Xylocaine

General Injectables & Vaccines, Inc

Xylocaine 0.5% (Lidocaine HCl and Epinephrine 1:200,000) 5mg/mL 50mL Multi dose vial

FULL PRESCRIBING INFORMATION: CONTENTS*

• XYLOCAINE DESCRIPTION
• CLINICAL PHARMACOLOGY
• INDICATIONS & USAGE
• XYLOCAINE CONTRAINDICATIONS
• WARNINGS
• PRECAUTIONS
• XYLOCAINE ADVERSE REACTIONS
• DOSAGE & ADMINISTRATION
• STERILIZATION, STORAGE AND TECHNICAL PROCEDURES
• HOW SUPPLIED
• PACKAGE LABEL

FULL PRESCRIBING INFORMATION

XYLOCAINE DESCRIPTION

XYLOCAINE - lidocaine hydrochloride injection, solution
XYLOCAINE - lidocaine hydrochloride and epinephrine bitartrate injection, solution
XYLOCAINE MPF - lidocaine hydrochloride injection, solution
XYLOCAINE - lidocaine hydrochloride and epinephrine bitartrate injection, solution
XYLOCAINE MPF - lidocaine hydrochloride and epinephrine bitartrate injection, solution
APP Pharmaceuticals, LLC
For Infiltration and Nerve Block
Rx only
DESCRIPTION
Xylocaine (lidocaine HCl) Injections are sterile, nonpyrogenic, aqueous solutions that contain a local anesthetic agent with or without
epinephrine and are administered parenterally by injection. See INDICATIONS for specific uses.
Xylocaine solutions contain lidocaine HCl, which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-,
monohydrochloride and has the molecular wt. 270.8. Lidocaine HCl (C14H22N2O • HCl) has the following structural formula:

CLINICAL PHARMACOLOGY

Mechanism of Action
Lidocaine HCl 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 HCl 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.

INDICATIONS & USAGE

Xylocaine (lidocaine HCl) Injections are 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.

XYLOCAINE CONTRAINDICATIONS

Lidocaine HCl is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type.

WARNINGS

XYLOCAINE INJECTIONS 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 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.
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 (eg, 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.
Xylocaine with epinephrine solutions contain 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 non-asthmatic people.

PRECAUTIONS

General
The safety and effectiveness of lidocaine HCl 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 HCl 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 HCl 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, Xylocaine Injection 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. Xylocaine Injection 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 HCl 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 HCl.
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 injection 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

XYLOCAINE ADVERSE REACTIONS

Systemic
Adverse experiences following the administration of lidocaine HCl 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 HCl 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 the multiple dose vials.
Allergic reactions as result of sensitivity to lidocaine HCl 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 HCl 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 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 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 the use of local

DOSAGE & ADMINISTRATION

Table 1 (Recommended Dosages) summarizes the recommended volumes and concentrations of Xylocaine Injection for various
types of anesthetic procedures. The dosages suggested in this table are for normal healthy adults and refer to the use of epinephrinefree
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. Xylocaine 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 the 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 (ie, total dose) of local anesthetic used. Thus, an increase in volume and concentration of Xylocaine 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 Xylocaine Injection may result in a more
profound fall in blood pressure when used in epidural anesthesia. Although the incidence of side effects with lidocaine HCl 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 Xylocaine (lidocaine HCl) 0.5% Injection should be
used.
Epidural Anesthesia
For epidural anesthesia, only the following dosage forms Xylocaine Injection are recommended:
1% without epinephrine 10 mL Polyamp DuoFit™
1% without epinephrine 30 mL single dose solutions
1% with epinephrine 30 mL single dose solutions
1:200,000
1.5% without epinephrine 10 mL Polyamp DuoFit™
1.5% without epinephrine 20 mL Polyamp DuoFit™
1.5% with epinephrine 30 mL ampules, 30 mL single dose solutions
1:200,000
2% without epinephrine 10 mL Polyamp DuoFit™
2% with epinephrine 20 mL ampules, 20 mL single dose solutions
1:200,000
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 to 3 mL of the indicated
concentration per dermatome).
Caudal and Lumbar Epidural Block
As a precaution against the adverse experience sometimes observed following unintentional penetration of the subarachnoid space,
a test dose such as 2 to 3 mL of 1.5% lidocaine HCl 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 to 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

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 incidents of swelling and edema. When chemical disinfection
of multi-dose vials is desired, either isopropyl alcohol (91%) or ethyl alcohol (70%) 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.
Dosage forms listed as Xylocaine-MPF indicate single dose solutions that are Methyl Paraben Free (MPF).

HOW SUPPLIED

PACKAGE LABEL