Marcaine with Epinephrine BUPIVACAINE HYDROCHLORIDE AND 5 mg/mL; .0091 mg/mL Injection, Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Amide Local Anesthetic class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- This injection is a long-acting local anesthetic used to numb a specific part of your body during a procedure — things like surgery, dental work, or certain diagnostic tests. Your...
- What is this injection actually for — why did my doctor order it?
- That depends on where and how the injection is given, but bupivacaine is known for being one of the longest-acting local anesthetics available. For dental injections, numbness can...
- How long will the numbness last, and what will it feel like wearing off?
Patient education
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII PQ6CK8PD0R
Ascorbic acid, also known as vitamin C, is a white crystalline powder. It serves as an antioxidant to prevent degradation of other ingredients and may also function as a preservative in the formulation.
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Edetate calcium disodium is a chelating agent, a chemical that binds to metal ions. It's used in some medications to prevent unwanted metals from interfering with the drug's stability and effectiveness.
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A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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Monothioglycerol is a clear liquid derived from glycerin with a sulfur-containing group added. It works as an antioxidant and reducing agent in medicines, helping prevent degradation of active ingredients during storage.
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Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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A salt derived from lactic acid, sodium lactate acts as a buffer and pH stabilizer in medicines. It helps maintain the product's acidity level and can also serve as a humectant to retain moisture.
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Sodium metabisulfite is a preservative derived from sulfur compounds. It prevents microbial growth and oxidation in medicines, helping extend shelf life and maintain product stability.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
9 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $780.12 | $234,036.12 / 300 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Marcaine with Epinephrine 5 mg/mL; .0091 mg/mL 00409-1749-10 | Hospira, | 10 vials | — | AP | FDA listed | — |
| Marcaine with Epinephrine 5 mg/mL; .0091 mg/mLthis 00409-4208-10 | Hospira, | 10 vials | — | AP | FDA listed | — |
| Bupivacaine Hydrochloride and Epinephrine 5 mg/mL; 5 ug/mL 00409-9045-01 | Hospira, | 10 vials | — | AP | FDA listed | — |
| Sensorcaine Mpf 5 mg/mL; .005 mg/mL 63323-0462-17 | Fresenius | 25 vials | — | AP | FDA listed | — |
| Marcaine with Epinephrine 5 mg/mL; .0091 mg/mL 00409-8126-10 | Hospira, | 10 vials | — | AP | FDA listed | — |
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⏳ Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
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🗺️ Medicaid utilization & spend
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00409-4208-10 You're viewing this | 10 VIAL, SINGLE-DOSE in 1 CARTON (0409-4208-10) / 30 mL in 1 VIAL, SINGLE-DOSE (0409-4208-01) | 2022-09-26 | Active |
🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: RISK OF CARDIAC ARREST WITH USE OF MARCAINE IN OBSTETRICAL ANESTHESIA There have been reports of cardiac arrest with difficult resuscitation or death during use of MARCAINE 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 MARCAINE 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 [see Warnings and Precautions (5.1) ] . WARNING: RISK OF CARDIAC ARREST WITH USE OF MARCAINE IN OBSTETRICAL ANESTHESIA See full prescribing information for complete boxed warning.
There have been reports of cardiac arrest with difficult resuscitation or death during use of MARCAINE 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 MARCAINE 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 ( 5.1 ).
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE MARCAINE / MARCAINE WITH EPINEPHRINE is indicated in adults for the production of local or regional anesthesia or analgesia for surgery, dental and oral surgery procedures, diagnostic and therapeutic procedures, and for obstetrical procedures. Specific concentrations and presentations of MARCAINE / MARCAINE WITH EPINEPHRINE are recommended for each type of block indicated to produce local or regional anesthesia or analgesia [see Dosage and Administration (2.2) ]. MARCAINE contains bupivacaine, an amide local anesthetic, and MARCAINE WITH EPINEPHRINE is a combination of bupivacaine, an amide local anesthetic, and epinephrine, an alpha and beta-adrenergic agonist.
MARCAINE / MARCAINE WITH EPINEPHRINE is indicated in adults for the production of local or regional anesthesia or analgesia for surgery, dental and oral surgery procedures, diagnostic and therapeutic procedures, and for obstetrical procedures. For each type of block indicated to produce local or regional anesthesia or analgesia, specific concentrations and presentations are recommended. ( 1 , 2.2 ) Limitations of Use Not all blocks are indicated for use with MARCAINE / MARCAINE WITH EPINEPHRINE given clinically significant risks associated with use.
( 1 , 2.2 , 4 , 5.1 , 5.4 , 5.5 , 5.7 , 5.9 ) Limitations of Use Not all blocks are indicated for use with MARCAINE / MARCAINE WITH EPINEPHRINE given clinically significant risks associated with use [see Dosage and Administration (2.2) , Contraindications (4) , Warnings and Precautions (5.1 , 5.4 , 5.5 , 5.7 , 5.9) ] .
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Not for intrathecal use. ( 2.1 ) • Avoid use of solutions containing antimicrobial preservatives (i.e., multiple-dose vials) for epidural or caudal anesthesia. ( 2.1 , 5.4 ) • Three mL of MARCAINE WITH EPINEPHRINE without antimicrobial preservative (0.5% bupivacaine with 1:200,000 epinephrine ) is recommended for use as a test dose prior to caudal and lumbar epidural blocks when clinical conditions permit.
( 2.4 ) • See full prescribing information for: - Recommended concentrations and dosages of MARCAINE / MARCAINE WITH EPINEPHRINE according to type of block. ( 2.2 ) - Additional dosage and administration information pertaining to use in epidural anesthesia, test dose for caudal and lumbar epidural blocks, use in dentistry, and use in ophthalmic surgery. ( 2.3 , 2.4 , 2.5 , 2.6 )
2.1Important Dosage and Administration Information • MARCAINE / MARCAINE WITH EPINEPHRINE is not for intrathecal use. • Avoid use of MARCAINE / MARCAINE WITH EPINEPHRINE solutions containing antimicrobial preservatives (i.e., multiple-dose vials) for epidural or caudal anesthesia [see Warnings and Precautions (5.4) ] . • Discard unused portions of solution not containing preservatives, i.e., those supplied in single-dose vials, following initial use. • Visually inspect this product for particulate matter and discoloration prior to administration whenever solution and container permit.
MARCAINE / MARCAINE WITH EPINEPHRINE are clear, colorless solutions. Do not administer solutions which are discolored or contain particulate matter. • Mixing or the prior or intercurrent use of any other local anesthetic with MARCAINE / MARCAINE WITH EPINEPHRINE is not recommended because of insufficient data on the clinical use of such mixtures. Administration Precautions • MARCAINE / MARCAINE WITH EPINEPHRINE are to be administered in carefully adjusted dosages by or under the supervision of experienced clinicians who are well versed in the diagnosis and management of dose-related toxicity and other acute emergencies which might arise from the block to be employed. • Use MARCAINE / MARCAINE WITH EPINEPHRINE only if the following are immediately available: oxygen, cardiopulmonary resuscitative equipment and drugs, and the personnel resources needed for proper management of toxic reactions and related emergencies [see Warnings and Precautions (5.2) , Adverse Reactions (6) , Overdosage (10) ]. • The toxic effects of local anesthetics are additive.
Monitor for neurologic and cardiovascular effects related to local anesthetic systemic toxicity when additional local anesthetics are administered with MARCAINE / MARCAINE WITH EPINEPHRINE [see Warnings and Precautions (5.2) , Drug Interactions (7.1) , Overdosage (10) ]. • Aspirate for blood or cerebrospinal fluid (where applicable) prior to injecting MARCAINE / MARCAINE WITH EPINEPHRINE, both the initial dose and all subsequent doses, to avoid intravascular or intrathecal injection. However, a negative aspiration for blood or cerebrospinal fluid does not ensure against an intravascular or intrathecal injection [see Warnings and Precautions (5.9) ] . • Avoid rapid injection of a large volume of MARCAINE / MARCAINE WITH EPINEPHRINE and use fractional (incremental) doses when feasible. • During major regional nerve blocks, such as those of the brachial plexus or lower extremity, the patient should have an indwelling intravenous catheter to assure adequate intravenous access.
The lowest dosage of MARCAINE / MARCAINE WITH EPINEPHRINE that results in effective anesthesia should be used to avoid high plasma levels and serious adverse reactions. • Perform careful and constant monitoring of cardiovascular and respiratory (adequacy of oxygenation and ventilation) vital signs and the patient's level of consciousness after each local anesthetic injection. • Use MARCAINE WITH EPINEPHRINE in carefully restricted quantities in areas of the body supplied by end arteries or having otherwise compromised blood supp…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS MARCAINE with 1:200,000 epinephrine (bupivacaine hydrochloride and epinephrine) injection is a clear, colorless solution available as: • 0.25% (25 mg/10 mL) (2.5 mg/mL) in single-dose vials. • 0.25% (75 mg/30 mL) (2.5 mg/mL) in single-dose vials. • 0.25% (125 mg/50 mL) (2.5 mg/mL) in multiple-dose vials. • 0.5% (50 mg/10 mL) (5 mg/mL) in single-dose vials. • 0.5% (150 mg/30 mL) (5 mg/mL) in single-dose vials. • 0.5% (250 mg/50 mL) (5 mg/mL) in multiple-dose vials. MARCAINE WITH EPINEPHRINE injection is available in multiple concentrations.
See full prescribing information for detailed description of each formulation. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS MARCAINE / MARCAINE WITH EPINEPHRINE is contraindicated in: • obstetrical paracervical block anesthesia. Its use in this technique has resulted in fetal bradycardia and death. • intravenous regional anesthesia (Bier Block) [see Warnings and Precautions (5.7) ] . • patients with a known hypersensitivity to bupivacaine or to any local anesthetic agent of the amide-type or to other components of MARCAINE / MARCAINE WITH EPINEPHRINE. • Obstetrical paracervical block anesthesia. Its use in this technique has resulted in fetal bradycardia and death.
( 4 ) • Intravenous regional anesthesia (Bier Block). ( 4 ) • Known hypersensitivity to bupivacaine or to any local anesthetic agent of the amide-type or to other components of MARCAINE / MARCAINE WITH EPINEPHRINE. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Dose-Related Toxicity : Monitor cardiovascular and respiratory vital signs and patient's state of consciousness after injection of MARCAINE / MARCAINE WITH EPINEPHRINE. ( 5.2 ) • Methemoglobinemia : Cases of methemoglobinemia have been reported in association with local anesthetic use. See full prescribing information for more detail on managing these risks.
( 5.3 ) • Chondrolysis with Intra-Articular Infusion : Intra-articular infusions of local anesthetics including MARCAINE following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions. ( 5.5 ) • Risk of Cardiac Arrest with Intravenous Regional Anesthesia Use (Bier Block) : There have been reports of cardiac arrest and death during the use of bupivacaine for intravenous regional anesthesia (Bier Block). ( 5.7 ) • Allergic-Type Reactions to Sulfites in MARCAINE WITH EPINEPHRINE : MARCAINE WITH EPINEPHRINE contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.
( 5.8 ) • Risk of Systemic Toxicities with Unintended Intravascular or Intrathecal Injection : Unintended intravascular or intrathecal injection may be associated with systemic toxicities, including CNS or cardiorespiratory depression and coma, progressing ultimately to respiratory arrest. Aspirate for blood or cerebrospinal fluid (where applicable) prior to each dose and consider using a test dose of MARCAINE WITH EPINEPHRINE. ( 5.9 )
5.1Risk of Cardiac Arrest with Use of MARCAINE in Obstetrical Anesthesia There have been reports of cardiac arrest with difficult resuscitation or death during use of MARCAINE 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 MARCAINE 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.
5.2Dose-Related Toxicity The safety and effectiveness of MARCAINE / MARCAINE WITH EPINEPHRINE depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient's state of consciousness should be performed after injection of MARCAINE / MARCAINE WITH EPINEPHRINE solutions. Possible early warning signs of central nervous system (CNS) toxicity are restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, or drowsiness.
Delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest, and, possibly, death. During major regional nerve blocks, such as those of the brachial plexus or lower extremity, the patient should have an indwelling intravenous catheter to assure adequate intravenous access. Use the lowest dosage of MARCAINE / MARCAINE WITH EPINEPHRINE that results in effective anesthesia to avoid high plasma levels and serious adverse effects.
Avoid rapid injection of a large volume of MARCAINE / MARCAINE WITH EPINEPHRINE solution and administer fractional (incremental) doses when feasible. Injection of repeated doses of MARCAINE / MARCAINE WITH EPINEPHRINE may cause significant increases in plasma levels with each repeated dose due to slow accumulation of the drug or its…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions have been reported and described in the Warnings and Precautions section of the labeling: • Cardiac Arrest in Obstetrical Anesthesia [see Warnings and Precautions (5.1) ] • Dose-Related Toxicity [see Warnings and Precautions (5.2) ] • Methemoglobinemia [see Warnings and Precautions (5.3) ] • Chondrolysis with Intra-Articular Infusion [see Warnings and Precautions (5.5) ] • Severe, Persistent Hypertension, Cerebrovascular Accidents, and Bradycardia Due to Drug Interactions [see Warnings and Precautions (5.6) ] • Cardiac Arrest with Intravenous Regional Anesthesia Use [see Contraindications (4) , Warnings and Precautions (5.7) ] • Allergic-Type Reactions [see Warnings and Precautions (5.8) ] • Systemic Toxicities with Unintended Intravascular or Intrathecal Injection [see Warnings and Precautions (5.9) ] • Respiratory Arrest Following Retrobulbar Block [see Warnings and Precautions (5.15) ] The following adverse reactions from voluntary reports or clinical studies have been reported with bupivacaine or bupivacaine and epinephrine.
Because many of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Adverse reactions to MARCAINE / MARCAINE WITH EPINEPHRINE are characteristic of those associated with other amide-type local anesthetics. A major cause of adverse reactions to this group of drugs is excessive plasma levels, which may be due to overdosage, unintentional intravascular injection, or slow metabolic degradation.
The most commonly encountered acute adverse reactions that demand immediate counter-measures were related to the CNS and the cardiovascular system. These adverse reactions were generally dose-related and due to high plasma levels which may have resulted from overdosage, rapid absorption from the injection site, diminished tolerance, or from unintentional intravascular injection of the local anesthetic solution. In addition to systemic dose-related toxicity, unintentional intrathecal injection of drug during the intended performance of caudal or lumbar epidural block or nerve blocks near the vertebral column (especially in the head and neck region) has resulted in underventilation or apnea ("Total or High Spinal").
Also, hypotension due to loss of sympathetic tone and respiratory paralysis or underventilation due to cephalad extension of the motor level of anesthesia have occurred. This has led to secondary cardiac arrest when untreated. Most common adverse reactions are related to the central nervous system and the cardiovascular system.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . Nervous System Disorders : Adverse reactions were characterized by excitation and/or depression of the central nervous system and included restlessness, anxiety, dizziness, tinnitus, blurred vision, tremors, convulsions, drowsiness, unconsciousness, respiratory arrest, nausea, vomiting, chills, pupillary constriction. In the practice of caudal or lumbar epidural block, unintentional penetration of the subarachnoid space by the catheter or needle has occurred.
Subsequent adverse effects may have depended partially on the amount of drug administered intrathecally and the physiological and physical effects of a dural puncture. A high spinal has been characterized by paralysis of the legs, loss of consciousness, respiratory paralysis, and bradycardia. Neurologic effects following epidural or caudal anesthesia have included spinal block of varying magnitude (including high or total spinal block); hypotension secondary to spinal block; urinary retention; fecal and urinary incontinence; loss of perineal sensation and sexual function; persistent anesthesia, paresthesia, weakness, paralysis of the lower extremities and loss of sphincter control,…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • Local Anesthetics : The toxic effects of local anesthetics are additive. Monitor for neurologic and cardiovascular effects when additional local anesthetics are administered. ( 7.1 ) • Monoamine Oxidase Inhibitors and Tricyclic Antidepressants : Administration of MARCAINE WITH EPINEPHRINE to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension.
Concurrent use of these agents should generally be avoided. ( 5.6 , 7.2 ) • Ergot-Type Oxytocic Drugs : Concurrent administration of MARCAINE WITH EPINEPHRINE and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. ( 5.6 , 7.3 ) • Nonselective Beta-Adrenergic Antagonists : Administration of MARCAINE WITH EPINEPHRINE (containing a vasoconstrictor) in patients receiving nonselective beta-adrenergic antagonists may cause severe hypertension and bradycardia.
Concurrent use of these agents should generally be avoided. ( 5.6 , 7.4 ) • Drugs Associated with Methemoglobinemia : Patients are at increased risk of developing methemoglobinemia when concurrently exposed to nitrates, nitrites, local anesthetics, antineoplastic agents, antibiotics, antimalarials, anticonvulsants, and other drugs. ( 7.5 ) • Potent Inhalation Anesthetics : Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine are used in patients during or following the administration of potent inhalation anesthetics.
( 5.13 , 7.6 )
7.1Local Anesthetics The toxic effects of local anesthetics are additive. If coadministration of other local anesthetics with MARCAINE / MARCAINE WITH EPINEPHRINE cannot be avoided, monitor patients for neurologic and cardiovascular effects related to local anesthetic systemic toxicity [see Dosage and Administration (2.1) , Warnings and Precautions (5.2) ] .
7.2Monoamine Oxidase Inhibitors and Tricyclic Antidepressants The administration of MARCAINE WITH EPINEPHRINE to patients receiving monoamine oxidase inhibitors, or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful monitoring of the patient's hemodynamic status is essential [see Warnings and Precautions (5.6) ] .
7.3Ergot-Type Oxytocic Drugs Concurrent administration of MARCAINE WITH EPINEPHRINE and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. Avoid use of MARCAINE WITH EPINEPHRINE concomitantly with ergot-type oxytocic drugs [see Warnings and Precautions (5.6) ].
7.4Nonselective Beta-Adrenergic Antagonists Administration of MARCAINE WITH EPINEPHRINE (containing a vasoconstrictor) in patients receiving nonselective beta-adrenergic antagonists may cause severe hypertension and bradycardia. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful monitoring of the patient's blood pressure and heart rate is essential [see Warnings and Precautions (5.6) ].
7.5Drugs Associated with Methemoglobinemia Patients who are administered MARCAINE / MARCAINE WITH EPINEPHRINE are at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics [see Warnings and Precautions (5.3) ] . Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide,…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Pediatric Use : Administration of MARCAINE / MARCAINE WITH EPINEPHRINE in pediatric patients younger than 12 years is not recommended. ( 8.4 ) • Geriatric Use : Patients 65 years and over, particularly those with hypertension, may be at increased risk for developing hypotension while undergoing anesthesia with MARCAINE / MARCAINE WITH EPINEPHRINE. ( 8.5 ) • Moderate to Severe Hepatic Impairment : Consider increased monitoring for bupivacaine systemic toxicity.
( 8.6 )
8.1Pregnancy Risk Summary MARCAINE / MARCAINE WITH EPINEPHRINE is contraindicated for obstetrical paracervical block anesthesia. Its use in this technique has resulted in fetal bradycardia and death [see Contraindications (4) , Warnings and Precautions (5.1) ] . There are no available data on use of MARCAINE / MARCAINE WITH EPINEPHRINE in pregnant women to inform a drug-associated risk of adverse developmental outcomes.
In animal studies, embryo-fetal lethality was noted when bupivacaine was administered subcutaneously to pregnant rabbits during organogenesis at clinically relevant doses. Decreased pup survival was observed in a rat pre- and post-natal developmental study (dosing from implantation through weaning) at a dose level comparable to the daily maximum recommended human dose (MRHD) on a body surface area (BSA) basis. Based on animal data, advise pregnant women of the potential risks to a fetus (see Data ).
Local anesthetics rapidly cross the placenta, and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity [see Clinical Pharmacology (12.3) ]. The incidence and degree of toxicity depend upon the procedure performed, the type, and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus, and neonate involve alterations of the CNS, peripheral vascular tone, and cardiac function.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, inform the patient of the potential hazard to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Clinical Considerations Maternal Adverse Reactions Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. The supine position is dangerous in pregnant women at term because of aortocaval compression by the gravid uterus.
Therefore, during treatment of systemic toxicity, maternal hypotension or fetal bradycardia following regional block, the parturient should be maintained in the left lateral decubitus position if possible, or manual displacement of the uterus off the great vessels be accomplished. Elevating the patient's legs will also help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously and electronic fetal monitoring is highly advisable.
Labor or Delivery Epidural, caudal, or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. Epidural anesthesia has been reported to prolong the second stage of labor by removing the parturient's reflex urge to bear down or by interfering with motor function. The use of obstetrical anesthesia may increase the need for forceps assistance.
The use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life. This has not been reported with bupivacaine. It is extremely important to avoid aortocaval compression by the gravid uterus during administration of regional block to parturients.
To do this, the patient must be maintained in the left lateral decubitus position or a blanke…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary MARCAINE / MARCAINE WITH EPINEPHRINE is contraindicated for obstetrical paracervical block anesthesia. Its use in this technique has resulted in fetal bradycardia and death [see Contraindications (4) , Warnings and Precautions (5.1) ] . There are no available data on use of MARCAINE / MARCAINE WITH EPINEPHRINE in pregnant women to inform a drug-associated risk of adverse developmental outcomes.
In animal studies, embryo-fetal lethality was noted when bupivacaine was administered subcutaneously to pregnant rabbits during organogenesis at clinically relevant doses. Decreased pup survival was observed in a rat pre- and post-natal developmental study (dosing from implantation through weaning) at a dose level comparable to the daily maximum recommended human dose (MRHD) on a body surface area (BSA) basis. Based on animal data, advise pregnant women of the potential risks to a fetus (see Data ).
Local anesthetics rapidly cross the placenta, and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity [see Clinical Pharmacology (12.3) ]. The incidence and degree of toxicity depend upon the procedure performed, the type, and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus, and neonate involve alterations of the CNS, peripheral vascular tone, and cardiac function.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, inform the patient of the potential hazard to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Clinical Considerations Maternal Adverse Reactions Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. The supine position is dangerous in pregnant women at term because of aortocaval compression by the gravid uterus.
Therefore, during treatment of systemic toxicity, maternal hypotension or fetal bradycardia following regional block, the parturient should be maintained in the left lateral decubitus position if possible, or manual displacement of the uterus off the great vessels be accomplished. Elevating the patient's legs will also help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously and electronic fetal monitoring is highly advisable.
Labor or Delivery Epidural, caudal, or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. Epidural anesthesia has been reported to prolong the second stage of labor by removing the parturient's reflex urge to bear down or by interfering with motor function. The use of obstetrical anesthesia may increase the need for forceps assistance.
The use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life. This has not been reported with bupivacaine. It is extremely important to avoid aortocaval compression by the gravid uterus during administration of regional block to parturients.
To do this, the patient must be maintained in the left lateral decubitus position or a blanket roll or sandbag may be placed beneath the right hip and gravid uterus displaced to the left. Data Animal Data Bupivacaine hydrochloride produced developmental toxicity when administered subcutaneously to pregnant rats and rabbits at clinically relevant doses. Bupivacaine hydrochloride was administered subcutaneously to rats at doses of 4.4, 13.3, & 40 mg/kg and to rabbits at doses of 1.3, 5.8, & 22.2 mg/kg during the period of organogenesis (implantation to closure of the hard palate).
The high dos…
🧒 Pediatric Use ▾
8.4Pediatric Use MARCAINE / MARCAINE WITH EPINEPHRINE is approved for use in adults. Administration of MARCAINE / MARCAINE WITH EPINEPHRINE in pediatric patients younger than 12 years is not recommended. Continuous infusions of bupivacaine in pediatric patients have been reported to result in high systemic levels of bupivacaine and seizures; high plasma levels may also be associated with cardiovascular abnormalities.
🧓 Geriatric Use ▾
8.5Geriatric Use Patients 65 years and over, particularly those with hypertension, may be at increased risk for developing hypotension while undergoing anesthesia with MARCAINE / MARCAINE WITH EPINEPHRINE. In clinical studies of bupivacaine, elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger adult patients. Differences in various pharmacokinetic parameters have been observed between elderly and younger adult patients [see Clinical Pharmacology (12.3) ] .
This product is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Elderly patients may require lower doses of MARCAINE / MARCAINE WITH EPINEPHRINE.
🆘 Overdosage ▾
10 OVERDOSAGE Clinical Presentation Acute emergencies from use of MARCAINE / MARCAINE WITH EPINEPHRINE are generally related to high plasma levels encountered during therapeutic use or to unintended intrathecal injection [see Warnings and Precautions (5.2 , 5.9) , Adverse Reactions (6) ]. If not treated immediately, convulsions with simultaneous hypoxia, hypercarbia, and acidosis plus myocardial depression from the direct effects of bupivacaine may result in cardiac arrhythmias, bradycardia, asystole, ventricular fibrillation, or cardiac arrest.
Respiratory abnormalities, including apnea, may occur. Hypoventilation or apnea due to unintentional intrathecal injection of MARCAINE / MARCAINE WITH EPINEPHRINE may produce these same signs and also lead to cardiac arrest if ventilatory support is not instituted. If cardiac arrest should occur, successful outcome may require prolonged resuscitative efforts.
Management The first step in the management of systemic toxic reactions, as well as hypoventilation or apnea due to unintentional intrathecal injection of MARCAINE / MARCAINE WITH EPINEPHRINE, consists of immediate attention to the establishment and maintenance of a patent airway and effective assisted or controlled ventilation with 100% oxygen with a delivery system capable of permitting immediate positive airway pressure by mask. Endotracheal intubation, using drugs and techniques familiar to the clinician, may be indicated after initial administration of oxygen by mask if difficulty is encountered in the maintenance of a patent airway, or if prolonged ventilatory support (assisted or controlled) is indicated.
If necessary, use drugs to manage the convulsions. A bolus intravenous dose of a benzodiazepine will counteract CNS stimulation related to MARCAINE. Immediately after the institution of ventilatory measures, evaluate the adequacy of the circulation.
Supportive treatment of circulatory depression may require Advanced Cardiac Life Support measures.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Bupivacaine blocks the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone.
Epinephrine is a vasoconstrictor added to bupivacaine to slow absorption into the general circulation and thus prolong maintenance of an active tissue concentration.
12.2Pharmacodynamics Systemic absorption of bupivacaine produces effects on the cardiovascular system and CNS. At blood concentrations achieved with normal therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias, and cardiac arrest, sometimes resulting in fatalities.
In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. These cardiovascular changes are more likely to occur after unintended intravascular injection of bupivacaine [see Warnings and Precautions (5.9) ] . Following systemic absorption, bupivacaine can produce CNS stimulation, CNS depression, or both.
Apparent central stimulation is manifested as restlessness, tremors, and shivering, progressing to convulsions, followed by CNS depression and coma progressing ultimately to respiratory arrest. However, bupivacaine has a primary depressant effect on the medulla and on higher centers. The depressed stage may occur without a prior excited state.
The duration of local anesthesia after administration of MARCAINE is longer than that observed after administration of other commonly used short-acting local anesthetics. There appears to be a period of analgesia that persists after the resolution of the block and return of sensation. The onset of action following dental injections is usually 2 to 10 minutes and may last up to 7 hours.
The duration of anesthetic effect is prolonged by the addition of epinephrine 1:200,000.
12.3Pharmacokinetics Systemic plasma levels of bupivacaine following administration of MARCAINE do not correlate with local efficacy. Absorption The rate of systemic absorption of bupivacaine is dependent upon the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic solution. A dilute concentration of epinephrine (1:200,000) usually reduces the rate of absorption and peak plasma concentration of bupivacaine, permitting the use of moderately larger total doses and sometimes prolonging the duration of action [see Dosage and Administration (2) ] .
After injection of MARCAINE for caudal, epidural, or peripheral nerve block, peak levels of bupivacaine in the blood are reached in 30 to 45 minutes, followed by a decline to insignificant levels during the next three to six hours. Distribution Bupivacaine appears to cross the placenta by passive diffusion. The rate and degree of diffusion is governed by (1) the degree of plasma protein binding, (2) the degree of ionization, and (3) the degree of lipid solubility.
Fetal/ maternal ratios of bupivacaine appear to be inversely related to the degree of plasma protein binding, because only the free, unbound drug is available for placental transfer. Bupivacaine with a high protein binding capacity (95%) has a low fetal/maternal ratio (0.2 to 0.4). The extent of placental transfer is also determined by the degree of ionization…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Bupivacaine blocks the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone.
Epinephrine is a vasoconstrictor added to bupivacaine to slow absorption into the general circulation and thus prolong maintenance of an active tissue concentration.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Store at 20 °C to 25 °C (68 °F to 77 °F); excursions permitted between 15 °C to 30 °C (59 °F to 86 °F). [See USP Controlled Room Temperature.] MARCAINE with epinephrine 1:200,000 (as bitartrate)―Do not autoclave solutions of MARCAINE that contain epinephrine and protect from light. This product is clear and colorless. Do not use the solution if it is discolored or if it contains a precipitate.
Unit of Sale Concentration Each 0.25% with epinephrine 1:200,000—Contains 2.5 mg bupivacaine hydrochloride per mL. NDC 0409-5738-10 Carton of 10 25 mg/10 mL (2.5 mg/mL) NDC 0409-5738-01 single-dose vial NDC 0409-1541-10 Carton of 10 75 mg/30 mL (2.5 mg/mL) NDC 0409-1541-01 single-dose vial NDC 0409-3812-01 Carton of 1 125 mg/50 mL (2.5 mg/mL) NDC 0409-3812-01 multiple-dose vial 0.5% with epinephrine 1:200,000—Contains 5 mg bupivacaine hydrochloride per mL. NDC 0409-8126-10 Carton of 10 50 mg/10 mL (5 mg/mL) NDC 0409-8126-01 single-dose vial NDC 0409-4208-10 Carton of 10 150 mg/30 mL (5 mg/mL) NDC 0409-4208-01 single-dose vial NDC 0409-6581-01 Carton of 1 250 mg/50 mL (5 mg/mL) NDC 0409-6581-01 multiple-dose vial For single-dose vials: Discard unused portion.
Also supplied in the following manufacturer-supplied dosage forms for MARCAINE (without epinephrine). • 0.25% (25 mg/10 mL) (2.5 mg/mL) in single-dose vials. • 0.25% (75 mg/30 mL) (2.5 mg/mL) in single-dose vials. • 0.25% (125 mg/50 mL) (2.5 mg/mL) in multiple-dose vials. • 0.5% (50 mg/10 mL) (5 mg/mL) in single-dose vials. • 0.5% (150 mg/30 mL) (5 mg/mL) in single-dose vials. • 0.5% (250 mg/50 mL) (5 mg/mL) in multiple-dose vials. • 0.75% (75 mg/10 mL) (7.5 mg/mL) in single-dose vials. • 0.75% (225 mg/30 mL) (7.5 mg/mL) in single-dose vials.
📦 Storage and Handling ▾
Store at 20 °C to 25 °C (68 °F to 77 °F); excursions permitted between 15 °C to 30 °C (59 °F to 86 °F). [See USP Controlled Room Temperature.] MARCAINE with epinephrine 1:200,000 (as bitartrate)―Do not autoclave solutions of MARCAINE that contain epinephrine and protect from light. This product is clear and colorless. Do not use the solution if it is discolored or if it contains a precipitate.
Unit of Sale Concentration Each 0.25% with epinephrine 1:200,000—Contains 2.5 mg bupivacaine hydrochloride per mL. NDC 0409-5738-10 Carton of 10 25 mg/10 mL (2.5 mg/mL) NDC 0409-5738-01 single-dose vial NDC 0409-1541-10 Carton of 10 75 mg/30 mL (2.5 mg/mL) NDC 0409-1541-01 single-dose vial NDC 0409-3812-01 Carton of 1 125 mg/50 mL (2.5 mg/mL) NDC 0409-3812-01 multiple-dose vial 0.5% with epinephrine 1:200,000—Contains 5 mg bupivacaine hydrochloride per mL. NDC 0409-8126-10 Carton of 10 50 mg/10 mL (5 mg/mL) NDC 0409-8126-01 single-dose vial NDC 0409-4208-10 Carton of 10 150 mg/30 mL (5 mg/mL) NDC 0409-4208-01 single-dose vial NDC 0409-6581-01 Carton of 1 250 mg/50 mL (5 mg/mL) NDC 0409-6581-01 multiple-dose vial
📋 Description ▾
11 DESCRIPTION MARCAINE / MARCAINE WITH EPINEPHRINE contains bupivacaine hydrochloride, an amide local anesthetic, as the active pharmaceutical ingredient. The route of administration for MARCAINE (without epinephrine) is by injection, for infiltration, perineural, caudal, epidural, or retrobulbar use. The route of administration for MARCAINE WITH EPINEPHRINE is by injection, for infiltration, perineural, caudal, or epidural use.
Multiple-dose vials contain methylparaben [see Warnings and Precautions (5.4) ] . Bupivacaine hydrochloride is 2-piperidinecarboxamide, 1-butyl- N -(2,6-dimethylphenyl)-, monohydrochloride, monohydrate. It is a white crystalline powder that is freely soluble in 95 percent ethanol, soluble in water, and slightly soluble in chloroform or acetone.
It has the following structural formula: MARCAINE with 1:200,000 epinephrine, contains bupivacaine hydrochloride and epinephrine bitartrate (an alpha and beta-adrenergic agonist) as active pharmaceutical ingredients. This product is for injection via local infiltration, peripheral nerve block, and caudal and lumbar epidural blocks. Multiple dose vials contain methylparaben and they should not be used for caudal and lumbar epidural blocks.
Epinephrine bitartrate is (–) - 3,4-Dihydroxy-α-[(methylamino)methyl] benzyl alcohol (+)-tartrate (1:1) salt. Epinephrine is a vasoconstrictor. It has the following structural formula: MARCAINE (bupivacaine hydrochloride) is a clear and colorless sterile isotonic solution.
Each mL of single-dose vial contains 2.5 mg, 5 mg or 7.5 mg of bupivacaine hydrochloride (equivalent to 2.22 mg, 4.44 mg or 6.66 mg of bupivacaine, respectively), sodium chloride for isotonicity, sodium hydroxide or hydrochloric acid to adjust the pH between 4 and 6.5, in water for injection. For the Multiple-dose vials, each mL also contains 1 mg methylparaben as preservative. MARCAINE with epinephrine 1:200,000 (as bitartrate) is a clear and colorless sterile isotonic solution.
Each mL contains 2.5 mg or 5 mg bupivacaine hydrochloride (equivalent to 2.22 mg or 4.44 mg of bupivacaine, respectively), and 0.0091 mg epinephrine bitartrate (equivalent to 0.005 mg of epinephrine), with sodium chloride for isotonicity, 0.5 mg sodium metabisulfite, 0.001 mL monothioglycerol, and 2 mg ascorbic acid as antioxidants, 0.0017 mL 60% sodium lactate buffer, and 0.1 mg edetate calcium disodium as stabilizer. The pH of these solutions is adjusted to between 3.4 and 4.5 with sodium hydroxide or hydrochloric acid.
For the Multiple-dose vials, each mL also contains 1 mg methylparaben as preservative. The specific gravity of MARCAINE 0.5% with epinephrine 1:200,000 (as bitartrate) at 25 °C is 1.008 and at 37 °C is 1.008. Chemical Structure Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Allergic-Type Reactions Assess if the patient has had allergic-type reactions to amide-type local anesthetics or to other formulation ingredients, such as the antimicrobial preservative methylparaben contained in multiple-dose vials or sulfites in epinephrine-containing solutions [see Contraindications (4) , Warnings and Precautions (5.8) , Adverse Reactions (6) ] . Temporary Loss of Sensation and Motor Activity After Caudal or Epidural Anesthesia When appropriate, patients should be informed in advance that they may experience temporary loss of sensation and motor activity, usually in the lower half of the body, following proper administration of caudal or epidural anesthesia.
Instructions After Dental Injection of MARCAINE Advise patients receiving dental injections of MARCAINE not to chew solid foods or to test the anesthetized area by biting or probing until anesthesia has worn off (up to 7 hours) [see Warnings and Precautions (5.16) ] . Methemoglobinemia Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly. Advise patients or caregivers to seek immediate medical attention if they or someone in their care experience the following signs or symptoms: pale, gray, or blue colored skin (cyanosis); headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue [see Warnings and Precautions (5.3) ] .