Xylocaine 1% (10mg/mL)

DESCRIPTION

XYLOCAINE - lidocaine hydrochloride injection, solutionXYLOCAINE - lidocaine hydrochloride and epinephrine bitartrate injection, solutionXYLOCAINE MPF - lidocaine hydrochloride injection, solutionXYLOCAINE - lidocaine hydrochloride and epinephrine bitartrate injection, solutionXYLOCAINE MPF - lidocaine hydrochloride and epinephrine bitartrate injection, solutionAPP Pharmaceuticals, LLCFor Infiltration and Nerve BlockRx onlyDESCRIPTIONXylocaine (lidocaine HCl) Injections are sterile, nonpyrogenic, aqueous solutions that contain a local anesthetic agent with or withoutepinephrine 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 ActionLidocaine HCl stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulsesthereby effecting local anesthetic action.HemodynamicsExcessive blood levels may cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. With centralneural blockade these changes may be attributable to block of autonomic fibers, a direct depressant effect of the local anesthetic agenton various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine whenpresent. The net effect is normally a modest hypotension when the recommended dosages are not exceeded.Pharmacokinetics and MetabolismInformation derived from diverse formulations, concentrations and usages reveals that lidocaine HCl is completely absorbed followingparenteral administration, its rate of absorption depending, for example, upon various factors such as the site of administration andthe presence or absence of a vasoconstrictor agent. Except for intravascular administration, the highest blood levels are obtainedfollowing 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 suchas percutaneous injection and intravenous regional anesthesia by peripheral nerve block techniques such as brachial plexus andintercostal and by central neural techniques such as lumbar and caudal epidural blocks, when the accepted procedures for thesetechniques as described in standard textbooks are observed.

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 CLINICIANSWHO ARE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER ACUTEEMERGENCIES THAT MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED AND THEN ONLY AFTER ENSURING THEIMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS, CARDIOPULMONARY EQUIPMENT ANDTHE PERSONNEL NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES (seealso 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 OFACIDOSIS, CARDIAC ARREST AND, POSSIBLY, DEATH.Intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there havebeen post-marketing reports of chondrolysis in patients receiving such infusions. The majority of reported cases of chondrolysis haveinvolved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intraarticularinfusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. There is insufficient information todetermine 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 effectivetreatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures andsome required arthroplasty or shoulder replacement.To avoid intravascular injection, aspiration should be performed before the local anesthetic solution is injected. The needle must berepositioned until no return of blood can be elicited by aspiration. Note, however, that the absence of blood in the syringe does notguarantee that intravascular injection has been avoided.Local anesthetic solutions containing antimicrobial preservatives (eg, methylparaben) should not be used for epidural or spinalanesthesia because the safety of these agents has not been established with regard to intrathecal injection, either intentional oraccidental.Xylocaine with epinephrine solutions contain sodium metabisulfite, a sulfite that may cause allergic-type reactions includinganaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence ofsulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic thanin non-asthmatic people.

PRECAUTIONS

GeneralThe safety and effectiveness of lidocaine HCl depend on proper dosage, correct technique, adequate precautions, and readinessfor emergencies. Standard textbooks should be consulted for specific techniques and precautions for various regional anestheticprocedures.Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use (see WARNINGS andADVERSE REACTIONS). The lowest dosage that results in effective anesthesia should be used to avoid high plasma levelsand serious adverse effects. Syringe aspirations should also be performed before and during each supplemental injection whenusing indwelling catheter techniques. During the administration of epidural anesthesia, it is recommended that a test dose beadministered initially and that the patient be monitored for central nervous system toxicity and cardiovascular toxicity, as well asfor signs of unintended intrathecal administration, before proceeding. When clinical conditions permit, consideration should begiven to employing local anesthetic solutions that contain epinephrine for the test dose because circulatory changes compatible withepinephrine may also serve as a warning sign of unintended intravascular injection. An intravascular injection is still possible even ifaspirations for blood are negative. Repeated doses of lidocaine HCl may cause significant increases in blood levels with each repeateddose because of slow accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with the status of thepatient. Debilitated, elderly patients, acutely ill patients, and children should be given reduced doses commensurate with their age andphysical 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: existingneurological disease, spinal deformities, septicemia, and severe hypertension.Local anesthetic solutions containing a vasoconstrictor should be used cautiously and in carefully circumscribed quantities in areasof the body supplied by end arteries or having otherwise compromised blood supply. Patients with peripheral vascular disease andthose 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 potentgeneral 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 ofconsciousness 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 systemtoxicity.Since amide-type local anesthetics are metabolized by the liver, Xylocaine Injection should be used with caution in patients withhepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at greaterrisk of developing toxic plasma concentrations. Xylocaine Injection should also be used with caution in patients with impairedcardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of A-Vconduction 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 generalanesthesia cannot be predicted in advance, it is suggested that a standard protocol for the management of malignant hyperthermiashould be available. Early unexplained signs of tachycardia, tachypnea, labile blood pressure and metabolic acidosis may precedetemperature 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 sodiumintravenous package insert before using).Proper tourniquet technique, as described in publications and standard textbooks, is essential in the performance of intravenousregional 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 acidderivatives (procaine, tetracaine, benzocaine, etc) have not shown cross-sensitivity to lidocaine HCl.Use in the Head and Neck AreaSmall doses of local anesthetics injected into the head and neck area, including retrobulbar, dental and stellate ganglion blocks, mayproduce 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. Patientsreceiving these blocks should have their circulation and respiration monitored and be constantly observed. Resuscitative equipmentand personnel for treating adverse reactions should be immediately available. Dosage recommendations should not be exceeded (seeDOSAGE AND ADMINISTRATION).Information for PatientsWhen 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 oxidaseinhibitors 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 patientmonitoring is essential.Concurrent administration of vasopressor drugs (for the treatment of hypotension related to obstetric blocks) and ergot-type oxytocicdrugs may cause severe, persistent hypertension or cerebrovascular accidents.Drug/Laboratory Test InteractionsThe intramuscular injection of lidocaine HCl may result in an increase in creatine phosphokinase levels. Thus, the use of this enzymedetermination, without isoenzyme separation, as a diagnostic test for the presence of acute myocardial infarction may be compromisedby the intramuscular injection of lidocaine HCl.Carcinogenesis, Mutagenesis, Impairment of FertilityStudies of lidocaine HCl in animals to evaluate the carcinogenic and mutagenic potential or the effect on fertility have not beenconducted.PregnancyTeratogenic Effects: Pregnancy Category B. Reproduction studies have been performed in rats at doses up to 6.6 times thehuman dose and have revealed no evidence of harm to the fetus caused by lidocaine HCl. There are, however, no adequate andwell-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response. Generalconsideration should be given to this fact before administering lidocaine HCl to women of childbearing potential, especially duringearly pregnancy when maximum organogenesis takes place.Labor and DeliveryLocal anesthetics rapidly cross the placenta and when used for epidural, paracervical, pudendal or caudal block anesthesia, cancause varying degrees of maternal, fetal and neonatal toxicity (see CLINICAL PHARMACOLOGY, Pharmacokinetics andMetabolism). The potential for toxicity depends upon the procedure performed, the type and amount of drug used, and the techniqueof 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 ormaternal expulsive efforts. In one study, paracervical block anesthesia was associated with a decrease in the mean duration of firststage labor and facilitation of cervical dilation. However, spinal and epidural anesthesia have also been reported to prolong the secondstage of labor by removing the parturient’s reflex urge to bear down or by interfering with motor function. The use of obstetricalanesthesia 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 tonefor the first day or two of life. The long-term significance of these observations is unknown. Fetal bradycardia may occur in 20 to30 percent of patients receiving paracervical nerve block anesthesia with the amide-type local anesthetics and may be associated withfetal acidosis. Fetal heart rate should always be monitored during paracervical anesthesia. The physician should weigh the possibleadvantages against risks when considering a paracervical block in prematurity, toxemia of pregnancy, and fetal distress. Carefuladherence to recommended dosage is of the utmost importance in obstetrical paracervical block. Failure to achieve adequate analgesiawith recommended doses should arouse suspicion of intravascular or fetal intracranial injection. Cases compatible with unintendedfetal 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 localanesthetic 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 inearly pregnancy (as anesthesia for elective abortion) suggest that systemic absorption under these circumstances may be rapid. Therecommended 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 MothersIt is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should beexercised when lidocaine HCl is administered to a nursing woman.Pediatric UseDosages in children should be reduced, commensurate with age, body weight and physical condition, see DOSAGE ANDADMINISTRATION.

ADVERSE REACTIONS

SystemicAdverse experiences following the administration of lidocaine HCl are similar in nature to those observed with other amide localanesthetic agents. These adverse experiences are, in general, dose-related and may result from high plasma levels caused by excessivedosage, rapid absorption or inadvertent intravascular injection, or may result from a hypersensitivity, idiosyncrasy or diminishedtolerance on the part of the patient. Serious adverse experiences are generally systemic in nature. The following types are those mostcommonly reported:Central Nervous SystemCNS 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 verybrief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness andrespiratory 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 aconsequence of rapid absorption.Cardiovascular SystemCardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, and cardiovascular collapse,which may lead to cardiac arrest.AllergicAllergic reactions are characterized by cutaneous lesions, urticaria, edema or anaphylactoid reactions. Allergic reactions may occuras 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 conventionalmeans. The detection of sensitivity by skin testing is of doubtful value.NeurologicThe incidences of adverse reactions associated with the use of local anesthetics may be related to the total dose of local anestheticadministered 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 reactionswere reported to be about 3 percent each for positional headaches, hypotension and backache; 2 percent for shivering; and less than 1percent each for peripheral nerve symptoms, nausea, respiratory inadequacy and double vision. Many of these observations may berelated 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 cathetermay occur. Subsequent adverse effects may depend partially on the amount of drug administered subdurally. These may includespinal block of varying magnitude (including total spinal block), hypotension secondary to spinal block, loss of bladder and bowelcontrol, and loss of perineal sensation and sexual function. Persistent motor, sensory and/or autonomic (sphincter control) deficit ofsome lower spinal segments with slow recovery (several months) or incomplete recovery have been reported in rare instances whencaudal or lumbar epidural block has been attempted. Backache and headache have also been noted following use of these anestheticprocedures.There have been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbaradministration.

OVERDOSAGE

Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of localanesthetics or to unintended subarachnoid injection of local anesthetic solution (see ADVERSE REACTIONS, WARNINGS, andPRECAUTIONS).Management of Local Anesthetic EmergenciesThe first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vitalsigns and the patient’s state of consciousness after each local anesthetic injection. At the first sign of change, oxygen should beadministered.The first step in the management of convulsions, as well as underventilation or apnea due to unintended subarachnoid injectionof drug solution, consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation withoxygen and a delivery system capable of permitting immediate positive airway pressure by mask. Immediately after the institution ofthese ventilatory measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat convulsionssometimes 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) ora 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 varioustypes of anesthetic procedures. The dosages suggested in this table are for normal healthy adults and refer to the use of epinephrinefreesolutions. When larger volumes are required, only solutions containing epinephrine should be used except in those cases wherevasopressor drugs may be contraindicated.There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of local anesthetics followingarthroscopic and other surgical procedures. Xylocaine is not approved for this use (see WARNINGS and DOSAGE ANDADMINISTRATION).These recommended doses serve only as a guide to the amount of anesthetic required for most routine procedures. The actual volumesand concentrations to be used depend on a number of factors such as type and extent of surgical procedure, depth of anesthesia anddegree of muscular relaxation required, duration of anesthesia required, and the physical condition of the patient. In all cases thelowest concentration and smallest dose that will produce the desired result should be given. Dosages should be reduced for childrenand 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 andconcentration (ie, total dose) of local anesthetic used. Thus, an increase in volume and concentration of Xylocaine Injection willdecrease the onset of anesthesia, prolong the duration of anesthesia, provide a greater degree of muscular relaxation and increasethe segmental spread of anesthesia. However, increasing the volume and concentration of Xylocaine Injection may result in a moreprofound fall in blood pressure when used in epidural anesthesia. Although the incidence of side effects with lidocaine HCl is quitelow, caution should be exercised when employing large volumes and concentrations, since the incidence of side effects is directlyproportional 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 beused.Epidural AnesthesiaFor 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 solutions1% with epinephrine 30 mL single dose solutions1:200,0001.5% 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 solutions1:200,0002% without epinephrine 10 mL Polyamp DuoFit™2% with epinephrine 20 mL ampules, 20 mL single dose solutions1:200,000Although these solutions are intended specifically for epidural anesthesia, they may also be used for infiltration and peripheral nerveblock, 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 indicatedconcentration per dermatome).Caudal and Lumbar Epidural BlockAs 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 volumerequired for a lumbar or caudal epidural block. The test dose should be repeated if the patient is moved in a manner that may havedisplaced the catheter. Epinephrine, if contained in the test dose (10 to 15 mcg have been suggested), may serve as a warning ofunintentional intravascular injection. If injected into a blood vessel, this amount of epinephrine is likely to produce a transient

STORAGE AND HANDLING

Disinfecting agents containing heavy metals, which cause release of respective ions (mercury, zinc, copper, etc) should not be usedfor skin or mucous membrane disinfection as they have been related to incidents of swelling and edema. When chemical disinfectionof multi-dose vials is desired, either isopropyl alcohol (91%) or ethyl alcohol (70%) is recommended. Many commercially availablebrands of rubbing alcohol, as well as solutions of ethyl alcohol not of USP grade, contain denaturants which are injurious to rubberand 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