A3928-20 SINGLE SHOT EPIDURAL 20G TUOHY - regional anesthesia kit

United States - English - NLM (National Library of Medicine)

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Active ingredient:
SODIUM CHLORIDE (UNII: 451W47IQ8X) (CHLORIDE ION - UNII:Q32ZN48698)
Available from:
Smiths Medical ASD, Inc.
INN (International Name):
SODIUM CHLORIDE
Composition:
SODIUM CHLORIDE 9 mg in 1 mL
Therapeutic indications:
Lidocaine Hydrochloride Injection, USP is indicated for production of local or regional anesthesia by infiltration techniques such as percutaneous injection and intravenous regional anesthesia by peripheral nerve block techniques such as brachial plexus and intercostal and by central neural techniques such as lumbar and caudal epidural blocks, when the accepted procedures for these techniques as described in standard textbooks are observed. Lidocaine is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type. INDICATIONS AND USAGE Sodium Chloride Injection is used to flush intravascular catheters or as a sterile, isontonic single dose vehicle, solvent, or diluent for substances to administered intravenously,k intramuscularly or sub-cutaneously and for other extemporaneously prepared single dose sterile solutions according to instructions of the manufacture of the drug to be administered. Bupivacaine Hydrochloride is indicated for the production of local o
Product summary:
Lidocaine Hydrochloride Injection, USP is supplied as follows: NDC Container Concentration Size Total (mg) Single-dose: 0409-4278-01 Glass Teartop Vial 0.5% (5 mg/mL) 50 mL 250 0409-4713-01 Glass Ampul 1% (10 mg/mL) 2 mL (bulk – 400 units) 20 0409-4713-02 Glass Ampul 1% (10 mg/mL) 5 mL 50 0409-4713-05 Glass Ampul 1% (10 mg/mL) 5 mL (bulk – 400 units) 50 0409-4713-20 Glass Ampul 1% (10 mg/mL) 20 mL 200 0409-4713-32 Glass Ampul 1% (10 mg/mL) 2 mL 20 0409-4713-62 Glass Ampul 1% (10 mg/mL) 2 mL (bulk – 800 units) 20 0409-4713-65 Glass Ampul 1% (10 mg/mL) 5 mL (bulk – 800 units) 50 0409-4279-02 Glass Teartop Vial 1% (10 mg/mL) 30 mL 300 0409-4270-01 Sterile Glass Teartop Vial 1% (10 mg/mL) 30 mL 300 0409-4776-01 Glass Ampul 1.5% (15 mg/mL) 20 mL 300 0409-4056-01 Sterile Glass Ampul 1.5% (15 mg/mL) 20 mL 300 0409-4282-01 Glass Ampul 2% (20 mg/mL) 2 mL 40 0409-4282-02 Glass Ampul 2% (20 mg/mL) 10 mL 200 Multiple-dose: 0409-4275-01 Plastic Fliptop Vial 0.5% (5 mg/mL) 50 mL 250 0409-4276-01 Plastic Fliptop Vial 1% (10 mg/mL) 20 mL 200 0409-4276-02 Plastic Fliptop Vial 1% (10 mg/mL) 50 mL 500 0409-4277-01 Plastic Fliptop Vial 2% (20 mg/mL) 20 mL 400 0409-4277-02 Plastic Fliptop Vial 2% (20 mg/mL) 50 mL 1000 Single-dose products are preservative-free. Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Lidocaine Hydrochloride Injection, USP solutions packaged in ampuls and glass teartop vials may be autoclaved one time only. Autoclave at 15 pounds pressure, 121°C (250°F) for 15 minutes. DO NOT AUTOCLAVE PRODUCT IN PLASTIC VIALS. Revised: February, 2010 Printed in USA                            EN-2421 Hospira, Inc., Lake Forest, IL 60045 USA HOW SUPPLIED 5 mL ampuls packaged in box of 50 each (NDC-65282-1505-1) 10 mL ampuls packaged in box of 50 each (NDC-65282-1510-1) 30 mL ampuls packaged in box of 30 each (NDC-65282-1530-3) These solutions are not for spinal anesthesia. Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Bupivacaine Hydrochloride ─ Solutions of Bupivacaine Hydrochloride that do not contain epinephrine may be autoclaved. Autoclave at 15-pound pressure, 121°C (250°F) for 15 minutes. Do not autoclave product packaged in Abboject™ Syringes. 0.25% 30 mL 6.0 (4.0 to 6.5) Ampul 50 mL 6.0 (4.0 to 6.5) Ampul 0.25% 20 mL 6.0 (4.0 to 6.5) Sterile Pack Ampul 0.25% 10 mL 5.4 (4.0 to 6.5) Teartop Vial 30 mL 5.4 (4.0 to 6.5) Teartop Vial 0.25% 50 mL 5.4 (4.0 to 6.5) Fliptop Vial (Multiple-dose) 0.5% 30 mL 6.0 (4.0 to 6.5) Ampul 0.5% 20 mL 6.0 (4.0 to 6.5) Sterile Pack Ampul 0.5% 50 mL 5.4 (4.0 to 6.5) Fliptop Vial (Multiple-dose) 0.5% 10 mL 5.4 (4.0 to 6.5) Teartop Vial 30 mL 5.4 (4.0 to 6.5) Teartop Vial 0.75% 20 mL 6.0 (4.0 to 6.5) Sterile Pack Ampul 0.75% 30 mL 6.0 (4.0 to 6.5) Ampul 0.75% 10 mL 5.4 (4.0 to 6.5) Teartop Vial 30 mL 5.4 (4.0 to 6.5) Teartop Vial Bupivacaine Hydrochloride with epinephrine 1:200,000 (as bitartrate)─Solutions of Bupivacaine Hydrochloride that contain epinephrine should not be autoclaved and should be protected from light. Do not use the solution if its color is pinkish or darker than slightly yellow or if it contains a precipitate. 0.25% 30 mL 4.0 (3.3 to 5.5) Teartop Vial 0.25% 50 mL 4.0 (3.3 to 5.5) Fliptop Vial (Multiple-dose) 0.5% 10 mL 4.0 (3.3 to 5.5) Teartop Vial 0.5% 30 mL 4.0 (3.3 to 5.5) Teartop Vial 0.5% 50 mL 4.0 (3.3 to 5.5) Fliptop Vial (Multiple-dose) Revised: April, 2010   Printed in USA                            EN-2490 Hospira, Inc., Lake Forest, IL 60045 USA
Authorization status:
Premarket Notification
Authorization number:
0409-1158-01, 0409-4282-02, 51688-6248-2, 65282-1510-1

A3928-20 SINGLE SHOT EPIDURAL 20G TUOHY - regional anesthesia kit

Smiths Medical ASD, Inc.

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LIDOCAINE HYDROCHLORIDE (lidocaine hydrochloride anhydrous) injection, solution

AQUEOUS SOLUTIONS FOR INFILTRATION

AND NERVE BLOCK

Ampul

Plastic Multiple-dose Fliptop Vial

Glass Teartop Vial

Rx only

DESCRIPTION

Lidocaine Hydrochloride Injection, USP is a sterile, nonpyrogenic solution of lidocaine hydrochloride

in water for injection for parenteral administration in various concentrations with characteristics as

follows:

Concentration

0.5% 1% 1.5% 2%

mg/mL lidocaine HCl (anhyd.)5

mg/mL sodium chloride

Multiple-dose vials contain 0.1% of methylparaben added as preservative. May contain sodium

hydroxide and/or hydrochloric acid for pH adjustment. The pH is 6.5 (5.0 to 7.0). See HOW SUPPLIED

section for various sizes and strengths.

Lidocaine is a local anesthetic of the amide type.

Lidocaine Hydrochloride, USP is chemically designated 2-(diethylamino)-N-(2,6-dimethylphenyl)-

acetamide monohydrochloride monohydrate, a white powder freely soluble in water. The molecular

weight is 288.82. It has the following structural formula:

The semi-rigid vial used for the plastic vials is fabricated from a specially formulated polyolefin. It is a

copolymer of ethylene and propylene. The safety of the plastic has been confirmed by tests in animals

according to USP biological standards for plastic containers. The container requires no vapor barrier to

maintain the proper drug concentration.

CLINICAL PHARMACOLOGY

Mechanism of action: Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes

required for the initiation and conduction of impulses, thereby effecting local anesthetic action.

Hemodynamics: Excessive blood levels may cause changes in cardiac output, total peripheral

resistance, and mean arterial pressure. With central neural blockade these changes may be attributable to

block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various

components of the cardiovascular system and/or the beta-adrenergic receptor stimulating action of

epinephrine when present. The net effect is normally a modest hypotension when the recommended

dosages are not exceeded.

Pharmacokinetics and metabolism: Information derived from diverse formulations, concentrations

and usages reveals that lidocaine is completely absorbed following parenteral administration, its rate of

absorption depending, for example, upon various factors such as the site of administration and the

presence or absence of a vasoconstrictor agent. Except for intravascular administration, the highest

blood levels are obtained following intercostal nerve block and the lowest after subcutaneous

administration.

The plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases

with increasing concentration. At concentrations of 1 to 4 mcg of free base per mL, 60 to 80 percent of

lidocaine is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid

glycoprotein.

Lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion.

Lidocaine is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the

kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide

linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites

monoethylglycinexylidide and glycinexylidide. The pharmacological/toxicological actions of these

metabolites are similar to, but less potent than, those of lidocaine. Approximately 90% of lidocaine

administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged.

The primary metabolite in urine is a conjugate of 4-hydroxy-2, 6-dimethylaniline.

The elimination half-life of lidocaine following an intravenous bolus injection is typically 1.5 to 2.0

hours. Because of the rapid rate at which lidocaine is metabolized, any condition that affects liver

function may alter lidocaine kinetics. The half-life may be prolonged two-fold or more in patients with

liver dysfunction. Renal dysfunction does not affect lidocaine kinetics but may increase the

accumulation of metabolites.

Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of

lidocaine required to produce overt systemic effects. Objective adverse manifestations become

increasingly apparent with increasing venous plasma levels above 6.0 mcg free base per mL. In the

rhesus monkey arterial blood levels of 18-21 mcg/mL have been shown to be threshold for convulsive

activity.

INDICATIONS AND USAGE

Lidocaine Hydrochloride Injection, USP is indicated for production of local or regional anesthesia by

infiltration techniques such as percutaneous injection and intravenous regional anesthesia by peripheral

nerve block techniques such as brachial plexus and intercostal and by central neural techniques such as

lumbar and caudal epidural blocks, when the accepted procedures for these techniques as described in

standard textbooks are observed.

CONTRAINDICATIONS

Lidocaine is contraindicated in patients with a known history of hypersensitivity to local anesthetics of

the amide type.

WARNINGS

LIDOCAINE HYDROCHLORIDE INJECTION, FOR INFILTRATION AND NERVE BLOCK,

SHOULD BE EMPLOYED ONLY BY CLINICIANS WHO ARE WELL VERSED IN DIAGNOSIS

AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER ACUTE EMERGENCIES

THAT MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED AND THEN ONLY AFTER

ENSURING THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE

DRUGS, CARDIOPULMONARY EQUIPMENT, AND THE PERSONNEL NEEDED FOR PROPER

MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES (See also ADVERSE

REACTIONS and PRECAUTIONS). 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.

Intra-articular infusions of local anesthetics 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 not associated with these

findings. 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.

To avoid intravascular injection, aspiration should be performed before the local anesthetic solution is

injected. The needle must be repositioned until no return of blood can be elicited by aspiration. Note,

however, that the absence of blood in the syringe does not guarantee that intravascular injection has

been avoided.

Local anesthetic solutions containing antimicrobial preservatives (e.g., methylparaben) should not be

used for epidural or spinal anesthesia because the safety of these agents has not been established with

regard to intrathecal injection, either intentional or accidental.

PRECAUTIONSGeneral:

The safety and effectiveness of lidocaine depend on proper dosage, correct technique, adequate

precautions, and readiness for emergencies. Standard textbooks should be consulted for specific

techniques and precautions for various regional anesthetic procedures.

Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use.

(See WARNINGS and ADVERSE REACTIONS). The lowest dosage that results in effective

anesthesia should be used to avoid high plasma levels and serious adverse effects. Syringe aspirations

should also be performed before and during each supplemental injection when using indwelling catheter

techniques. During the administration of epidural anesthesia, it is recommended that a test dose be

administered initially and that the patient be monitored for central nervous system toxicity and

cardiovascular toxicity, as well as for signs of unintended intrathecal administration before proceeding.

When clinical conditions permit, consideration should be given to employing local anesthetic solutions

that contain epinephrine for the test dose because circulatory changes compatible with epinephrine may

also serve as a warning sign of unintended intravascular injection. An intravascular injection is still

possible even if aspirations for blood are negative. Repeated doses of lidocaine may cause significant

increases in blood levels with each repeated dose because of slow accumulation of the drug or its

metabolites. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly

patients, acutely ill patients and children should be given reduced doses commensurate with their age

and physical condition. Lidocaine should also be used with caution in patients with severe shock or

heart block. Lumbar and caudal epidural anesthesia should be used with extreme caution in persons with

the following conditions: existing neurological disease, spinal deformities, septicemia and severe

hypertension.

Local anesthetic solutions containing a vasoconstrictor should be used cautiously and in carefully

circumscribed quantities in areas of the body supplied by end arteries or having otherwise

compromised blood supply. Patients with peripheral vascular disease and those with hypertensive

vascular disease may exhibit exaggerated vasoconstrictor response. Ischemic injury or necrosis may

result. Preparations containing a vasoconstrictor should be used with caution in patients during or

following the administration of potent general anesthetic agents, since cardiac arrhythmias may occur

under such conditions.

Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs

and the patient’s state of consciousness should be accomplished after each local anesthetic injection. It

should be kept in mind at such times that restlessness, anxiety, tinnitus, dizziness, blurred vision,

tremors, depression or drowsiness may be early warning signs of central nervous system toxicity.

Since amide-type local anesthetics are metabolized by the liver, lidocaine should be used with caution

in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to

metabolize local anesthetics normally, are at greater risk of developing toxic plasma concentrations.

Lidocaine should also be used with caution in patients with impaired cardiovascular function since they

may be less able to compensate for functional changes associated with the prolongation of A-V

conduction produced by these drugs. Many drugs used during the conduct of anesthesia are considered

potential triggering agents for familial malignant hyperthermia. Since it is not known whether amide-type

local anesthetics may trigger this reaction and since the need for supplemental general anesthesia cannot

be predicted in advance, it is suggested that a standard protocol for the management of malignant

hyperthermia should be available. Early unexplained signs of tachycardia, tachypnea, labile blood

pressure and metabolic acidosis may precede temperature elevation. Successful outcome is dependent

on early diagnosis, prompt discontinuance of the suspect triggering agent(s) and institution of treatment,

including oxygen therapy, indicated supportive measures and dantrolene (consult dantrolene sodium

intravenous package insert before using).

Proper tourniquet technique, as described in publications and standard textbooks, is essential in the

performance of intravenous regional anesthesia. Solutions containing epinephrine or other

vasoconstrictors should not be used for this technique.

Lidocaine should be used with caution in persons with known drug sensitivities. Patients allergic to

para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross

sensitivity to lidocaine.

Use in the Head and Neck Area: Small doses of local anesthetics 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. Confusion,

convulsions, respiratory depression and/or respiratory arrest and cardiovascular stimulation or

depression have been reported. These reactions may be due to intra-arterial injections of the local

anesthetic with retrograde flow to the cerebral circulation. Patients receiving these blocks should have

their circulation and respiration monitored and be constantly observed. Resuscitative equipment and

personnel for treating adverse reactions should be immediately available. Dosage recommendations

should not be exceeded. (See DOSAGE AND ADMINISTRATION).

Information for Patients:

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

epidural anesthesia.

Clinically Significant Drug Interactions:

The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients

receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe prolonged

hypertension.

Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.

Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is

necessary, careful patient monitoring is essential.

Concurrent administration of vasopressor drugs (for the treatment of hypotension related to obstetric

blocks) and ergot-type oxytoxic drugs may cause severe persistent hypertension or cerebrovascular

accidents.

Drug Laboratory Test Interactions:

The intramuscular injection of lidocaine may result in an increase in creatine phosphokinase levels.

Thus, the use of this enzyme determination without isoenzyme separation as a diagnostic test for the

presence of acute myocardial infarction may be compromised by the intramuscular injection of

lidocaine.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Studies of lidocaine in animals to evaluate the carcinogenic and mutagenic potential or the effect on

fertility have not been conducted.

Pregnancy:

Teratogenic Effects. Pregnancy Category B. Reproduction studies have been performed in rats at doses

up to 6.6 times the human dose and have revealed no evidence of harm to the fetus caused by lidocaine.

There are, however, no adequate and well-controlled studies in pregnant women. Animal reproduction

studies are not always predictive of human response. General consideration should be given to this fact

before administering lidocaine to women of childbearing potential, especially during early pregnancy

when maximum organogenesis takes place.

Labor and Delivery:

Local anesthetics rapidly cross the placenta and when used for epidural, paracervical, pudendal or

caudal block anesthesia, can cause varying degrees of maternal, fetal and neonatal toxicity (See

CLINICAL PHARMACOLOGY—Pharmacokinetics). The potential for toxicity depends 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 central nervous system

peripheral vascular tone and cardiac function.

Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by

blocking sympathetic nerves. Elevating the patient’s legs and positioning her on her left side will help

prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously, and

electronic fetal monitoring is highly advisable.

Epidural, spinal, paracervical, or pudendal anesthesia may alter the forces of parturition through

changes in uterine contractility or maternal expulsive efforts. In one study, paracervical block

anesthesia was associated with a decrease in the mean duration of first stage labor and facilitation of

cervical dilation. However, spinal and epidural anesthesia have also 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. The long-term significance of these

observations is unknown. Fetal bradycardia may occur in 20 to 30 percent of patients receiving

paracervical nerve block anesthesia with the amide-type local anesthetics and may be associated with

fetal acidosis. Fetal heart rate should always be monitored during paracervical anesthesia. The

physician should weigh the possible advantages against risks when considering paracervical block in

prematurity, toxemia of pregnancy and fetal distress. Careful adherence to recommended dosage is of

the utmost importance in obstetrical paracervical block. Failure to achieve adequate analgesia with

recommended doses should arouse suspicion of intravascular or fetal intracranial injection. Cases

compatible with unintended fetal intracranial injection of local anesthetic solution have been reported

following intended paracervical or pudendal block or both. Babies so affected present with unexplained

neonatal depression at birth, which correlates with high local anesthetic serum levels, and often

manifest seizures within six hours. Prompt use of supportive measures combined with forced urinary

excretion of the local anesthetic has been used successfully to manage this complication.

Case reports of maternal convulsions and cardiovascular collapse following use of some local

anesthetics for paracervical block in early pregnancy (as anesthesia for elective abortion) suggest that

systemic absorption under these circumstances may be rapid. The recommended maximum dose of each

drug should not be exceeded. Injection should be made slowly and with frequent aspiration. Allow a 5-

minute interval between sides.

Nursing Mothers:

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human

milk, caution should be exercised when lidocaine is administered to a nursing woman.

Pediatric Use:

Dosages in pediatric patients should be reduced, commensurate with age, body weight and physical

condition. See DOSAGE AND ADMINISTRATION.

ADVERSE REACTIONS

Systemic: Adverse experiences following the administration of lidocaine are similar in nature to those

observed with other amide local anesthetic agents. These adverse experiences are, in general, dose-

related and may result from high plasma levels caused by excessive dosage, rapid absorption or

inadvertent intravascular injection, or may result from a hypersensitivity, idiosyncrasy or diminished

tolerance on the part of the patient. Serious adverse experiences are generally systemic in nature. The

following types are those most commonly reported:

Central Nervous System: CNS manifestations are excitatory and/or depressant and may be

characterized by lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness,

drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness,

twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest. The excitatory

manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity

may be drowsiness merging into unconsciousness and respiratory arrest.

Drowsiness following the administration of lidocaine is usually an early sign of a high blood level of

the drug and may occur as a consequence of rapid absorption.

Cardiovascular System: Cardiovascular manifestations are usually depressant and are characterized by

bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest.

Allergic: Allergic reactions are characterized by cutaneous lesions, urticaria, edema or anaphylactoid

reactions. Allergic reactions may occur as a result of sensitivity either to local anesthetic agents or to

the methylparaben used as a preservative in multiple dose vials. Allergic reactions as a result of

sensitivity to lidocaine are extremely rare and, if they occur, should be managed by conventional means.

The detection of sensitivity by skin testing is of doubtful value.

Neurologic: The incidences of adverse reactions associated with the use of local anesthetics may be

related to the total dose of local anesthetic administered and are also dependent upon the particular drug

used, the route of administration and the physical status of the patient. In a prospective review of 10,440

patients who received lidocaine for spinal anesthesia, the incidences of adverse reactions were

reported to be about 3 percent each for positional headaches, hypotension and backache; 2 percent for

shivering; and less than 1 percent each for peripheral nerve symptoms, nausea, respiratory inadequacy

and double vision. Many of these observations may be related to local anesthetic techniques, with or

without a contribution from the local anesthetic.

In the practice of caudal or lumbar epidural block, occasional unintentional penetration of the

subarachnoid space by the catheter may occur. Subsequent adverse effects may depend partially on the

amount of drug administered subdurally.

These may include spinal block of varying magnitude (including total spinal block), hypotension

secondary to spinal block, loss of bladder and bowel control, and loss of perineal sensation and sexual

function. Persistent motor, sensory and/or autonomic (sphincter control) deficit of some lower spinal

segments with slow recovery (several months) or incomplete recovery have been reported in rare

instances when caudal or lumbar epidural block has been attempted. Backache and headache have also

been noted following use of these anesthetic procedures.

There have been reported cases of permanent injury to extraocular muscles requiring surgical repair

following retrobulbar administration.

OVERDOSAGE

Acute emergencies from local anesthetics are generally related to high plasma levels encountered

during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic

solution (see ADVERSE REACTIONS, WARNINGS and PRECAUTIONS).

Management of Local Anesthetic Emergencies: The first consideration is prevention, best

accomplished by careful monitoring of cardiovascular and respiratory vital signs and the patient’s state

of consciousness after each local anesthetic injection. At the first sign of change, oxygen should be

administered.

The first step in the management of convulsions, as well as underventilation or apnea due to unintended

subarachnoid injection of drug solution, consists of immediate attention to the maintenance of a patent

airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting

immediate positive airway pressure by mask. Immediately after the institution of these ventilatory

measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat

convulsions sometimes depress the circulation when administered intravenously. Should convulsions

persist despite adequate respiratory support, and if the status of the circulation permits, small increments

of an ultra-short acting barbiturate (such as thiopental or thiamylal) or a benzodiazepine (such as

diazepam) may be administered intravenously. The clinician should be familiar, prior to use of local

anesthetics, with these anticonvulsant drugs. Supportive treatment of circulatory depression may require

administration of intravenous fluids and, when appropriate, a vasopressor as directed by the clinical

situation (e.g., ephedrine).

If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia,

acidosis, bradycardia, arrhythmias and cardiac arrest. Underventilation or apnea due to unintentional

subarachnoid injection of local anesthetic solution may produce these same signs and also lead to

cardiac arrest if ventilatory support is not instituted. If cardiac arrest should occur standard

cardiopulmonary resuscitative measures should be instituted.

Endotracheal intubation, employing 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.

Dialysis is of negligible value in the treatment of acute overdosage with lidocaine.

The oral LD of lidocaine HCl in non-fasted female rats is 459 (346−773) mg/kg (as the salt) and 214

(159−324) mg/kg (as the salt) in fasted female rats.

DOSAGE AND ADMINISTRATION

Table 1 (Recommended Dosages) summarizes the recommended volumes and concentrations of

Lidocaine Hydrochloride Injection, USP for various types of anesthetic procedures. The dosages

suggested in this table are for normal healthy adults and refer to the use of epinephrine-free solutions.

When larger volumes are required only solutions containing epinephrine should be used, except in

those cases where vasopressor drugs may be contraindicated.

There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of

local anesthetics following arthroscopic and other surgical procedures. Lidocaine is not approved for

this use (see WARNINGS and DOSAGE AND ADMINISTRATION).

These recommended doses serve only as a guide to the amount of anesthetic required for most routine

procedures. The actual volumes and concentrations to be used depend on a number of factors such as

type and extent of surgical procedure, depth of anesthesia and degree of muscular relaxation required,

duration of anesthesia required, and the physical condition of the patient. In all cases the lowest

concentration and smallest dose that will produce the desired result should be given. Dosages should

be reduced for children and for elderly and debilitated patients and patients with cardiac and/or liver

disease.

The onset of anesthesia, the duration of anesthesia and the degree of muscular relaxation are

proportional to the volume and concentration (i.e., total dose) of local anesthetic used. Thus, an increase

in volume and concentration of Lidocaine Hydrochloride Injection will decrease the onset of

anesthesia, prolong the duration of anesthesia, provide a greater degree of muscular relaxation and

increase the segmental spread of anesthesia. However, increasing the volume and concentration of

Lidocaine Hydrochloride Injection may result in a more profound fall in blood pressure when used in

epidural anesthesia. Although the incidence of side effects with lidocaine is quite low, caution should

be exercised when employing large volumes and concentrations, since the incidence of side effects is

directly proportional to the total dose of local anesthetic agent injected.

For intravenous regional anesthesia, only the 50 mL single-dose vial containing 0.5% Lidocaine

Hydrochloride Injection, USP should be used.

Epidural Anesthesia

For epidural anesthesia, only the following available specific products of Lidocaine Hydrochloride

Injection by Hospira are recommended:

1%. . . . . . . . . . . . . . . . . . . . 30 mL single-dose teartop vials

1.5%. . . . . . . . . . . . . . . . . . . . . . . 20 mL single-dose ampuls

2%. . . . . . . . . . . . . . . . . . . . . . . . . 10 mL single-dose ampuls

Although these solutions are intended specifically for epidural anesthesia, they may also be used for

infiltration and peripheral nerve block provided they are employed as single dose units. These solutions

contain no bacteriostatic agent. In epidural anesthesia, the dosage varies with the number of dermatomes

to be anesthetized (generally 2−3 mL of the indicated concentration per dermatome).

Caudal and Lumbar Epidural Block: As a precaution against the adverse experiences sometimes

observed following unintentional penetration of the subarachnoid space, a test dose such as 2−3 mL of

1.5% lidocaine hydrochloride should be administered at least 5 minutes prior to injecting the total

volume required for a lumbar or caudal epidural block. The test dose should be repeated if the patient is

moved in a manner that may have displaced the catheter. Epinephrine, if contained in the test dose (10−15

mcg have been suggested), may serve as a warning of unintentional intravascular injection. If injected

into a blood vessel, this amount of epinephrine is likely to produce a transient "epinephrine response"

within 45 seconds, consisting of an increase in heart rate and systolic blood pressure, circumoral

pallor, palpitations and nervousness in the unsedated patient. The sedated patient may exhibit only a

pulse rate increase of 20 or more beats per minute for 15 or more seconds. Patients on beta-blockers

may not manifest changes in heart rate, but blood pressure monitoring can detect an evanescent rise in

systolic blood pressure. Adequate time should be allowed for onset of anesthesia after administration

of each test dose. The rapid injection of a large volume of Lidocaine Hydrochloride Injection through

the catheter should be avoided, and, when feasible, fractional doses should be administered.

In the event of the known injection of a large volume of local anesthetic solutions into the subarachnoid

space, after suitable resuscitation and if the catheter is in place, consider attempting the recovery of

drug by draining a moderate amount of cerebrospinal fluid (such as 10 mL) through the epidural

catheter.

Maximum Recommended Dosages

NOTE: The products accompanying this insert do not contain epinephrine.

Adults: For normal healthy adults, the individual maximum recommended dose of lidocaine HCl with

epinephrine should not exceed 7 mg/kg (3.5 mg/lb) of body weight and in general it is recommended that

the maximum total dose not exceed 500 mg. When used without epinephrine, the maximum individual

dose should not exceed 4.5 mg/kg (2 mg/lb) of body weight and in general it is recommended that the

maximum total dose does not exceed 300 mg. For continuous epidural or caudal anesthesia, the

maximum recommended dosage should not be administered at intervals of less than 90 minutes. When

continuous lumbar or caudal epidural anesthesia is used for non-obstetrical procedures, more drug may

be administered if required to produce adequate anesthesia.

The maximum recommended dose per 90 minute period of lidocaine hydrochloride for paracervical

block in obstetrical patients and non-obstetrical patients is 200 mg total. One-half of the total dose is

usually administered to each side. Inject slowly five minutes between sides. (See also discussion of

paracervical block in PRECAUTIONS).

For intravenous regional anesthesia, the dose administered should not exceed 4 mg/kg in adults.

Children: It is difficult to recommend a maximum dose of any drug for children, since this varies as a

function of age and weight. For children over 3 years of age who have a normal lean body mass and

normal body development, the maximum dose is determined by the child’s age and weight. For example,

in a child of 5 years weighing 50 lbs., the dose of lidocaine HCl should not exceed 75 — 100 mg (1.5

— 2 mg/lb). The use of even more dilute solutions (i.e., 0.25 — 0.5%) and total dosages not to exceed 3

mg/kg (1.4 mg/lb) are recommended for induction of intravenous regional anesthesia in children.

In order to guard against systemic toxicity, the lowest effective concentration and lowest effective dose

should be used at all times. In some cases it will be necessary to dilute available concentrations with

0.9% sodium chloride injection in order to obtain the required final concentration.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to

administration whenever the solution and container permit. Solutions that are discolored and/or contain

particulate matter should not be used.

Table 1

Recommended Dosages of Lidocaine

Hydrochloride Injection, USP for Various

Anes thetic

Procedures in Normal Healthy Adults

Lidocaine Hydrochloride

Injection, USP (without

Epinephrine)

Procedure

Conc. (%)

Vol.

(mL)

Total

Dos e

(mg)

Infiltration

Percutaneous

0.5 or 1.0

1−60

5−300

Intravenous Regional

10−60 50−300

Peripheral Nerve Blocks, e.g.

Brachial

15−20 225−300

Dental

1−5

20−100

Intercostal

Paravertebral

3−5

30−50

Pudendal (each side)

Paracervical

Obstetrical Analgesia

(each side)

Sympathetic Nerve Blocks, e.g.

Cervical (stellate ganglion)

Lumbar

5−10

50−100

Central Neural Blocks

Epidural*

Thoracic

20−30 200−300

Lumbar

Analgesia

25−30 250−300

Anesthesia

15−20 225−300

10−15 200−300

Caudal

Obstetrical Analgesia

20−30 200−300

Surgical Anesthesia

15−20 225−300

*Dose determined by number of dermatomes to be

anesthetized (2 to 3 mL/dermatome).

THE ABOVE SUGGESTED CONCENTRATIONS AND VOLUMES SERVE ONLY AS A GUIDE.

OTHER VOLUMES AND CONCENTRATIONS MAY BE USED PROVIDED THE TOTAL

MAXIMUM RECOMMENDED DOSE IS NOT EXCEEDED.

Sterilization, Storage and Technical Procedures: Disinfecting agents containing heavy metals, which

cause release of respective ions (mercury, zinc, copper, etc.) should not be used for skin or mucous

membrane disinfection as they have been related to incidence of swelling and edema. When chemical

disinfection of multi-dose vials is desired, either isopropyl alcohol (91%) or 70% ethyl alcohol is

recommended. Many commercially available brands of rubbing alcohol, as well as solutions of ethyl

alcohol not of USP grade, contain denaturants which are injurious to rubber and, therefore, are not to be

used. It is recommended that chemical disinfection be accomplished by wiping the vial stopper

thoroughly with cotton or gauze that has been moistened with the recommended alcohol just prior to

use.

HOW SUPPLIED

Lidocaine Hydrochloride Injection, USP is supplied as follows:

NDC

Container

Concentration

Size

Total (mg)

Single-dos e:

0409-4278-01 Glass Teartop Vial

0.5% (5 mg/mL)

50 mL

0409-4713-01 Glass Ampul

1% (10 mg/mL)

2 mL (bulk – 400 units)20

0409-4713-02 Glass Ampul

1% (10 mg/mL)

5 mL

0409-4713-05 Glass Ampul

1% (10 mg/mL)

5 mL (bulk – 400 units)50

0409-4713-20 Glass Ampul

1% (10 mg/mL)

20 mL

0409-4713-32 Glass Ampul

1% (10 mg/mL)

2 mL

0409-4713-62 Glass Ampul

1% (10 mg/mL)

2 mL (bulk – 800 units)20

0409-4713-65 Glass Ampul

1% (10 mg/mL)

5 mL (bulk – 800 units)50

0409-4279-02 Glass Teartop Vial

1% (10 mg/mL)

30 mL

0409-4270-01 Sterile Glass Teartop Vial 1% (10 mg/mL)

30 mL

0409-4776-01 Glass Ampul

1.5% (15 mg/mL)20 mL

0409-4056-01 Sterile Glass Ampul

1.5% (15 mg/mL)20 mL

0409-4282-01 Glass Ampul

2% (20 mg/mL)

2 mL

0409-4282-02 Glass Ampul

2% (20 mg/mL)

10 mL

Multiple-dos e:

0409-4275-01 Plastic Fliptop Vial

0.5% (5 mg/mL)

50 mL

0409-4276-01 Plastic Fliptop Vial

1% (10 mg/mL)

20 mL

0409-4276-02 Plastic Fliptop Vial

1% (10 mg/mL)

50 mL

0409-4277-01 Plastic Fliptop Vial

2% (20 mg/mL)

20 mL

0409-4277-02 Plastic Fliptop Vial

2% (20 mg/mL)

50 mL

1000

Single-dose products are preservative-free.

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

Lidocaine Hydrochloride Injection, USP solutions packaged in ampuls and glass teartop vials may be

autoclaved one time only. Autoclave at 15 pounds pressure, 121°C (250°F) for 15 minutes. DO NOT

AUTOCLAVE PRODUCT IN PLASTIC VIALS.

Revised: February, 2010

Printed in USA EN-2421

Hospira, Inc., Lake Forest, IL 60045 USA

Lidocaine Hydrochloride Pack Label

Spectra Medical Devices, Inc.

SODIUM CHLORIDE

INJECTION, USP, 0.9%

DESCRIPTION

Sodium Chloride Injection, USP is a sterile, nonpyrogenic, isotonic solution of sodium chloride 0.9%

(9mg/mL) in Water for Injection containing no antimicrobial agent or other added substance. The pH is

between 4.5 and 7.0. Its chloride and sodium ion concentrates are approximately 0.154 mEq of each per

milliliter and its calculated osmolality is 0.308 milliosmols per mL.

Sodium chloride occurs as colorless cubic crystals or white crystalline powder and has a saline taste.

Sodium Chloride is freely soluble in water. It is soluble in glycerin and slightly soluble in alcohol.

The empirical formula for sodium chloride is NaCl, and the molecular weight is 58.44.

CLINICAL PHARMACOLOGY

Sodium chloride comprises over 90% of the inorganic constituents of the blood serum. Sodium

chloride in water dissociates to provide sodium (Na+) and (Cl-) ions. These ions are normal

constituents of the body fluids (principally extracellular) and are essential for maintaining electrolyte

balance. The small volume of fluid and amount of sodium chloride provided by Sodium Chloride

Injection, USP, 0.9% when used only as a vehicle for parenteral injection of drugs, is unlikely to exert a

significant effect on fluid and electrolyte balance except possibly in very small infants.

INDICATIONS AND USAGE

Sodium Chloride Injection is used to flush intravascular catheters or as a sterile, isontonic single dose

vehicle, solvent, or diluent for substances to administered intravenously,k intramuscularly or sub-

cutaneously and for other extemporaneously prepared single dose sterile solutions according to

instructions of the manufacture of the drug to be administered.

WARNING

Sodium Chloride must be used with caution in the presence of congestive heart failure, circulatory

insufficiency, kidney dysfunction or hypoproteinemia.

Excessive amounts of sodium chloride by any route may cause hypokalemia and acidosis. Excessive

amounts by parental routes may precipitate congestive heart failure and acute pulmonary edema,

especially seen in patients with preexisting cardiovascular disease and those receiving coricos-teroids,

corticotrophin or other drugs that may give rise to sodium retention. For use in newborns, when a

Sodium Chloride solution is required for preparation or diluting medications, or in flushing intravenous

catheters, only preservative-free Sodium Chloride Injection, USP, 0.9% should be used.

PRECAUTIONS

GENERAL

Since Sodium Chloride Injection does not contain antimicrobial agents and is intended for single use,

any unused amount must be discarded immediately following withdrawal of any portion of the contents

of the vial or ampul. Do not open ampul until it is to be used.

Consult the manufactures instructions for choice of vehicle, appropriate dilution or volume for

dissolving the drug to be injected, including the route and rate of injection.

PREGNANCY

CATEGORY C-Animal reproduction studies have not been conducted with Sodium Chloride Injection.

It is also not known whether Sodium Chloride Injection can cause fetal harm when administered to a

pregnant woman or can effect reproduction capacity. Sodium Chloride Injection should be given to a

pregnant woman only if clearly needed.

ADVERSE REACTIONS

Reactions which may occur because of this solution, added drugs or the technique of reconstitution or

administration include febrile response, local tenderness, abscess, tissue necrosis or infection at the

site of injection, venous thrombosis or phlebitis extending from the site of injection and extravasations.

If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate

countermeasures and if possible, retrieve and save the remainder of unused vehicle for examination.

OVERDOSAGE

When used as a diluent, solvent or intravascular flushing solution, this parental preparation is unlikely to

pose a threat of sodium chloride or fluid overload except possible in very small infants. In the event

these should occur, reevaluate the patient and institute appropriate corrective measures.

DOSAGE AND ADMINISTRATION

Before Sodium Chloride Injection, USP, 0.9% is used as a vehicle for the administration of a

drug;specific references should be checked for any possible incompatibility with sodium chloride.

The volume of the preparation to be used for diluting or dissolving any drug for injection is dependent

on the vehicle concentration, dose and route of administration as recommended by the manufacture.

Sodium Chloride Injection, USP, 0.9% is also indicated for use in flushing intravenous catheters. Prior

to and after administration of the medication, the intravenous catheter should be flushed in its entirety

with Sodium Chloride Injection, USP, 0.9%. Use in accord with any warnings or precautions

appropriate to the medication being administered as recommended by the manufacture. Parental drug

products should be inspected visually for particulate matter and discoloration prior to

administration, whenever solution and container permit.

HOW SUPPLIED

5 mL ampuls packaged in box of 50 each (NDC-65282-1505-1)

10 mL ampuls packaged in box of 50 each (NDC-65282-1510-1)

30 mL ampuls packaged in box of 30 each (NDC-65282-1530-3)

STORAGE

Store at controlled room temperature 15-30 C (59-86 F). Avoid freezing.

Manufactured for:

Spectra Medical Devices, Inc. 260-F Fordham Road, Wilmington, MA 01887

By: KM. Pharm Co., LTD.

BUPIVACAINE HYDROCHLORIDE injection, solution

BUPIVACAINE HYDROCHLORIDE AND EPINEPHRINE (bupivacaine hydrochloride and

epinephrine bitartrate) injection, solution

[Hospira, Inc.]

Rx only

THE 0.75% CONCENTRATION OF BUPIVACAINE HYDROCHLORIDE IS NOT

RECOMMENDED FOR OBSTETRICAL ANESTHESIA.

THERE HAVE BEEN REPORTS OF CARDIAC ARREST WITH DIFFICULT

RESUSCITATION OR DEATH DURING USE OF BUPIVACAINE HYDROCHLORIDE FOR

EPIDURAL ANESTHESIA IN OBSTETRICAL PATIENTS. IN MOST CASES, THIS HAS

FOLLOWED USE OF THE 0.75% 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% CONCENTRATION

SHOULD BE RESERVED FOR SURGICAL PROCEDURES WHERE A HIGH DEGREE OF

MUSCLE RELAXATION AND PROLONGED EFFECT ARE NECESSARY.

DESCRIPTION

Bupivacaine Hydrochloride is 2-Piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)-,

monohydrochloride, monohydrate, 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:

Epinephrine is (-)-3,4-Dihydroxy-α-[(methylamino)methyl] benzyl alcohol. It has the following

structural formula:

infiltration, peripheral nerve block, and caudal and lumbar epidural blocks. Solutions of Bupivacaine

Hydrochloride may be autoclaved if they do not contain epinephrine. Solutions are clear and colorless.

Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics. It is a

homologue of mepivacaine and is chemically related to lidocaine. All three of these anesthetics contain

an amide linkage between the aromatic nucleus and the amino, or piperidine group. They differ in this

respect from the procaine-type local anesthetics, which have an ester linkage.

Bupivacaine Hydrochloride Injection, USP is available in sterile, isotonic solutions containing

bupivacaine hydrochloride in water for injection with characteristics as follows:

Bupivacaine Hydrochloride Injection, USP (without

epinephrine)

Concentration

Bupivacaine Hydrochloride

mg/mL

Sodium Chloride

mg/mL

0.25%

0.5%

0.75%

May contain sodium hydroxide and/or hydrochloric acid for pH adjustment. (See HOW SUPPLIED

section for pH information.) Multiple-dose vials contain methylparaben 1 mg/mL added as a

preservative.

Bupivacaine and Epinephrine Injection, USP is available in sterile, isotonic solutions containing

bupivacaine hydrochloride and epinephrine 1:200,000 with characteristics as follows:

Bupivacaine and Epinephrine Injection, USP

Concentration

(Bupivacaine HCl)

Bupivacaine

Hydrochloride

(mg/mL)

Epinephrine

1:200,000

(mcg/mL)

Sodium

Chloride

(mg/mL)

0.25%

0.5%

0.75%

Sodium metabisulfite 0.1 mg/mL added as antioxidant and edetate calcium disodium, anhydrous 0.1

mg/mL added as stabilizer. May contain sodium hydroxide and/or hydrochloric acid for pH adjustment.

(See HOW SUPPLIED section for pH information.) Multiple-dose vials contain methylparaben 1 mg/mL

added as a preservative.

Single-dose solutions contain no added bacteriostat or anti-microbial agent and unused portions should

be discarded after use.

CLINICAL PHARMACOLOGY

Local anesthetics block 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.

Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous

systems (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. Recent clinical reports and animal research suggest that

these cardiovascular changes are more likely to occur after unintended intravascular injection of

bupivacaine. Therefore, incremental dosing is necessary.

Following systemic absorption, local anesthetics can produce central nervous system stimulation,

depression, or both. Apparent central stimulation is manifested as restlessness, tremors and shivering

progressing to convulsions, followed by depression and coma progressing ultimately to respiratory

arrest. However, the local anesthetics have a primary depressant effect on the medulla and on higher

centers. The depressed stage may occur without a prior excited state.

Pharmacokinetics: The rate of systemic absorption of local anesthetics 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 or 5 mcg/mL) usually reduces the rate of absorption and peak

plasma concentration of Bupivacaine Hydrochloride, permitting the use of moderately larger total doses

and sometimes prolonging the duration of action.

The onset of action with Bupivacaine Hydrochloride is rapid and anesthesia is long lasting. The

duration of anesthesia is significantly longer with Bupivacaine Hydrochloride than with any other

commonly used local anesthetic. It has also been noted that there is a period of analgesia that persists

after the return of sensation, during which time the need for strong analgesics is reduced.

Local anesthetics are bound to plasma proteins in varying degrees. Generally, the lower the plasma

concentration of drug the higher the percentage of drug bound to plasma proteins.

Local anesthetics appear 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 local anesthetics appear to be inversely related to the degree of

plasma protein binding, because only the free, unbound drug is available for placental transfer.

Bupivacaine Hydrochloride 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 and lipid

solubility of the drug. Lipid soluble, nonionized drugs readily enter the fetal blood from the maternal

circulation.

Depending upon the route of administration, local anesthetics are distributed to some extent to all body

tissues, with high concentrations found in highly perfused organs such as the liver, lungs, heart, and

brain.

Pharmacokinetic studies on the plasma profile of Bupivacaine Hydrochloride after direct intravenous

injection suggest a three-compartment open model. The first compartment is represented by the rapid

intravascular distribution of the drug. The second compartment represents the equilibration of the drug

throughout the highly perfused organs such as the brain, myocardium, lungs, kidneys, and liver. The

third compartment represents an equilibration of the drug with poorly perfused tissues, such as muscle

and fat. The elimination of drug from tissue distribution depends largely upon the ability of binding sites

in the circulation to carry it to the liver where it is metabolized.

After injection of Bupivacaine Hydrochloride for caudal, epidural, or peripheral nerve block in man,

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.

Various pharmacokinetic parameters of the local anesthetics can be significantly altered by the presence

of hepatic or renal disease, addition of epinephrine, factors affecting urinary pH, renal blood flow, the

route of drug administration, and the age of the patient. The half-life of Bupivacaine Hydrochloride in

adults is 2.7 hours and in neonates 8.1 hours.

In clinical studies, elderly patients reached the maximal spread of analgesia and maximal motor blockade

more rapidly than younger patients. Elderly patients also exhibited higher peak plasma concentrations

following administration of this product. The total plasma clearance was decreased in these patients.

Amide-type local anesthetics such as Bupivacaine Hydrochloride are metabolized primarily in the liver

via conjugation with glucuronic acid. Patients with hepatic disease, especially those with severe

hepatic disease, may be more susceptible to the potential toxicities of the amide-type local anesthetics.

Pipecoloxylidine is the major metabolite of Bupivacaine Hydrochloride.

The kidney is the main excretory organ for most local anesthetics and their metabolites. Urinary

excretion is affected by urinary perfusion and factors affecting urinary pH. Only 6% of bupivacaine is

excreted unchanged in the urine.

When administered in recommended doses and concentrations, Bupivacaine Hydrochloride does not

ordinarily produce irritation or tissue damage and does not cause methemoglobinemia.

INDICATIONS AND USAGE

Bupivacaine Hydrochloride is indicated 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. Only the 0.25% and 0.5% concentrations are indicated for obstetrical

anesthesia. (See WARNINGS.)

Experience with nonobstetrical surgical procedures in pregnant patients is not sufficient to recommend

use of 0.75% concentration of Bupivacaine Hydrochloride in these patients.

Bupivacaine Hydrochloride is not recommended for intravenous regional anesthesia (Bier Block). (See

WARNINGS.)

The routes of administration and indicated Bupivacaine Hydrochloride concentrations are:

local infiltration 0.25%

peripheral nerve block 0.25% and 0.5%

retrobulbar block 0.75%

sympathetic block 0.25%

lumbar epidural 0.25%, 0.5%, and 0.75% (0.75% not for obstetrical anesthesia)

caudal 0.25% and 0.5%

epidural test dose 0.5% with epinephrine 1:200,000

(See DOSAGE AND ADMINISTRATION for additional information.)

Standard textbooks should be consulted to determine the accepted procedures and techniques for the

administration of Bupivacaine Hydrochloride.

CONTRAINDICATIONS

Bupivacaine Hydrochloride is contraindicated in obstetrical paracervical block anesthesia. Its use in

this technique has resulted in fetal bradycardia and death.

Bupivacaine Hydrochloride is contraindicated in patients with a known hypersensitivity to it or to any

local anesthetic agent of the amide-type or to other components of Bupivacaine Hydrochloride

solutions.

WARNINGS

THE 0.75% CONCENTRATION OF BUPIVACAINE HYDROCHLORIDE IS NOT

RECOMMENDED FOR OBSTETRICAL ANESTHESIA.

THERE HAVE BEEN REPORTS OF CARDIAC ARREST WITH DIFFICULT

RESUSCITATION OR DEATH DURING USE OF BUPIVACAINE HYDROCHLORIDE FOR

EPIDURAL ANESTHESIA IN OBSTETRICAL PATIENTS. IN MOST CASES, THIS HAS

FOLLOWED USE OF THE 0.75% 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% CONCENTRATION

SHOULD BE RESERVED FOR SURGICAL PROCEDURES WHERE A HIGH DEGREE OF

MUSCLE RELAXATION AND PROLONGED EFFECT ARE NECESSARY.

LOCAL ANESTHETICS SHOULD ONLY BE EMPLOYED BY CLINICIANS WHO ARE WELL

VERSED IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER

ACUTE EMERGENCIES WHICH MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED, AND

THEN ONLY AFTER INSURING THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER

RESUSCITATIVE DRUGS, CARDIOPULMONARY RESUSCITATIVE EQUIPMENT, AND THE

PERSONNEL RESOURCES NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS

AND RELATED EMERGENCIES. (See also ADVERSE REACTIONS, PRECAUTIONS, and

OVERDOSAGE.) 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.

Local anesthetic solutions containing antimicrobial preservatives, i.e., those supplied in multiple-dose

vials, should not be used for epidural or caudal anesthesia because safety has not been established with

regard to intrathecal injection, either intentionally or unintentionally, of such preservatives.

Intra-articular infusions of local anesthetics 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 not associated with these

findings. 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.

It is essential that aspiration for blood or cerebrospinal fluid (where applicable) be done prior to

injecting any local anesthetic, both the original dose and all subsequent doses, to avoid intravascular or

subarachnoid injection. However, a negative aspiration does not ensure against an intravascular or

subarachnoid injection.

Bupivacaine Hydrochloride with epinephrine 1:200,000 or other vasopressors should not be used

concomitantly with ergot-type oxytocic drugs, because a severe persistent hypertension may occur.

Likewise, solutions of Bupivacaine Hydrochloride containing a vasoconstrictor, such as epinephrine,

should be used with extreme caution in patients receiving monoamineoxidase inhibitors (MAOI) or

antidepressants of the triptyline or imipramine types, because severe prolonged hypertension may result.

Until further experience is gained in pediatric patients younger than 12 years, administration of

Bupivacaine Hydrochloride in this age group is not recommended.

Mixing or the prior or intercurrent use of any other local anesthetic with Bupivacaine Hydrochloride

cannot be recommended because of insufficient data on the clinical use of such mixtures. There have

been reports of cardiac arrest and death during the use of Bupivacaine Hydrochloride for intravenous

regional anesthesia (Bier Block). Information on safe dosages and techniques of administration of

Bupivacaine Hydrochloride in this procedure is lacking. Therefore, Bupivacaine Hydrochloride is not

recommended for use in this technique.

Bupivacaine Hydrochloride with epinephrine 1:200,000 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. Single-dose ampuls and single-dose vials of Bupivacaine Hydrochloride

without epinephrine do not contain sodium metabisulfite.

PRECAUTIONS

General: The safety and effectiveness of local anesthetics depend on proper dosage, correct technique,

adequate precautions, and readiness for emergencies. Resuscitative equipment, oxygen, and other

resuscitative drugs should be available for immediate use. (See WARNINGS, ADVERSE

REACTIONS, and OVERDOSAGE.) During major regional nerve blocks, the patient should have IV

fluids running via an indwelling catheter to assure a functioning intravenous pathway. The lowest

dosage of local anesthetic that results in effective anesthesia should be used to avoid high plasma

levels and serious adverse effects. The rapid injection of a large volume of local anesthetic solution

should be avoided and fractional (incremental) doses should be used when feasible.

Epidural Anesthesia: During epidural administration of Bupivacaine Hydrochloride, 0.5% and 0.75%

solutions should be administered in incremental doses of 3 mL to 5 mL with sufficient time between

doses to detect toxic manifestations of unintentional intravascular or intrathecal injection. Injections

should be made slowly, with frequent aspirations before and during the injection to avoid intravascular

injection. Syringe aspirations should also be performed before and during each supplemental injection

in continuous (intermittent) catheter techniques. An intravascular injection is still possible even if

aspirations for blood are negative.

During the administration of epidural anesthesia, it is recommended that a test dose 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 original and all reinforcing doses, because

plastic tubing in the epidural space can migrate into a blood vessel or through the dura. When clinical

conditions permit, the test dose should contain epinephrine (10 mcg to 15 mcg has been suggested) to

serve as a warning of unintended intravascular injection. If injected into a blood vessel, this amount of

epinephrine is likely to produce a transient “epinephrine response” within 45 seconds, consisting of an

increase in heart rate and/or systolic blood pressure, circumoral pallor, palpitations, and nervousness in

the unsedated patient. The sedated patient may exhibit only a pulse rate increase of 20 or more beats per

minute for 15 or more seconds. Therefore, following the test dose, the heart rate should be monitored

for a heart rate increase. Patients on beta-blockers may not manifest changes in heart rate, but blood

pressure monitoring can detect a transient rise in systolic blood pressure. The test dose should also

contain 10 mg to 15 mg of Bupivacaine Hydrochloride or an equivalent amount of another local

anesthetic to detect an unintended intrathecal administration. This will be evidenced within a few minutes

by signs of spinal block (e.g., decreased sensation of the buttocks, paresis of the legs, or, in the sedated

patient, absent knee jerk). The Test Dose formulation of Bupivacaine Hydrochloride contains 15 mg of

bupivacaine and 15 mcg of epinephrine in a volume of 3 mL. An intravascular or subarachnoid 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 epinephrine-induced cardiovascular effects.

Injection of repeated doses of local anesthetics 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. Local anesthetics should also be used with caution in patients with hypotension or

heartblock.

Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs

and the patient’s state of consciousness should be performed after each local anesthetic injection. It

should be kept in mind at such times that restlessness, anxiety, incoherent speech, lightheadedness,

numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors,

twitching, depression, or drowsiness may be early warning signs of central nervous system toxicity.

Local anesthetic solutions containing a vasoconstrictor should be used cautiously and 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.

Because amide-local anesthetics such as Bupivacaine Hydrochloride are metabolized by the liver,

these drugs, especially repeat doses, should be used cautiously in patients with hepatic disease. Patients

with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a

greater risk of developing toxic plasma concentrations. Local anesthetics should also be used with

caution in patients with impaired cardiovascular function because they may be less able to compensate

for functional changes associated with the prolongation of AV conduction produced by these drugs.

Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such

as epinephrine are employed in patients during or following the administration of potent inhalation

anesthetics. In deciding whether to use these products concurrently 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.

Many drugs used during the conduct of anesthesia are considered potential triggering agents for

familial malignant hyperthermia. Because it is not known whether amide-type local anesthetics may

trigger this reaction and because the need for supplemental general anesthesia cannot be predicted in

advance, it is suggested that a standard protocol for management should be available. Early unexplained

signs of tachycardia, tachypnea, labile blood pressure, and metabolic acidosis may precede temperature

elevation. Successful outcome is dependent on early diagnosis, prompt discontinuance of the suspect

triggering agent(s) and prompt institution of treatment, including oxygen therapy, indicated supportive

measures and dantrolene. (Consult dantrolene sodium intravenous package insert before using.)

Use in Head and Neck Area: Small doses of local anesthetics 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. Patients receiving these blocks should

have their circulation and respiration monitored and be constantly observed. Resuscitative equipment

and personnel for treating adverse reactions should be immediately available. Dosage recommendations

should not be exceeded. (See DOSAGE AND ADMINISTRATION.)

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, as

with all other regional procedures, the immediate availability of equipment, drugs, and personnel to

manage respiratory arrest or depression, convulsions, and cardiac stimulation or depression should be

assured (see also WARNINGS and Use In Head and Neck Area, above). 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 and PRECAUTIONS,

General). Mixing Bupivacaine Hydrochloride with other local anesthetics is not recommended because

of insufficient data on the clinical use of such mixtures.

When Bupivacaine Hydrochloride 0.75% 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.

Information for Patients: 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. Also, when appropriate, the physician

should discuss other information including adverse reactions in the package insert of Bupivacaine

Hydrochloride.

Clinically Significant Drug Interactions: The administration of local anesthetic solutions containing

epinephrine or norepinephrine 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 patient monitoring is

essential.

Concurrent administration of vasopressor drugs and of ergot-type oxytocic drugs may cause severe,

persistent hypertension or cerebrovascular accidents.

Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals of most local

anesthetics including bupivacaine to evaluate the carcinogenic potential have not been conducted.

Mutagenic potential or the effect on fertility has not been determined. There is no evidence from human

data that Bupivacaine Hydrochloride may be carcinogenic or mutagenic or that it impairs fertility.

Pregnancy Category C: Decreased pup survival in rats and an embryocidal effect in rabbits have been

observed when bupivacaine hydrochloride was administered to these species in doses comparable to

nine and five times respectively the maximum recommended daily human dose (400 mg). There are no

adequate and well-controlled studies in pregnant women of the effect of bupivacaine on the developing

fetus. Bupivacaine hydrochloride should be used during pregnancy only if the potential benefit justifies

the potential risk to the fetus. This does not exclude the use of Bupivacaine Hydrochloride at term for

obstetrical anesthesia or analgesia. (See Labor and Delivery.)

Labor and Delivery: SEE BOXED WARNING REGARDING OBSTETRlCAL USE OF 0.75%

BUPIVACAINE HYDROCHLORIDE.

Bupivacaine Hydrochloride is contraindicated for obstetrical paracervical block anesthesia.

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, Pharmacokinetics.) 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 central

nervous system, peripheral vascular tone, and cardiac function.

Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by

blocking sympathetic nerves. Elevating the patient’s legs and positioning her on her left side will help

prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously and

electronic fetal monitoring is highly advisable.

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.

Nursing Mothers: Bupivacaine has been reported to be excreted in human milk suggesting that the

nursing infant could be theoretically exposed to a dose of the drug. Because of the potential for serious

adverse reactions in nursing infants from bupivacaine, a decision should be made whether to discontinue

nursing or not administer bupivacaine, taking into account the importance of the drug to the mother.

Pediatric Use: Until further experience is gained in pediatric patients younger than 12 years,

administration of Bupivacaine Hydrochloride in this age group is not recommended. Continuous

infusions of bupivacaine in children have been reported to result in high systemic levels of bupivacaine

and seizures; high plasma levels may also be associated with cardiovascular abnormalities. (See

WARNINGS, PRECAUTIONS, and OVERDOSAGE.)

Geriatric Use: Patients over 65 years, particularly those with hypertension, may be at increased risk for

developing hypotension while undergoing anesthesia with Bupivacaine Hydrochloride. (See

ADVERSE REACTIONS.)

Elderly patients may require lower doses of Bupivacaine Hydrochloride. (See PRECAUTIONS,

Epidural Anesthesia and DOSAGE AND ADMINISTRATION.)

In clinical studies, differences in various pharmacokinetic parameters have been observed between

elderly and younger patients. (See CLINICAL PHARMACOLOGY.)

This product is known to be substantially excreted by the kidney, and the risk of toxic 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. (See CLINICAL PHARMACOLOGY.)

ADVERSE REACTIONS

Reactions to Bupivacaine Hydrochloride 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 experiences which demand immediate counter-measures

are related to the central nervous system and the cardiovascular system. These adverse experiences are

generally dose related and due to high plasma levels which may result 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 subarachnoid

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) may result 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 may occur. This

may lead to secondary cardiac arrest if untreated. Patients over 65 years, particularly those with

hypertension, may be at increased risk for experiencing the hypotensive effects of Bupivacaine

Hydrochloride. Factors influencing plasma protein binding, such as acidosis, systemic diseases which

alter protein production, or competition of other drugs for protein binding sites, may diminish individual

tolerance.

Central Nervous System Reactions: These are characterized by excitation and/or depression.

Restlessness, anxiety, dizziness, tinnitus, blurred vision, or tremors may occur, possibly proceeding to

convulsions. However, excitement may be transient or absent, with depression being the first

manifestation of an adverse reaction. This may quickly be followed by drowsiness merging into

unconsciousness and respiratory arrest. Other central nervous system effects may be nausea, vomiting,

chills, and constriction of the pupils.

The incidence of convulsions associated with the use of local anesthetics varies with the procedure

used and the total dose administered. In a survey of studies of epidural anesthesia, overt toxicity

progressing to convulsions occurred in approximately 0.1% of local anesthetic administrations.

Cardiovascular System Reactions: High doses or unintentional intravascular injection may lead to

high plasma levels and related depression of the myocardium, decreased cardiac output, heartblock,

hypotension, bradycardia, ventricular arrhythmias, including ventricular tachycardia and ventricular

fibrillation, and cardiac arrest. (See WARNINGS, PRECAUTIONS, and OVERDOSAGE sections.)

Allergic: Allergic-type reactions are rare and may occur as a result of sensitivity to the local anesthetic

or to other formulation ingredients, such as the antimicrobial preservative methylparaben contained in

multiple-dose vials or sulfites in epinephrine-containing solutions. These reactions are characterized

by signs such as urticaria, pruritus, erythema, angioneurotic edema (including laryngeal edema),

tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature,

and possibly, anaphylactoid-like symptomatology (including severe hypotension). Cross sensitivity

among members of the amide-type local anesthetic group has been reported. The usefulness of

screening for sensitivity has not been definitely established.

Neurologic: The incidences of adverse neurologic reactions associated with the use of local

anesthetics may be related to the total dose of local anesthetic administered and are also dependent upon

the particular drug used, the route of administration, and the physical status of the patient. Many of these

effects may be related to local anesthetic techniques, with or without a contribution from the drug.

In the practice of caudal or lumbar epidural block, occasional unintentional penetration of the

subarachnoid space by the catheter or needle may occur. Subsequent adverse effects may depend

partially on the amount of drug administered intrathecally and the physiological and physical effects of a

dural puncture. A high spinal is characterized by paralysis of the legs, loss of consciousness,

respiratory paralysis, and bradycardia.

Neurologic effects following epidural or caudal anesthesia may include 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 all of

which may have slow, incomplete, or no recovery; headache; backache; septic meningitis; meningismus;

slowing of labor; increased incidence of forceps delivery; and cranial nerve palsies due to traction on

nerves from loss of cerebrospinal fluid.

Neurologic effects following other procedures or routes of administration may include persistent

anesthesia, paresthesia, weakness, paralysis, all of which may have slow, incomplete, or no recovery.

OVERDOSAGE

Acute emergencies from local anesthetics are generally related to high plasma levels encountered

during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic

solution. (See ADVERSE REACTIONS, WARNINGS, and PRECAUTIONS.)

Management of Local Anesthetic Emergencies: The first consideration is prevention, best

accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the

patient’s state of consciousness after each local anesthetic injection. At the first sign of change, oxygen

should be administered.

The first step in the management of systemic toxic reactions, as well as underventilation or apnea due to

unintentional subarachnoid injection of drug solution, 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. This may prevent

convulsions if they have not already occurred.

If necessary, use drugs to control the convulsions. A 50 mg to 100 mg bolus IV injection of

succinylcholine will paralyze the patient without depressing the central nervous or cardiovascular

systems and facilitate ventilation. A bolus IV dose of 5 mg to 10 mg of diazepam or 50 mg to 100 mg of

thiopental will permit ventilation and counteract central nervous system stimulation, but these drugs also

depress central nervous system, respiratory, and cardiac function, add to postictal depression and may

result in apnea. Intravenous barbiturates, anticonvulsant agents, or muscle relaxants should only be

administered by those familiar with their use. Immediately after the institution of these ventilatory

measures, the adequacy of the circulation should be evaluated. Supportive treatment of circulatory

depression may require administration of intravenous fluids, and when appropriate, a vasopressor

dictated by the clinical situation (such as ephedrine or epinephrine to enhance myocardial contractile

force).

Endotracheal intubation, employing 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.

Recent clinical data from patients experiencing local anesthetic-induced convulsions demonstrated rapid

development of hypoxia, hypercarbia, and acidosis with bupivacaine within a minute of the onset of

convulsions. These observations suggest that oxygen consumption and carbon dioxide production are

greatly increased during local anesthetic convulsions and emphasize the importance of immediate and

effective ventilation with oxygen which may avoid cardiac arrest.

If not treated immediately, convulsions with simultaneous hypoxia, hypercarbia, and acidosis plus

myocardial depression from the direct effects of the local anesthetic may result in cardiac arrhythmias,

bradycardia, asystole, ventricular fibrillation, or cardiac arrest. Respiratory abnormalities, including

apnea, may occur. Underventilation or apnea due to unintentional subarachnoid injection of local

anesthetic solution 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.

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.

The mean seizure dosage of bupivacaine in rhesus monkeys was found to be 4.4 mg/kg with mean

arterial plasma concentration of 4.5 mcg/mL. The intravenous and subcutaneous LD in mice is 6 mg/kg

to 8 mg/kg and 38 mg/kg to 54 mg/kg respectively.

DOSAGE AND ADMINISTRATION

The dose of any local anesthetic 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. The smallest dose and concentration required to

produce the desired result should be administered. Dosages of Bupivacaine Hydrochloride should be

reduced for elderly and/or debilitated patients and patients with cardiac and/or liver disease. The rapid

injection of a large volume of local anesthetic solution should be avoided and fractional (incremental)

doses should be used when feasible.

For specific techniques and procedures, refer to standard textbooks.

There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of

local anesthetics following arthroscopic and other surgical procedures. Bupivacaine Hydrochloride is

not approved for this use (see WARNINGS and DOSAGE AND ADMINISTRATION).

In recommended doses, Bupivacaine Hydrochloride produces complete sensory block, but the effect on

motor function differs among the three concentrations.

0.25%─ when used for caudal, epidural, or peripheral nerve block, produces incomplete motor block.

Should be used for operations in which muscle relaxation is not important, or when another means of

providing muscle relaxation is used concurrently. Onset of action may be slower than with the 0.5% or

0.75% solutions.

0.5% ─ provides motor blockade for caudal, epidural, or nerve block, but muscle relaxation may be

inadequate for operations in which complete muscle relaxation is essential.

0.75% ─ produces complete motor block. Most useful for epidural block in abdominal operations

requiring complete muscle relaxation, and for retrobulbar anesthesia. Not for obstetrical anesthesia.

The duration of anesthesia with Bupivacaine Hydrochloride is such that for most indications, a single

dose is sufficient.

Maximum dosage limit must be individualized in each case after evaluating the size and physical status

of the patient, as well as the usual rate of systemic absorption from a particular injection site. Most

experience to date is with single doses of Bupivacaine Hydrochloride up to 225 mg with epinephrine

1:200,000 and 175 mg without epinephrine; more or less drug may be used depending on

individualization of each case.

These doses may be repeated up to once every three hours. In clinical studies to date, total daily doses

have been up to 400 mg. Until further experience is gained, this dose should not be exceeded in 24

hours. The duration of anesthetic effect may be prolonged by the addition of epinephrine.

The dosages in Table 1 have generally proved satisfactory and are recommended as a guide for use in

the average adult. These dosages should be reduced for elderly or debilitated patients. Until further

experience is gained, Bupivacaine Hydrochloride is not recommended for pediatric patients younger

than 12 years. Bupivacaine Hydrochloride is contraindicated for obstetrical paracervical blocks, and is

not recommended for intravenous regional anesthesia (Bier Block).

Use in Epidural Anesthesia: During epidural administration of Bupivacaine Hydrochloride, 0.5% and

0.75% solutions should be administered in incremental doses of 3 mL to 5 mL with sufficient time

between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection. In

obstetrics, only the 0.5% and 0.25% concentrations should be used; incremental doses of 3 mL to 5 mL

of the 0.5% 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 contraindicated. Use only the

single-dose ampuls and single-dose vials for caudal or epidural anesthesia; the multiple-dose vials

contain a preservative and therefore should not be used for these procedures.

Test Dose for Caudal and Lumbar Epidural Blocks: The Test Dose of Bupivacaine Hydrochloride (0.5%

bupivacaine with 1:200,000 epinephrine in a 3 mL ampul) is recommended for use as a test dose when

clinical conditions permit prior to caudal and lumbar epidural blocks. This may serve as a warning of

unintended intravascular or subarachnoid injection. (See PRECAUTIONS.) The pulse rate and other

signs should be monitored carefully immediately following each test dose administration to detect

possible intravascular injection, and adequate time for onset of spinal block should be allotted to detect

possible intrathecal injection. An intravascular or subarachnoid 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 OVERDOSAGE.)

Unused portions of solution not containing preservatives, i.e., those supplied in single-dose ampuls and

single-dose vials, should be discarded following initial use.

This product should be inspected visually for particulate matter and discoloration prior to

administration whenever solution and container permit. Solutions which are discolored or which contain

particulate matter should not be administered.

Table 1. Recommended Concentrations and Doses of Bupivacaine Hydrochloride

Type of

Block

Conc.

Each

Dos e

Motor

Block

(mL)

(mg)

Local infiltration

0.25%

up to

max.

up to max.

Epidural

0.75%

75-150

complete

0.5%

50-100

moderate

complete

0.25%

25-50

partial to

moderate

Caudal

0.5%

75-150

moderate

complete

0.25%

37.5-75

moderate

Peripheral nerves

0.5%

5 to

max.

25 to max.

moderate

complete

0.25%

5 to

max.

12.5 to max.

moderate

complete

Retrobulbar

0.75%

15-30

complete

Sympathetic

0.25%

50-125

1

Sympathetic

0.25%

50-125

Epidural

0.5%

10-15

Test Dose

w/epi

(10-15

micrograms

epinephrine)

With continuous (intermittent) techniques, repeat doses increase

the degree of motor block. The first repeat dose of 0.5% may

produce complete motor block. Intercostal nerve block with

0.25% may also produce complete motor block for intra-

abdominal surgery.

For single-dose use, not for intermittent epidural technique. Not

for obstetrical anesthesia.

See PRECAUTIONS.

Solutions with or without epinephrine.

HOW SUPPLIED

These solutions are not for spinal anesthesia.

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

Bupivacaine Hydrochloride ─ Solutions of Bupivacaine Hydrochloride that do not contain epinephrine

may be autoclaved. Autoclave at 15-pound pressure, 121°C (250°F) for 15 minutes. Do not autoclave

product packaged in Abboject

Syringes.

NDC No.

Conc.

Size

pH

Package

0409-1158-01 0.25% 30 mL 6.0 (4.0 to 6.5)Ampul

0409-1158-02

50 mL 6.0 (4.0 to 6.5)Ampul

0409-4272-01 0.25% 20 mL 6.0 (4.0 to 6.5)Sterile Pack Ampul

0409-1159-01 0.25% 10 mL 5.4 (4.0 to 6.5) Teartop Vial

0409-1159-02

30 mL 5.4 (4.0 to 6.5) Teartop Vial

0409-1160-01 0.25% 50 mL 5.4 (4.0 to 6.5)

Fliptop Vial

(Multiple-dose)

0409-1161-01 0.5% 30 mL 6.0 (4.0 to 6.5)Ampul

0409-4273-01 0.5% 20 mL 6.0 (4.0 to 6.5)Sterile Pack Ampul

0409-1163-01 0.5% 50 mL 5.4 (4.0 to 6.5)

Fliptop Vial

(Multiple-dose)

0409-1162-01 0.5% 10 mL 5.4 (4.0 to 6.5) Teartop Vial

0409-1162-02

30 mL 5.4 (4.0 to 6.5) Teartop Vial

0409-4274-01 0.75% 20 mL 6.0 (4.0 to 6.5)Sterile Pack Ampul

0409-1164-01 0.75% 30 mL 6.0 (4.0 to 6.5)Ampul

0409-1165-01 0.75% 10 mL 5.4 (4.0 to 6.5) Teartop Vial

0409-1165-02

30 mL 5.4 (4.0 to 6.5) Teartop Vial

Bupivacaine Hydrochloride with epinephrine 1:200,000 (as bitartrate)─Solutions of Bupivacaine

Hydrochloride that contain epinephrine should not be autoclaved and should be protected from light. Do

not use the solution if its color is pinkish or darker than slightly yellow or if it contains a precipitate.

NDC No.

Concentration

Bupivacaine

HCl

Size

pH

Package

0409-9042-01 0.25%

10 mL 4.0 (3.3 to 5.5)Teartop Vial

0409-9042-02 0.25%

30 mL 4.0 (3.3 to 5.5)Teartop Vial

0409-9042-17 0.25%

30 mL 4.0 (3.3 to 5.5)Teartop Vial

0409-9043-01 0.25%

50 mL 4.0 (3.3 to 5.5)

Fliptop Vial

(Multiple-dose)

0409-9045-01 0.5%

10 mL 4.0 (3.3 to 5.5)Teartop Vial

0409-9045-02 0.5%

30 mL 4.0 (3.3 to 5.5)Teartop Vial

0409-9045-17 0.5%

30 mL 4.0 (3.3 to 5.5)Teartop Vial

0409-9046-01 0.5%

50 mL 4.0 (3.3 to 5.5)

Fliptop Vial

(Multiple-dose)

Revised: April, 2010

Printed in USA EN-2490

Hospira, Inc., Lake Forest, IL 60045 USA

Package Label Display Panel

Package Label Display Panel

A3928-20 SINGLE SHOT EPIDURAL 20G TUOHY

regional anesthesia kit kit

Product Information

Product T ype

MEDICAL DEVICE

Ite m Code (Source )

NHRIC:516 8 8 -6 248

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NHRIC:516 8 8 -6 248 -2

10 in 1 CASE

1

1 in 1 PACKAGE, COMBINATION

Quantity of Parts

Part #

Package Quantity

Total Product Quantity

Pa rt 1

1 AMPULE

10 mL

Pa rt 2

1 AMPULE

10 mL

Pa rt 3

1 AMPULE

30 mL

Part 1 of 3

SODIUM CHLORIDE

sodium chloride solution

Product Information

Ite m Code (Source )

NDC:6 528 2-1510

Route of Administration

EPIDURAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

SO DIUM CHLO RIDE (UNII: 451W47IQ8 X) (CHLORIDE ION - UNII:Q32ZN48 6 9 8 )

SODIUM CHLORIDE

9 mg in 1 mL

Inactive Ingredients

Ingredient Name

Stre ng th

WATER (UNII: 0 59 QF0 KO0 R)

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 528 2-1510 -1

10 mL in 1 AMPULE

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

unappro ved drug o ther

12/0 1/20 0 0

Part 2 of 3

LIDOCAINE HYDROCHLORIDE

lidocaine hydrochloride anhydrous injection, solution

Product Information

Ite m Code (Source )

NDC:0 40 9 -428 2

Route of Administration

EPIDURAL, INFILTRATION

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

LIDO CAINE HYDRO CHLO RIDE ANHYDRO US (UNII: EC2CNF7XFP)

(LIDOCAINE - UNII:9 8 PI20 0 9 8 7)

LIDOCAINE HYDROCHLORIDE

ANHYDROUS

20 mg

in 1 mL

Inactive Ingredients

Ingredient Name

Stre ng th

SO DIUM CHLO RIDE (UNII: 451W47IQ8 X)

6 mg in 1 mL

WATER (UNII: 0 59 QF0 KO0 R)

SO DIUM HYDRO XIDE (UNII: 55X0 4QC32I)

HYDRO CHLO RIC ACID (UNII: QTT1758 2CB)

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 40 9 -428 2-0 2

10 mL in 1 AMPULE

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 8 8 29 4

0 3/30 /20 10

Part 3 of 3

BUPIVACAINE HYDROCHLORIDE

bupivacaine hydrochloride injection, solution

Product Information

Ite m Code (Source )

NDC:0 40 9 -1158

Route of Administration

EPIDURAL, INFILTRATION, INTRACAUDAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

BUPIVACAINE HYDRO CHLO RIDE (UNII: 7TQO7W3VT8 ) (BUPIVACAINE -

UNII:Y8 33539 4RO)

BUPIVACAINE

HYDROCHLORIDE

2.5 mg

in 1 mL

Inactive Ingredients

Ingredient Name

Stre ng th

SO DIUM CHLO RIDE (UNII: 451W47IQ8 X)

8 .6 mg in 1 mL

SO DIUM HYDRO XIDE (UNII: 55X0 4QC32I)

HYDRO CHLO RIC ACID (UNII: QTT1758 2CB)

WATER (UNII: 0 59 QF0 KO0 R)

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 40 9 -1158 -0 1

30 mL in 1 AMPULE

Smiths Medical ASD, Inc.

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 70 58 6

0 1/0 6 /20 10

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

premarket no tificatio n

K9 6 50 17

11/30 /20 11

Labeler -

Smiths Medical ASD, Inc. (137835299)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Smiths Medical ASD, Inc.

1378 3529 9

relabel, manufacture

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Ho spira, Inc.

0 30 6 0 6 222

ma nufa c ture

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Ho spira, Inc.

0 9 31328 19

ma nufa c ture

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Kwang Myung Pharm. Co ., Ltd.

6 310 9 9 38 4

ma nufa c ture

Revised: 12/2012

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