Included as part of the PRECAUTIONS section.
Even a used ZTLIDO topical system contains residual
lidocaine after use. The potential exists for a small child or a pet to suffer
serious adverse effects from chewing or ingesting a new or used ZTLIDO. It is
important for patients to store and dispose of ZTLIDO properly, and keep out of
the reach of children, pets, and others [see DOSAGE AND ADMINISTRATION].
Excessive Dosing/Overexposure To Lidocaine
Lidocaine toxicity can be expected at lidocaine blood
concentrations above 5 mcg/mL. The blood concentration of lidocaine is
determined by the rate and extent of lidocaine absorption and elimination.
Longer duration of application, application of more than the recommended number
of ZTLIDO, smaller patients, or impaired elimination may all contribute to
increasing the blood concentration of lidocaine.
If lidocaine overdose is suspected, check drug blood
concentration. Management of overdose includes close monitoring, supportive
care, and symptomatic treatment [see OVERDOSAGE].
Improper Application And Duration Of Use
Application of more than the recommended number of ZTLIDO
or applying ZTLIDO for longer than the recommended wearing time (12 hours of
every 24 hours) could result in increased absorption and high blood
concentrations of lidocaine, leading to adverse effects. Advise patients on
proper application and duration [see PATIENT INFORMATION].
Impaired elimination may contribute to increasing blood
concentrations of lidocaine. Patients with severe hepatic disease are at
greater risk of developing toxic blood concentrations of lidocaine because of
their inability to metabolize lidocaine normally.
Use On Non-Intact Skin
Application to broken or inflamed skin, although not
tested, may result in higher blood concentrations of lidocaine from increased
absorption. ZTLIDO is only recommended for use on intact skin. Advise patients not
to apply ZTLIDO to non-intact skin [see PATIENT INFORMATION].
External Heat Sources
External heat sources may increase drug exposure, leading
to overexposure to lidocaine. Advise patients not to apply external heat
sources to ZTLIDO during administration [see CLINICAL PHARMACOLOGY, PATIENT INFORMATION].
Application Site Reactions
During or immediately after treatment with ZTLIDO, the
skin at the site of application may develop blisters, bruising, burning
sensation, depigmentation, dermatitis, discoloration, edema, erythema,
exfoliation, irritation, papules, petechia, pruritus, vesicles, or may be the
locus of abnormal sensation. These reactions are generally mild and transient,
resolving spontaneously within a few minutes to hours. Inform patients of these
potential reactions and that severe skin irritation may occur with ZTLIDO if
applied for a longer period than instructed.
Patients allergic to para-aminobenzoic acid (PABA)
derivatives (procaine, tetracaine, benzocaine, etc.) have not shown
cross-sensitivity to lidocaine. However, be aware of the potential for
cross-sensitivity in patients allergic to PABA derivatives, especially if the
etiologic agent is uncertain. Manage hypersensitivity reactions by conventional
means. The detection of sensitivity by skin testing is of doubtful value.
The contact of ZTLIDO with eyes, although not studied,
should be avoided based on findings of severe eye irritation with the
application of similar products in animals. If eye contact occurs, immediately
wash out the eye with water or saline and protect the eye (such as, eye
glasses/eye wear) until sensation returns.
Patient Counseling Information
Advise the patient to read the FDA-approved Patient
Labeling and Instructions for Use.
Accidental Exposure And Disposal
Advise patients to store ZTLIDO out of the reach of
children, pets, and others. Advise patients to dispose of used ZTLIDO by
folding used ZTLIDO so that the adhesive side sticks to itself and safely
discarding used ZTLIDO or pieces of cut ZTLIDO where children, pets, and others
cannot come in contact with them.
- to avoid getting ZTLIDO wet (e.g., bathing, showering,
swimming) [see DOSAGE AND ADMINISTRATION].
- not to apply more than the prescribed number (up to 3
ZTLIDO) [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS].
- not to wear ZTLIDO longer than the recommended wearing
time (12 hours of every 24 hours) [see DOSAGE AND ADMINISTRATION, WARNINGS
- not to apply ZTLIDO to non-intact skin [see WARNINGS
- to reattach by pressing firmly on the edges, ZTLIDO that
are lifting at the edges. If a ZTLIDO topical system comes off completely and
will not stick to patient's skin, it should be thrown away and a new ZTLIDO
topical system should be applied for a total duration of 12 hours of used and
new topical system together [see DOSAGE AND ADMINISTRATION].
Advise patients to wash hands immediately after handling
ZTLIDO and to avoid contact with eyes. Instruct patients to, if eye contact
should occur, immediately wash out the eye with water or saline and protect the
eye until sensation returns [see DOSAGE AND ADMINISTRATION, WARNINGS
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals specifically designed to
evaluate the carcinogenic potential of lidocaine or ZTLIDO have not been
A metabolite, 2,6-xylidine, has been found to be
carcinogenic in rats. The clinical significance is not known.
Lidocaine HCl was not mutagenic in the in vitro bacterial
reverse mutagenicity assay (Ames test). Lidocaine HCl was not clastogenic in
the in vitro chromosome aberration assay with human lymphocytes or in the in
vivo mouse micronucleus test.
Impairment Of Fertility
In a published study, female Sprague-Dawley rats were
treated subcutaneously with lidocaine via osmotic pumps starting two weeks
prior to mating, and reproductive effects were assessed. Rats dosed up to the
high dose of 500 mg/kg/day (approximately 45 times the MRDD on a mg/m² basis)
showed no effects on copulatory rate, pregnancy rate, or the numbers of corpora
lutea or implantations.
Use In Specific Populations
The limited human data with lidocaine in pregnant woman
are not sufficient to inform drug-associated risk for major birth defects and
The use of lidocaine for labor neuraxial analgesia has
not been associated with an increased incidence of adverse fetal effects either
during delivery or during the neonatal period [see Data]. Should ZTLIDO
be used concomitantly with other products containing lidocaine, consider total
drug doses contributed by all formulations.
In a published animal reproduction study, pregnant rats
administered lidocaine by continuous subcutaneous infusion at a dose
approximately 45 times the maximum recommended daily dose (MRDD) of 108 mg in
ZTLIDO during the period of organogenesis resulted in lower fetal body weights.
In a published animal reproduction study, pregnant rats administered lidocaine,
containing 1:100,000 epinephrine, injected into the masseter muscle of the jaw
or into the gum of the lower jaw at 0.5 times the MRDD on Gestation Day 11
resulted in developmental delays in neonates [see Data].
The estimated background risk of major birth defects and
miscarriage for the indicated population is unknown. All pregnancies carry some
risk of birth defects, loss, or other adverse outcomes. In the U.S. general population,
the estimated background risk of major birth defects and miscarriage in
clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
In 22 parturient women given 1.5% lidocaine epidural
anesthesia, there were no effects on neonatal behavior, using the early
neonatal neurobehavioral scale (ENNS). Neuraxial analgesia also did not affect
fetal heart rate, beat-to-beat variability, or uterine activity.
Reproductive studies with lidocaine have been performed
in rats at doses up to 30 mg/kg (2.7 times the maximum recommended daily dose
[MRDD] of 108 mg from ZTLIDO on a mg/m² basis) subcutaneously and
have revealed no evidence of harm to the fetus due to lidocaine.
In a published study, lidocaine administered to pregnant
rats by continuous subcutaneous infusion during the period of organogenesis at
100, 250, and 500 mg/kg/day, did not produce any structural abnormalities, but
did result in lower fetal weights at 500 mg/kg/day dose (approximately 45 times
the MRDD on a mg/m² basis) in the absence of maternal toxicity.
In a published study, lidocaine containing 1:100,000
epinephrine at a dose of 6 mg/kg (approximately 0.5 times the MRDD on a mg/m² basis)
injected into the masseter muscle of the jaw or into the gum of the lower jaw
of pregnant Long-Evans hooded rats on Gestation Day 11 resulted in
developmental delays in the neonates. Developmental delays were observed for
negative geotaxis, static righting reflex, visual discrimination response,
sensitivity and response to thermal and electrical shock stimuli, and water
maze acquisition. The developmental delays of the neonatal animals were
transient, with responses becoming comparable to untreated animals later in
life. The clinical relevance of these animal data is uncertain.
Lidocaine is excreted into human milk. When lidocaine was
used as an epidural anesthetic for cesarean section in 27 women, a milk:plasma
ratio of 1.07 was observed using AUC values. Lactating women undergoing a
dental procedure had an 0.4 milk:plasma ratio. In another dental procedure
study, a single patient was administered 20 mg of lidocaine and the milk:plasma
ratio was reported as 1.1 at five to six hours after injection. These data and
the low concentrations of lidocaine in the plasma after topical administration
of ZTLIDO in recommended doses, suggest that a small amount of lidocaine would
be ingested orally by a suckling infant. However, caution should be exercised
when ZTLIDO is administered to a nursing mother, especially when administered
with other local anesthetics.
Safety and effectiveness in pediatric patients have not
Clinical studies of ZTLIDO did not include sufficient
numbers of subjects aged 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 done with caution,
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.