Bupivacaine and epinephrine: Pediatric drug information

For additional information see "Bupivacaine and epinephrine: Drug information" and "Bupivacaine and epinephrine: Patient drug information"

For abbreviations, symbols, and age group definitions show table

ALERT: US Boxed Warning

Obstetrical anesthesia:

There have been reports of cardiac arrest with difficult resuscitation or death during use of bupivacaine for epidural anesthesia in obstetrical patients. In most cases, this has followed use of the 0.75% (7.5 mg/mL) concentration. Resuscitation has been difficult or impossible despite apparently adequate preparation and appropriate management. Cardiac arrest has occurred after convulsions resulting from systemic toxicity, presumably following unintentional intravascular injection. The 0.75% (7.5 mg/mL) concentration of bupivacaine is not recommended for obstetrical anesthesia and should be reserved for surgical procedures where a high degree of muscle relaxation and prolonged effect are necessary.

Brand Names: US

Marcaine/Epinephrine;
Marcaine/Epinephrine PF;
Sensorcaine-MPF/EPINEPHrine;
Sensorcaine/EPINEPHrine

Brand Names: Canada

Marcaine;
Marcaine E;
Sensorcaine/Epinephrine PF;
Vivacaine

Therapeutic Category

Local Anesthetic

Dosing: Pediatric

Note: Dose varies with procedure, depth of anesthesia, vascularity of tissues, duration of anesthesia, and condition of patient; commercially available epinephrine concentrations may not be appropriate in pediatric patients. 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 (Ref). Should only be administered under the supervision of a qualified physician experienced in the use of anesthetics. In obese pediatric patients, the preferred weight used for dose calculation is undefined and specific pediatric data are sparse (Ref); some have suggested the use of lean body mass/weight not ideal body weight (IBW) (Ref). Refer to Bupivacaine monograph for specific bupivacaine with or without epinephrine dosing details.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; use with caution.

Dosing: Liver Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; use with caution.

Dosing: Adult

(For additional information see "Bupivacaine and epinephrine: Drug information")

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. Doses may be repeated up to once every 3 hours (maximum: 400 mg/day of bupivacaine).

Caudal and lumbar epidural block test dose

Caudal and lumbar epidural block test dose (preservative free): 2 to 3 mL of 0.5% (maximum: 15 mg/dose of bupivacaine or 15 mcg/dose of epinephrine)

Caudal block

Caudal block (preservative free): 15 to 30 mL of 0.25% or 0.5% (maximum: 75 mg/dose of 0.25% bupivacaine or 150 mg/dose of 0.5% bupivacaine)

Epidural block

Epidural block (other than caudal block, preservative free): 10 to 20 mL of 0.25% or 0.5% (maximum: 50 mg/dose of 0.25% bupivacaine or 100 mg/dose of 0.5% bupivacaine). Administer in 3 to 5 mL increments, allowing sufficient time to detect toxic manifestations of inadvertent IV or intrathecal administration.

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 (maximum: 150 mg/dose of bupivacaine)

Local anesthesia

Local anesthesia: Infiltration: 0.25% infiltrated locally (maximum: 400 mg/day of bupivacaine)

Peripheral nerve block

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

Retrobulbar anesthesia

Retrobulbar anesthesia: 2 to 4 mL of 0.75% (maximum: 30 mg/dose of bupivacaine)

Sympathetic nerve block

Sympathetic nerve block: 20 to 50 mL of 0.25% (maximum: 125 mg/dose of bupivacaine)

Dental block

Dental block: 1.8 mL (9 mg) of bupivacaine as a 0.5% solution with epinephrine 1:200,000 per injection site. A second dose may be administered if necessary to produce adequate anesthesia after allowing up to 10 minutes for onset. Up to a maximum of 90 mg of bupivacaine per dental appointment. The effective anesthetic dose varies with procedure, intensity of anesthesia needed, duration of anesthesia required, and physical condition of the patient; always use the lowest effective dose along with careful aspiration.

The following numbers of dental carpules (1.8 mL) provide the indicated amounts of bupivacaine 0.5% and vasoconstrictor (epinephrine 1:200,000). See table.

# of Cartridges (1.8 mL)	Mg Bupivacaine (0.5%)	Mg Vasoconstrictor (Epinephrine 1:200,000)
1	9	0.009
2	18	0.018
3	27	0.027
4	36	0.036
5	45	0.045
6	54	0.054
7	63	0.063
8	72	0.072
9	81	0.081
10	90	0.090

Note: Adult doses of bupivacaine hydrochloride with epinephrine cited from USP Dispensing Information (USP DI), 17th ed, The United States Pharmacopeial Convention, Inc, Rockville, MD, 1997, 134.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no specific dosage adjustments provided in the manufacturer's labeling; use with caution.

Dosing: Liver Impairment: Adult

There are no specific dosage adjustments provided in the manufacturer's labeling. Risk of toxicity may be increased in patients with moderate to severe impairment; consider a reduced dose and more frequent monitoring.

Adverse Reactions

See individual agents.

Contraindications

Hypersensitivity to bupivacaine, epinephrine, amide-type local anesthetics, or any component of the formulation; obstetrical paracervical block anesthesia; IV regional anesthesia (Bier block).

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 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, lightheadedness, 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 heart block and hypotension) or compromised blood supply.

• 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.

• Older adult: Use with caution in the elderly; dose reduction may be required.

• Pediatric: Not recommended for use in children <12 years of age.

Dosage form specific issues:

• Obstetrical anesthesia: [US Boxed Warning]: The bupivacaine 0.75% (7.5 mg/mL) concentration is not recommended for obstetrical anesthesia. There have been reports of cardiac arrest with difficult resuscitation or death during use of bupivacaine for epidural anesthesia in obstetrical patients. In most cases, this has followed use of the 0.75% (7.5 mg/mL) concentration. Resuscitation has been difficult or impossible despite apparently adequate preparation and appropriate management. Cardiac arrest has occurred after convulsions resulting from systemic toxicity, presumably following unintentional intravascular injection. The 0.75% (7.5 mg/mL) concentration should be reserved for surgical procedures where a high degree of muscle relaxation and prolonged effect are necessary.

• Preservative-containing solutions: Do not use solutions containing preservatives for caudal or epidural block.

• Sodium metabisulfite: Some commercially available formulations contain sodium metabisulfite, which may cause allergic-type reactions.

Other warnings/precautions:

• Administration: Use the lowest effective dose and fractional (incremental) doses when possible; repeat administration may result in accumulation of bupivacaine and metabolites. Intravascular and intrathecal 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 or intrathecal injection has been avoided.

• 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: Dental practitioners and/or 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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Marcaine/Epinephrine: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (50 mL); Bupivacaine hydrochloride 0.25% and epinephrine 1:200,000 (50 mL) [contains edetate (edta) calcium disodium, methylparaben, sodium metabisulfite]

Marcaine/Epinephrine: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (1.8 mL) [contains edetate (edta) calcium disodium, sodium metabisulfite]

Marcaine/Epinephrine: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (50 mL); Bupivacaine hydrochloride 0.25% and epinephrine 1:200,000 (50 mL) [contains methylparaben, sodium metabisulfite]

Marcaine/Epinephrine PF: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (10 mL); Bupivacaine hydrochloride 0.25% and epinephrine 1:200,000 (10 mL, 30 mL) [contains edetate (edta) calcium disodium, sodium metabisulfite]

Sensorcaine/EPINEPHrine: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (50 mL); Bupivacaine hydrochloride 0.25% and epinephrine 1:200,000 (50 mL) [contains methylparaben, sodium metabisulfite]

Generic: Bupivacaine hydrochloride 0.25% and epinephrine 1:200,000 (50 mL); Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (50 mL)

Solution, Injection [preservative free]:

Marcaine/Epinephrine PF: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (30 mL) [contains edetate (edta) calcium disodium, sodium metabisulfite]

Marcaine/Epinephrine PF: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (10 mL, 30 mL); Bupivacaine hydrochloride 0.25% and epinephrine 1:200,000 (10 mL, 30 mL) [contains sodium metabisulfite]

Sensorcaine-MPF/EPINEPHrine: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (10 mL, 30 mL); Bupivacaine hydrochloride 0.75% and epinephrine 1:200000 (30 mL); Bupivacaine hydrochloride 0.25% and epinephrine 1:200,000 (10 mL, 30 mL) [methylparaben free; contains sodium metabisulfite]

Generic: Bupivacaine hydrochloride 0.25% and epinephrine 1:200,000 (10 mL, 30 mL); Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (10 mL, 30 mL)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (BUPivacaine-EPINEPHrine (PF) Injection)

0.25%-1:200000 (per mL): $0.64

0.5%-1:200000 (per mL): $0.38

Solution (BUPivacaine-EPINEPHrine Injection)

0.25%-1:200000 (per mL): $0.17

0.5%-1:200000 (per mL): $0.19

Solution (Marcaine/Epinephrine Injection)

0.25%-1:200000 (per mL): $0.41

0.25-1:200000% (per mL): $0.29

0.5%-1:200000 (per mL): $0.39

Solution (Marcaine/Epinephrine PF Injection)

0.25%-1:200000 (per mL): $0.81

0.25-1:200000% (per mL): $0.56

0.5%-1:200000 (per mL): $0.60

Solution (Sensorcaine-MPF/EPINEPHrine Injection)

0.25%-1:200000 (per mL): $0.92

0.5%-1:200000 (per mL): $0.33

0.75-1:200000% (per mL): $0.59

Solution (Sensorcaine/EPINEPHrine Injection)

0.25%-1:200000 (per mL): $0.47

0.5%-1:200000 (per mL): $0.50

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Marcaine: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (1.8 mL) [contains edetate (edta) calcium disodium, sodium metabisulfite]

Marcaine E: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (3 mL, 20 mL); Bupivacaine hydrochloride 0.25% and epinephrine 1:200,000 (20 mL)

Sensorcaine/Epinephrine PF: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (20 mL); Bupivacaine hydrochloride 0.25% and epinephrine 1:200,000 (20 mL) [contains sodium metabisulfite]

Vivacaine: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (1.8 mL) [contains edetate (edta) calcium disodium, sodium metabisulfite]

Generic: Bupivacaine hydrochloride 0.5% and epinephrine 1:200,000 (1.8 mL)

Administration: Pediatric

Parenteral: Solutions containing preservatives should not be used for epidural or caudal blocks; for epidural infusion, may use undiluted or diluted with preservative-free NS. 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 (Ref).

Administration: Adult

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 nerves for pre- or postoperative regional anesthesia. When infused directly into the shoulder, destruction of articular cartilage (chondrolysis) has occurred. On-Q® pumps should never be placed directly into any joint (see https://www.ismp.org/Newsletters/acutecare/archives/May09.asp).

Storage/Stability

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C to 30°C (59°F to 86°F). Protect from light. Do not autoclave.

Use

Local or regional anesthesia; spinal anesthesia; anesthesia for diagnostic and therapeutic procedures and obstetrical procedures (FDA approved in adults); specific uses vary by product.

Medication Safety Issues

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (epidural and intrathecal medications) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care Settings).

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program

Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Alpha1-Blockers: May decrease therapeutic effects of Alpha-/Beta-Agonists. Risk C: Monitor

Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification

Amisulpride (Oral): May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor

Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor

Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Articaine: May increase adverse/toxic effects of Local Anesthetics. Risk C: Monitor

Atomoxetine: May increase hypertensive effects of Sympathomimetics. Atomoxetine may increase tachycardic effects of Sympathomimetics. Risk C: Monitor

Azosemide: May decrease therapeutic effects of EPINEPHrine (Systemic). Risk C: Monitor

Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Benperidol: May decrease therapeutic effects of EPINEPHrine (Systemic). Risk C: Monitor

Benzylpenicilloyl Polylysine: Coadministration of Alpha-/Beta-Agonists and Benzylpenicilloyl Polylysine may alter diagnostic results. Management: Consider use of a histamine skin test as a positive control to assess a patient's ability to mount a wheal and flare response. Risk D: Consider Therapy Modification

Beta-Blockers (Beta1 Selective): May decrease therapeutic effects of EPINEPHrine (Systemic). Risk C: Monitor

Beta-Blockers (Nonselective): May increase hypertensive effects of EPINEPHrine (Systemic). Risk C: Monitor

Beta-Blockers (with Alpha-Blocking Properties): May decrease therapeutic effects of EPINEPHrine (Systemic). Risk C: Monitor

Blonanserin: May decrease therapeutic effects of EPINEPHrine (Systemic). Risk X: Avoid

Blood Pressure Lowering Agents: May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor

Bornaprine: Sympathomimetics may increase anticholinergic effects of Bornaprine. Risk C: Monitor

Bradycardia-Causing Agents: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor

Bretylium: May increase therapeutic effects of Alpha-/Beta-Agonists (Direct-Acting). Risk C: Monitor

Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Bromocriptine: May increase hypertensive effects of Alpha-/Beta-Agonists. Management: Consider alternatives to this combination when possible. If combined, monitor for hypertension and tachycardia, and do not coadminister these agents for more than 10 days. Risk D: Consider Therapy Modification

Bromperidol: May decrease therapeutic effects of EPINEPHrine (Systemic). Risk X: Avoid

BUPivacaine (Liposomal): BUPivacaine may increase adverse/toxic effects 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. Risk D: Consider Therapy Modification

Cannabinoid-Containing Products: May increase tachycardic effects of Sympathomimetics. Risk C: Monitor

Cardiac Glycosides: EPINEPHrine (Systemic) may increase arrhythmogenic effects of Cardiac Glycosides. Risk C: Monitor

Ceritinib: Bradycardia-Causing Agents may increase bradycardic effects of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider Therapy Modification

Chloroprocaine (Systemic): May increase hypertensive effects of Alpha-/Beta-Agonists. Risk C: Monitor

Chlorprothixene: May increase adverse/toxic effects of EPINEPHrine (Systemic). Specifically, paradoxical hypotension and tachycardia may be increased. EPINEPHrine (Systemic) may increase therapeutic effects of Chlorprothixene. Risk C: Monitor

CloZAPine: May decrease therapeutic effects of Alpha-/Beta-Agonists. Risk C: Monitor

Cocaine (Topical): May increase hypertensive effects of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider Therapy Modification

COMT Inhibitors: May increase serum concentration of COMT Substrates. Risk C: Monitor

CycloPHOSphamide: May increase adverse/toxic effects of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor

Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Dihydralazine: Sympathomimetics may decrease therapeutic effects of Dihydralazine. Risk C: Monitor

Diuretics: May increase arrhythmogenic effects of EPINEPHrine (Systemic). Diuretics may decrease vasopressor effects of EPINEPHrine (Systemic). Risk C: Monitor

Doxofylline: Sympathomimetics may increase adverse/toxic effects of Doxofylline. Risk C: Monitor

Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): May increase vasoconstricting effects of Alpha-/Beta-Agonists. Risk X: Avoid

Esketamine (Injection): May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for elevated heart rate, hypertension, and arrhythmias may be increased. Risk C: Monitor

Etrasimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor

Fexinidazole: Bradycardia-Causing Agents may increase arrhythmogenic effects of Fexinidazole. Risk X: Avoid

Fingolimod: Bradycardia-Causing Agents may increase bradycardic effects of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider Therapy Modification

Guanethidine: May increase hypertensive effects of Sympathomimetics. Guanethidine may increase arrhythmogenic effects of Sympathomimetics. Risk C: Monitor

Haloperidol: May decrease vasoconstricting effects of EPINEPHrine (Systemic). Management: Consider alternatives to this combination and monitor for reduced epinephrine efficacy, and possible paradoxical effects (ie, hypotension), when combined. Use of alternative vasopressor agents (eg, phenylephrine, metaraminol, norepinephrine) is preferred. Risk D: Consider Therapy Modification

Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Hexoprenaline: May increase adverse/toxic effects of Alpha-/Beta-Agonists. Risk X: Avoid

Hyaluronidase: May increase vasoconstricting effects of Alpha-/Beta-Agonists. Management: Do not use hyaluronidase to enhance the dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Risk D: Consider Therapy Modification

Hydroxyurea: May increase adverse/toxic effects of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor

Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor

Ifosfamide: May increase adverse/toxic effects of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor

Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Inhalational Anesthetics: May increase arrhythmogenic effects of EPINEPHrine (Systemic). Management: Administer epinephrine with added caution in patients receiving, or who have recently received, inhalational anesthetics. Use lower than normal doses of epinephrine and monitor for the development of cardiac arrhythmias. Risk D: Consider Therapy Modification

Isoproterenol: May increase therapeutic effects of EPINEPHrine (Systemic). Risk X: Avoid

Ivabradine: Bradycardia-Causing Agents may increase bradycardic effects of Ivabradine. Risk C: Monitor

Kratom: May increase adverse/toxic effects of Sympathomimetics. Risk X: Avoid

Lacosamide: Bradycardia-Causing Agents may increase AV-blocking effects of Lacosamide. Risk C: Monitor

Landiolol: Bradycardia-Causing Agents may increase bradycardic effects of Landiolol. Risk X: Avoid

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor

Levothyroxine: May increase therapeutic effects of Sympathomimetics. Sympathomimetics may increase therapeutic effects of Levothyroxine. Levothyroxine may increase adverse/toxic effects of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Risk C: Monitor

Linezolid: May increase hypertensive effects of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider Therapy Modification

Lisuride: May increase hypertensive effects of Alpha-/Beta-Agonists. Risk X: Avoid

Local Anesthetics: May increase adverse/toxic effects of BUPivacaine. Management: Avoid using any additional local anesthetics within 96 hours after insertion of the bupivacaine implant (Xaracoll) or bupivacaine and meloxicam periarticular solution (Zynrelef) or within 168 hours after subacromial infiltration (Posimir brand). Risk C: Monitor

Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Melperone: May increase adverse/toxic effects of EPINEPHrine (Systemic). Risk C: Monitor

Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor

Methemoglobinemia Associated Agents: May increase adverse/toxic effects of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor

Midodrine: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor

Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Monoamine Oxidase Inhibitors: May increase hypertensive effects of EPINEPHrine (Systemic). Risk C: Monitor

Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Neuromuscular-Blocking Agents: Local Anesthetics may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents. Risk C: Monitor

Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor

Nitrous Oxide: May increase adverse/toxic effects of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor

Obinutuzumab: May increase hypotensive effects 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. Risk D: Consider Therapy Modification

Ozanimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor

Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Pergolide: May increase hypertensive effects of Alpha-/Beta-Agonists. Risk C: Monitor

Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor

Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Ponesimod: Bradycardia-Causing Agents may increase bradycardic effects of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider Therapy Modification

Promethazine: May decrease vasoconstricting effects of EPINEPHrine (Systemic). Management: Avoid epinephrine and consider norepinephrine or phenylephrine when treating hypotension due to promethazine overdose. Consider alternative vasocontrictors in patients treated with promethazine. This combination may be indicated in anaphylaxis treatment. Risk D: Consider Therapy Modification

Propranolol: May increase serum concentration of BUPivacaine. Risk C: Monitor

Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

ROPivacaine: May increase adverse/toxic effects of Local Anesthetics. Risk C: Monitor

Serotonin/Norepinephrine Reuptake Inhibitor: May increase tachycardic effects of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitor may increase vasopressor effects of Alpha-/Beta-Agonists. Management: If possible, avoid coadministration of direct-acting alpha-/beta-agonists and serotonin/norepinephrine reuptake inhibitors. If coadministered, monitor for increased sympathomimetic effects (eg, increased blood pressure, chest pain, headache). Risk D: Consider Therapy Modification

Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Siponimod: Bradycardia-Causing Agents may increase bradycardic effects of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider Therapy Modification

Solriamfetol: Sympathomimetics may increase hypertensive effects of Solriamfetol. Sympathomimetics may increase tachycardic effects of Solriamfetol. Risk C: Monitor

Spironolactone: May decrease vasoconstricting effects of Alpha-/Beta-Agonists. Risk C: Monitor

Sympathomimetics: May increase adverse/toxic effects of Sympathomimetics. Risk C: Monitor

Technetium Tc 99m Tilmanocept: Coadministration of Local Anesthetics and Technetium Tc 99m Tilmanocept may alter diagnostic results. 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. Risk C: Monitor

Tedizolid: May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for increased blood pressure and heart rate may be increased. Risk C: Monitor

Tricyclic Antidepressants: May increase vasopressor effects of Alpha-/Beta-Agonists. Management: Avoid, if possible, the use of alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Risk D: Consider Therapy Modification

Valproic Acid and Derivatives: May increase adverse/toxic effects of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor

Vasopressin: Alpha-/Beta-Agonists (Direct-Acting) may increase hypertensive effects of Vasopressin. The effect of other hemodynamic parameters may also be enhanced. Risk C: Monitor

Pregnancy Considerations

[US Boxed Warning]: The bupivacaine 0.75% (7.5 mg/mL) concentration is not recommended for obstetrical anesthesia. There have been reports of cardiac arrest with difficult resuscitation or death during use of bupivacaine for epidural anesthesia in obstetrical patients. In most cases, this has followed use of the 0.75% (7.5 mg/mL) concentration. Resuscitation has been difficult or impossible despite apparently adequate preparation and appropriate management. Cardiac arrest has occurred after convulsions resulting from systemic toxicity, presumably following unintentional intravascular injection. The 0.75% (7.5 mg/mL) concentration should be reserved for surgical procedures where a high degree of muscle relaxation and prolonged effect are necessary.

Use in obstetrical paracervical block anesthesia is contraindicated (may cause fetal bradycardia and death).

Refer to individual monographs for additional information.

Mechanism of Action

Local anesthetics bind selectively to the intracellular surface of sodium channels to block influx of sodium into the axon. As a result, depolarization necessary for action potential propagation and subsequent nerve function is prevented. The block at the sodium channel is reversible. When drug diffuses away from the axon, sodium channel function is restored and nerve propagation returns.

Epinephrine prolongs the duration of the anesthetic actions of bupivacaine by causing vasoconstriction (alpha-adrenergic receptor agonist) of the vasculature surrounding the nerve axons. This prevents the diffusion of bupivacaine away from the nerves resulting in a longer retention in the axon

Pharmacokinetics (Adult Data Unless Noted)

Refer to Bupivacaine; epinephrine reduces the rate of absorption and peak plasma concentration of bupivacaine

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(NO) Norway: Bupivacaine/adrenaline;
(QA) Qatar: Marcaine with Epinephrine

Ayoub ST and Coleman AE, “A Review of Local Anesthetics,” Gen Dent, 1992, 40(4):285-7, 289-90. [PubMed 1397990]
Coté CJ, ed. A Practice of Anesthesia for Infants and Children. 6th ed. Elsevier Inc; 2018.
Dix SK, Rosner GF, Nayar M, et al, “Intractable Cardiac Arrest Due to Lidocaine Toxicity Successfully Resuscitated With Lipid Emulsion,” Crit Care Med, 2011, 39(4):872-4. [PubMed 21263316]
Finder RL and Moore PA, “Adverse Drug Reactions to Local Anesthesia,” Dent Clin North Am, 2002, 46(4):747-57, x. [PubMed 12436829]
Garisto GA, Gaffen AS, Lawrence HP, et al, "Occurrence of Paresthesia After Dental Local Anesthetic Administration in the United States," J Am Dent Assoc, 2010, 141(7):836-44. [PubMed 20592403]
Jastak JT and Yagiela JA, “Vasoconstrictors and Local Anesthesia: A Review and Rationale for Use,” J Am Dent Assoc, 1983, 107(4):623-30. [PubMed 6355236]
Lerman J, Becke K. Perioperative considerations for airway management and drug dosing in obese children. Curr Opin Anaesthesiol. 2018;31(3):320-326. [PubMed 29697466]
MacKenzie TA and Young ER, “Local Anesthetic Update,” Anesth Prog, 1993, 40(2):29-34. [PubMed 8185087]
Malamed SF, “Allergy and Toxic Reactions to Local Anesthetics,” Dent Today, 2003, 22(4):114-6, 118-21. [PubMed 12733413]
Marcaine with Epinephrine (bupivacaine/epinephrine) [prescribing information]. Lake Forest, IL: Hospira Inc; March 2023.
Mulroy MF, Hejtmanek MR. Prevention of local anesthetic systemic toxicity. Reg Anesth Pain Med. 2010;35(2):177-180. [PubMed 20216035]
Nafiu OO, Mills K, Tremper KK. Some cautionary tales about ideal body weight dosing of anesthetic medications: it is not all that ideal!. Anesth Analg. 2018;127(2):586-588. [PubMed 29200076]
Neal JM, Mulroy MF, and Weinberg GL, “American Society of Regional Anesthesia and Pain Medicine Checklist for Managing Local Anesthetic Systemic Toxicity: 2012 Version,” Reg Anesth Pain Med, 2012, 37(1):16-8. [PubMed 22189574]
Sensorcaine (bupivacaine and epinephrine) [prescribing information]. Lake Zurich, IL: Fresenius Kabi; November 2022.
Sensorcaine with Epinephrine (bupivacaine and epinephrine) [product monograph]. Oakville, Ontario, Canada: Aspen Pharmacare Canada Inc; November 2019.
Sensorcaine with Epinephrine and Sensorcaine-MPF with Epinephrine (bupivacaine and epinephrine) [prescribing information]. Lake Zurich, IL: Fresenius Kabi; July 2022.
Wynn RL, “Epinephrine Interactions With Beta-Blockers,” Gen Dent, 1994, 42(1):16, 18. [PubMed 7911769]
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Topic 129654 Version 149.0

خرید پکیج

Bupivacaine and epinephrine: Pediatric drug information