NESACAINE- chloroprocaine hydrochloride injection, solution

Nesacaine by

Drug Labeling and Warnings

Nesacaine by is a Prescription medication manufactured, distributed, or labeled by General Injectables & Vaccines, Inc. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

DESCRIPTION

NESACAINE - chloroprocaine hydrochloride injection, solution
NESACAINE MPF - chloroprocaine hydrochloride injection, solution
APP Pharmaceuticals, LLC
For Infiltration and Nerve Block
DESCRIPTION
Nesacaine and Nesacaine-MPF Injections are sterile non pyrogenic local anesthetics. The active ingredient in Nesacaine and
Nesacaine-MPF Injections is chloroprocaine HCl (benzoic acid, 4-amino-2-chloro-2-(diethylamino) ethyl ester, monohydrochloride),
which is represented by the following structural formula:

Table 1: Composition of Available Injections

The solutions are adjusted to pH 2.7–4.0 by means of sodium hydroxide and/or hydrochloric acid. Filled under nitrogen.

Nesacaine and Nesacaine-MPF Injections should not be resterilized by autoclaving.

CLINICAL PHARMACOLOGY

Chloroprocaine, like other local anesthetics, blocks the generation and the conduction of nerve impulses, presumably by increasing the
threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse and by reducing the rate of rise of the
action potential. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected
nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and
(5) skeletal muscle tone.
Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. 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 and ultimately to cardiac arrest. In addition, with toxic blood concentrations myocardial contractility may be
depressed and peripheral vasodilation may occur, leading to decreased cardiac output and arterial blood pressure.
Following systemic absorption, toxic blood concentrations of local anesthetics can produce central nervous system stimulation,
depression, or both. Apparent central stimulation may be manifested as restlessness, tremors and shivering, which may progress to
convulsions. Depression and coma may occur, possibly 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 stage of central nervous system stimulation.

PHARMACOKINETICS

The rate of systemic absorption of local anesthetic drugs 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
injection. Epinephrine usually reduces the rate of absorption and plasma concentration of local anesthetics and is sometimes added to
local anesthetic injections in order to prolong the duration of action.

The onset of action with chloroprocaine is rapid (usually within 6 to 12 minutes), and the duration of anesthesia, depending upon the
amount used and the route of administration, may be up to 60 minutes.

Local anesthetics appear to cross the placenta by passive diffusion. However, the rate and degree of diffusion varies considerably
among the different drugs as 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, since
only the free, unbound drug is available for placental transfer. Thus, drugs with the highest protein binding capacity may have the
lowest fetal/maternal ratios. 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.

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 administration, and the age of the patient. The in
vitro plasma half-life of chloroprocaine in adults is 21 ± 2 seconds for males and 25 ± 1 seconds for females. The in vitro plasma halflife
in neonates is 43 ± 2 seconds.

Chloroprocaine is rapidly metabolized in plasma by hydrolysis of the ester linkage by pseudocholinesterase. The hydrolysis of
chloroprocaine results in the production of ß-diethylaminoethanol and 2-chloro-4-aminobenzoic acid, which inhibits the action of the
sulfonamides (see PRECAUTIONS).

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.

INDICATIONS & USAGE

Nesacaine 1% and 2% Injections, in multidose vials with methylparaben as preservative, are indicated for the production of local
anesthesia by infiltration and peripheral nerve block. They are not to be used for lumbar or caudal epidural anesthesia.
Nesacaine-MPF 2% and 3% Injections, in single dose vials without preservative and without EDTA, are indicated for the production
of local anesthesia by infiltration, peripheral and central nerve block, including lumbar and caudal epidural blocks.
Nesacaine and Nesacaine-MPF Injections are not to be used for subarachnoid administration.

CONTRAINDICATIONS

Nesacaine and Nesacaine-MPF Injections are contraindicated in patients hypersensitive (allergic) to drugs of the PABA ester group.
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.

WARNINGS

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 ENSURING 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 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. NESACAINE (chloroprocaine HCl Injection, USP) contains
methylparaben and should not be used for lumbar or caudal epidural anesthesia because safety of this antimicrobial preservative has
not been established with regard to intrathecal injection, either intentional or unintentional. NESACAINE-MPF Injection contains no
preservative; discard unused injection remaining in vial after initial use.
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 intraarticular
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.
Vasopressors should not be used in the presence of ergot-type oxytocic drugs, since a severe persistent hypertension may occur.
To avoid intravascular injection, aspiration should be performed before the anesthetic solution is injected. The needle must be
repositioned until no blood return can be elicited. However, the absence of blood in the syringe does not guarantee that intravascular
injection has been avoided.
Mixtures of local anesthetics are sometimes employed to compensate for the slower onset of one drug and the shorter duration of
action of the second drug. Experiments in primates suggest that toxicity is probably additive when mixtures of local anesthetics
are employed, but some experiments in rodents suggest synergism. Caution regarding toxic equivalence should be exercised when
mixtures of local anesthetics are employed.

PRECAUTIONS

General
The safety and effective use of chloroprocaine 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 and ADVERSE REACTIONS). The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. 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. During the administration of epidural anesthesia, it is recommended that a test dose be administered (3 mL of 3% or 5 mL of 2% Nesacaine-MPF Injection) 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 a chloroprocaine solution that contains epinephrine for the test dose
because circulatory changes characteristic of 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. With the use of continuous catheter techniques, it is recommended that a fraction of each supplemental dose be administered as a test dose in order to verify proper location of the catheter.

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. Tolerance to elevated blood levels varies with the physical condition of the patient.

Debilitated, elderly patients, acutely ill patients, and children 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 heart block.

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.

Local anesthetic injections 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.
Since ester-type local anesthetics are hydrolyzed by plasma cholinesterase produced by the liver, chloroprocaine should be used
cautiously in patients with hepatic disease.

Local anesthetics 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.

Use in Ophthalmic Surgery: When local anesthetic injections are employed for retrobulbar block, lack of corneal sensation should
not be relied upon to determine whether or not the patient is ready for surgery. This is because complete lack of corneal sensation
usually precedes clinically acceptable external ocular muscle akinesia.

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, tricyclic antidepressants or phenothiazines may produce severe, prolonged hypotension or 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 (for the treatment of hypotension related to obstetric blocks) and ergot-type oxytocic
drugs may cause severe, persistent hypertension or cerebrovascular accidents.
The para-aminobenzoic acid metabolite of chloroprocaine inhibits the action of sulfonamides. Therefore, chloroprocaine should not be
used in any condition in which a sulfonamide drug is being employed.

Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long-term studies in animals to evaluate carcinogenic potential and reproduction studies to evaluate mutagenesis or impairment of
fertility have not been conducted with chloroprocaine.

Pregnancy: Category C
Animal reproduction studies have not been conducted with chloroprocaine. It is also not known whether chloroprocaine can cause
fetal harm when administered to a pregnant woman or can affect reproduction capacity. Chloroprocaine should be given to a pregnant
woman only if clearly needed. This does not preclude the use of chloroprocaine at term for the production of obstetrical anesthesia.

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 and 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, 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, epidural anesthesia has 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.
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 injection 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 usually 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.

There are no data concerning use of chloroprocaine for obstetrical paracervical block when toxemia of pregnancy is present or when
fetal distress or prematurity is anticipated in advance of the block; such use is, therefore, not recommended.
The following information should be considered by clinicians who select chloroprocaine for obstetrical paracervical block anesthesia:
1. Fetal bradycardia (generally a heart rate of less than 120 per minute for more than 2 minutes) has been noted by electronic
monitoring in about 5 to 10 percent of the cases (various studies) where initial total doses of 120 mg to 400 mg of chloroprocaine
were employed. The incidence of bradycardia, within this dose range, might not be dose related.
2. Fetal acidosis has not been demonstrated by blood gas monitoring around the time of bradycardia or afterwards. These data are
limited and generally restricted to non-toxemic cases where fetal distress or prematurity was not anticipated in advance of the
block.
3. No intact chloroprocaine and only trace quantities of a hydrolysis product, 2-chloro-4-aminobenzoic acid, have been demonstrated
in umbilical cord arterial or venous plasma following properly administered paracervical block with chloroprocaine.
4. The role of drug factors and non-drug factors associated with fetal bradycardia following paracervical block are unexplained at this
time.

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 chloroprocaine is administered to a nursing woman.

Pediatric Use
Guidelines for the administration of Nesacaine and Nesacaine-MPF Injections to children are presented in DOSAGE AND
ADMINISTRATION.

Geriatric Use
Clinical studies of Nesacaine and Nesacaine-MPF did not include sufficient numbers of subjects 65 and over to determine whether
they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between
the elderly and younger patients. In general, dose selection for an elderly patient should be cautious usually starting at the low end of
the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other
drug therapy.

This drug and its metabolites are 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.

ADVERSE REACTIONS

Systemic: The most commonly encountered acute adverse experiences that demand immediate countermeasures are related to the
central nervous system and the cardiovascular system. These adverse experiences are generally dose related and may result from 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 Spinal”). Factors influencing plasma protein binding, such as acidosis, systemic diseases that alter protein production, or competition of other drugs for protein binding sites, may diminish individual tolerance. Plasma cholinesterase deficiency may also account for diminished tolerance to ester-type local anesthetics.

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.

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
percent of local anesthetic administrations.

Cardiovascular System Reactions: High doses, or unintended intravascular injection, may lead to high plasma levels and related
depression of the myocardium, hypotension, bradycardia, ventricular arrhythmias, and, possibly, cardiac arrest.
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. 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 type symptomatology (including
severe hypotension). Cross sensitivity among members of the ester-type local anesthetic group has been reported. The usefulness of
screening for sensitivity has not been definitely established.

Neurologic: In the practice of caudal or lumbar epidural block, occasional unintentional penetration of the subarachnoid space
by the catheter may occur (see PRECAUTIONS). Subsequent adverse observations may depend partially on the amount of drug
administered intrathecally. These observations 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.
Arachnoiditis, 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 (see DOSAGE AND ADMINISTRATION
discussion of Caudal and Lumbar Epidural Block). Backache and headache have also been noted following lumbar epidural or caudal
block.

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).
In mice, the intravenous LD50 of chloroprocaine HCl is 97 mg/kg and the subcutaneous LD50 of chloroprocaine HCl is 950 mg/kg.
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 convulsions, as well as underventilation or apnea due to unintentional 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 the use of anesthetics,
with these anticonvulsant drugs. Supportive treatment of circulatory depression may require administration of intravenous fluids and,
when appropriate, a vasopressor dictated by the clinical situation (such as ephedrine to enhance myocardial contractile force).
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. Recovery has been reported after prolonged resuscitative efforts.
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.

DOSAGE & ADMINISTRATION

Chloroprocaine may be administered as a single injection or continuously through an indwelling catheter. As with all local
anesthetics, the dose administered varies with the anesthetic procedure, the vascularity of the tissues, the depth of anesthesia and
degree of muscle relaxation required, the duration of anesthesia desired, and the physical condition of the patient. The smallest
dose and concentration required to produce the desired result should be used. Dosage should be reduced for children, elderly and debilitated patients and patients with cardiac and/or liver disease. The maximum single recommended doses of chloroprocaine in adults are: without epinephrine, 11 mg/kg, not to exceed a maximum total dose of 800 mg; with epinephrine (1:200,000), 14 mg/kg, not to exceed a maximum total dose of 1000 mg. 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. Nesacaine is not approved for this use (see WARNINGS and DOSAGE AND
ADMINISTRATION).
Caudal and Lumbar Epidural Block: In order to guard against adverse experiences sometimes noted following unintended
penetration of the subarachnoid space, the following procedure modifications are recommended:
1. Use an adequate test dose (3 mL of Nesacaine-MPF 3% Injection or 5 mL of Nesacaine-MPF 2% Injection) prior to induction
of complete block. This test dose should be repeated if the patient is moved in such a fashion as to have displaced the epidural
catheter. Allow adequate time for onset of anesthesia following administration of each test dose.
2. Avoid the rapid injection of a large volume of local anesthetic injection through the catheter. Consider fractional doses, when
feasible.
3. In the event of the known injection of a large volume of local anesthetic injection 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.
As a guide for some routine procedures, suggested doses are given below:

1. Infiltration and Peripheral Nerve Block: NESACAINE or NESACAINE-MPF (chloroprocaine HCl Injection, USP)

2. Caudal and Lumbar Epidural Block: NESACAINE-MPF INJECTION.

For caudal anesthesia, the initial dose is 15 to 25 mL of a 2% or 3% solution. Repeated doses may be given at 40 to 60 minute
intervals.

For lumbar epidural anesthesia, 2 to 2.5 mL per segment of a 2% or 3% solution can be used. The usual total volume of
Nesacaine-MPF Injection is from 15 to 25 mL. Repeated doses 2 to 6 mL less than the original dose may be given at 40 to 50 minute
intervals.

The above dosages are recommended as a guide for use in the average adult. Maximum dosages of all local anesthetics must be
individualized after evaluating the size and physical condition of the patient and the rate of systemic absorption from a particular
injection site.

Pediatric Dosage: 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 and should not exceed 11 mg/kg (5 mg/lb). For example, in a child of 5 years weighing
50 lbs (23 kg), the dose of chloroprocaine HCl without epinephrine would be 250 mg. Concentrations of 0.5–1% are suggested for
infiltration and 1–1.5% for nerve block. In order to guard against systemic toxicity, the lowest effective concentration and lowest
effective dose should be used at all times. Some of the lower concentrations for use in infants and smaller children are not available
in prepackaged containers; it will be necessary to dilute available concentrations with the amount of 0.9% sodium chloride injection
necessary to obtain the required final concentration of chloroprocaine injection.

Preparation of Epinephrine Injections—To prepare a 1:200,000 epinephrine-chloroprocaine HCl injection, add 0.1 mL of a 1 to
1000 Epinephrine Injection USP to 20 mL of Nesacaine-MPF Injection.

Chloroprocaine is incompatible with caustic alkalis and their carbonates, soaps, silver salts, iodine and iodides.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever
injection and container permit. As with other anesthetics having a free aromatic amino group, Nesacaine and Nesacaine-MPF
Injections are slightly photosensitive and may become discolored after prolonged exposure to light. It is recommended that these vials
be stored in the original outer containers, protected from direct sunlight. Discolored injection should not be administered. If exposed
to low temperatures, Nesacaine and Nesacaine-MPF Injections may deposit crystals of chloroprocaine HCl which will redissolve with
shaking when returned to room temperature. The product should not be used if it contains undissolved (eg, particulate) material.

HOW SUPPLIED

HOW SUPPLIED
NESACAINE (chloroprocaine HCl Injection, USP) with preservatives is supplied as follows:

Keep from freezing. Protect from light. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].NESACAINE-MPF (chloroprocaine HCl Injection, USP) without preservatives and without EDTA is supplied as follows:

All trademarks are the property of APP Pharmaceuticals, LLC.

APP
Fresenius Kabi, LLC

Lake Zurich, IL 60047

451109E/Revised: December 2013

SAMPLE PACKAGE LABEL

INGREDIENTS AND APPEARANCE

NESACAINE 
chloroprocaine hydrochloride injection, solution

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 52584-475(NDC:63323-475)
Route of Administration	INFILTRATION, PERINEURAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
Chloroprocaine Hydrochloride (UNII: LT7Z1YW11H) (Chloroprocaine - UNII:5YVB0POT2H)	Chloroprocaine Hydrochloride	10 mg  in 1 mL

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 52584-475-37	1 in 1 BAG	10/03/2011
1		30 mL in 1 VIAL; Type 0: Not a Combination Product

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA009435	10/03/2011

Labeler - General Injectables & Vaccines, Inc (108250663)