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721838-
XYLOCAINE 2% JELLY
(lidocaine hydrochloride)
DESCRIPTION
Xylocaine (lidocaine HCl) 2% Jelly is a sterile aqueous product that contains a local anesthetic
agent and is administered topically. (See INDICATIONS for specific uses.)
Xylocaine 2% Jelly contains lidocaine HCl which is chemically designated as acetamide, 2-
(diethyl-amino)-N-(2,6-dimethylphenyl)-, monohydrochloride and has the following structural
formula:
Xylocaine 2% Jelly also contains hypromellose, and the resulting mixture maximizes contact
with mucosa and provides lubrication for instrumentation. The unused portion should be
discarded after initial use.
Composition of Xylocaine 2% Jelly 30 mL and 5 mL tubes: Each mL contains 20 mg of
lidocaine HCl. The formulation also contains methylparaben, propylparaben, hypromellose, and
sodium hydroxide and/or hydrochloric acid to adjust pH to 6.0–7.0.
CLINICAL PHARMACOLOGY
Mechanism of Action
Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the
initiation and conduction of impulses, thereby effecting local anesthetic action.
Onset of Action
The onset of action is 3–5 minutes. It is ineffective when applied to intact skin.
Hemodynamics
Excessive blood levels may cause changes in cardiac output, total peripheral resistance, and
mean arterial pressure. These changes may be attributable to a direct depressant effect of the
local anesthetic agent on various components of the cardiovascular system.
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Pharmacokinetics and Metabolism
Lidocaine may be absorbed following topical administration to mucous membranes, its rate and
extent of absorption depending upon concentration and total dose administered, the specific site
of application, and duration of exposure. In general, the rate of absorption of local anesthetic
agents following topical application occurs most rapidly after intratracheal administration.
Lidocaine is also well-absorbed from the gastrointestinal tract, but little intact drug may appear
in the circulation because of biotransformation in the liver.
Lidocaine is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted
by the kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation,
cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of
biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. The
pharmacological/toxicological actions of these metabolites are similar to, but less potent than,
those of lidocaine. Approximately 90% of lidocaine administered is excreted in the form of
various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is
a conjugate of 4-hydroxy-2,6-dimethylaniline.
The plasma binding of lidocaine is dependent on drug concentration, and the fraction bound
decreases with increasing concentration. At concentrations of 1 to 4 µg of free base per mL, 60
to 80 percent of lidocaine is protein bound. Binding is also dependent on the plasma
concentration of the alpha-l-acid glycoprotein.
Lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion.
Studies of lidocaine metabolism following intravenous bolus injections have shown that the
elimination half-life of this agent is typically 1.5 to 2.0 hours. Because of the rapid rate at which
lidocaine is metabolized, any condition that affects liver function may alter lidocaine kinetics.
The half-life may be prolonged twofold or more in patients with liver dysfunction. Renal
dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites.
Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of
lidocaine required to produce overt systemic effects. Objective adverse manifestations become
increasingly apparent with increasing venous plasma levels above 6.0 µg free base per mL. In the
rhesus monkey arterial blood levels of 18-21 µg/mL have been shown to be threshold for
convulsive activity.
INDICATIONS AND USAGE
Xylocaine (lidocaine HCl) 2% Jelly is indicated for prevention and control of pain in procedures
involving the male and female urethra, for topical treatment of painful urethritis, and as an
anesthetic lubricant for endotracheal intubation (oral and nasal).
CONTRAINDICATIONS
Lidocaine is contraindicated in patients with a known history of hypersensitivity to local
anesthetics of the amide type or to other components of Xylocaine 2% Jelly.
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WARNINGS
EXCESSIVE DOSAGE, OR SHORT INTERVALS BETWEEN DOSES, CAN RESULT IN
HIGH PLASMA LEVELS AND SERIOUS ADVERSE EFFECTS. PATIENTS SHOULD BE
INSTRUCTED TO STRICTLY ADHERE TO THE RECOMMENDED DOSAGE AND
ADMINISTRATION GUIDELINES AS SET FORTH IN THIS PACKAGE INSERT.
THE MANAGEMENT OF SERIOUS ADVERSE REACTIONS MAY REQUIRE THE USE
OF RESUSCITATIVE EQUIPMENT, OXYGEN, AND OTHER RESUSCITATIVE DRUGS.
Xylocaine 2% Jelly should be used with extreme caution in the presence of sepsis or severely
traumatized mucosa in the area of application, since under such conditions there is the potential
for rapid systemic absorption.
When used for endotracheal tube lubrication care should be taken to avoid introducing the
product into the lumen of the tube. Do not use the jelly to lubricate the endotracheal stylettes. If
allowed into the inner lumen, the jelly may dry on the inner surface leaving a residue which
tends to clump with flexion, narrowing the lumen. There have been rare reports in which this
residue has caused the lumen to occlude. (See also ADVERSE REACTIONS and DOSAGE
AND ADMINISTRATION.)
PRECAUTIONS
General:
The safety and effectiveness of lidocaine depend on proper dosage, correct technique, adequate
precautions, and readiness for emergencies. (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.
Xylocaine 2% Jelly should be used with caution in patients with known drug sensitivities.
Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.)
have not shown cross sensitivity to lidocaine.
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).
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Information for Patients:
When topical anesthetics are used in the mouth, the patient should be aware that the production
of topical anesthesia may impair swallowing and thus enhance the danger of aspiration. For this
reason, food should not be ingested for 60 minutes following use of local anesthetic preparations
in the mouth or throat area. This is particularly important in children because of their frequency
of eating.
Numbness of the tongue or buccal mucosa may enhance the danger of unintentional biting
trauma. Food and chewing gum should not be taken while the mouth or throat area is
anesthetized.
Carcinogenesis – Long-term studies in animals have not been performed to evaluate the
carcinogenic potential of lidocaine.
Mutagenesis – The mutagenic potential of lidocaine has been tested in the Ames Salmonella
reverse mutation assay, an in vitro chromosome aberrations assay in human lymphocytes and in
an in vivo mouse micronucleus assay. There was no indication of any mutagenic effect in these
studies.
Impairment of Fertility: The effect of lidocaine on fertility was examined in the rat model.
Administration of 30 mg/kg, s.c. (180 mg/m2 ) to the mating pair did not produce alterations in
fertility or general reproductive performance of rats. There are no studies that examine the effect
of lidocaine on sperm parameters. There was no evidence of altered fertility.
Use in Pregnancy:
Teratogenic Effects: Pregnancy Category B
Reproduction studies for lidocaine have been performed in both rats and rabbits. There was no
evidence of harm to the fetus at subcutaneous doses of up to 50 mg/kg lidocaine (300 mg/m2 on a
body surface area basis) in the rat model. In the rabbit model, there was no evidence of harm to
the fetus at a dose of 5 mg/kg, s.c. (60 mg/m2 on a body surface area basis). Treatment of rabbits
with 25 mg/kg (300 mg/m2) produced evidence of maternal toxicity and evidence of delayed
fetal development, including a non-significant decrease in fetal weight (7%) and an increase in
minor skeletal anomalies (skull and sternebral defect, reduced ossification of the phalanges).
The effect of lidocaine on post-natal development was examined in rats by treating pregnant
female rats daily subcutaneously at doses of 2, 10, and 50 mg/kg (12, 60, and 300 mg/m2) from
day 15 of pregnancy and up to 20 days post partum. No signs of adverse effects were seen either
in dams or in the pups up to and including the dose of 10 mg/kg (60 mg/m2); however, the
number of surviving pups was reduced at 50 mg/kg (300 mg/m2), both at birth and the duration
of lactation period, the effect most likely being secondary to maternal toxicity. No other effects
on litter size, litter weight, abnormalities in the pups and physical developments of the pups were
seen in this study.
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A second study examined the effects of lidocaine on post-natal development in the rat that
included assessment of the pups from weaning to sexual maturity. Rats were treated for 8
months with 10 or 30 mg/kg, s.c. lidocaine (60 mg/m2 and 180mg/m2 on a body surface area
basis, respectively). This time period encompassed 3 mating periods. There was no evidence of
altered post-natal development in any offspring; however, both doses of lidocaine significantly
reduced the average number of pups per litter surviving until weaning of offspring from the first
2 mating period.
There are, however, no adequate and well-controlled studies in pregnant women. Because animal
reproduction studies are not always predictive of human response, this drug should be used
during pregnancy only if clearly needed.
Labor and Delivery:
Lidocaine is not contraindicated in labor and delivery. Should Xylocaine 2% Jelly be used
concomitantly with other products containing lidocaine, the total dose contributed by all
formulations must be kept in mind.
Nursing Mothers:
Lidocaine is secreted in human milk. The clinical significance of this observation is unknown.
Caution should be exercised when lidocaine is administered to a nursing woman.
Pediatric Use:
Although, the safety and effectiveness of Xylocaine 2% Jelly in pediatric patients have not been
established, a study of 19 premature neonates (gestational age <33 weeks) found no correlation
between the plasma concentration of lidocaine or monoethylglycinexylidide and infant body
weight when moderate amounts of lidocaine (i.e. 0.3 mL/kg of lidocaine gel 20 mg/ml) were
used for lubricating both intranasal and endotracheal tubes. No neonate had plasma levels of
lidocaine above 750 mcg/L. Dosages in children should be reduced, commensurate with age,
body weight, and physical condition. (See DOSAGE AND ADMINISTRATION.)
ADVERSE REACTIONS
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 or rapid
absorption, 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:
There have been rare reports of endotracheal tube occlusion associated with the presence of dried
jelly residue in the inner lumen of the tube. (See also WARNINGS and DOSAGE AND
ADMINISTRATION.)
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Central Nervous System:
CNS manifestations are excitatory and/or depressant and may be characterized by
lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus,
blurred or double vision, vomiting, sensations of heat, cold or numbness, twitching, tremors,
convulsions, unconsciousness, respiratory depression, and arrest. The excitatory manifestations
may be very brief or may not occur at all, in which case the first manifestation of toxicity may be
drowsiness merging into unconsciousness and respiratory arrest.
Drowsiness following the administration of lidocaine is usually an early sign of a high blood
level of the drug and may occur as a consequence of rapid absorption.
Cardiovascular System:
Cardiovascular manifestations are usually depressant and are characterized by bradycardia,
hypotension, and cardiovascular collapse, which may lead to cardiac arrest.
Allergic:
Allergic reactions are characterized by cutaneous lesions, urticaria, edema, or anaphylactoid
reactions. Allergic reactions may occur as a result of sensitivity either to the local anesthetic
agent or to other components in the formulation. 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.
OVERDOSAGE
Acute emergencies from local anesthetics are generally related to high plasma levels encountered
during therapeutic use of local anesthetics. (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 administration. 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
(e.g., ephedrine).
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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.
Dialysis is of negligible value in the treatment of acute overdosage with lidocaine.
The oral LD50 of lidocaine HCl in non-fasted female rats is 459 (346-773) mg/kg (as the salt) and
214 (159-324) mg/kg (as the salt) in fasted female rats.
DOSAGE AND ADMINISTRATION
When Xylocaine 2% Jelly 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 Xylocaine 2%
Jelly is quite low, caution should be exercised, particularly when employing large amounts, since
the incidence of adverse effects is directly proportional to the total dose of local anesthetic agent
administered.
For Surface Anesthesia of the Male Adult Urethra:
When using Xylocaine 2% Jelly 30 mL tubes, sterilize the plastic cone for 5 minutes in boiling
water, cool, and attach to the tube. The cone may be gas sterilized or cold sterilized, as preferred.
Slowly instill approximately 15 mL (300 mg of lidocaine HCl) into the urethra or until the
patient has a feeling of tension. A penile clamp is then applied for several minutes at the corona.
An additional dose of not more than 15 mL (300 mg) can be instilled for adequate anesthesia.
Prior to sounding or cystoscopy, a penile clamp should be applied for 5 to 10 minutes to obtain
adequate anesthesia. A total dose of 30 mL (600 mg) is usually required to fill and dilate the
male urethra.
Prior to catheterization, smaller volumes of 5-10 mL (100-200 mg) are usually adequate for
lubrication.
For Surface Anesthesia of the Female Adult Urethra:
When using Xylocaine 2% Jelly 30 mL tubes, sterilize the plastic cone for 5 minutes in boiling
water, cool, and attach to the tube. The cone may be gas sterilized or cold sterilized, as preferred.
Slowly instill 3–5 mL (60–100 mg of lidocaine HCl) of the jelly into the urethra. If desired, some
jelly may be deposited on a cotton swab and introduced into the urethra. In order to obtain
adequate anesthesia, several minutes should be allowed prior to performing urological
procedures.
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Lubrication for Endotracheal Intubation:
Apply a moderate amount of jelly to the external surface of the endotracheal tube shortly before
use. Care should be taken to avoid introducing the product into the lumen of the tube. Do not use
the jelly to lubricate endotracheal stylettes. See WARNINGS and ADVERSE REACTIONS
concerning rare reports of inner lumen occlusion. It is also recommended that use of
endotracheal tubes with dried jelly on the external surface be avoided for lack of lubricating
effect.
MAXIMUM DOSAGE
No more than 600 mg of lidocaine HCl should be given in any 12 hour period.
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 less than ten years who have a normal lean body mass
and a normal lean body development, the maximum dose may be determined by the application
of one of the standard pediatric drug formulas (e.g., Clark’s rule). For example, in a child of five
years
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