Brand names: Exparel, Marcaine, Marcaine Spinal, Sensorcaine, Sensorcaine-MPF
Drug class: Local Anesthetics

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Long-acting local anesthetic (amide type).^{211 213 a}

Uses for Bupivacaine Hydrochloride, Bupivacaine Liposomal (Local)

Local or Regional Anesthesia or Analgesia

Local or regional anesthesia or analgesia in surgical, obstetrical, dental, diagnostic, and therapeutic procedures.^{211 213 214 216}

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).^{211 213 214 215 216}

Conventional preparations are used for local infiltration and nerve block techniques including peripheral, sympathetic, epidural (including caudal), retrobulbar, and dental block.^{211 213 215} Do not use 0.75% concentration for obstetrical anesthesia.^{211 213} (See Boxed Warning.) A hyperbaric solution containing 0.75% bupivacaine hydrochloride in 8.25% dextrose is used for spinal anesthesia.²¹⁴

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.^{216 218 222 223} Because of possible differences in physiochemical and functional properties, do not use liposomal bupivacaine interchangeably with other bupivacaine-containing preparations.^{216 234}

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.^{216 220}

Studies comparing relative efficacy of liposomal bupivacaine and conventional bupivacaine hydrochloride for postsurgical analgesia have shown variable results.^{218 225 226 227 228 229 230 231 232}

Do not use for obstetric paracervical block.^{211 213 216}

Bupivacaine Hydrochloride, Bupivacaine Liposomal (Local) 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.^{211 213 214 216 220}

• Resuscitative equipment, oxygen, drugs, and personnel required for treatment of adverse reactions should be immediately available.^{211 213 214 216}

• Administer slowly in incremental doses to reduce risk of adverse effects (e.g., local anesthetic systemic toxicity).^{211 213 216 234}

• 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.^{211 213 214 216}

• During major regional nerve blocks, administer IV fluids via an indwelling catheter to ensure a functioning IV pathway.^{211 213}

• 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.^{211 213}

• Carefully and constantly monitor patients for possible cardiovascular, respiratory, or CNS complications during and after administration.^{211 213 214 216}

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.^{211 213 215} Administer 0.75% bupivacaine hydrochloride in 8.25% dextrose solution by subarachnoid injection for spinal anesthesia.²¹⁴

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.²¹⁶

Do not administer using Bier block technique (IV regional anesthesia) due to risk of cardiac arrest and death.^{211 213}

Has been administered by continuous intra-articular infusion^{† [off-label]} (e.g., for control of postoperative pain); however, such use associated with chondrolysis.^{200 201 202 203 204 205 206 207 208 209 211 213 214 216} (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.^{211 213 214}

Do not use liposomal bupivacaine interchangeably with other bupivacaine formulations.²¹⁶

Do not use bupivacaine solutions containing preservatives for epidural or caudal block; discard partially used solutions that do not contain preservatives.^{211 213}

Liposomal Bupivacaine

May administer undiluted or diluted (if an increased volume of drug is necessary to cover a larger surgical area).²¹⁶

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.²¹⁶ Use diluted suspension within 4 hours of preparation in a syringe.²¹⁶

Invert vial multiple times to resuspend drug particles immediately prior to drug withdrawal.²¹⁶ Administer using 25-gauge or larger bore needle.²¹⁶ Do not filter.²¹⁶

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.²¹⁶ Delay administration of liposomal bupivacaine for ≥20 minutes after administration of lidocaine.²¹⁶

Compatibility between liposomal bupivacaine and conventional bupivacaine hydrochloride is concentration dependent.²¹⁶ 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 1:2.²¹⁶ Consider potential for additive toxic effects when the drugs are used concomitantly.^{216 236} Avoid additional administration of local anesthetics for ≥96 hours after liposomal bupivacaine is administered.²¹⁶

Avoid contact with topical antiseptics (e.g., povidone iodine); allow topical antiseptic to dry before liposomal bupivacaine is administered.²¹⁶

Standardize 4 Safety

Standardized concentrations for bupivacaine have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care.²⁵¹ Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label.²⁵¹ For additional information on S4S (including updates that may be available), see [Web].²⁵¹

Potential Administration Errors

Because of similarity in appearance (milky white suspension), potential exists for confusion between liposomal bupivacaine and propofol.²³⁷

Take special precautions (e.g., proper labeling of syringes, storage segregation, routine double-checks) to ensure that such confusion does not occur.²³⁷

If mistaken for propofol, inadvertent IV administration of liposomal bupivacaine may occur and cause substantial patient harm (e.g., cardiac arrhythmias, arrest).²³⁷

Instructions for treatment of bupivacaine toxicity should be readily available in all surgical areas where liposomal bupivacaine is used.²³⁷

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.^{211 213}

Liposomal preparation available as bupivacaine (as free base) in suspension of multivesicular liposomes.²¹⁶

Individualize dosage based on anesthetic procedure, degree of anesthesia required, surgical site, and individual patient response.^{211 213 214 216} Use lowest effective dosage.^{211 213 214 234}

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.^{211 213} 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).^{211 213} Following injection of test dose, monitor for increase in heart rate.^{211 213}

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.²¹¹ (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).^{211 213}

Liposomal bupivacaine: Single dose of up to 266 mg recommended.²¹⁶ 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).²¹⁶ 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.^{216 222}

Lumbar Epidural Block (Bupivacaine Hydrochloride)

0.75% solution is for single-dose use; not for intermittent epidural technique.^{211 213} Reserve for surgical procedures requiring a high degree of muscle relaxation and prolonged anesthetic effect.^{211 213}

0.75% solution is not for obstetrical anesthesia; in obstetrics, use 0.25 or 0.5% solutions only.^{211 213} (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.^{211 213} Administer in incremental doses of 3–5 mL.^{211 213} Allow sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection.^{211 213}

50–100 mg (10–20 mL) of bupivacaine hydrochloride 0.5% solution (with or without epinephrine) produces moderate to complete motor blockade.^{211 213} Administer in incremental doses of 3–5 mL.^{211 213} Allow sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection.^{211 213}

25–50 mg (10–20 mL) of bupivacaine hydrochloride 0.25% solution (with or without epinephrine) produces partial motor blockade.^{211 213}

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.^{211 213}

37.5–75 mg (15–30 mL) of bupivacaine hydrochloride 0.25% solution (with or without epinephrine) produces moderate motor blockade.^{211 213}

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.^{211 213}

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.^{211 213}

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.²¹⁶

Retrobulbar Block (Bupivacaine Hydrochloride)

15–30 mg (2–4 mL) of bupivacaine hydrochloride 0.75% solution (with or without epinephrine) produces complete motor blockade.^{211 213}

Sympathetic Block (Bupivacaine Hydrochloride)

50–125 mg (20–50 mL) of bupivacaine hydrochloride 0.25% solution.^{211 213}

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.^{211 213}

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.²¹⁴

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.²¹⁴

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.²¹⁴

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.²¹⁴

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.^{211 213}

Most experience to date has involved single doses up to 175 mg (without epinephrine) or 225 mg (with epinephrine 1:200,000).^{211 213}

Until further experience, manufacturer recommends that a maximum dose of 400 mg not be exceeded in any 24-hour period.^{211 213}

Liposomal Bupivacaine

Local Infiltration

Maximum dose of 266 mg.²¹⁶

Special Populations

Hepatic Impairment

Use with caution and monitor carefully in patients with liver disease.^{211 213}

Renal Impairment

Consider possibility of increased risk of toxicity in patients with renal impairment and select appropriate dosage accordingly.²¹⁶

Geriatric Patients

Geriatric patients may require reduced dosages.^{211 213 215}

Other Populations

Patients with cardiac disease, debilitated patients, and acutely ill patients may require reduced dosages.^{211 215} Reduced dosages also may be required in patients with increased intra-abdominal pressure (including obstetrical patients) undergoing spinal anesthesia.²¹⁴

Cautions for Bupivacaine Hydrochloride, Bupivacaine Liposomal (Local)

Contraindications

• Obstetrical paracervical block (this technique has resulted in fetal bradycardia and death).^{211 213 216}

• 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.²¹⁴

• Known hypersensitivity to bupivacaine, other local anesthetics of the amide type, or any ingredients in the formulation.^{211 213 214}

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.^{211 213} (See Boxed Warning.)

Not recommended for obstetrical anesthesia.²¹¹ Reserve for surgical procedures requiring a high degree of muscle relaxation and prolonged anesthetic effect.²¹¹

Administration Precautions

Because of the potential for serious adverse effects, take special precautions during administration.^{211 213 214 216} (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.^{211 213} Delay in proper management of dose-related toxicity may result in acidosis, cardiac arrest, and, possibly, death.^{211 213}

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.^{200 201 202 203 204 205 206 207 208 209 211 213 214} Primarily observed in the shoulder joint following arthroscopic or other shoulder surgery.^{200 211 213 214} May result in long-term disability; often requires intervention (e.g., debridement, arthroplasty).^{200 202 203 204 205 206 209 211 213 214} Not known whether the drug, infusion device, and/or other factors contributed to the development of chondrolysis.^{200 201} Neither local anesthetics nor elastomeric infusion devices are approved for use for continuous intra-articular infusion therapy.^{200 201 211 213 214}

Accidental Intravascular Injection

Accidental intravascular injection may result in confusion, seizures, CNS excitement and/or depression, myocardial depression, coma, and/or respiratory arrest.^{211 213} (See CNS Effects and also see Cardiovascular Effects, under Cautions.)

Aspirate prior to administration to guard against intravascular injection.^{211 213}

Warnings Associated with Spinal Anesthesia

Do not inject spinal anesthetics during uterine contractions, since spinal fluid current may carry drug further cephalad than desired.²¹⁴

Epinephrine Administration

Some bupivacaine hydrochloride preparations contain epinephrine, which may cause ischemic injury or necrosis.^{211 213} Consider usual precautions associated with epinephrine administration.^{211 213} (See Cardiovascular Effects under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions and Cross Hypersensitivity

Allergic reactions are rare.^{211 213} May be caused by sensitivity to the local anesthetic or other ingredient in the formulation (e.g., methylparaben, sulfites).^{211 213}

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).^{211 213}

Cross hypersensitivity between amide-type local anesthetics reported.^{211 213}

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.^{211 213}

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).^{211 213}

Carefully monitor level of consciousness after each local anesthetic injection.^{211 213}

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).^{211 213} Carefully monitor cardiovascular and respiratory vital signs after each local anesthetic injection.^{211 213}

Use with caution in patients with impaired cardiovascular function, hypotension, or heart block.^{211 213}

Possible peripheral vasodilation and hypotension following spinal anesthesia; monitor BP carefully, particularly in early phases of anesthesia.²¹⁴ Use spinal anesthesia with caution in patients with severe disturbances of cardiac rhythm, shock, or heart block.²¹⁴

Some bupivacaine hydrochloride preparations contain epinephrine; risk of exaggerated vasoconstrictor response in patients with hypertensive vascular disease.^{211 213} 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).^{211 213}

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.^{211 213} However, standard protocol for management should be available.^{211 213} Early unexplained signs of tachycardia, tachypnea, labile BP, and metabolic acidosis may precede temperature elevation.^{211 213} If familial malignant hyperthermia is confirmed, discontinue triggering agent and initiate appropriate therapy (e.g., oxygen, dantrolene) and other supportive measures.^{211 213}

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.²¹⁴

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.^{211 213 216} Use during pregnancy only if potential benefit justifies potential risk to fetus.^{211 213}

Labor and Delivery

Maternal hypotension reported.^{211 213} To prevent decreases in BP, elevate patient’s legs and position patient on her left side.²¹¹ Monitor fetal heart rate continuously; electronic fetal monitoring highly advisable.^{211 213}

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.^{211 213}

Possible diminished muscle strength and tone on neonate’s first or second day of life.^{211 213}

Lactation

Distributed into milk.^{211 213} Discontinue nursing or the drug.^{211 213}

Pediatric Use

Conventional bupivacaine hydrochloride with or without epinephrine not recommended in children <12 years of age.^{211 213}

Bupivacaine hydrochloride in dextrose injection for spinal anesthesia not recommended in children <18 years of age.²¹⁴

Efficacy and safety of liposomal bupivacaine not established in pediatric patients.²¹⁶

Continuous infusions in children have resulted in high plasma concentrations (which may increase the risk of adverse cardiovascular effects) and seizures.^{211 213}

Geriatric Use

Geriatric patients ≥65 years of age, particularly those with hypertension, may be more sensitive to the hypotensive effects of bupivacaine.^{211 213} Some manufacturers recommend reduced dosages.^{211 213}

Possible increased risk of toxicity in geriatric patients with renal impairment; monitor renal function.^{211 213 216}

No overall differences in safety or efficacy of liposomal bupivacaine in geriatric patients ≥65 years of age compared with younger patients.²¹⁶

Hepatic Impairment

Possible increased risk of toxicity, particularly in patients with severe hepatic impairment.^{211 213} Use with caution and closely monitor for local anesthetic systemic toxicity in patients with moderate to severe hepatic impairment.^{211 213 216} (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Substantially excreted by kidneys; possible increased risk of toxicity in patients with renal impairment.^{211 213 216} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Adverse effects are similar to those of other amide-type local anesthetics.^{211 213 214} Most common adverse effects are usually a result of excessive plasma concentrations and include CNS and cardiovascular effects.^{211 213} (See CNS Effects and also see Cardiovascular Effects, under Cautions.)

Most common serious adverse effects following spinal anesthesia include hypotension, respiratory paralysis, and underventilation.²¹⁴

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.²¹⁶

Drug Interactions

Consider usual drug interactions associated with epinephrine administration.^{211 213}

Specific Drugs

Bupivacaine Hydrochloride, Bupivacaine Liposomal (Local) 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.^{211 213 214 216}

Conventional bupivacaine: Peak blood concentrations achieved approximately 30–45 minutes following caudal, epidural, or peripheral nerve block.^{211 213}

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.²¹⁶ Peak plasma concentrations following interscalene brachial plexus nerve block for total shoulder arthroplasty achieved in approximately 48 hours.²¹⁶

Onset

Onset within 2–10 minutes following local infiltration or nerve block (for dental anesthesia) with 0.5% bupivacaine hydrochloride.^{211 213 215}

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

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.²¹⁴

Onset of action of liposomal bupivacaine <2 minutes, which appears to be similar to conventional bupivacaine hydrochloride.²²¹

Duration

Longer duration of anesthesia compared with other commonly used local anesthetics.²¹¹

Duration of up to 7 minutes following local infiltration or nerve block (for dental anesthesia) with 0.5% bupivacaine hydrochloride solution.^{215 a}

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

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).²¹⁴ Similar duration of sensory blockade but shorter duration of motor blockade compared with mg-equivalent dose of tetracaine.²¹⁴

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.²¹⁶ Duration of analgesic effect appears to be ≤24 hours.²²¹

Special Populations

Increased peak plasma concentrations in geriatric patients.²¹¹ Maximal spread of analgesia and maximal motor blockade achieved more rapidly than in younger patients.²¹¹

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).^{211 213}

Lower degree of placental transmission than other parenteral local anesthetics.^a Distributed into milk.^{211 213}

Distribution of liposomal bupivacaine is expected to be similar to that of other bupivacaine formulations after bupivacaine is released from the multivesicular liposome.²¹⁶

Plasma Protein Binding

95%.^{211 213}

Elimination

Metabolism

Systemically absorbed bupivacaine is metabolized in the liver via conjugation with glucuronic acid.^{211 213}

Elimination of liposomal bupivacaine is expected to be similar to that of other bupivacaine formulations after bupivacaine is released from the multivesicular liposome.²¹⁶

Elimination Route

Excreted principally in urine as inactive metabolites and small amounts (6%) of unchanged drug.^{211 213}

Half-life

Bupivacaine hydrochloride: Approximately 2.7–3.5 hours (in adults) or 8.1 hours (in neonates).^{211 213}

Liposomal bupivacaine: Approximately 24–34 hours (local infiltration) or 11 hours (interscalene brachial plexus nerve block).²¹⁶

Special Populations

Decreased total plasma clearance in geriatric patients.^{211 213}

Stability

Storage

Parenteral

Injection

Bupivacaine hydrochloride: 20–25°C.^{211 213 214} If preparation contains epinephrine, protect from light.^{211 213}

Liposomal bupivacaine: 2–8°C; do not freeze or expose to high temperatures (>40°C).²¹⁶ Alternatively, may store intact vials at room temperature for ≤30 days; do not re-refrigerate once the drug has been stored at room temperature.²¹⁶

Compatibility

Parenteral

Solution Compatibility

Bupivacaine hydrochloride solutions are compatible with sodium chloride 0.9%.^HID 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.²¹⁶

Drug Compatibility

Do not mix bupivacaine hydrochloride with other local anesthetics (insufficient clinical data).^{211 213}

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 1:2.²¹⁶ Do not mix liposomal bupivacaine with other drugs.²¹⁶

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.^{211 213}

• Bupivacaine exhibits analgesic effects that persist after return of sensation; thus need for strong analgesics is reduced.^{211 213}

• Some preparations formulated with epinephrine to decrease bupivacaine’s rate and extent of systemic absorption and to prolong its duration of action.^{211 213}

• Considered a long-acting local anesthetic.^{211 213}

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).^{211 213}

• 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).^{211 213}

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{211 213}

• Importance of informing patients of other important precautionary information.^{211 213 214 216} (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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

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