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Bupivacaine Hydrochloride

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

Medically reviewed on Nov 19, 2018

Warning

    Bupivacaine Hydrochloride 0.75% Concentration
  • Use of the 0.75% solution of bupivacaine hydrochloride not recommended for obstetrical epidural anesthesia.211 213 Cardiac arrest with difficult resuscitation or death reported, presumably from systemic toxicity following unintentional intravascular injection.211 213

  • Reserve 0.75% solution for surgical procedures that require a high degree of muscle relaxation and prolonged anesthetic effect.211 213

Introduction

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

Uses for Bupivacaine Hydrochloride

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 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 (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

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

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

Interactions for Bupivacaine Hydrochloride

Consider usual drug interactions associated with epinephrine administration.211 213

Specific Drugs

Drug

Interaction

Comments

Anesthetics, general

Bupivacaine preparations containing epinephrine: Possible serious cardiac arrhythmias due to epinephrine component211 213

 

Antidepressants, tricyclics

Bupivacaine preparations containing epinephrine: Possible severe, prolonged hypertension due to epinephrine component211 213

Avoid concomitant use;211 213 if concomitant use is necessary, carefully monitor patient211

Butyrophenones

Bupivacaine preparations containing epinephrine: Possible reduction or reversal of pressor effect of epinephrine211 213

 

Ergot alkaloid oxytocics (ergonovine, methylergonovine)

Bupivacaine preparations containing epinephrine: Possible severe, persistent hypertension or cerebrovascular accidents due to epinephrine component211 213

Avoid concomitant use211 213

MAO inhibitors

Bupivacaine preparations containing epinephrine: Possible severe, prolonged hypertension due to epinephrine component211 213

Avoid concomitant use;211 213 if concomitant use is necessary, carefully monitor patient211 213

Phenothiazines

Bupivacaine preparations containing epinephrine: Possible reduction or reversal of pressor effect of epinephrine211 213

Bupivacaine Hydrochloride 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

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

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

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.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.)

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 2018, 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.

References

200. Food and Drug Administration. Information for healthcare professionals: Chondrolysis reported with continuously infused local anesthetics (marketed as bupivacaine, chloroprocaine, lidocaine, mepivacaine, procaine, and ropivacaine). Rockville, MD; Updated 2010 Feb 16. From FDA website (http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm190302.htm).

201. Todd JF. Chondrolysis linked to intra-articular infusions. Medical Devices Alerts and Notices. Silver Spring, MD: Food and Drug Administration; 2010 June. From FDA website (http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/TipsandArticlesonDeviceSafety/ucm214699.htm).

202. Hansen BP, Beck CL, Beck EP et al. Postarthroscopic glenohumeral chondrolysis. Am J Sports Med. 2007; 35:1628-34. http://www.ncbi.nlm.nih.gov/pubmed/17609526?dopt=AbstractPlus

203. Bailie DS, Ellenbecker TS. Severe chondrolysis after shoulder arthroscopy: a case series. J Shoulder Elbow Surg. 2009 Sep-Oct; 18:742-7.

204. Anakwenze OA, Hosalkar H, Huffman GR. Case Reports: Two Cases of Glenohumeral Chondrolysis after Intraarticular Pain Pumps. Clin Orthop Relat Res. 2010; :. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2919888&blobtype=pdf

205. Anderson SL, Buchko JZ, Taillon MR et al. Chondrolysis of the glenohumeral joint after infusion of bupivacaine through an intra-articular pain pump catheter: a report of 18 cases. Arthroscopy. 2010; 26:451-61. http://www.ncbi.nlm.nih.gov/pubmed/20362823?dopt=AbstractPlus

206. Rapley JH, Beavis RC, Barber FA. Glenohumeral chondrolysis after shoulder arthroscopy associated with continuous bupivacaine infusion. Arthroscopy. 2009; 25:1367-73. http://www.ncbi.nlm.nih.gov/pubmed/19962061?dopt=AbstractPlus

207. Scheffel PT, Clinton J, Lynch JR et al. Glenohumeral chondrolysis: A systematic review of 100 cases from the English language literature. J Shoulder Elbow Surg. 2010; :. http://www.ncbi.nlm.nih.gov/pubmed/20421168?dopt=AbstractPlus

208. Ballieul RJ, Jacobs TF, Herregods S et al. The peri-operative use of intra-articular local anesthetics: a review. Acta Anaesthesiol Belg. 2009; 60:101-8. http://www.ncbi.nlm.nih.gov/pubmed/19594092?dopt=AbstractPlus

209. Busfield BT, Romero DM. Pain pump use after shoulder arthroscopy as a cause of glenohumeral chondrolysis. Arthroscopy. 2009; 25:647-52. http://www.ncbi.nlm.nih.gov/pubmed/19501296?dopt=AbstractPlus

211. Fresenius Kabi. Sensorcaine (bupivacaine hydrochloride injection, USP), Sensorcaine-MPF (bupivacaine hydrochloride injection, USP), Sensorcaine with epinephrine (bupivacaine hydrochloride and epinephrine injection, USP), and Sensorcaine-MPF with epinephrine (bupivacaine hydrochloride and epinephrine injection, USP) prescribing information. Lake Zurich, IL; 2016 Jan.

213. Hospira. Marcaine (bupivacaine hydrochloride injection, USP), Marcaine with epinephrine (bupivacaine hydrochloride and epinephrine injection, USP) prescribing information. Lake Forest, IL; 2017 Nov.

214. Hospira. Marcaine Spinal (bupivacaine hydrochloride in dextrose injection, USP) prescribing information. Lake Forest, IL; 2017 Nov.

215. Hospira. Bupivacaine hydrochloride and epinephrine injection prescribing information. Lake Forest, IL; 2006 Nov.

216. Pacira. Exparel (bupivacaine liposome injectable suspension) prescribing information. San Diego, CA; 2018 Apr.

217. . Bupivacaine liposomal injection (Exparel) for post surgical pain. Med Lett Drugs Ther. 2012; 54:26-7. http://www.ncbi.nlm.nih.gov/pubmed/22469650?dopt=AbstractPlus

218. Hamilton TW, Athanassoglou V, Mellon S et al. Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain. Cochrane Database Syst Rev. 2017; 2:CD011419. http://www.ncbi.nlm.nih.gov/pubmed/28146271?dopt=AbstractPlus

219. Hamilton TW, Athanassoglou V, Trivella M et al. Liposomal bupivacaine peripheral nerve block for the management of postoperative pain. Cochrane Database Syst Rev. 2016; :CD011476. http://www.ncbi.nlm.nih.gov/pubmed/27558150?dopt=AbstractPlus

220. Chou R, Gordon DB, de Leon-Casasola OA et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016; 17:131-57. http://www.ncbi.nlm.nih.gov/pubmed/26827847?dopt=AbstractPlus

221. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 022496Orig1s000: Cross discipline team leader review. From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022496Orig1s000CrossR.pdf

222. Gorfine SR, Onel E, Patou G et al. Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Dis Colon Rectum. 2011; 54:1552-9. http://www.ncbi.nlm.nih.gov/pubmed/22067185?dopt=AbstractPlus

223. Golf M, Daniels SE, Onel E. A phase 3, randomized, placebo-controlled trial of DepoFoam bupivacaine (extended-release bupivacaine local analgesic) in bunionectomy. Adv Ther. 2011; 28:776-88. http://www.ncbi.nlm.nih.gov/pubmed/21842428?dopt=AbstractPlus

225. Zlotnicki JP, Hamlin BR, Plakseychuk AY et al. Liposomal Bupivacaine vs Plain Bupivacaine in Periarticular Injection for Control of Pain and Early Motion in Total Knee Arthroplasty: A Randomized, Prospective Study. J Arthroplasty. 2018; 33:2460-2464. http://www.ncbi.nlm.nih.gov/pubmed/29656977?dopt=AbstractPlus

226. Dasta J, Ramamoorthy S, Patou G et al. Bupivacaine liposome injectable suspension compared with bupivacaine HCl for the reduction of opioid burden in the postsurgical setting. Curr Med Res Opin. 2012; 28:1609-15. http://www.ncbi.nlm.nih.gov/pubmed/22900785?dopt=AbstractPlus

227. Asche CV, Ren J, Kim M et al. Local infiltration for postsurgical analgesia following total hip arthroplasty: a comparison of liposomal bupivacaine to traditional bupivacaine. Curr Med Res Opin. 2017; 33:1283-1290. http://www.ncbi.nlm.nih.gov/pubmed/28375752?dopt=AbstractPlus

228. Wang X, Xiao L, Wang Z et al. Comparison of peri-articular liposomal bupivacaine and standard bupivacaine for postsurgical analgesia in total knee arthroplasty: A systematic review and meta-analysis. Int J Surg. 2017; 39:238-248. http://www.ncbi.nlm.nih.gov/pubmed/28192247?dopt=AbstractPlus

229. Alijanipour P, Tan TL, Matthews CN et al. Periarticular Injection of Liposomal Bupivacaine Offers No Benefit Over Standard Bupivacaine in Total Knee Arthroplasty: A Prospective, Randomized, Controlled Trial. J Arthroplasty. 2017; 32:628-634. http://www.ncbi.nlm.nih.gov/pubmed/27667533?dopt=AbstractPlus

230. Haas E, Onel E, Miller H et al. A double-blind, randomized, active-controlled study for post-hemorrhoidectomy pain management with liposome bupivacaine, a novel local analgesic formulation. Am Surg. 2012; 78:574-81. http://www.ncbi.nlm.nih.gov/pubmed/22546131?dopt=AbstractPlus

231. Perets I, Walsh JP, Mu BH et al. Intraoperative Infiltration of Liposomal Bupivacaine vs Bupivacaine Hydrochloride for Pain Management in Primary Total Hip Arthroplasty: A Prospective Randomized Trial. J Arthroplasty. 2018; 33:441-446. http://www.ncbi.nlm.nih.gov/pubmed/29033152?dopt=AbstractPlus

232. Uskova A, O'Connor JE. Liposomal bupivacaine for regional anesthesia. Curr Opin Anaesthesiol. 2015; 28:593-7. http://www.ncbi.nlm.nih.gov/pubmed/26308513?dopt=AbstractPlus

233. Sakamoto B, Keiser S, Meldrum R et al. Efficacy of Liposomal Bupivacaine Infiltration on the Management of Total Knee Arthroplasty. JAMA Surg. 2017; 152:90-95. http://www.ncbi.nlm.nih.gov/pubmed/27732710?dopt=AbstractPlus

234. Neal JM, Barrington MJ, Fettiplace MR et al. The Third American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity: Executive Summary 2017. Reg Anesth Pain Med. 2018; 43:113-123. http://www.ncbi.nlm.nih.gov/pubmed/29356773?dopt=AbstractPlus

236. Aggarwal N. Local anesthetics systemic toxicity association with exparel (bupivacaine liposome)- a pharmacovigilance evaluation. Expert Opin Drug Saf. 2018; 17:581-587. http://www.ncbi.nlm.nih.gov/pubmed/28538107?dopt=AbstractPlus

237. Institute for Safe Medication Practices. Potential for wrong route errors with Exparel (bupivacaine liposome injectable suspension). ISMP Medication Safety Alerts. Horsham, PA; 2012 Mar. From ISMP website https://www.ismp.org/alerts/potential-wrong-route-errors-exparel-bupivacaine-liposome-injectable-suspension

a. AHFS drug information 2019. McEvoy GK, ed. Bupivacaine Hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2019

HID. Trissel LA. Handbook on injectable drugs. 19th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2017: 177–80.

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