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Bupivacaine

Class: Local Anesthetics
CAS Number: 14252-80-3
Brands: Exparel, Marcaine, Marcaine Spinal, Sensorcaine, Sensorcaine-MPF

Medically reviewed by Drugs.com on Nov 9, 2021. Written by ASHP.

Warning

    Bupivacaine Hydrochloride 0.75% Concentration
  • Use of the 0.75% solution of bupivacaine hydrochloride not recommended for obstetrical epidural anesthesia. Cardiac arrest with difficult resuscitation or death reported, presumably from systemic toxicity following unintentional intravascular injection.

  • Reserve 0.75% solution for surgical procedures that require a high degree of muscle relaxation and prolonged anesthetic effect.

Introduction

Long-acting local anesthetic (amide type).

Uses for Bupivacaine

Local or Regional Anesthesia or Analgesia

Local or regional anesthesia or analgesia in surgical, obstetrical, dental, diagnostic, and therapeutic procedures.

Available as conventional bupivacaine hydrochloride preparations with or without epinephrine or as a liposomal injection containing bupivacaine in an aqueous suspension of multivesicular liposomes (Exparel).

Conventional preparations are used for local infiltration and nerve block techniques including peripheral, sympathetic, epidural (including caudal), retrobulbar, and dental block. Do not use 0.75% concentration for obstetrical anesthesia. (See Boxed Warning.) A hyperbaric solution containing 0.75% bupivacaine hydrochloride in 8.25% dextrose is used for spinal anesthesia.

Liposomal bupivacaine (Exparel) is used for local infiltration or interscalene brachial plexus nerve block to provide postsurgical analgesia; safety and efficacy not established for other nerve blocks. Because of possible differences in physiochemical and functional properties, do not use liposomal bupivacaine interchangeably with other bupivacaine-containing preparations.

Local anesthetics should be used as a component of multimodal analgesia (i.e., simultaneous use of a combination of analgesic drugs and techniques that target different mechanisms) in the management of postoperative pain.

Studies comparing relative efficacy of liposomal bupivacaine and conventional bupivacaine hydrochloride for postsurgical analgesia have shown variable results.

Do not use for obstetric paracervical block.

Bupivacaine Dosage and Administration

General

Dispensing and Administration Precautions

  • Administer only by clinicians experienced in the diagnosis and management of toxicities and other complications associated with local anesthetics.

  • Resuscitative equipment, oxygen, drugs, and personnel required for treatment of adverse reactions should be immediately available.

  • Administer slowly in incremental doses to reduce risk of adverse effects (e.g., local anesthetic systemic toxicity).

  • Perform frequent aspirations for blood or cerebrospinal fluid (when applicable) to avoid intravascular administration and to either confirm entry into the subarachnoid space (for spinal anesthesia) or avoid inadvertent subarachnoid injection.

  • During major regional nerve blocks, administer IV fluids via an indwelling catheter to ensure a functioning IV pathway.

  • Injections into the head and neck area (e.g., retrobulbar, dental, or stellate ganglion blocks) require particular care; serious adverse effects reported due to complications from the anesthetic technique.

  • Carefully and constantly monitor patients for possible cardiovascular, respiratory, or CNS complications during and after administration.

Administration

Injection

For solution and drug compatibility information, see Compatibility under Stability.

Administer conventional bupivacaine hydrochloride preparations by local infiltration, peripheral nerve block, retrobulbar block, sympathetic block, lumbar epidural block, caudal block, or dental block. Administer 0.75% bupivacaine hydrochloride in 8.25% dextrose solution by subarachnoid injection for spinal anesthesia.

Administer liposomal bupivacaine (Exparel) by local infiltration or interscalene brachial plexus nerve block; do not administer liposomal formulation by epidural or intrathecal routes, or for other regional nerve blocks.

Do not administer using Bier block technique (IV regional anesthesia) due to risk of cardiac arrest and death.

Has been administered by continuous intra-articular infusion (e.g., for control of postoperative pain); however, such use associated with chondrolysis. (See Risk of Chondrolysis Associated with Intra-articular Infusions of Local Anesthetics under Cautions.)

Consult specialized references for specific techniques and procedures for administering local anesthetics.

Do not use liposomal bupivacaine interchangeably with other bupivacaine formulations.

Do not use bupivacaine solutions containing preservatives for epidural or caudal block; discard partially used solutions that do not contain preservatives.

Liposomal Bupivacaine

May administer undiluted or diluted (if an increased volume of drug is necessary to cover a larger surgical area).

If dilution desired, dilute with preservative-free 0.9% sodium chloride injection or lactated Ringer’s injection up to a final concentration of 0.89 mg/mL (1:14 dilution by volume); do not use sterile water for injection or other hypotonic solution since disruption of liposomal particles may occur. Use diluted suspension within 4 hours of preparation in a syringe.

Invert vial multiple times to resuspend drug particles immediately prior to drug withdrawal. Administer using 25-gauge or larger bore needle. Do not filter.

When administered concomitantly with lidocaine (or other non-bupivacaine local anesthetic), immediate release of free (unencapsulated) bupivacaine may occur, potentially resulting in toxic plasma concentrations. Delay administration of liposomal bupivacaine for ≥20 minutes after administration of lidocaine.

Compatibility between liposomal bupivacaine and conventional bupivacaine hydrochloride is concentration dependent. May administer bupivacaine hydrochloride and liposomal bupivacaine simultaneously in the same syringe, or inject bupivacaine hydrochloride immediately before liposomal bupivacaine as long as the ratio (based on mg dose) of conventional to liposomal drug does not exceed 1:2. Consider potential for additive toxic effects when the drugs are used concomitantly. Avoid additional administration of local anesthetics for ≥96 hours after liposomal bupivacaine is administered.

Avoid contact with topical antiseptics (e.g., povidone iodine); allow topical antiseptic to dry before liposomal bupivacaine is administered.

Potential Administration Errors

Because of similarity in appearance (milky white suspension), potential exists for confusion between liposomal bupivacaine and propofol.

Take special precautions (e.g., proper labeling of syringes, storage segregation, routine double-checks) to ensure that such confusion does not occur.

If mistaken for propofol, inadvertent IV administration of liposomal bupivacaine may occur and cause substantial patient harm (e.g., cardiac arrhythmias, arrest).

Instructions for treatment of bupivacaine toxicity should be readily available in all surgical areas where liposomal bupivacaine is used.

Dosage

Conventional preparations available as bupivacaine hydrochloride, as fixed combination containing bupivacaine hydrochloride and epinephrine bitartrate, and as bupivacaine hydrochloride in dextrose injection; dosage expressed in terms of bupivacaine hydrochloride.

Liposomal preparation available as bupivacaine (as free base) in suspension of multivesicular liposomes.

Individualize dosage based on anesthetic procedure, degree of anesthesia required, surgical site, and individual patient response. Use lowest effective dosage.

Prior to epidural anesthesia, administer test dose and monitor patient (e.g., pulse, BP, signs of spinal block) to detect accidental intravascular or subarachnoid injection. Test dose should contain 10–15 mcg epinephrine (when clinical conditions permit) and 10–15 mg (2–3 mL of a 0.5% solution) of bupivacaine hydrochloride (or equivalent dose of another local anesthetic). Following injection of test dose, monitor for increase in heart rate.

Pediatric Patients

Local or Regional Anesthesia/Analgesia
Local Infiltration, Peripheral/Sympathetic Nerve Block, Lumbar Epidural/Caudal Block

Children ≥12 years of age: Manufacturer makes no specific dosage recommendations; individualize dosage. (See Pediatric Use under Cautions.)

Adults

Local or Regional Anesthesia/Analgesia
Local Infiltration

Conventional bupivacaine hydrochloride: Administer 0.25% solution (with or without epinephrine) up to maximum recommended dose (see Prescribing Limits under Dosage and Administration).

Liposomal bupivacaine: Single dose of up to 266 mg recommended. In clinical studies, patients undergoing bunionectomy received a single dose of 106 mg (total volume of 8 mL, with 7 mL infiltrated into tissues surrounding osteotomy and 1 mL infiltrated throughout the subcutaneous tissue). Patients undergoing hemorrhoidectomy received a single dose of 266 mg (20 mL of drug diluted with 10 mL of 0.9% sodium chloride injection); the total volume of 30 mL was divided into 5-mL increments and infiltrated into 6 sites in the perianal tissue using a standard anal block procedure with moving-needle technique.

Lumbar Epidural Block (Bupivacaine Hydrochloride)

0.75% solution is for single-dose use; not for intermittent epidural technique. Reserve for surgical procedures requiring a high degree of muscle relaxation and prolonged anesthetic effect.

0.75% solution is not for obstetrical anesthesia; in obstetrics, use 0.25 or 0.5% solutions only. (See Boxed Warning and see Risks Associated with Obstetrical Use of Bupivacaine Hydrochloride 0.75% Injection under Cautions.)

75–150 mg (10–20 mL) of bupivacaine hydrochloride 0.75% solution (with or without epinephrine) produces complete motor blockade. Administer in incremental doses of 3–5 mL. Allow sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection.

50–100 mg (10–20 mL) of bupivacaine hydrochloride 0.5% solution (with or without epinephrine) produces moderate to complete motor blockade. Administer in incremental doses of 3–5 mL. Allow sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection.

25–50 mg (10–20 mL) of bupivacaine hydrochloride 0.25% solution (with or without epinephrine) produces partial motor blockade.

Caudal Block (Bupivacaine Hydrochloride)

75–150 mg (15–30 mL) of bupivacaine hydrochloride 0.5% solution (with or without epinephrine) produces moderate to complete motor blockade.

37.5–75 mg (15–30 mL) of bupivacaine hydrochloride 0.25% solution (with or without epinephrine) produces moderate motor blockade.

Peripheral Nerve Block (Bupivacaine Hydrochloride)

25 mg (5 mL) to maximum dosage (see Prescribing Limits under Dosage and Administration) of bupivacaine hydrochloride 0.5% solution (with or without epinephrine) produces moderate to complete motor blockade.

12.5 mg (5 mL) to maximum dosage (see Prescribing Limits under Dosage and Administration) of bupivacaine hydrochloride 0.25% solution (with or without epinephrine) produces moderate to complete motor blockade.

Interscalene Brachial Plexus Nerve Block (Liposomal Bupivacaine)

Single dose of 133 mg (10 mL) of liposomal bupivacaine recommended based on a study in patients undergoing total shoulder arthroplasty or rotator cuff repair.

Retrobulbar Block (Bupivacaine Hydrochloride)

15–30 mg (2–4 mL) of bupivacaine hydrochloride 0.75% solution (with or without epinephrine) produces complete motor blockade.

Sympathetic Block (Bupivacaine Hydrochloride)

50–125 mg (20–50 mL) of bupivacaine hydrochloride 0.25% solution.

Dental Infiltration or Block Injection into Maxillary and Mandibular Area (Bupivacaine Hydrochloride)

9 mg (1.8 mL) up to 90 mg (18 mL) of bupivacaine hydrochloride 0.5% solution per dental sitting.

Subarachnoid (Spinal) Block for Vaginal Delivery (Bupivacaine Hydrochloride 0.75% in Dextrose 8.25%)

6 mg (0.8 mL) of bupivacaine hydrochloride 0.75% in dextrose 8.25% injection produces complete motor and sensory block.

Subarachnoid (Spinal) Block for Cesarean Section (Bupivacaine Hydrochloride 0.75% in Dextrose 8.25%)

7.5–10.5 mg (1–1.4 mL) of bupivacaine hydrochloride 0.75% in dextrose 8.25% injection produces complete motor and sensory block.

Subarachnoid (Spinal) Block for Lower Extremity and Perineal Procedures (Bupivacaine Hydrochloride 0.75% in Dextrose 8.25%)

7.5 mg (1 mL) of bupivacaine hydrochloride 0.75% in dextrose 8.25% injection produces complete motor and sensory block.

Subarachnoid (Spinal) Block for Lower Abdominal Procedures (Bupivacaine Hydrochloride 0.75% in Dextrose 8.25%)

12 mg (1.6 mL) of bupivacaine hydrochloride 0.75% in dextrose 8.25% injection produces complete motor and sensory block.

Prescribing Limits

Adults

Local or Regional Anesthesia/Analgesia
Bupivacaine Hydrochloride
Local Infiltration, Peripheral/Sympathetic Nerve Block, Epidural/Caudal Block, Retrobulbar Block, Dental Block

Individualize maximum dosage limit for each patient.

Most experience to date has involved single doses up to 175 mg (without epinephrine) or 225 mg (with epinephrine 1:200,000).

Until further experience, manufacturer recommends that a maximum dose of 400 mg not be exceeded in any 24-hour period.

Liposomal Bupivacaine
Local Infiltration

Maximum dose of 266 mg.

Special Populations

Hepatic Impairment

Use with caution and monitor carefully in patients with liver disease.

Renal Impairment

Consider possibility of increased risk of toxicity in patients with renal impairment and select appropriate dosage accordingly.

Geriatric Patients

Geriatric patients may require reduced dosages.

Other Populations

Patients with cardiac disease, debilitated patients, and acutely ill patients may require reduced dosages. Reduced dosages also may be required in patients with increased intra-abdominal pressure (including obstetrical patients) undergoing spinal anesthesia.

Cautions for Bupivacaine

Contraindications

  • Obstetrical paracervical block (this technique has resulted in fetal bradycardia and death).

  • Contraindications to spinal anesthesia: Severe hemorrhage, severe hypotension or shock, arrhythmias (e.g., complete heart block) that severely restrict cardiac output, local infection at site of lumbar puncture, and septicemia.

  • Known hypersensitivity to bupivacaine, other local anesthetics of the amide type, or any ingredients in the formulation.

Warnings/Precautions

Warnings

Risks Associated with Obstetrical Use of Bupivacaine Hydrochloride 0.75% Injection

Risk of seizures, cardiac arrest, difficult resuscitation, or death following obstetrical epidural block (possibly due to systemic toxicity secondary to unintentional intravascular injection) with 0.75% bupivacaine hydrochloride. (See Boxed Warning.)

Not recommended for obstetrical anesthesia. Reserve for surgical procedures requiring a high degree of muscle relaxation and prolonged anesthetic effect.

Administration Precautions

Because of the potential for serious adverse effects, take special precautions during administration. (See General and see Potential Administration Errors under Dosage and Administration.)

Ensure that oxygen, resuscitative equipment, drugs, and personnel required for treatment of adverse reactions are immediately available. Delay in proper management of dose-related toxicity may result in acidosis, cardiac arrest, and, possibly, death.

Risk of Chondrolysis Associated with Intra-articular Infusions of Local Anesthetics

Chondrolysis (necrosis and destruction of articular cartilage) reported in patients receiving continuous intra-articular infusions of local anesthetics, administered for 48–72 hours via elastomeric infusion devices, for treatment of postoperative pain. Primarily observed in the shoulder joint following arthroscopic or other shoulder surgery. May result in long-term disability; often requires intervention (e.g., debridement, arthroplasty). Not known whether the drug, infusion device, and/or other factors contributed to the development of chondrolysis. Neither local anesthetics nor elastomeric infusion devices are approved for use for continuous intra-articular infusion therapy.

Accidental Intravascular Injection

Accidental intravascular injection may result in confusion, seizures, CNS excitement and/or depression, myocardial depression, coma, and/or respiratory arrest. (See CNS Effects and also see Cardiovascular Effects, under Cautions.)

Aspirate prior to administration to guard against intravascular injection.

Warnings Associated with Spinal Anesthesia

Do not inject spinal anesthetics during uterine contractions, since spinal fluid current may carry drug further cephalad than desired.

Epinephrine Administration

Some bupivacaine hydrochloride preparations contain epinephrine, which may cause ischemic injury or necrosis. Consider usual precautions associated with epinephrine administration. (See Cardiovascular Effects under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions and Cross Hypersensitivity

Allergic reactions are rare. May be caused by sensitivity to the local anesthetic or other ingredient in the formulation (e.g., methylparaben, sulfites).

Manifestations include urticaria, pruritus, erythema, angioedema (including laryngeal edema), tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and anaphylactoid reactions (including severe hypotension).

Cross hypersensitivity between amide-type local anesthetics reported.

Sulfite Sensitivity

Some epinephrine-containing bupivacaine preparations contain sodium metabisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

General Precautions

CNS Effects

Toxic plasma concentrations of local anesthetics (resulting from systemic absorption) associated with adverse CNS effects (e.g., restlessness, anxiety, dizziness, tinnitus, blurred vision, tremors, drowsiness, seizures).

Carefully monitor level of consciousness after each local anesthetic injection.

Cardiovascular Effects

Toxic plasma concentrations of local anesthetics (resulting from systemic absorption) associated with adverse cardiovascular effects (e.g., decreased cardiac output, heart block, hypotension, bradycardia, ventricular arrhythmias, cardiac arrest). Carefully monitor cardiovascular and respiratory vital signs after each local anesthetic injection.

Use with caution in patients with impaired cardiovascular function, hypotension, or heart block.

Possible peripheral vasodilation and hypotension following spinal anesthesia; monitor BP carefully, particularly in early phases of anesthesia. Use spinal anesthesia with caution in patients with severe disturbances of cardiac rhythm, shock, or heart block.

Some bupivacaine hydrochloride preparations contain epinephrine; risk of exaggerated vasoconstrictor response in patients with hypertensive vascular disease. Use with caution and in carefully restricted quantities in areas of the body supplied by end arteries or having otherwise compromised blood supply (e.g., digits, nose, external ear, penis).

Familial Malignant Hyperthermia

Many drugs used during the conduct of anesthesia may trigger familial malignant hyperthermia; not known whether amide-type local anesthetics trigger this reaction. However, standard protocol for management should be available. Early unexplained signs of tachycardia, tachypnea, labile BP, and metabolic acidosis may precede temperature elevation. If familial malignant hyperthermia is confirmed, discontinue triggering agent and initiate appropriate therapy (e.g., oxygen, dantrolene) and other supportive measures.

Preexisting Conditions Precluding Use of Spinal Anesthesia

Conditions that may preclude the use of spinal anesthesia (depending upon the clinician’s evaluation of the situation and ability to manage potential complications) include preexisting CNS disease (e.g., disease associated with pernicious anemia, poliomyelitis, syphilis, tumor); hematological disorders predisposing to coagulopathies; current anticoagulant therapy; chronic backache; preoperative headache; hypotension or hypertension; technical problems (persistent paresthesias, persistent bloody tap); arthritis or spinal deformity; extremes of age; and psychosis or other causes of poor patient cooperation.

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

No adequate and well-controlled studies in pregnant women; developmental toxicity and embryofetal deaths (following sub-Q administration) observed in animals. Use during pregnancy only if potential benefit justifies potential risk to fetus.

Labor and Delivery

Maternal hypotension reported. To prevent decreases in BP, elevate patient’s legs and position patient on her left side. Monitor fetal heart rate continuously; electronic fetal monitoring highly advisable.

Epidural anesthesia may prolong second stage of labor (by removing parturient’s reflex urge to bear down or by interfering with motor function); may increase need for forceps assistance.

Possible diminished muscle strength and tone on neonate’s first or second day of life.

Lactation

Distributed into milk. Discontinue nursing or the drug.

Pediatric Use

Conventional bupivacaine hydrochloride with or without epinephrine not recommended in children <12 years of age.

Bupivacaine hydrochloride in dextrose injection for spinal anesthesia not recommended in children <18 years of age.

Efficacy and safety of liposomal bupivacaine not established in pediatric patients.

Continuous infusions in children have resulted in high plasma concentrations (which may increase the risk of adverse cardiovascular effects) and seizures.

Geriatric Use

Geriatric patients ≥65 years of age, particularly those with hypertension, may be more sensitive to the hypotensive effects of bupivacaine. Some manufacturers recommend reduced dosages.

Possible increased risk of toxicity in geriatric patients with renal impairment; monitor renal function.

No overall differences in safety or efficacy of liposomal bupivacaine in geriatric patients ≥65 years of age compared with younger patients.

Hepatic Impairment

Possible increased risk of toxicity, particularly in patients with severe hepatic impairment. Use with caution and closely monitor for local anesthetic systemic toxicity in patients with moderate to severe hepatic impairment. (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Substantially excreted by kidneys; possible increased risk of toxicity in patients with renal impairment. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Adverse effects are similar to those of other amide-type local anesthetics. Most common adverse effects are usually a result of excessive plasma concentrations and include CNS and cardiovascular effects. (See CNS Effects and also see Cardiovascular Effects, under Cautions.)

Most common serious adverse effects following spinal anesthesia include hypotension, respiratory paralysis, and underventilation.

Most common adverse effects of liposomal bupivacaine via local infiltration include nausea, constipation, vomiting; most common adverse effects of liposomal bupivacaine via interscalene brachial plexus nerve block include nausea, pyrexia, and constipation.

Interactions for Bupivacaine

Consider usual drug interactions associated with epinephrine administration.

Specific Drugs

Drug

Interaction

Comments

Anesthetics, general

Bupivacaine preparations containing epinephrine: Possible serious cardiac arrhythmias due to epinephrine component

Antidepressants, tricyclics

Bupivacaine preparations containing epinephrine: Possible severe, prolonged hypertension due to epinephrine component

Avoid concomitant use; if concomitant use is necessary, carefully monitor patient

Butyrophenones

Bupivacaine preparations containing epinephrine: Possible reduction or reversal of pressor effect of epinephrine

Ergot alkaloid oxytocics (ergonovine, methylergonovine)

Bupivacaine preparations containing epinephrine: Possible severe, persistent hypertension or cerebrovascular accidents due to epinephrine component

Avoid concomitant use

MAO inhibitors

Bupivacaine preparations containing epinephrine: Possible severe, prolonged hypertension due to epinephrine component

Avoid concomitant use; if concomitant use is necessary, carefully monitor patient

Phenothiazines

Bupivacaine preparations containing epinephrine: Possible reduction or reversal of pressor effect of epinephrine

Bupivacaine Pharmacokinetics

Absorption

Bioavailability

Systemic absorption dependent upon total dose and concentration administered, route of administration, vascularity of administration site, and presence or absence of epinephrine in formulation.

Conventional bupivacaine: Peak blood concentrations achieved approximately 30–45 minutes following caudal, epidural, or peripheral nerve block.

Liposomal bupivacaine: Peak plasma concentrations achieved approximately 2 hours following local infiltration in patients undergoing bunionectomy and approximately 0.5 hours following local infiltration in patients undergoing hemorrhoidectomy. Peak plasma concentrations following interscalene brachial plexus nerve block for total shoulder arthroplasty achieved in approximately 48 hours.

Onset

Onset within 2–10 minutes following local infiltration or nerve block (for dental anesthesia) with 0.5% bupivacaine hydrochloride.

Onset within 4–17 minutes following epidural, caudal, peripheral, or sympathetic block with 0.25 or 0.5% bupivacaine hydrochloride. More rapid onset following epidural block with 0.75% solution.

Following 12-mg injection of 0.75% bupivacaine hydrochloride in 8.25% dextrose solution for spinal block, sensory blockade occurs within 1 minute; motor blockade occurs within 15 minutes.

Onset of action of liposomal bupivacaine <2 minutes, which appears to be similar to conventional bupivacaine hydrochloride.

Duration

Longer duration of anesthesia compared with other commonly used local anesthetics.

Duration of up to 7 minutes following local infiltration or nerve block (for dental anesthesia) with 0.5% bupivacaine hydrochloride solution.

Duration of 3–7 minutes following epidural, caudal, peripheral, or sympathetic block with 0.25 or 0.5% bupivacaine hydrochloride solution. Slightly longer duration (6–9 hours) with 0.75% solution.

Following a 12-mg injection of 0.75% bupivacaine hydrochloride in 8.25% dextrose solution for spinal block, sensory blockade persists for 2 hours (with or without 0.2 mg epinephrine); motor blockade persists for 3.5 hours (without epinephrine) or 4.5 hours (with 0.2 mg epinephrine). Similar duration of sensory blockade but shorter duration of motor blockade compared with mg-equivalent dose of tetracaine.

Systemic concentrations of liposomal bupivacaine can persist for 96 hours after local infiltration or 120 hours after interscalene brachial plexus nerve block; however, systemic concentrations not correlated with local efficacy. Duration of analgesic effect appears to be ≤24 hours.

Special Populations

Increased peak plasma concentrations in geriatric patients. Maximal spread of analgesia and maximal motor blockade achieved more rapidly than in younger patients.

Distribution

Extent

Local anesthetics are distributed to some extent to all body tissues, with high concentrations found in highly perfused organs (e.g., liver, lungs, heart, brain).

Lower degree of placental transmission than other parenteral local anesthetics. Distributed into milk.

Distribution of liposomal bupivacaine is expected to be similar to that of other bupivacaine formulations after bupivacaine is released from the multivesicular liposome.

Plasma Protein Binding

95%.

Elimination

Metabolism

Systemically absorbed bupivacaine is metabolized in the liver via conjugation with glucuronic acid.

Elimination of liposomal bupivacaine is expected to be similar to that of other bupivacaine formulations after bupivacaine is released from the multivesicular liposome.

Elimination Route

Excreted principally in urine as inactive metabolites and small amounts (6%) of unchanged drug.

Half-life

Bupivacaine hydrochloride: Approximately 2.7–3.5 hours (in adults) or 8.1 hours (in neonates).

Liposomal bupivacaine: Approximately 24–34 hours (local infiltration) or 11 hours (interscalene brachial plexus nerve block).

Special Populations

Decreased total plasma clearance in geriatric patients.

Stability

Storage

Parenteral

Injection

Bupivacaine hydrochloride: 20–25°C. If preparation contains epinephrine, protect from light.

Liposomal bupivacaine: 2–8°C; do not freeze or expose to high temperatures (>40°C). Alternatively, may store intact vials at room temperature for ≤30 days; do not re-refrigerate once the drug has been stored at room temperature.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Bupivacaine hydrochloride solutions are compatible with sodium chloride 0.9%. Bupivacaine liposomal injection (Exparel) is compatible with sodium chloride 0.9% and lactated Ringer’s injection; the liposomal formulation is incompatible with water for injection or other hypotonic solutions since disruption of the liposomal particles may occur.

Drug Compatibility

Do not mix bupivacaine hydrochloride with other local anesthetics (insufficient clinical data).

Do not mix bupivacaine liposomal injection (Exparel) with local anesthetics other than bupivacaine; may administer liposomal bupivacaine and bupivacaine hydrochloride in same syringe, or may administer bupivacaine hydrochloride immediately before liposomal bupivacaine as long as mg ratio of the conventional to liposomal drug does not exceed 1:2. Do not mix liposomal bupivacaine with other drugs.

Admixture Compatibility of Bupivacaine HydrochlorideHID

Compatible

Buprenorphine HCl

Clonidine HCl

Epinephrine bitartrate

Epinephrine HCl

Fentanyl citrate

Hydromorphone HCl

Morphine sulfate

Sufentanil citrate

Ziconotide acetate

Syringe Compatibility of Bupivacaine HydrochlorideHID

Compatible

Clonidine HCl

Clonidine HCl with fentanyl citrate

Clonidine HCl with morphine sulfate

Hydromorphone HCl

Ketamine with fentanyl citrate

Morphine sulfate

Variable

Sodium bicarbonate

Actions

  • Local anesthetics block the generation and conduction of nerve impulses by increasing the threshold for electrical excitation, slowing the propagation of the nerve impulse, and reducing the rate of rise of the action potential.

  • Bupivacaine exhibits analgesic effects that persist after return of sensation; thus need for strong analgesics is reduced.

  • Some preparations formulated with epinephrine to decrease bupivacaine’s rate and extent of systemic absorption and to prolong its duration of action.

  • Considered a long-acting local anesthetic.

Advice to Patients

  • Prior to administration, advise patients of the possibility of temporary loss of sensation and muscle function (e.g., in lower half of body following caudal, lumbar epidural, or subarachnoid block).

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular or liver disease).

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Bupivacaine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

0.25%*

Bupivacaine Hydrochloride Injection

Marcaine

Hospira

Sensorcaine

Fresenius Kabi

Sensorcaine-MPF

0.5%*

Bupivacaine Hydrochloride Injection

Marcaine

Hospira

Sensorcaine

Fresenius Kabi

Sensorcaine-MPF

Fresenius Kabi

0.75%*

Bupivacaine Hydrochloride Injection

Marcaine

Hospira

Sensorcaine-MPF

Fresenius Kabi

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Bupivacaine Hydrochloride in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

0.75% in 8.25% Dextrose*

Bupivacaine Hydrochloride in 8.25% Dextrose Injection Spinal

Marcaine Spinal

Hospira

Bupivacaine Liposomal

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injectable suspension

13.3 mg (of bupivacaine) per mL (133 or 266 mg)

Exparel

Pacira

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Bupivacaine Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

0.25% with Epinephrine Bitartrate 1:200,000 (of epinephrine)*

Bupivacaine Hydrochloride and Epinephrine Injection

Marcaine with Epinephrine

Hospira

Sensorcaine with Epinephrine

Fresenius Kabi

Sensorcaine-MPF with Epinephrine

Fresenius Kabi

0.5% with Epinephrine Bitartrate 1:200,000 (of epinephrine)*

Bupivacaine Hydrochloride and Epinephrine Injection

Marcaine with Epinephrine

Hospira

Sensorcaine with Epinephrine

Fresenius Kabi

Sensorcaine-MPF with Epinephrine

Fresenius Kabi

0.75% with Epinephrine Bitartrate 1:200,000 (of epinephrine)

Sensorcaine-MPF with Epinephrine

Fresenius Kabi

AHFS DI Essentials™. © Copyright 2022, Selected Revisions November 19, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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