Version May 2024
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.
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 (preservative free): 2 to 3 mL of 0.5% (maximum: 15 mg/dose of bupivacaine or 15 mcg/dose of epinephrine)
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 (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: Infiltration: 0.25% infiltrated locally (maximum: 400 mg/day of bupivacaine)
Peripheral nerve block: 5 mL of 0.25% or 0.5% (maximum: 400 mg/day of bupivacaine)
Retrobulbar anesthesia: 2 to 4 mL of 0.75% (maximum: 30 mg/dose of bupivacaine)
Sympathetic nerve block: 20 to 50 mL of 0.25% (maximum: 125 mg/dose of bupivacaine)
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.
There are no specific dosage adjustments provided in the manufacturer's labeling; use with caution.
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.
Refer to adult dosing.
(For additional information see "Bupivacaine and epinephrine: Pediatric drug information")
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 (Mulroy 2010). 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 (Lerman 2018; Nafiu 2018); some have suggested the use of lean body mass/weight not ideal body weight (IBW) (Coté 2018). Refer to Bupivacaine monograph for specific bupivacaine with or without epinephrine dosing details.
There are no dosage adjustments provided in manufacturer's labeling; use with caution.
There are no dosage adjustments provided in manufacturer's labeling; use with caution.
See individual agents.
Hypersensitivity to bupivacaine, epinephrine, amide-type local anesthetics, or any component of the formulation; obstetrical paracervical block anesthesia; IV regional anesthesia (Bier block).
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.
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 (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 0.25% and epinephrine 1:200,000 (10 mL, 30 mL); Bupivacaine hydrochloride 0.75% and epinephrine 1:200,000 (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)
Yes
Solution (BUPivacaine-EPINEPHrine (PF) Injection)
0.25%-1:200000 (per mL): $0.53 - $0.54
0.5%-1:200000 (per mL): $0.32
Solution (BUPivacaine-EPINEPHrine Injection)
0.25%-1:200000 (per mL): $0.14
0.5%-1:200000 (per mL): $0.16
Solution (Marcaine/Epinephrine Injection)
0.25%-1:200000 (per mL): $0.29
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): $0.56
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): $0.74
0.5%-1:200000 (per mL): $0.33
0.75-1:200000% (per mL): $0.47
Solution (Sensorcaine/EPINEPHrine Injection)
0.25%-1:200000 (per mL): $0.37
0.5%-1:200000 (per mL): $0.40
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.
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)
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).
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 (Mulroy 2010).
Anesthesia/analgesia: Local or regional anesthesia or analgesia for surgery, dental and oral procedures, diagnostic and therapeutic procedures, and obstetrical procedure
0.25%: Local infiltration, peripheral nerve block, sympathetic block, lumbar epidural, or caudal
0.5%: Peripheral nerve block, lumbar epidural, caudal, epidural test dose, or dental blocks
0.75% (not for obstetrical anesthesia): Retrobulbar block or lumbar epidural; Note: Reserve for surgical procedures where a high degree of muscle relaxation and prolonged effect are necessary.
The Institute for Safe Medication Practices (ISMP) includes this medication (epidural administration) among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Refer to individual components.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect 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 enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Azosemide: May diminish the therapeutic effect of EPINEPHrine (Systemic). Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May diminish the therapeutic effect of EPINEPHrine (Systemic). Risk C: Monitor therapy
Benzylpenicilloyl Polylysine: Alpha-/Beta-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. 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 diminish the therapeutic effect of EPINEPHrine (Systemic). Risk C: Monitor therapy
Beta-Blockers (Nonselective): May enhance the hypertensive effect of EPINEPHrine (Systemic). Risk C: Monitor therapy
Beta-Blockers (with Alpha-Blocking Properties): May diminish the therapeutic effect of EPINEPHrine (Systemic). Risk C: Monitor therapy
Blonanserin: May diminish the therapeutic effect of EPINEPHrine (Systemic). Risk X: Avoid combination
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Bretylium: May enhance the therapeutic effect of Alpha-/Beta-Agonists (Direct-Acting). Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromocriptine: May enhance the hypertensive effect 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 diminish the therapeutic effect of EPINEPHrine (Systemic). Risk X: 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. Risk D: Consider therapy modification
Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect 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 enhance the hypertensive effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy
CloZAPine: May diminish the therapeutic effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy
Cocaine (Topical): May enhance the hypertensive effect 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 the serum concentration of COMT Substrates. Risk C: Monitor therapy
CycloPHOSphamide: May enhance the adverse/toxic effect of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Risk C: Monitor therapy
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): May enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Risk X: Avoid combination
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect 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 enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Haloperidol: May diminish the vasoconstricting effect 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 enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hyaluronidase: May enhance the vasoconstricting effect 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 enhance the adverse/toxic effect of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Ifosfamide: May enhance the adverse/toxic effect of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor therapy
Inhalational Anesthetics: May enhance the arrhythmogenic effect 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 enhance the therapeutic effect of EPINEPHrine (Systemic). Risk X: Avoid combination
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Levothyroxine: May enhance the adverse/toxic effect of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Levothyroxine may enhance the therapeutic effect of Sympathomimetics. Sympathomimetics may enhance the therapeutic effect of Levothyroxine. Risk C: Monitor therapy
Linezolid: May enhance the hypertensive effect 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 enhance the hypertensive effect of Alpha-/Beta-Agonists. Risk X: Avoid combination
Local Anesthetics: May enhance the adverse/toxic effect 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 therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methemoglobinemia Associated Agents: May enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of EPINEPHrine (Systemic). Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Local Anesthetics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Nitrous Oxide: May enhance the adverse/toxic effect of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: 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. Risk D: Consider therapy modification
Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pergolide: May enhance the hypertensive effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect 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 diminish the vasoconstricting effect 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 the serum concentration of BUPivacaine. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect 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 enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect 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 enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: 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. Risk C: Monitor therapy
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the vasopressor effect 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
Valproate Products: May enhance the adverse/toxic effect of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor therapy
Vasopressin: Alpha-/Beta-Agonists (Direct-Acting) may enhance the hypertensive effect of Vasopressin. The effect of other hemodynamic parameters may also be enhanced. Risk C: Monitor therapy
[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.
Bupivacaine is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Refer to individual monographs for additional information.
Vital signs, state of consciousness; signs of CNS toxicity
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
Refer to Bupivacaine; epinephrine reduces the rate of absorption and peak plasma concentration of bupivacaine
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