Bupivacaine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Kit, Injection, as hydrochloride:

P-Care M: 0.5%

Kit, Injection, as hydrochloride [preservative free]:

ReadySharp Bupivacaine: 0.5% [DSC]

Solution, Injection, as hydrochloride:

Marcaine: 0.25% (50 mL); 0.5% (50 mL) [contains methylparaben]

Sensorcaine: 0.25% (50 mL); 0.5% (50 mL) [contains methylparaben]

Generic: 0.25% (30 mL [DSC], 50 mL); 0.5% (50 mL)

Solution, Injection, as hydrochloride [preservative free]:

Bupivacaine Fisiopharma: 2.5 mg/mL (5 mL, 10 mL); 5 mg/mL (5 mL, 10 mL)

Marcaine: 0.75% (10 mL, 30 mL)

Marcaine Preservative Free: 0.25% (10 mL, 30 mL); 0.5% (10 mL, 30 mL)

Sensorcaine-MPF: 0.25% (10 mL, 30 mL); 0.5% (10 mL, 30 mL); 0.75% (10 mL, 30 mL) [methylparaben free]

Generic: 0.25% (10 mL, 30 mL); 0.5% (10 mL, 20 mL [DSC], 30 mL); 0.75% (10 mL, 20 mL [DSC], 30 mL)

Solution, Intrathecal, as hydrochloride:

Generic: 0.75% [7.5 mg/mL] (2 mL)

Solution, Intrathecal, as hydrochloride [preservative free]:

Bupivacaine Spinal: 0.75% [7.5 mg/mL] (2 mL)

Marcaine Spinal: 0.75% [7.5 mg/mL] (2 mL)

Sensorcaine-MPF Spinal: 0.75% [7.5 mg/mL] (2 mL [DSC])

Pharmacology

Mechanism of Action

Blocks both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions, which results in inhibition of depolarization with resultant blockade of conduction

Pharmacokinetics/Pharmacodynamics

Distribution

Infants: 3.9 ± 2 L/kg

Children: 2.7 ± 0.2 L/kg

Metabolism

Hepatic; forms metabolite (pipecoloxylidine [PPX])

Excretion

Excretion: Urine (~6% unchanged)

Clearance: Infants: 7.1 ± 3.2 mL/kg/minute; Children: 10 ± 0.7 mL/kg/minute

Onset of Action

Anesthesia (route and dose dependent):

Epidural: Up to 17 minutes to spread to T6 dermatome (Scott 1980)

Infiltration: Fast (Barash 2009); Dental injection: 2 to 10 minutes

Spinal: Within 1 minute; maximum dermatome level achieved within 15 minutes in most cases

Time to Peak

Plasma: Caudal, epidural, or peripheral nerve block: 30 to 45 minutes

Duration of Action

Route and dose dependent:

Epidural: 2 to 7.7 hours (Barash 2009)

Infiltration: 2 to 8 hours (Barash 2009); Dental injection: Up to 7 hours

Spinal: 1.5 to 2.5 hours (Tsai 2007)

Half-Life Elimination

Age dependent: Neonates: 8.1 hours; Adults: 2.7 hours

Protein Binding

84% to 95%

Use in Specific Populations

Special Populations: Elderly

Elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger patients. Elderly patients also exhibited higher peak plasma concentrations following administration of this product. The total plasma clearance was decreased in these patients.

Use: Labeled Indications

Local or regional anesthesia; spinal anesthesia (0.75% in dextrose 8.25% injection); diagnostic and therapeutic procedures; obstetrical procedures (only 0.25% and 0.5% concentrations)

0.25%: Local infiltration, peripheral nerve block, sympathetic block, caudal or epidural block

0.5%: Peripheral nerve block, caudal and epidural block

0.75% (not for obstetrical anesthesia): Retrobulbar block, epidural block. Note: Reserve for surgical procedures where a high degree of muscle relaxation and prolonged effect are necessary

Contraindications

Hypersensitivity to bupivacaine hydrochloride, amide-type local anesthetics, or any component of the formulation; obstetrical paracervical block anesthesia

Note: Use as intravenous regional anesthesia (Bier block) is considered contraindicated per accepted clinical practice due to reports of cardiac arrest and death.

Canadian labeling: Additional contraindications (not in US labeling): IV regional anesthesia (Bier block); severe shock and in heart block where there is inflammation and/or sepsis near the proposed injection site (Marcaine only).

Dosage and Administration

Dosing: Adult

Note: Dose varies with procedure, depth of anesthesia, vascularity of tissues, duration of anesthesia, and condition of patient. Do not use solutions containing preservatives for caudal or epidural block.

Local anesthesia: Infiltration: 0.25% infiltrated locally; maximum: 175 mg. Note: Aspiration should be performed prior to each injection; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided (Mulroy 2010).

Caudal block (preservative free): 15 to 30 mL of 0.25% or 0.5%

Epidural block (other than caudal block; preservative free): Administer in 3 to 5 mL increments, allowing sufficient time to detect toxic manifestations of inadvertent IV or intrathecal administration: 10 to 20 mL of 0.25% or 0.5%

Surgical procedures requiring a high degree of muscle relaxation and prolonged effects only: 10 to 20 mL of 0.75% (Note: Not to be used in obstetrical cases)

Peripheral nerve block: 5 mL of 0.25% or 0.5%; maximum: 400 mg/day

Sympathetic nerve block: 20 to 50 mL of 0.25%

Retrobulbar anesthesia: 2 to 4 mL of 0.75%

Spinal anesthesia: Preservative free solution of 0.75% bupivacaine in 8.25% dextrose:

Lower extremity and perineal procedures: 1 mL

Lower abdominal procedures: 1.6 mL

Normal vaginal delivery: 0.8 mL (higher doses may be required in some patients)

Cesarean delivery: 1 to 1.4 mL

Combined spinal-epidural (CSE) technique for labor analgesia (off-label dosing [spinal component]): 1.75 to 2.5 mg combined with fentanyl 15 mcg (Eltzschig 2003; Ngan Kee 2014; Whitty 2007).

Combined spinal-epidural (CSE) technique for anesthesia for Cesarean delivery (off-label dosing [spinal component]): 9 to 12 mg combined with fentanyl 15 mcg; in addition to fentanyl, may also include a longer-acting opioid (ie, morphine 100 to 150 mcg) for postoperative analgesia (Santos 2015).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dose varies with procedure, depth of anesthesia, vascularity of tissues, duration of anesthesia, and condition of patient. Preservative-free formulations are recommended for administration into the CNS space (eg, epidural, caudal, spinal). Consider incremental administration with negative aspiration prior to each injection; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided (Mulroy 2010). Should only be administered under the supervision of a qualified physician experienced in the use of anesthetics. In pediatric patients, dosing should be based on lean body mass (Coté 2013).

Central nerve block/anesthesia:

Caudal block: Reported dosing variable based on procedure; dependent on necessary dermatome level and corresponding volume of space:

Infants and Children: Limited data available: Usual concentration ≤0.25% solution with or without epinephrine: Usual reported dose range: 0.5 to 1.3 mL/kg (maximal volume of drug: 20 mL); dose should not exceed 2 mg/kg plain solution, or 3 mg/kg with epinephrine. In infants, routine use of concentrations ≤0.25% have been suggested to reduce risk of bupivacaine cardiotoxicity (Coté 2013; Ingelmo 2007; Ivani 1998; Ivani 2002; Karkera 2016; Miller 2015; Payne 1993; Schrock 2003; Schwartz 2010)

Adolescents: Usual concentration 0.25 to 0.5% solution with or without epinephrine: 15 to 30 mL

Epidural block: Reported dosing variable; among other factors, dose dependent on necessary dermatome level and corresponding volume of epidural space (Coté 2013):

Infants: Limited data available: Usual concentration ≤0.25% with or without epinephrine: 0.7 to 0.75 mL/kg; maximum dose: 2.5 mg/kg; Note: For infants (particularly young infants), if repeat injections necessary, a decreased dose may be necessary to prevent drug accumulation. Some experts suggest if at least 45 minutes since initial dose, reduce dose to ¹/₃ of the initial or if at least 90 minutes since initial dose, then reduce dose to half of the initial. If additional doses are necessary, doses should be reduced to half of the previous dose (Ivani 1999; Miller 2015; Monsel 2007).

Children: Limited data available: Usual concentration 0.25% solution: Initial: 0.3 to 0.6 mL/kg (maximal volume of drug: 20 mL); maximum dose: 2.5 mg/kg (Ingelmo 2007; Ingelmo 2007a)

Adolescents: 0.25% or 0.5% solution: 10 to 20 mL administered in 3 to 5 mL increments; if high degree of muscle relaxation and prolonged effects needed, may consider 0.75% solution: 10 to 20 mL

Epidural, continuous infusion: Limited data available in infants and children <12 years (Berde 1992; Miller 2015; Moriarty 2012): Note: Use has generally been replaced by other agents (eg, ropivacaine) (Miller 2015; Moriarty 2012).

Loading dose: Usual concentration: 0.25%: 2 to 2.5 mg/kg

Infusion:

Infants <4 months: 0.2 mg/kg/hour

Infants ≥4 months: 0.25 mg/kg/hour

Children and Adolescents: 0.3 mg/kg/hour

Peripheral nerve block: Limited data available in infants and children: Note: Dose varies with location of block (ie, procedure), depth of anesthesia, vascularity of tissues, duration of anesthesia, and condition of patient.

Infants ≥6 months and Children: Usual concentration 0.125% or 0.25% solution with or without epinephrine: The volume of dose (mL/kg) and concentration of solution are site specific based upon anatomy and variable among patients and procedure; see below ranges. For infants <6 months, maximum doses should be reduced by 30% (Coté 2013; Miller 2015). Maximum dose plain solution: 2 mg/kg or 150 mg whichever is less or maximum dose with epinephrine: 3 mg/kg or 200 mg of bupivacaine whichever is less.

Commonly suggested doses (Coté 2013):

Head and neck: 0.05 mL/kg

Upper extremity:

Brachial plexus: 0.2 to 0.3 mL/kg

Digital nerve: 0.05 mL/kg

Truncal blocks:

Transversus abdominis plane: 0.2 to 0.5 mL (Jöhr 2015)

Rectus sheath: 0.1 mL/kg

Ilioinguinal: 0.075 mL/kg

Lower extremity blocks:

Femoral nerve: 0.2 to 0.3 mL/kg

Sciatic nerve: 0.2 to 0.3 mL/kg

Adolescents: 0.25% or 0.5% solution with or without epinephrine: 5 mL; maximum daily dose: 400 mg/day

Local anesthesia: Infants, Children, and Adolescents: Limited data in infants and children: Usual concentration 0.25% solution: Infiltrate area local; maximum dose in infants and children: 2.5 mg/kg or 150 mg whichever is less; maximum dose in adolescents: 175 mg (Coté 2013)

Administration

Solutions containing preservatives should not be used for epidural or caudal blocks. The On-Q infusion pump is used to slowly administer local anesthetics (eg, bupivacaine, lidocaine, ropivacaine) to or around surgical wound sites and/or in close proximity to peripheral nerves for postoperative analgesia. When infused directly into the shoulder, destruction of articular cartilage (chondrolysis) has occurred. On-Q pumps should never be placed directly into any joint.

Storage

Store at controlled room temperature of 20°C to 25°C (68°F to 77˚F).

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Beta-Blockers: May increase the serum concentration of Bupivacaine. Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Bupivacaine (Liposomal): Bupivacaine may enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Bupivacaine may be administered immediately before, or administered in the same admixture syringe as liposomal bupivacaine as long as the ratio of the milligram dose of bupivacaine to liposomal bupivacaine does not exceed 1:2. Consider therapy modification

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hyaluronidase: May enhance the adverse/toxic effect of Local Anesthetics. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Methemoglobinemia Associated Agents: May enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Neuromuscular-Blocking Agents: Local Anesthetics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Technetium Tc 99m Tilmanocept: Local Anesthetics may diminish the diagnostic effect of Technetium Tc 99m Tilmanocept. Management: Avoid mixing and simultaneously co-injecting technetium Tc 99m tilmanocept with local anesthetics. This interaction does not appear to apply to other uses of these agents in combination. Monitor therapy

Adverse Reactions

Frequency not defined. Reactions listed are based on reports for other agents in this same pharmacologic class and may not be specifically reported for bupivacaine.

Cardiovascular: Bradycardia, cardiac insufficiency, circulatory shock, heart block, hypotension, ventricular arrhythmia

Central nervous system: Anxiety, arachnoiditis, central nervous system depression, central nervous system stimulation, chills, cranial nerve palsy, dizziness, headache, localized numbness (perineal), meningism, paralysis, paraplegia, paresthesia, persistent anesthesia, restlessness, seizure, shivering

Gastrointestinal: Fecal incontinence, loss of anal sphincter control, nausea, vomiting

Genitourinary: Prolonged labor, sexual disorder (loss of function), urinary incontinence, urinary retention

Hematologic & oncologic: Methemoglobinemia

Hypersensitivity: Hypersensitivity reaction

Infection: Septic meningitis

Neuromuscular & skeletal: Asthenia, back pain, lower extremity weakness, tremor

Ophthalmic: Blurred vision, miosis

Otic: Tinnitus

Respiratory: Apnea, hypoventilation (usually associated with unintentional subarachnoid injection during high spinal anesthesia), respiratory paralysis

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: Bupivacaine-containing products have been associated with rare occurrences of arrhythmias, cardiac arrest, and death.
• Intra-articular infusion related chondrolysis: Continuous intra-articular infusion of local anesthetics after arthroscopic or other surgical procedures is not an approved use; chondrolysis (primarily shoulder joint) has occurred following infusion, with some patients requiring arthroplasty or shoulder replacement.
• Methemoglobinemia: Has been reported with local anesthetics; clinically significant methemoglobinemia requires immediate treatment along with discontinuation of the anesthetic and other oxidizing agents. Onset may be immediate or delayed (hours) after anesthetic exposure. Patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, exposure to oxidizing agents or their metabolites, or infants <6 months of age are more susceptible and should be closely monitored for signs and symptoms of methemoglobinemia (eg, cyanosis, headache, rapid pulse, shortness of breath, light-headedness, fatigue).
• Respiratory arrest: Local anesthetics have been associated with rare occurrences of sudden respiratory arrest, especially when administered near the head or neck.
• Seizures: Convulsions due to systemic toxicity leading to cardiac arrest have also been reported, presumably following unintentional intravascular injection or administration near the head or neck.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease including patients with hypotension or heart block.
• Hepatic impairment: Use with caution in patients with hepatic impairment.

Special populations:

• Acutely ill patients: Use with caution in acutely ill patients; dose reduction may be required.
• Debilitated patients: Use with caution in debilitated patients; dose reduction may be required.
• Elderly: Use with caution in the elderly; dose reduction may be required.

Dosage form specific issues:

• Obstetrical anesthesia: [US Boxed Warning]: The 0.75% concentration is not recommended for obstetrical anesthesia; cardiac arrest with difficult resuscitation or death has occurred.
• Preservative-containing solutions: Do not use solutions containing preservatives for caudal or epidural block.
• Sodium metabisulfite: May contain sodium metabisulfite; use caution in patients with asthma or a sulfite allergy.

Other warnings/precautions:

• Administration: Intravascular injections should be avoided; aspiration should be performed prior to administration; the needle must be repositioned until no return of blood can be elicited by aspiration; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided. Intravenous regional anesthesia (Bier block) is not recommended; cardiac arrest and death have occurred with this method of administration.
• Test dose: A test dose is recommended prior to epidural administration (prior to initial dose) and all reinforcing doses with continuous catheter technique.
• Trained personnel: Clinicians using local anesthetic agents should be well trained in diagnosis and management of emergencies that may arise from the use of these agents. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use.

Monitoring Parameters

Vital signs, state of consciousness; signs of CNS toxicity

Pregnancy

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Bupivacaine crosses the placenta. Bupivacaine is approved for use at term in obstetrical anesthesia or analgesia. [US Boxed Warning]: The 0.75% is not recommended for obstetrical anesthesia. Bupivacaine 0.75% solutions have been associated with cardiac arrest following epidural anesthesia in obstetrical patients and use of this concentration is not recommended for this purpose. Use in obstetrical paracervical block anesthesia is contraindicated.

Patient Education

What is this drug used for?

• It is used to numb an area before a procedure.

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Acidosis like confusion, fast breathing, fast heartbeat, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy.
• Methemoglobinemia like blue or gray color of the lips, nails, or skin; abnormal heartbeat; seizures; severe dizziness or passing out; severe headache; fatigue; loss of strength and energy; or shortness of breath.
• Slow heartbeat
• Chest pain
• Dizziness
• Passing out
• Lightheadedness
• Fatigue
• Confusion
• Change in balance
• Anxiety
• Change in speech
• Agitation
• Tremors
• Blurred vision
• Twitching
• Noise or ringing in the ears
• Depression
• Difficulty breathing
• Slow breathing
• Shallow breathing
• Seizures
• Numbness or tingling in the mouth
• Metallic taste
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.