
Children should be given appropriate treatment in doses commensurate with their age and weight. Should cardiac arrest occur, immediate cardiopulmonary resuscitation should be instituted. Optimal oxygenation and ventilation and circulatory support as well as treatment of acidosis are of vital importance, since hypoxia and acidosis will increase the systemic toxicity of local anaesthetics.
A successful resuscitation may require prolonged efforts. BUPIVACAINE INJECTION BP Page 11 of 33 Lipid emulsion formulations should be made immediately available as part of the anaesthetic emergency preparedness in the health care facility.
When symptoms and signs of local anaesthetic system toxicity are observed, lipid emulsion therapy should be considered if clinical events warrant intervention and after the airway is secured. The supine position is dangerous in pregnant women at term because of aortocaval compression by the gravid uterus.
Therefore, during treatment of systemic toxicity, maternal hypotension or foetal bradycardia following regional block, the parturient should be maintained in the left lateral decubitus position if possible, or manual displacement of the uterus off the great vessels should be accomplished.
Resuscitation of obstetrical patients may take longer than resuscitation of nonpregnant patients and closed-chest cardiac compression may be ineffective. Rapid delivery of the foetus may improve the response to resuscitative efforts.
For management of a suspected drug overdose, contact your regional poison control centre. 5 mg / mL and 5 mg / mL bupivacaine hydrochloride Sodium chloride, sodium hydroxide and/or hydrochloric acid, water for injection Dosage Forms Bupivacaine Injection BP is a sterile isotonic solution.
5% (5 mg/mL) Bupivacaine Injection BP are available in 10 mL and 20 mL vials. 7 WARNINGS AND PRECAUTIONS General Local anaesthetics should only be used by clinicians who are well versed in diagnosis and management of dose-related toxicity and other acute emergencies which may arise BUPIVACAINE INJECTION […]
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[2]
2 Geriatrics Geriatrics (> 65 years of age): Elderly patients should be given reduced doses commensurate with their age and physical condition. 2 CONTRAINDICATIONS Bupivacaine Injection BP (bupivacaine hydrochloride) is contraindicated: In patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. In patients with hypersensitivity to any local anaesthetic agent of the amide type. For intravenous regional anaesthesia (Bier block) since unintentional leakage of bupivacaine over the tourniquet may cause systemic toxic reactions.
Cardiac arrest and death have occurred (see 4 DOSAGE AND ADMINISTRATION). BUPIVACAINE INJECTION BP Page 5 of 33 In obstetric paracervical block anaesthesia. Use of other local anaesthetics in this technique has resulted in foetal bradycardia and death.
4 DOSAGE AND ADMINISTRATION Note: SteriMax Inc. is currently not marketing bupivacaine hydrochloride with epinephrine solutions. 1 Dosing Considerations General The dosage varies and depends upon the area to be anaesthetized, the number of neuronal segments to be blocked, the depth of anaesthesia and degree of muscle relaxation required, individual tolerance, tissue vascularity, and the technique of anaesthesia.
The lowest concentration of anaesthetic and the lowest dosage needed to provide effective anaesthesia should be administered. The rapid injection of a large volume of local anaesthetic solution should be avoided and fractional doses should be used when feasible.
In general, complete block of all nerve fibres in large nerves requires the higher concentrations of drug. , in the relief of labour pain), the lower concentrations are indicated. The volume of drug used will affect the extent of spread of anaesthesia.
The use of bupivacaine with epinephrine will prolong the anaesthetic action. There have been adverse event reports of irreversible chondrolysis in patients receiving intra-articular infusions of local anaesthetics following arthroscopic and other surgical procedures.
Bupivacaine Injection BP is not approved for this use (see 7 WARNINGS AND PRECAUTIONS, General). Special Populations Local anaesthetics should be used with caution in patients in poor general condition due to aging or other compromising factors such as advanced liver disease or severe renal dysfunction although regional anaesthesia is frequently indicated in these patients.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[2]
Bupivacaine Injection BP (bupivacaine hydrochloride) is contraindicated: In patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. In patients with hypersensitivity to any local anaesthetic agent of the amide type. For intravenous regional anaesthesia (Bier block) since unintentional leakage of bupivacaine over the tourniquet may cause systemic toxic reactions.
Cardiac arrest and death have occurred (see
This is not medical advice. Consult a qualified healthcare professional.
9) ] .
How to take
USOfficial regulatory label· revised March 9, 2026[3]
2 DOSAGE AND ADMINISTRATION • Not for intrathecal use. , multiple-dose vials) for epidural or caudal anesthesia. 5% bupivacaine with 1:200,000 epinephrine) is recommended for use as a test dose prior to caudal and lumbar epidural blocks when clinical conditions permit.
4 ) • See full prescribing information for: - Recommended concentrations and dosages of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection according to type of block. 2 ) - Additional dosage and administration information pertaining to use in epidural anesthesia, test dose for caudal and lumbar epidural blocks, use in dentistry, and use in ophthalmic surgery.
1 Important Dosage and Administration Information • Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is not for intrathecal use. 4) ] . , those supplied in single-dose vials, following initial use.
• Visually inspect this product for particulate matter and discoloration prior to administration whenever solution and container permit. Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection are clear, colorless solutions.
Do not administer solutions which are discolored or contain particulate matter. • Mixing or the prior or intercurrent use of any other local anesthetic with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is not recommended because of insufficient data on the clinical use of such mixtures.
Administration Precautions • Bupivacaine Hydrochloride Injection Injection/Bupivacaine Hydrochloride and Epinephrine Injection are to be administered in carefully adjusted dosages by or under the supervision of experienced clinicians who are well versed in the diagnosis and management of dose-related toxicity and other acute emergencies which might arise from the block to be employed.
2) , Adverse Reactions (6) , Overdosage (10) ] . • The toxic effects of local anesthetics are additive. 1) , Overdosage (10) ] . • Aspirate for blood or cerebrospinal fluid (where applicable) prior to injecting Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection, both the initial dose and all subsequent doses, to avoid intravascular or intrathecal injection.
9) ] . • Avoid rapid injection of a large volume of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection and use fractional (incremental) doses when feasible. • During major regional nerve blocks, such as those of the brachial plexus or lower extremity, the patient should have an indwelling intravenous catheter to assure adequate intravenous access.
The lowest dosage of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection that results in effective anesthesia should be used to avoid high plasma levels and serious adverse reactions. • Perform careful and constant monitoring of cardiovascular and respiratory (adequacy of oxygenation and ventilation) vital signs and the patient's level of consciousness after each local anesthetic injection.
12) ] . 2 Recommended Concentrations and Dosages of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection The dosage of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection administered varies with the anesthetic procedure, the area to be anesthetized, the vascularity of the tissues, the number of neuronal segments to be blocked, the depth of anesthesia and degree of muscle relaxation required, the duration of anesthesia desired, individual tolerance, and the physical condition of the patient.
Administer the smallest dosage and concentration required to produce the desired result. The types of block and recommended Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection concentrations are shown in Table 1.
Table 1. 1) ]. 5 mg/mL) is not recommended for nonobstetrical surgical procedures in pregnant patients. 4) ] . ✓ ✓ ✓ ✓ Lumbar epidural block ✓ ✓ ✓ (not for obstetrical anesthesia) ✓ ✓ Epidural test dose ✓ Dental block ✓ At recommended dosages, Bupivacaine Hydrochloride/Bupivacaine Hydrochloride and Epinephrine produces complete sensory block, but the effect on motor function differs among the three concentrations.
Table 2 provides information on the expected effect on motor function for the three concentrations. Table 2. 5 mg/mL) These products include Bupivacaine Hydrochloride Injection and Bupivacaine Hydrochloride and Epinephrine Injection [the epinephrine concentration (1:200,000) is not included in the table].
When used for caudal, epidural, or peripheral nerve block, produces incomplete motor block. Should be used for operations in which muscle relaxation is not important, or when another means of providing muscle relaxation is used concurrently.
5 mg/mL) solutions. 5% (5 mg/mL) Provides motor blockade for caudal, epidural, or nerve block, but muscle relaxation may be inadequate for operations in which complete muscle relaxation is essential. 5 mg/mL) concentration for Bupivacaine Hydrochloride and Epinephrine Injection].
Produces complete motor block. Most useful for epidural block in abdominal operations requiring complete muscle relaxation, and for retrobulbar anesthesia. Not for obstetrical anesthesia. The duration of anesthesia with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is such that for most indications, a single dose is sufficient.
The maximum dosage limit within the recommended dosage range must be individualized in each case after evaluating the size and physical status of the patient, as well as the anticipated rate of systemic absorption from a particular injection site.
The dosages in Table 3 are recommended as a guide for use in the average adult. These doses may be repeated once every three hours. Do not exceed a total daily dosage of 400 mg in 24 hours. The duration of anesthetic effect may be prolonged by the addition of epinephrine.
Table 3. Recommended Concentrations and Doses of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection in Adults Type of Block Concentration of Bupivacaine Hydrochloride Injection Each Dose Motor Block With continuous (intermittent) techniques, repeat doses increase the degree of motor block.
5% (5 mg/mL) may produce complete motor block. 5 mg/mL) also may produce complete motor block for intra-thoracic and upper intra-abdominal surgery. , applies to Bupivacaine Hydrochloride Injection and Bupivacaine Hydrochloride and Epinephrine Injection).
The Bupivacaine Hydrochloride and Epinephrine Injection products include epinephrine (1:200,000). 5 mg/mL) For single-dose use; not for intermittent epidural technique. Not for obstetrical anesthesia. 5% bupivacaine with 1:200,000 epinephrine) be administered initially and the effects monitored before the full dose is given.
4) ] . 5 mg/mL) solutions in incremental doses of 3 mL to 5 mL with sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection. Administer injections slowly, with frequent aspirations before and during the injection to avoid intravascular injection.
Perform syringe aspirations before and during each supplemental injection in continuous (intermittent) catheter techniques. 5% (5 mg/mL) solution not exceeding 50 mg to 100 mg at any dosing interval are recommended. Repeat doses should be preceded by a test dose containing epinephrine if not clinically contraindicated.
9) ] . 5% bupivacaine with 1:200,000 epinephrine) is recommended for use as a test dose prior to caudal and lumbar epidural blocks when clinical conditions permit. This test dose may serve as a warning of unintended intravascular or intrathecal injection.
9) ] . Allot adequate time for onset of spinal block to detect possible intrathecal injection. An intravascular or intrathecal injection is still possible even if results of the test dose are negative. 9) , Overdosage (10) ]. 5% (5 mg/mL) is recommended for infiltration and block injection in the maxillary and mandibular area when a longer duration of local anesthesia is desired, such as for procedures generally associated with significant postoperative pain.
2) ]. 5% (5 mg/mL) Bupivacaine Hydrochloride and Epinephrine Injection). Inject slowly and with frequent aspirations. 5 mg/mL) is used for retrobulbar block, complete corneal anesthesia usually precedes onset of clinically acceptable external ocular muscle akinesia.
15) ] .
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 823 reports total. [5]
USOfficial regulatory label· Adverse reactions· revised March 9, 2026[3]
15) ] The following adverse reactions from voluntary reports or clinical studies have been reported with bupivacaine or bupivacaine and epinephrine. Because many of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Adverse reactions to Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection are characteristic of those associated with other amide-type local anesthetics. A major cause of adverse reactions to this group of drugs is excessive plasma levels, which may be due to overdosage, unintentional intravascular injection, or slow metabolic degradation.
The most commonly encountered acute adverse reactions that demand immediate counter-measures were related to the CNS and the cardiovascular system. These adverse reactions were generally dose-related and due to high plasma levels which may have resulted from overdosage, rapid absorption from the injection site, diminished tolerance, or from unintentional intravascular injection of the local anesthetic solution.
In addition to systemic dose-related toxicity, unintentional intrathecal injection of drug during the intended performance of caudal or lumbar epidural block or nerve blocks near the vertebral column (especially in the head and neck region) has resulted in underventilation or apnea ("Total or High Spinal").
Also, hypotension due to loss of sympathetic tone and respiratory paralysis or underventilation due to cephalad extension of the motor level of anesthesia have occurred. This has led to secondary cardiac arrest when untreated. Most common adverse reactions are related to the central nervous system and the cardiovascular system.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. gov/medwatch . Nervous System Disorders Adverse reactions were characterized by excitation and/or depression of the central nervous system and included restlessness, anxiety, dizziness, tinnitus, blurred vision, tremors, convulsions, drowsiness, unconsciousness, respiratory arrest, nausea, vomiting, chills, pupillary constriction.
In the practice of caudal or lumbar epidural block, unintentional penetration of the subarachnoid space by the catheter or needle has occurred. Subsequent adverse effects may have depended partially on the amount of drug administered intrathecally and the physiological and physical effects of a dural puncture.
A high spinal has been characterized by paralysis of the legs, loss of consciousness, respiratory paralysis, and bradycardia. Neurologic effects following epidural or caudal anesthesia have included spinal block of varying magnitude (including high or total spinal block); hypotension secondary to spinal block; urinary retention; fecal and urinary incontinence; loss of perineal sensation and sexual function; persistent anesthesia, paresthesia, weakness, paralysis of the lower extremities and loss of sphincter control, all of which had slow, incomplete, or no recovery; headache; backache; septic meningitis; meningismus; slowing of labor; increased incidence of forceps delivery; and cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid.
Neurologic effects following other procedures or routes of administration have included persistent anesthesia, paresthesia, weakness, paralysis, all with slow, incomplete, or no recovery.
Convulsions :
Incidence varied with the procedure used and the total dose administered. 1% of local anesthetic administrations. The incidences of adverse neurologic reactions associated with the use of local anesthetics may be related to the total dose of local anesthetic administered and are also dependent upon the particular drug used, the route of administration, and the physical status of the patient.
9) ]. Immune System Disorders Allergic-type reactions have occurred as a result of sensitivity to bupivacaine or to other formulation ingredients, such as the antimicrobial preservative methylparaben contained in multiple-dose vials or sulfites in epinephrine-containing solutions.
These reactions were characterized by signs such as urticaria, pruritus, erythema, angioneurotic edema (including laryngeal edema), tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and severe hypotension.
8) ] .
USOfficial regulatory label· Warnings and precautions· revised March 9, 2026[3]
5 WARNINGS AND PRECAUTIONS • Dose-Related Toxicity : Monitor cardiovascular and respiratory vital signs and patient's state of consciousness after injection of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection.
2 ) • Methemoglobinemia : Cases of methemoglobinemia have been reported in association with local anesthetic use. See full prescribing information for more detail on managing these risks. 3 ) • Chondrolysis with Intra-Articular Infusion : Intra-articular infusions of local anesthetics including Bupivacaine Hydrochloride Injection following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions.
5 ) • Risk of Cardiac Arrest with Intravenous Regional Anesthesia Use (Bier Block) : There have been reports of cardiac arrest and death during the use of bupivacaine for intravenous regional anesthesia (Bier Block). 7 ) • Allergic-Type Reactions to Sulfites in Bupivacaine Hydrochloride and Epinephrine Injection : Bupivacaine Hydrochloride and Epinephrine Injection contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.
8 ) • Risk of Systemic Toxicities with Unintended Intravascular or Intrathecal Injection : Unintended intravascular or intrathecal injection may be associated with systemic toxicities, including CNS or cardiorespiratory depression and coma, progressing ultimately to respiratory arrest.
Aspirate for blood or cerebrospinal fluid (where applicable) prior to each dose and consider using a test dose of Bupivacaine Hydrochloride and Epinephrine Injection. 1 Risk of Cardiac Arrest with Use of Bupivacaine Hydrochloride Injection in Obstetrical Anesthesia There have been reports of cardiac arrest with difficult resuscitation or death during use of Bupivacaine Hydrochloride Injection for epidural anesthesia in obstetrical patients.
5 mg/mL) concentration. Resuscitation has been difficult or impossible despite apparently adequate preparation and appropriate management. Cardiac arrest has occurred after convulsions resulting from systemic toxicity, presumably following unintentional intravascular injection.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised March 9, 2026[3]
4 CONTRAINDICATIONS Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is contraindicated in: • obstetrical paracervical block anesthesia. Its use in this technique has resulted in fetal bradycardia and death.
7) ]. • patients with a known hypersensitivity to bupivacaine or to any local anesthetic agent of the amide-type or to other components of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection. • Obstetrical paracervical block anesthesia.
Its use in this technique has resulted in fetal bradycardia and death. ( 4 ) • Intravenous regional anesthesia (Bier Block). ( 4 ) • Known hypersensitivity to bupivacaine or to any local anesthetic agent of the amide-type or to other components of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection.
( 4 )
This is not medical advice. Consult a qualified healthcare professional.
EXPAREL liposomal should be administered in a setting where trained personnel and appropriate resuscitation equipment are available to promptly treat patients who show evidence of neurological or cardiac toxicity. Posology The recommended dose of EXPAREL liposomal in adults and children aged 6 years or older is based on the following factors: • Size of the surgical site • Volume required to cover the area • Individual patient factors A maximum dosage of 266 mg (20 mL of undiluted medicinal product) must not be exceeded.
3 Field block (infiltration around small- to medium-sized surgical wounds) • In patients undergoing bunionectomy, a total of 106 mg (8 mL) of EXPAREL liposomal was administered, with 7 mL infiltrated into the tissues surrounding the osteotomy and 1 mL infiltrated into the subcutaneous tissue.
• In patients undergoing haemorrhoidectomy, a total of 266 mg (20 mL) of EXPAREL liposomal was diluted with 10 mL of normal saline, for a total of 30 mL, divided into six 5 mL aliquots, injected by visualizing the anal sphincter as a clock face and slowly infiltrating one aliquot to each of the even numbers to produce a field block.
• In paediatric patients aged 6 years and older, EXPAREL liposomal should be administered at a dose of 4 mg/kg (maximum not to exceed 266 mg). 89 mg/mL (ie, 1:14 dilution by volume). The total volume of expansion will be dependent on the incision length.
6. Peripheral nerve block (femoral and brachial plexus) • In patients undergoing total knee arthroplasty (TKA), a total of 266 mg (20 mL) of EXPAREL liposomal was administered as a femoral nerve block. • In patients undergoing total shoulder arthroplasty or rotator cuff repair, a total of 133 mg (10 mL) of EXPAREL liposomal was diluted with 10 mL of normal saline, for a total volume of 20 mL, was administered as a brachial plexus nerve block.
Co-administration with other local anaesthetics The toxic effects of local anaesthetics are additive and their co-administration, taking into account the dose of local anaesthetic and the extended pharmacokinetic profile of EXPAREL liposomal, should be used with caution including monitoring for neurologic and cardiovascular effects related to local anaesthetic systemic toxicity.
5. EXPAREL liposomal is a liposomal preparation and should not be used interchangeably with any other formulations of bupivacaine. Bupivacaine hydrochloride (immediate release formulations) and EXPAREL liposomal may be administered simultaneously in the same syringe as long as the ratio of the milligram dose of bupivacaine solution to EXPAREL liposomal does not exceed 1:2.
If preparing admixture, the total amount of bupivacaine used (EXPAREL liposomal + bupivacaine HCl) should not exceed 400 mg equivalents of bupivacaine HCl in adults. For more information, see section
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised August 13, 2025[4]
5%). The most important serious adverse reactions associated with EXPAREL liposomal were systemic toxic reactions. Systemic toxic reactions usually present shortly after administration of bupivacaine but may be delayed in some cases.
001% from post-marketing data). 001% from post-marketing data). Tabulated list of adverse reactions in adults The adverse reactions associated with EXPAREL liposomal in adults from clinical trials and post- marketing surveillance are presented below in Table 1 according to the MedDRA System Organ Classification and by frequency.
Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000) and very rare (< 1/10 000) and frequency not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 9 Table 1 Table of adverse drug reactions (ADRs) in adults System organ class Frequency Adverse drug reactions Immune system disorders Not known Hypersensitivity Psychiatric disorders Rare Confusional state, anxiety Nervous system disorders Common Dysgeusia Uncommon Motor dysfunction, sensory loss, dizziness, somnolence, hypoaesthesia, burning sensation, headache Rare Syncope, monoplegia, presyncope, lethargy Not known Seizure, palsy Eye disorders Rare Visual impairment, vision blurred Ear and labyrinth disorders Rare Diplacusis Cardiac disorders Uncommon Bradycardia, tachycardia Rare Atrial fibrillation, tachyarrhythmia, sinus tachycardia Not known Cardiac arrest Vascular disorders Uncommon Hypotension Rare Hypertension, flushing Respiratory, thoracic, and mediastinal disorders Rare Apnoea, hypoxia, atelectasis, dyspnoea, oropharyngeal pain Gastrointestinal disorders Common Vomiting, constipation, hypoaesthesia oral, nausea Rare Haematochezia, dysphagia, abdominal distension, abdominal discomfort, abdominal pain upper, diarrhoea, salivary hypersecretion, dry mouth, dyspepsia, oral pruritus, paraesthesia oral Skin and subcutaneous tissue disorders Uncommon Urticaria, pruritus generalised, pruritus, skin irritation Rare Drug eruption, hyperhidrosis, erythema, rash, nail discolouration Musculoskeletal and connective tissue disorders Uncommon Mobility decreased, muscular weakness, muscle spasms, muscle twitching, arthralgia Rare Joint swelling, groin pain, joint stiffness, musculoskeletal chest pain, pain in extremity Renal and urinary disorders Not known Urinary retention General disorders and administration site conditions Uncommon Pyrexia Rare Peripheral swelling, non-cardiac chest pain, chills, feeling hot, injection site pain, pain Not known Lack of efficacy Investigations Uncommon Blood creatinine increased, alanine aminotransferase increased, aspartate aminotransferase increased Rare Electrocardiogram ST segment elevation, hepatic enzyme increased, white blood cell count increased Injury, poisoning, and procedural complications Uncommon Contusion, post procedural oedema, fall Rare Muscle injury, seroma, wound complication, incision site erythema, procedural pain Not known Local anaesthetic systemic toxicity (LAST) Tabulated list of adverse reactions in the paediatric population Adverse reactions associated with EXPAREL liposomal in paediatrics from clinical trials and post- marketing surveillance are presented below in Table 2 according to the MedDRA System Organ Classification and by frequency.
Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000) and very rare (< 1/10 000) and frequency not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 10 Table 2 Table of adverse drug reactions (ADRs) in children System organ class Frequency Adverse drug reactions Blood and lymphatic system disorders Very common Anaemia Immune system disorders Common Hypersensitivity Psychiatric disorders Common Anxiety Nervous system disorders Common Hypoaesthesia, paraesthesia, burning sensation, dizziness, dysgeusia and syncope Not known Somnolence Eye disorders Common Visual impairment, vision blurred Ear and labyrinth disorders Common Hypoacusis Cardiac disorders Very common Tachycardia Common Bradycardia Vascular disorders Very common Hypotension Common Hypertension Respiratory, thoracic, and mediastinal disorders Common Dyspnoea, tachypnoea Gastrointestinal disorders Very common Vomiting, constipation, nausea Common Abdominal pain, diarrhoea, hypoaesthesia oral, dyspepsia Skin and subcutaneous tissue disorders Very common Pruritus Common Rash Musculoskeletal and connective tissue disorders Very common Muscle twitching Common Musculoskeletal chest pain, pain in extremity, muscular weakness, muscle spasms General disorders and administration site conditions Common Chest pain, pyrexia Injury, poisoning, and procedural complications Common Delayed recovery from anaesthesia, seroma, fall Not known Local anaesthetic systemic toxicity (LAST) Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation 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 via the national reporting system listed in Appendix V.
EUOfficial regulatory label· Warnings and precautions· revised August 13, 2025[4]
4. Special populations Elderly patients (65 years of age or older) Care should be taken in dose selection of EXPAREL liposomal in elderly patients because bupivacaine is known to be substantially excreted by the kidney, and the risk of toxic reactions to bupivacaine may be greater in patients with impaired renal function.
2). The risk of falls may increase for the elderly patients. Renal impairment Bupivacaine or its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function.
2). 4 Hepatic impairment Bupivacaine is metabolized by the liver. No dosage adjustment is required in patients with mild hepatic impairment (Child-Pugh score 5-6) or moderate hepatic impairment (Child Pugh score 7-9). 2). Paediatric population The safety and efficacy of EXPAREL liposomal have not yet been established for administration as a field block in children aged 1 to less than 6 years of age, nor as a nerve block in children aged 1 to less than 18 years of age.
No data are available. EXPAREL liposomal should not be used in children aged less than 1 year of age because neonates and infants have a decreased ability to metabolize anaesthetics due to an immature hepatic system. Method of administration EXPAREL liposomal is for administration by infiltration or perineural use only.
EXPAREL liposomal is intended for single-dose administration only. EXPAREL liposomal should be injected slowly (generally 1 to 2 mL per injection) with frequent aspiration, when clinically appropriate, to check for blood and minimize the risk of inadvertent intravascular injection.
EXPAREL liposomal is to be administered with a 25 gauge or larger bore needle to maintain the structural integrity of the liposomal bupivacaine particles. 6. 1. • Hypersensitivity to local anaesthetic medicinal products of the amide type.
• Obstetrical paracervical block anaesthesia due to risk of foetal bradycardia or death. • Intravascular administration. 4). 4 Special warnings and precautions for use Efficacy and safety have not been established in major abdominal, vascular and thoracic surgeries.
Local anaesthetic systemic toxicity (LAST) As there is a potential risk of severe life-threatening adverse reactions associated with the administration of bupivacaine, any bupivacaine-containing product should be administered in a setting where trained personnel and equipment are available to promptly treat patients who show evidence of neurological or cardiac toxicity.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised August 13, 2025[4]
1. • Hypersensitivity to local anaesthetic medicinal products of the amide type. • Obstetrical paracervical block anaesthesia due to risk of foetal bradycardia or death. • Intravascular administration. 4).
This is not medical advice. Consult a qualified healthcare professional.
Regional anaesthetic procedures should always be performed in a properly equipped and staffed area. Resuscitative equipment and drugs should be immediately available and the anaesthetist should remain in constant attendance. g. v. infusion, should be in place before starting the intrathecal anaesthesia.
The clinician responsible should take the necessary precautions to avoid intravascular injection and be appropriately trained and familiar with the diagnosis and treatment of side effects, systemic toxicity and other complications.
9. Like all local anaesthetic drugs, bupivacaine may cause acute toxicity effects on the central nervous and cardiovascular systems, if utilised for local anaesthetic procedures resulting in high blood concentrations of the drug. This is especially the case after unintentional intravascular administration or injection into highly vascular areas.
Ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death have been reported in connection with high systemic concentrations of bupivacaine. Should cardiac arrest occur, a successful outcome may require prolonged resuscitative efforts.
High systemic concentrations are not expected with doses normally used for intrathecal anaesthesia. There is an increased risk of high or total spinal blockade, resulting in cardiovascular and respiratory depression, in the elderly and in patients in the late stages of pregnancy.
The dose should therefore be reduced in these patients. Intrathecal anaesthesia can cause hypotension and bradycardia. , by injecting a vasopressor. If hypotension develops it should be treated promptly with a sympathomimetic intravenously, repeated as necessary.
Severe hypotension may result from hypovolaemia due to haemorrhage or dehydration, or aorto-caval occlusion in patients with massive ascites, large abdominal tumours or late pregnancy. Marked hypotension should be avoided in patients with cardiac decompensation.
Patients with hypovolaemia due to any cause can develop sudden and severe hypotension during intrathecal anaesthesia. Intrathecal anaesthesia can cause intercostal paralysis and patients with pleural effusions may suffer respiratory embarrassment.
Septicaemia can increase the risk of intraspinal abscess formation in the postoperative period. Neurological injury is a rare consequence of intrathecal anaesthesia and may result in paraesthesia, anaesthesia, motor weakness and paralysis.
Occasionally these are permanent. Before treatment is instituted, consideration should be taken if the benefits outweigh the possible risks for the patient. Patients in poor general condition due to ageing or other compromising factors such as partial or complete heart conduction block, advanced liver or renal dysfunction require special attention, although regional anaesthesia may be the optimal choice for surgery in these patients.
g. amiodarone) should be kept under […]
Debilitated, elderly, and acutely ill patients should be given reduced doses commensurate with their age and physical condition. 2 Recommended Dose and Dosage Adjustment Adults: The dosages in Table 1 are recommended as a guide for use in the average adult for the more commonly used techniques.
The clinician’s experience and BUPIVACAINE INJECTION BP Page 6 of 33 knowledge of the patient’s physical condition are of importance in calculating the required dose. When prolonged blocks are used, the risks of reaching a toxic plasma concentration or inducing a local neural injury must be considered.
The maximum dosage limit must be determined by evaluating the size and physical condition of the patient and considering the usual rate of systemic absorption from a specific injection site. Experience to date indicates that 400 mg administered over 24 hours is well tolerated in average adults.
Until further experience is gained, this dose should not be exceeded in 24 hours. In order to avoid intravascular injection, aspiration should be repeated prior to and during administration of the main dose, which should be injected slowly or in incremental doses, at a rate of 25-50 mg/min, while closely observing the patient’s vital functions and maintaining verbal contact.
An inadvertent intravascular injection may be recognized by a temporary increase in heart rate and an accidental intrathecal injection by signs of a spinal block. If toxic symptoms occur, the injection should be stopped immediately.
Intra-articular infusion of a local anaesthetic is an unapproved use (See 7 WARNINGS AND PRECAUTIONS). Sympathetic stellate block requires utmost caution (See 7 WARNINGS AND PRECAUTIONS, Injection in Head and Neck Area). 25% and 5% (3 – 5 mL) should be used only as a test dose for epidural block in labour analgesia.
1 Pregnant Women).
Table 1:
Dosage recommendations in adults for Bupivacaine Injection BP or bupivacaine hydrochloride with epinephrine isotonic solutions. TYPE OF BLOCK CONC. 5 up to 60b up to 30b up to 150b up to 150b 1-3 1-3 3-4 4-8 Surgical operations and postoperative analgesia.
5 2-3 10-15 3-5 4-8 Pain relief for surgery, postoperative and trauma. 5 30 150 15-30 4-8 Surgical operations. 5 10-20 50-100 15-30 4-8 Surgical operations. 5 2-5 3-4 Surgical operations. 25 up to 40b up to 100b 10-20 3-5 Therapeutic (pain relief).
5 up to 30b up to 150b 5-10 4-8 Surgical operations. 5 25-50 50-100 10-20 10-20 10-20 3-6 3-6 3-6 Ischemic conditions or sympathetic maintained […]
5 mg/mL) concentration of Bupivacaine Hydrochloride Injection is not recommended for obstetrical anesthesia and should be reserved for surgical procedures where a high degree of muscle relaxation and prolonged effect are necessary.
2 Dose-Related Toxicity The safety and effectiveness of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies.
Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient's state of consciousness should be performed after injection of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection solutions.
Possible early warning signs of central nervous system (CNS) toxicity are restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, or drowsiness.
Delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest, and, possibly, death. During major regional nerve blocks, such as those of the brachial plexus or lower extremity, the patient should have an indwelling intravenous catheter to assure adequate intravenous access.
Use the lowest dosage of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection that results in effective anesthesia to avoid high plasma levels and serious adverse effects. Avoid rapid injection of a large volume of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection solution and administer fractional (incremental) doses when feasible.
Injection of repeated doses of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection may cause significant increases in plasma levels with each repeated dose due to slow accumulation of the drug or its metabolites, or to slow metabolic degradation.
Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients and acutely ill patients should be given reduced doses commensurate with their age and physical status. 3 Methemoglobinemia Cases of methemoglobinemia have been reported in association with local anesthetic use.
5) ] . If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended. Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure, and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood.
Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious CNS and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection and any other oxidizing agents.
, oxygen therapy, hydration. A more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. , those supplied in multiple-dose vials, for epidural or caudal anesthesia because safety has not been established with such use.
5 Chondrolysis with Intra-Articular Infusion Intra-articular infusions of local anesthetics including Bupivacaine Hydrochloride Injection following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions.
The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours.
There is insufficient information to determine whether shorter infusion periods are associated with chondrolysis. The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2 nd month after surgery.
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. 6 Risk of Adverse Reactions Due to Drug Interactions with Bupivacaine Hydrochloride and Epinephrine Injection Risk of Severe, Persistent Hypertension Due to Drug Interactions Between Bupivacaine Hydrochloride and Epinephrine Injection and Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Administration of Bupivacaine Hydrochloride and Epinephrine Injection (containing a vasoconstrictor) in patients receiving monoamine oxidase inhibitors (MAOI) or tricyclic antidepressants may result in severe, prolonged hypertension.
Concurrent use of these agents should generally be avoided. 2) ]. Risk of Severe, Persistent Hypertension or Cerebrovascular Accidents Due to Drug Interactions Between Bupivacaine Hydrochloride and Epinephrine Injection and Ergot-Type Oxytocic Drugs Concurrent administration of Bupivacaine Hydrochloride and Epinephrine Injection and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents.
3) ] . Risk of Hypertension and Bradycardia Due to Drug Interactions Between Bupivacaine Hydrochloride and Epinephrine Injection and Nonselective Beta-Adrenergic Antagonists Administration of Bupivacaine Hydrochloride and Epinephrine Injection (containing a vasoconstrictor) in patients receiving nonselective beta-adrenergic antagonists may cause severe hypertension and bradycardia.
Concurrent use of these agents should generally be avoided. 4) ] . 7 Risk of Cardiac Arrest with Intravenous Regional Anesthesia Use (Bier Block) There have been reports of cardiac arrest and death during the use of bupivacaine for intravenous regional anesthesia (Bier Block).
Information on safe dosages and techniques of administration of Bupivacaine Hydrochloride Injection in this procedure is lacking. Therefore, Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is contraindicated for use with this technique [see Contraindications (4) ] .
8 Allergic-Type Reactions to Sulfites in Bupivacaine Hydrochloride and Epinephrine Injection Bupivacaine Hydrochloride and Epinephrine Injection contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.
The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people. Bupivacaine Hydrochloride Injection without epinephrine does not contain sodium metabisulfite.
9 Risk of Systemic Toxicities with Unintended Intravascular or Intrathecal Injection Unintended intravascular or intrathecal injection of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection may be associated with systemic toxicities, including CNS or cardiorespiratory depression and coma, progressing ultimately to respiratory arrest.
Unintentional intrathecal injection during the intended performance of caudal or lumbar epidural block or nerve blocks near the vertebral column has resulted in underventilation or apnea ("Total or High Spinal"). A high spinal has been characterized by paralysis of the legs, loss of consciousness, respiratory paralysis, and bradycardia [see Adverse Reactions (6) ] .
Aspirate for blood or cerebrospinal fluid (where applicable) before injecting Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection, both the initial dose and all subsequent doses, to avoid intravascular or intrathecal injection.
However, a negative aspiration for blood or cerebrospinal fluid does not ensure against an intravascular or intrathecal injection. 4) ] . 5% bupivacaine with 1:200,000 epinephrine) contains 15 mg bupivacaine and 15 mcg epinephrine. An intravascular or intrathecal injection is still possible even if results of the test dose are negative.
Signs/symptoms of unintended intravascular or intrathecal injection of the test dose of Bupivacaine Hydrochloride and Epinephrine Injection and monitoring recommendations are described below. • Unintended intravascular injection: Likely to produce a transient "epinephrine response" within 45 seconds, consisting of an increase in heart rate and/or systolic blood pressure, circumoral pallor, palpitations, and nervousness in the unsedated patient.
The sedated patient may exhibit only a pulse rate increase of 20 or more beats per minute for 15 or more seconds. Therefore, following the test dose, the heart rate should be monitored for increases. Patients on beta-blockers may not manifest changes in heart rate, but blood pressure monitoring can detect a transient rise in systolic blood pressure.
, decreased sensation of the buttocks, paresis of the legs, or, in the sedated patient, absent knee jerk). The test dose itself may produce a systemic toxic reaction, high spinal or epinephrine-induced cardiovascular effects [see Overdosage (10) ] .
6) ]. , hypotension, heartblock) because they may be less able to compensate for functional changes associated with the prolongation of AV conduction produced by Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection.
Monitor patients closely for blood pressure, heart rate, and ECG changes. 12 Risk of Ischemic Injury or Necrosis in Body Areas with Limited Blood Supply Use Bupivacaine Hydrochloride and Epinephrine Injection in carefully restricted quantities in areas of the body supplied by end arteries or having otherwise compromised blood supply such as digits, nose, external ear, or penis.
Patients with hypertensive vascular disease may exhibit exaggerated vasoconstrictor response. Ischemic injury or necrosis may result. 6) ] . In deciding whether to concurrently use Bupivacaine Hydrochloride and Epinephrine Injection with potent inhalation anesthetics in the same patient, the combined action of both agents upon the myocardium, the concentration and volume of vasoconstrictor used, and the time since injection, when applicable, should be taken into account.
, Bupivacaine Hydrochloride Injection) 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.
The injection procedures require the utmost care. Confusion, convulsions, respiratory depression, and/or respiratory arrest, and cardiovascular stimulation or depression have been reported. These reactions may be due to intra-arterial injection of the local anesthetic with retrograde flow to the cerebral circulation.
They may also be due to puncture of the dural sheath of the optic nerve during retrobulbar block with diffusion of any local anesthetic along the subdural space to the midbrain. Monitor circulation and respiration and constantly observe patients receiving Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection blocks.
Resuscitative equipment and drugs, and personnel for treating adverse reactions should be immediately available. 2) ]. 15 Risk of Respiratory Arrest with Use in Ophthalmic Surgery Clinicians who perform retrobulbar blocks should be aware that there have been reports of respiratory arrest following local anesthetic injection.
14) ]. As with other anesthetic procedures, patients should be constantly monitored following ophthalmic blocks for signs of these adverse reactions, which may occur following relatively low total doses. 75% bupivacaine is indicated for retrobulbar block; however, this concentration is not indicated for any other peripheral nerve block, including the facial nerve, and not indicated for local infiltration, including the conjunctiva [see Indications and Usage (1) ].
5% (5 mg/mL) of bupivacaine] is used for dental injections, warn patients about the possibility of inadvertent trauma to tongue, lips, and buccal mucosa and advise them not to chew solid foods until sensation returns [see Patient Counseling Information (17) ] .
Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient’s state of consciousness should be performed after injection of bupivacaine. Restlessness, anxiety, incoherent speech, light headedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, depression, or drowsiness may be early warning signs of central nervous system toxicity.
Toxic local anaesthetic blood concentrations depress cardiac conductivity and excitability, which may lead to atrioventricular block, ventricular arrhythmia, and cardiac arrest, which can be fatal. 5 In addition, toxic local anaesthetic blood concentrations depress myocardial contractility and cause peripheral vasodilation, leading to decreased cardiac output and arterial blood pressure.
9). Injection of multiple doses of bupivacaine and other amide-containing products may cause significant increases in plasma concentrations with each repeated dose due to slow accumulation of the active substance or its metabolites or due to slow metabolic degradation.
Tolerance to elevated blood concentrations varies with the status of the patient. Potential cases of LAST have been observed in the post-marketing setting. Although the majority with a recorded time to onset were observed within less than 1 hour of EXPAREL liposomal administration, a small number with a time to onset greater than 24 hours was reported.
5). Neurologic effects Central nervous system reactions are characterized by excitation and/or depression. Restlessness, anxiety, dizziness, tinnitus, blurred vision, or tremors may occur, possibly proceeding to convulsions. However, excitation may be transient or absent, with depression being the first manifestation of an adverse reaction.
This may quickly be followed by drowsiness merging into unconsciousness and respiratory arrest. Other central nervous system effects may include nausea, vomiting, chills, and constriction of the pupils. The incidence of convulsions associated with the use of local anaesthetics varies with the procedure used and the total dose administered.
Neurologic effects following field block may include […]