Xylocaine MPF (Lidocaine hydrochloride)

4% Xylocaine-MPF (lidocaine HCl) Sterile Solution, 5 mL ampule.

Store at 20° to 25°C (68° to 77°F).

Manufactured for: APP Pharmaceuticals, LLC, Schaumburg, IL 6017. Revised: February 2010

4% Xylocaine-MPF (lidocaine HCl) Sterile Solution is indicated for the production of topical anesthesia of the mucous membranes of the respiratory tract or the genito-urinary tract. It may be injected transtracheally to anesthetize the larynx and trachea, and it may be administered by retrobulbar injection to provide anesthesia for ophthalmic surgery.

When 4% Xylocaine-MPF Sterile Solution is used concomitantly with other products containing lidocaine, the total dose contributed by all formulations must be kept in mind.

The dosage varies and depends upon the area to be anesthetized, vascularity of the tissues, individual tolerance and the technique of anesthesia. The lowest dosage needed to provide effective anesthesia should be administered. Dosages should be reduced for children and for elderly and debilitated patients.

Although the incidence of adverse effects with 4% Xylocaine-MPF Sterile Solution is quite low, caution should be exercised, particularly when employing large volumes and concentrations of 4% Xylocaine-MPF Sterile Solution since the incidence of adverse effects is directly proportional to the total dose of local anesthetic agent administered. 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. 4% Xylocaine-MPF is not approved for this use (see WARNINGS).

The dosages below are for normal, healthy adults.

RETROBULBAR INJECTION: The suggested dose for a 70 kg person is 3-5 mL (120200 mg of lidocaine HCl), ie, 1.7-3 mg/kg or 0.9-1.5 mg/lb body weight. A portion of this is injected retrobulbarly and the rest may be used to block the facial nerve.

TRANSTRACHEAL INJECTION: For local anesthesia by the transtracheal route 2-3 mL should be injected through a large enough needle so that the injection can be made rapidly. By injecting during inspiration some of the drug will be carried into the bronchi and the resulting cough will distribute the rest of the drug over the vocal cords and the epiglottis.

Occasionally it may be necessary to spray the pharynx by oropharyngeal spray to achieve complete analgesia. For the combination of the injection and spray, it should rarely be necessary to utilize more than 5 mL (200 mg of lidocaine HCl), ie, 3 mg/kg or 1.5 mg/lb body weight.

TOPICAL APPLICATION: For laryngoscopy, bronchoscopy and endotracheal intubation, the pharynx may be sprayed with 1-5 mL (40-200 mg of lidocaine HCl), ie, 0.6-3 mg/kg or 0.3-1.5 mg/lb body weight.

Maximum Recommended Dosages

Normal Healthy Adults: The maximum recommended dose of 4% Xylocaine-MPF Sterile Solution should be such that the dose of lidocaine HCl is kept below 300 mg and in any case should not exceed 4.5 mg/kg (2 mg/lb) body weight.

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 of less than ten years who have a normal lean body mass and normal body development, the maximum dose may be determined by the application of one of the standard pediatric drug formulas (eg, Clark's rule). For example, in a child of five years weighing 50 lbs., the dose of lidocaine hydrochloride should not exceed 75-100 mg when calculated according to Clark's rule. In any case, the maximum dose of Xylocaine Solution with epinephrine should not exceed 7 mg/kg (3.2 mg/lb) of body weight. When used without epinephrine, the amount of Xylocaine Solution administered should be such that the dose of lidocaine is kept below 300 mg and in any case should not exceed 4.5 mg/kg (2 mg/lb) of body weight.

NOTE: 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.

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

WARNINGS

4% XYLOCAINE-MPF STERILE SOLUTION 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 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.

4% Xylocaine-MPF Sterile Solution should be used with extreme caution if there is sepsis or severely traumatized mucosa in the area of application, since under such conditions there is the potential for rapid systemic absorption.

PRECAUTIONS

General

The safety and effectiveness of lidocaine 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. 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 status. Lidocaine should also be used with caution in patients with severe shock or heart block.

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, 4% Xylocaine-MPF Sterile Solution should be used with caution in patients with hepatic disease.

Patients with severe hepatic disease, because of their inability to metabolize local anesthetic normally, are at greater risk of developing toxic plasma concentrations. 4% Xylocaine-MPF Sterile Solution 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 solutions 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 since corneal sensation usually precedes clinically acceptable external ocular muscle akinesia.

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 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 institution of treatment, including oxygen therapy, indicated supportive measures and dantrolene (consult dantrolene sodium intravenous package insert before using).

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 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.)

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.

Use in 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

Lidocaine is not contraindicated in labor and delivery. Should 4% Xylocaine-MPF Sterile Solution be used concomitantly with other products containing lidocaine, the total dose contributed by all formulations must be kept in mind.

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 children should be reduced, commensurate with age and body weight. See DOSAGE AND ADMINISTRATION.

SIDE EFFECTS

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 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.

There have been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbar administration.

DRUG INTERACTIONS

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.

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 myocardiac infarction may be compromised by the intramuscular injection of lidocaine.

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 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.

There have been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbar administration.

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 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 (eg, ephedrine).

If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest. 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 intravenous LD₅₀ of lidocaine HCl in female mice is 26 (21-31) mg/kg and the subcutaneous LD₅₀ is 264 (203-304) mg/kg.