^ Risk Of Adverse Reactions With Use In Head And Neck Area
Small doses of local anesthetics (e.g., Bupivacaine Hydrochloride Injection) injected into the head and neck area, including retrobulbar, dental, and stellate ganglion blocks, may produce adverse reactions similar to systemic toxicity seen with unintentional intravascular injections of larger doses. The injection procedures require the utmost care. Confusion, convulsions, respiratory depression, and/or respiratory arrest, and cardiovascular stimulation or depression have been reported. These reactions may be due to intra-arterial injection of the local anesthetic with retrograde flow to the cerebral circulation. They may also be due to puncture of the dural sheath of the optic nerve during retrobulbar block with diffusion of any local anesthetic along the subdural space to the midbrain. Monitor circulation and respiration and constantly observe patients receiving Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection blocks. Resuscitative equipment and drugs, and personnel for treating adverse reactions should be immediately available. Dosage recommendations should not be exceeded [see Dosage and Administration (2.2)].
^ Nonselective Beta-adrenergic Antagonists
Administration of Bupivacaine Hydrochloride and Epinephrine Injection (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)].
^ Mechanism 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.
^Principal Display Panel - Mg/ Ml Vial Label -
10 mL Single-dose Teartop Vial
0.25% Bupivacaine HCl 25 mg/10 mL (2.5 mg/mL)
and epinephrine 1:200,000 Injection
Bupivacaine Hydrochloride and Epinephrine Injection, USP Rx only
FOR INFILTRATION, NERVE BLOCK, CAUDAL AND EPIDURAL ANESTHESIA.
Warning: Contains Sulfites
Distributed by Hospira, Inc., Lake Forest, IL 60045 USA
0
^ Renal Impairment
Bupivacaine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with renal impairment. This should be considered when selecting the Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection dosage [see Use in Specific Populations (8.5)].
^Principal Display Panel - Mg/ Ml Vial Label -
10 mL Single-dose Teartop Vial
0.75% Bupivacaine Hydrochloride Injection, USP 75 mg/10 mL (7.5 mg/mL)
For EPIDURAL and RETROBULBAR ANESTHESIA.
Not for OBSTETRIC or INTRATHECAL ANESTHESIA.
Dist. by Hospira, Inc. Lake Forest, IL 60045 USA
4
^Principal Display Panel - Mg/ Ml Vial Label -
30 mL Single-dose VialDiscard unused portionNDC 0409-9045-16Rx only
0.5% Bupivacaine HCl 150 mg/30 mL (5 mg/mL)
and epinephrine 1:200,000 Injection
Bupivacaine Hydrochloride and Epinephrine Injection, USP
FOR NERVE BLOCK, CAUDAL AND EPIDURAL ANESTHESIA ONLY.
Warning: Contains Sulfites
Distributed by Hospira, Inc.Lake Forest, IL 60045 USAHospira
^Principal Display Panel - Mg/ Ml Vial Label -
30 mL Single-dose Teartop Vial Preservative-Free
0.5% Bupivacaine Hydrochloride Injection, USP 150 mg/30 mL (5 mg/mL)
For NERVE BLOCK, CAUDAL and EPIDURAL ANESTHESIA.
Not for intrathecal anesthesia.
Distributed by Hospira, Inc.Lake Forest, IL 60045 USAHospira
0
^Principal Display Panel - Mg/ Ml Vial Tray -
10 mL Single-dose Teartop Vial Preservative-Free
Rx only NDC 0409-1162-01 Contains 25 of NDC 0409-1162-18
0.5% Bupivacaine Hydrochloride Injection, USP 50 mg/10 mL (5 mg/mL)
For NERVE BLOCK, CAUDAL and EPIDURAL ANESTHESIA.
Not for intrathecal anesthesia
9
^Warning: Risk Of Cardiac Arrest With Use Of Bupivacaine Hydrochloride Injection In Obstetrical Anesthesia
There have been reports of cardiac arrest with difficult resuscitation or death during use of Bupivacaine Hydrochloride Injection 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 Hydrochloride Injection 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)].
^ Pharmacodynamics
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 Bupivacaine Hydrochloride Injection 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.
^4 Contraindications
Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is contraindicated in:
^Principal Display Panel - Mg/ Ml Vial Label -
10 mL Single-dose Teartop Vial Preservative-Free
0.25% Bupivacaine Hydrochloride Injection, USP 25 mg/10 mL (2.5 mg/mL)
For INFILTRATION, NERVE BLOCK, CAUDAL and EPIDURAL ANESTHESIA.
Not for intrathecal anesthesia.Hospira
Dist. by Hospira, Inc., Lake Forest, IL 60045 USA
2
^ Use In Ophthalmic Surgery
When Bupivacaine Hydrochloride Injection 0.75% (7.5 mg/mL) is used for retrobulbar block, complete corneal anesthesia usually precedes onset of clinically acceptable external ocular muscle akinesia. Therefore, presence of akinesia rather than anesthesia alone should determine readiness of the patient for surgery [see Warnings and Precautions (5.15)].
^ Methemoglobinemia
Cases of methemoglobinemia have been reported in association with local anesthetic use. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition [see Drug Interactions (7.5)]. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.
Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure, and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood. Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious CNS and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection and any other oxidizing agents. Depending on the severity of the signs and symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. A more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
^Principal Display Panel - Mg/ Ml Vial Label -
30 mL Single-dose Teartop Vial Preservative-Free
0.25% Bupivacaine Hydrochloride Injection, USP 75 mg/30 mL (2.5 mg/mL)
For INFILTRATION, NERVE BLOCK, CAUDAL and EPIDURAL ANESTHESIA.
Not for intrathecal anesthesia.
Distributed by Hospira, Inc.Lake Forest, IL 60045 USAHospira
4
^Principal Display Panel - Mg/ Ml Vial Label -
50 mL Multiple-dose Fliptop Vial
0.5% Bupivacaine Hydrochloride Injection, USP 250 mg/50 mL (5 mg/mL)
For NERVE BLOCK.
Not for caudal, epidural or intrathecal anesthesia.
Distributed by Hospira, Inc.,Lake Forest, IL 60045 USAHospira
2
^Principal Display Panel - Mg/ Ml Vial Tray -
30 mL Single-dose Teartop Vial
Rx only NDC 0409-9042-17 Contains 25 of NDC 0409-9042-16
0.25% Bupivacaine Hydrochloride 75 mg/30 mL (2.5 mg/mL)and epinephrine 1:200,000 Injection
Sterile, nonpyrogenic
Bupivacaine Hydrochloride and Epinephrine Injection, USP FOR INFILTRATION, NERVE BLOCK, CAUDAL AND EPIDURAL ANESTHESIA. Not for intrathecal anesthesia.
Warning: Contains Sulfites
Hospira
9
^Principal Display Panel - Mg/ Ml Vial Label -
50 mL Multiple-dose Vial
0.5% Bupivacaine HCl 250 mg/50 mL (5 mg/mL)
and epinephrine 1:200,000 Injection
Bupivacaine and Epinephrine Inj., USP
FOR NERVE BLOCK ONLY
Warning: Contains Sulfites
Distributed by Hospira, Inc.,Lake Forest, IL 60045 USA
Hospira
^ Risk Of Use In Patients With Impaired Cardiovascular Function
Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection should be given in reduced doses in patients with impaired cardiovascular function (e.g., hypotension, heartblock) because they may be less able to compensate for functional changes associated with the prolongation of AV conduction produced by Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection. Monitor patients closely for blood pressure, heart rate, and ECG changes.
^ Test Dose For Caudal And Lumbar Epidural Blocks
Three mL of Bupivacaine Hydrochloride and Epinephrine Injection 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. This test dose may serve as a warning of unintended intravascular or intrathecal injection. Closely monitor for early clinical signs of toxicity following each test dose [see Warnings and Precautions (5.9)]. Allot adequate time for onset of spinal block to detect possible intrathecal injection. An intravascular or intrathecal injection is still possible even if results of the test dose are negative. The test dose itself may produce a systemic toxic reaction, high spinal, or cardiovascular effects from the epinephrine [see Warnings and Precautions (5.2, 5.9), Overdosage (10)].
^Principal Display Panel - Mg/ Ml Vial Carton -
10 mL Single-dose Teartop Vial Sterile, nonpyrogenic
0.25% Bupivacaine Hydrochloride 25 mg/10 mL (2.5 mg/mL)
and epinephrine 1:200,000 Injection
Bupivacaine Hydrochloride and Epinephrine Injection, USP FOR INFILTRATION, NERVE BLOCK, CAUDAL AND EPIDURAL ANESTHESIA. Not for intrathecal anesthesia.
Warning: Contains Sulfites
NDC 0409-9042-01Contains 10 of NDC 0409-9042-11
Rx only
Hospira
1
^ Ergot-type Oxytocic Drugs
Concurrent administration of Bupivacaine Hydrochloride and Epinephrine Injection and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. Avoid use of Bupivacaine Hydrochloride and Epinephrine concomitantly with ergot-type oxytocic drugs [see Warnings and Precautions (5.6)].
^ Antimicrobial Preservatives In Multiple-dose Vials
Avoid use of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection solutions containing antimicrobial preservatives, i.e., those supplied in multiple-dose vials, for epidural or caudal anesthesia because safety has not been established with such use.
^ Geriatric Use
Patients 65 years and over, particularly those with hypertension, may be at increased risk for developing hypotension while undergoing anesthesia with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection.
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 Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection.
^ Pharmacokinetics
Systemic plasma levels of bupivacaine following administration of Bupivacaine Hydrochloride Injection do not correlate with local efficacy.
^Principal Display Panel - Mg/ Ml Vial Label -
50 mL Multiple-dose Fliptop Vial
0.25% Bupivacaine HCl 125 mg/50 mL (2.5 mg/mL)
and epinephrine 1:200,000 Injection
Bupivacaine and Epinephrine Injection., USP FOR INFILTRATION AND NERVE BLOCK ONLY
Warning: Contains Sulfites
Distributed by Hospira, Inc.,Lake Forest, IL 60045 USA
Hospira
^Principal Display Panel - Mg/ Ml Vial Label -
50 mL Multiple-dose Fliptop Vial
0.25% Bupivacaine Hydrochloride Injection, USP 125 mg/50 mL (2.5 mg/mL)
For INFILTRATION and NERVE BLOCK.
Not for caudal, epidural or intrathecal anesthesia.
Distributed by Hospira, Inc.Lake Forest, IL 60045 USAHospira
6
^Principal Display Panel - Mg/ Ml Vial Carton -
One/NDC 0409-9046-11
50 mL Multiple-dose Fliptop Vial
Sterile, nonpyrogenic
0.5% Bupivacaine Hydrochloride 250 mg/50 mL (5 mg/mL)
and epinephrine 1:200,000 Injection
Bupivacaine and Epinephrine Injection, USPRx only
FOR NERVE BLOCK ONLY.
Not for caudal, epidural or intrathecal anesthesia.
Warning: Contains Sulfites
Hospira
^Principal Display Panel - Mg/ Ml Vial Label -
30 mL Single-dose Teartop Vial Preservative-Free
0.75% Bupivacaine Hydrochloride Injection, USP 225 mg/30 mL (7.5 mg/mL)
For EPIDURAL and RETROBULBAR ANESTHESIA.
Not for OBSTETRIC or INTRATHECAL ANESTHESIA.
Distributed by Hospira, Inc.,Lake Forest, IL 60045 USAHospira
6
^Principal Display Panel - Mg/ Ml Vial Carton -
One/NDC 0409-9043-11
50 mL Multiple-dose Fliptop Vial
Sterile, nonpyrogenic
0.25% Bupivacaine Hydrochloride 125 mg/50 mL (2.5 mg/mL)
and epinephrine 1:200,000 Injection
Bupivacaine and Epinephrine Injection, USP Rx only
FOR INFILTRATION AND NERVE BLOCK ONLY
Not for caudal, epidural or intrathecal anesthesia.
Warning: Contains Sulfites
Hospira
^Principal Display Panel - Mg/ Ml Vial Tray -
30 mL Single-dose Teartop Vial Preservative-Free
Rx only NDC 0409-1159-02Contains 25 of NDC 0409-1159-19
0.25% Bupivacaine Hydrochloride Injection, USP 75 mg/30 mL (2.5 mg/mL)
For INFILTRATION, NERVE BLOCK, CAUDAL and EPIDURAL ANESTHESIA.
Not for intrathecal anesthesia.
5
^ Description
Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection contains bupivacaine hydrochloride, an amide local anesthetic, as the active pharmaceutical ingredient. The route of administration for Bupivacaine Hydrochloride Injection (without epinephrine) is by injection, for infiltration, perineural, caudal, epidural, or retrobulbar use. The route of administration for Bupivacaine Hydrochloride and Epinephrine Injection 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:
Bupivacaine hydrochloride with 1:200,000 epinephrine, contains bupivacaine hydrochloride and epinephrine (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 is (-)-3,4-Dihydroxy-α-[(methylamino)methyl] benzyl alcohol. Epinephrine is a vasoconstrictor. It has the following structural formula:
Bupivacaine Hydrochloride Injection, USP 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.
Bupivacaine Hydrochloride and Epinephrine Injection, USP 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 0.005 mg of epinephrine, with sodium chloride for isotonicity, 0.1 mg sodium metabisulfite as antioxidant, and 0.1 mg edetate calcium disodium anhydrous as stabilizer. The pH of these solutions is adjusted to between 3.3 and 5.5 with sodium hydroxide or hydrochloric acid.
For the multiple-dose vials, each mL also contains 1 mg methylparaben as preservative.
The specific gravity of Bupivacaine Hydrochloride and Epinephrine Injection [0.5% (5 mg/mL) of bupivacaine] at 25 ºC is 1.007.
^ Allergic-type Reactions To Sulfites In Bupivacaine Hydrochloride And Epinephrine Injection
Bupivacaine Hydrochloride and Epinephrine Injection 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. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people. Bupivacaine Hydrochloride Injection without epinephrine does not contain sodium metabisulfite.
^ Risk Of Systemic Toxicities With Unintended Intravascular Or Intrathecal Injection
Unintended intravascular or intrathecal injection of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection may be associated with systemic toxicities, including CNS or cardiorespiratory depression and coma, progressing ultimately to respiratory arrest. Unintentional intrathecal injection during the intended performance of caudal or lumbar epidural block or nerve blocks near the vertebral column has resulted in underventilation or apnea ("Total or High Spinal"). A high spinal has been characterized by paralysis of the legs, loss of consciousness, respiratory paralysis, and bradycardia [see Adverse Reactions (6)].
Aspirate for blood or cerebrospinal fluid (where applicable) before injecting Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection, 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.
^ Risk Of Cardiac Arrhythmias With Concomitant Use Of Potent Inhalation Anesthetics
Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine (e.g., Bupivacaine Hydrochloride and Epinephrine Injection) are used in patients during or following the administration of potent inhalation anesthetics [see Drug Interactions (7.6)]. In deciding whether to concurrently use Bupivacaine Hydrochloride and Epinephrine Injection with potent inhalation anesthetics in the same patient, the combined action of both agents upon the myocardium, the concentration and volume of vasoconstrictor used, and the time since injection, when applicable, should be taken into account.
^ Hepatic Impairment
Amide-type local anesthetics, such as bupivacaine, are metabolized by the liver. Patients with severe hepatic impairment, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations, and potentially local anesthetic systemic toxicity. Therefore, consider reduced dosing and increased monitoring for local anesthetic systemic toxicity in patients with moderate to severe hepatic impairment treated with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection, especially with repeat doses [see Warnings and Precautions (5.10)].
^ Dose-related Toxicity
The safety and effectiveness of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection 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 Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection 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 Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection that results in effective anesthesia to avoid high plasma levels and serious adverse effects. Avoid rapid injection of a large volume of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection solution and administer fractional (incremental) doses when feasible.
Injection of repeated doses of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection may cause significant increases in plasma levels with each repeated dose due to slow accumulation of the drug or its metabolites, or to slow metabolic degradation. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients and acutely ill patients should be given reduced doses commensurate with their age and physical status.
^Principal Display Panel - Mg/ Ml Vial Tray -
10 mL Single-dose Teartop Vial Preservative-Free
Rx only NDC 0409-1165-01 Contains 25 of NDC 0409-1165-18
0.75% Bupivacaine Hydrochloride Injection, USP 75 mg/10 mL (7.5 mg/mL)
For EPIDURAL and RETROBULBAR ANESTHESIA.
Not for OBSTETRIC or INTRATHECAL ANESTHESIA.
5
^ Important Dosage And Administration Information
^ Risk Of Toxicity In Patients With Hepatic Impairment
Because amide local anesthetics such as bupivacaine are metabolized by the liver, consider reduced dosing and increased monitoring for bupivacaine systemic toxicity in patients with moderate to severe hepatic impairment who are treated with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection, especially with repeat doses [see Use in Specific Populations (8.6)].
^ Monoamine Oxidase Inhibitors And Tricyclic Antidepressants
The administration of Bupivacaine Hydrochloride and Epinephrine Injection 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)].
^ Use In Epidural Anesthesia
During the administration of epidural anesthesia, it is recommended that a test dose of Bupivacaine Hydrochloride and Epinephrine Injection without antimicrobial preservative (0.5% bupivacaine with 1:200,000 epinephrine) be administered initially and the effects monitored before the full dose is given. When using a "continuous" catheter technique, test doses should be given prior to both the initial and all supplemental doses, because a catheter in the epidural space can migrate into a blood vessel or through the dura [see Dosage and Administration (2.4)].
During epidural administration, administer Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection, 0.5% (5 mg/mL) and Bupivacaine Hydrochloride Injection 0.75% (7.5 mg/mL) solutions in incremental doses of 3 mL to 5 mL with sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection. Administer injections slowly, with frequent aspirations before and during the injection to avoid intravascular injection. Perform syringe aspirations before and during each supplemental injection in continuous (intermittent) catheter techniques. In obstetrics, use ONLY the 0.5% (5 mg/mL) and 0.25% (2.5 mg/mL) concentrations of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection [see Warnings and Precautions (5.1)]; incremental doses of 3 mL to 5 mL of the 0.5% (5 mg/mL) solution not exceeding 50 mg to 100 mg at any dosing interval are recommended. Repeat doses should be preceded by a test dose containing epinephrine if not clinically contraindicated. Use only the single-dose vials for caudal or epidural anesthesia; avoid use of the multiple-dose vials for these procedures, which contain a preservative [see Dosage and Administration (2.1, 2.4), Warnings and Precautions (5.4, 5.9)].
^Principal Display Panel - Mg/ Ml Vial Carton -
10 mL Single-dose Teartop Vial Sterile, Nonpyrogenic
0.5% Bupivacaine Hydrochloride 50 mg/10 mL (5 mg/mL)
and epinephrine 1:200,000 Injection
Bupivacaine Hydrochloride and Epinephrine Injection, USP FOR NERVE BLOCK, CAUDAL AND EPIDURAL ANESTHESIA ONLY. Not for intrathecal anesthesia.
Warning: Contains Sulfites
NDC 0409-9045-01Contains 10 of NDC 0409-9045-11
Rx only
Hospira
^Principal Display Panel - Mg/ Ml Vial Tray -
50 mL Multiple-dose Fliptop Vial
Rx only NDC 0409-1163-01 Contains 25 of NDC 0409-1163-18
0.5% Bupivacaine Hydrochloride Injection, USP 250 mg/50 mL (5 mg/mL)
For NERVE BLOCK.
Not for caudal, epidural or intrathecal anesthesia.
^3 Dosage Forms And Strengths
Bupivacaine Hydrochloride Injection, USP is a clear, colorless solution available as:
Bupivacaine Hydrochloride and Epinephrine Injection, USP is a clear, colorless solution available as:
^ Potent Inhalation Anesthetics
Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine (e.g., Bupivacaine Hydrochloride and Epinephrine Injection) are used in patients during or following the administration of potent inhalation anesthetics [see Warnings and Precautions (5.13)].
^ Pediatric Use
Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is approved for use in adults. Administration of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection 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.
^Principal Display Panel - Mg/ Ml Vial Tray -
30 mL Single-dose Teartop VialPreservative-Free
Rx onlyNDC 0409-1165-02Contains 25 of NDC 0409-1165-19
0.75% BupivacaineHydrochloride Injection, USP225 mg/30 mL (7.5 mg/mL)
For EPIDURAL and RETROBULBAR ANESTHESIA.
Not for OBSTETRIC or INTRATHECAL ANESTHESIA.
7
^ 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). Information on safe dosages and techniques of administration of Bupivacaine Hydrochloride Injection in this procedure is lacking. Therefore, Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is contraindicated for use with this technique [see Contraindications (4)].
^Principal Display Panel - Mg/ Ml Vial Tray -
50 mL Multiple-dose Fliptop Vial
Rx only NDC 0409-1160-01 Contains 25 of NDC 0409-1160-18
0.25% Bupivacaine Hydrochloride Injection, USP 125 mg/50 mL (2.5 mg/mL)
For INFILTRATION and NERVE BLOCK.
Not for caudal, epidural or intrathecal anesthesia.
7
^ Risk Of Ischemic Injury Or Necrosis In Body Areas With Limited Blood Supply
Use Bupivacaine Hydrochloride and Epinephrine Injection in carefully restricted quantities in areas of the body supplied by end arteries or having otherwise compromised blood supply such as digits, nose, external ear, or penis. Patients with hypertensive vascular disease may exhibit exaggerated vasoconstrictor response. Ischemic injury or necrosis may result.
^ Local Anesthetics
The toxic effects of local anesthetics are additive. If coadministration of other local anesthetics with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection 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)].
^ Drugs Associated With Methemoglobinemia
Patients who are administered Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection 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)].
^ Risk Of Cardiac Arrest With Use Of Bupivacaine Hydrochloride Injection In Obstetrical Anesthesia
There have been reports of cardiac arrest with difficult resuscitation or death during use of Bupivacaine Hydrochloride Injection 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 Hydrochloride Injection 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.
^Principal Display Panel - Mg/ Ml Vial Label -
30 mL Single-dose Teartop Vial Rx only
0.25% Bupivacaine HCl 75 mg/30 mL (2.5 mg/mL)
and epinephrine 1:200,000 Injection
Bupivacaine Hydrochloride and Epinephrine Injection, USP
FOR INFILTRATION, NERVE BLOCK, CAUDAL AND EPIDURAL ANESTHESIA.
Warning: Contains Sulfites
Distributed by Hospira, Inc.,Lake Forest, IL 60045 USAHospira
^6 Adverse Reactions
The following clinically significant adverse reactions have been reported and described in the Warnings and Precautions section of the labeling:
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 Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection 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.
^Principal Display Panel - Mg/ Ml Vial Tray -
10 mL Single-dose Teartop Vial Preservative-Free
Rx only NDC 0409-1159-01 Contains 25 of NDC 0409-1159-18
0.25% Bupivacaine Hydrochloride Injection, USP 25 mg/10 mL (2.5 mg/mL)
For INFILTRATION, NERVE BLOCK, CAUDAL and EPIDURAL ANESTHESIA.
Not for intrathecal anesthesia.
3
^ Chondrolysis With Intra-articular Infusion
Intra-articular infusions of local anesthetics including Bupivacaine Hydrochloride Injection following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions. The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. There is insufficient information to determine whether shorter infusion periods are associated with chondrolysis. The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2nd month after surgery. Currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement.
^ Recommended Concentrations And Dosages Of Bupivacaine Hydrochloride Injection/bupivacaine Hydrochloride And Epinephrine Injection
The dosage of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection administered varies with the anesthetic procedure, the area to be anesthetized, the vascularity of the tissues, the number of neuronal segments to be blocked, the depth of anesthesia and degree of muscle relaxation required, the duration of anesthesia desired, individual tolerance, and the physical condition of the patient. Administer the smallest dosage and concentration required to produce the desired result.
The types of block and recommended Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection concentrations are shown in Table 1.
At recommended dosages, Bupivacaine Hydrochloride/Bupivacaine Hydrochloride and Epinephrine produces complete sensory block, but the effect on motor function differs among the three concentrations. Table 2 provides information on the expected effect on motor function for the three concentrations.
The duration of anesthesia with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is such that for most indications, a single dose is sufficient.
The maximum dosage limit within the recommended dosage range must be individualized in each case after evaluating the size and physical status of the patient, as well as the anticipated rate of systemic absorption from a particular injection site.
The dosages in Table 3 are recommended as a guide for use in the average adult. These doses may be repeated once every three hours. Do not exceed a total daily dosage of 400 mg in 24 hours. The duration of anesthetic effect may be prolonged by the addition of epinephrine.
^ Phenothiazines And Butyrophenones
Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine. Concurrent use of Bupivacaine Hydrochloride and Epinephrine Injection and these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential.
^ Risk Of Respiratory Arrest With Use In Ophthalmic Surgery
Clinicians who perform retrobulbar blocks should be aware that there have been reports of respiratory arrest following local anesthetic injection. Prior to retrobulbar block (e.g., with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection), as with all other regional procedures, resuscitative equipment and drugs, and personnel to manage respiratory arrest or depression, convulsions, and cardiac stimulation or depression should be immediately available [see Warnings and Precautions (5.14)]. As with other anesthetic procedures, patients should be constantly monitored following ophthalmic blocks for signs of these adverse reactions, which may occur following relatively low total doses.
A concentration of 0.75% bupivacaine is indicated for retrobulbar block; however, this concentration is not indicated for any other peripheral nerve block, including the facial nerve, and not indicated for local infiltration, including the conjunctiva [see Indications and Usage (1)].
^ Risk Of Inadvertent Trauma To Tongue, Lips, And Buccal Mucosa In Dental Applications
Because of the long duration of anesthesia, when Bupivacaine Hydrochloride and Epinephrine Injection [0.5% (5 mg/mL) of bupivacaine] is used for dental injections, warn patients about the possibility of inadvertent trauma to tongue, lips, and buccal mucosa and advise them not to chew solid foods until sensation returns [see Patient Counseling Information (17)].
^Principal Display Panel - Mg/ Ml Vial Label -
10 mL Single-dose Teartop Vial Rx only
0.5% Bupivacaine HCl 50 mg/10 mL (5 mg/mL)
and epinephrine 1:200,000 Injection
Bupivacaine Hydrochloride and Epinephrine Injection, USP
FOR NERVE BLOCK, CAUDAL AND EPIDURAL ANESTHESIA ONLY.
Warning: Contains Sulfites
Hospira
Distributed by Hospira, Inc., Lake Forest, IL 60045 USA
^1 Indications And Usage
Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection 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 Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection are recommended for each type of block indicated to produce local or regional anesthesia or analgesia [see Dosage and Administration (2.2)].
^ Use In Dentistry
Bupivacaine Hydrochloride and Epinephrine Injection 0.5% (5 mg/mL) is recommended for infiltration and block injection in the maxillary and mandibular area when a longer duration of local anesthesia is desired, such as for procedures generally associated with significant postoperative pain. The average dose of 1.8 mL (9 mg) per injection site will usually suffice; an occasional second dose of 1.8 mL (9 mg) may be used if necessary to produce adequate anesthesia after allowing 2 to 10 minutes for block onset [see Clinical Pharmacology (12.2)]. Use the lowest effective dose and allow time between injections; it is recommended that the total dose for all injection sites, spread out over a single dental sitting, not exceed 90 mg for a healthy adult patient (ten 1.8 mL injections of 0.5% (5 mg/mL) Bupivacaine Hydrochloride and Epinephrine Injection). Inject slowly and with frequent aspirations.
^Principal Display Panel - Mg/ Ml Vial Tray -
30 mL Single-dose Teartop Vial Preservative-Free
Rx only NDC 0409-1162-02 Contains 25 of NDC 0409-1162-19
0.5% Bupivacaine Hydrochloride Injection, USP 150 mg/30 mL (5 mg/mL)
For NERVE BLOCK, CAUDAL and EPIDURAL ANESTHESIA.
Not for intrathecal anesthesia.
1
^Principal Display Panel - Mg/ Ml Vial Tray -
30 mL Single-dose Teartop Vial Sterile, Nonpyrogenic
Rx only NDC 0409-9045-17 Contains 25 of NDC 0409-9045-16
0.5% Bupivacaine Hydrochloride 150 mg/30 mL (5 mg/mL)and epinephrine 1:200,000 Injection
Bupivacaine Hydrochloride and Epinephrine Injection, USP FOR NERVE BLOCK, CAUDAL AND EPIDURAL ANESTHESIA ONLY.
Not for intrathecal anesthesia. Warning: Contains Sulfites
^Principal Display Panel - Mg/ Ml Vial Label -
10 mL Single-dose Teartop Vial Preservative-Free
0.5% Bupivacaine Hydrochloride Injection, USP 50 mg/10 mL (5 mg/mL)
For NERVE BLOCK, CAUDAL and EPIDURAL ANESTHESIA.
Not for intrathecal anesthesia.
Distributed by Hospira, Inc.Lake Forest, IL 60045 USAHospira
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