Additions and/or
revisions underlined:
The
following adverse reactions associated with the use of Xylocaine Jelly were
identified in
clinical
studies or postmarketing reports. Because some of these reactions were reported
voluntarily
from a population of uncertain size, it is not always possible to reliably
estimate
their
frequency or establish a causal relationship to drug exposure.
Adverse
experiences following the administration of lidocaine are similar in nature to
those
observed
with other amide local anesthetic agents. A major cause of adverse reactions
to this
group
of drugs is excessive plasma levels, which may be due to overdosage or slow
metabolic
degradation.
The
most commonly encountered acute adverse reactions that demand immediate counter
measures
were related to the CNS and the cardiovascular system. 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.
Nervous
System Disorders
Adverse
reactions were characterized
by excitation and/or depression of the central nervous
system
and included
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.
Cardiac Disorders
High doses have led to high plasma levels and
related depression of the myocardium,
decreased cardiac output, heartblock, hypotension, bradycardia, and cardiovascular collapse,
which may lead to cardiac arrest.
Immune System Disorders
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.
8.1 Pregnancy
PLLR conversion:
Risk
Summary
Available
published data and decades of clinical use with Xylocaine in pregnant women
have
not
identified any drug-associated risk for major birth defects, miscarriage, or
other adverse
maternal
or fetal outcomes. Local anesthetics may cause varying degrees of toxicity to
the
mother
and fetus and adverse reactions include alterations of the central nervous
system,
peripheral
vascular tone and cardiac function (see Clinical Considerations).
There
was no evidence of teratogenicity when lidocaine was administered to pregnant
rats
and
rabbits subcutaneously at 0.8 and 0.16 times, respectively, the maximum
recommended
human
dose (MRHD) of 600 mg during the period of organogenesis. In a published animal
reproduction
study, pregnant rats administered lidocaine by continuous subcutaneous infusion
at
8 times the MRHD during the period of organogenesis resulted in lower fetal
body weights
[see
Data].
The
background risk of major birth defects and miscarriage for the indicated
population is
unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse
outcomes.
In the U.S. general population, the estimated background risks of major birth
defects
and miscarriage in clinically recognized pregnancies is 2-4% and 15- 20%,
respectively.
Clinical
Considerations
Maternal
adverse reactions
During
treatment of systemic toxicity, which may appear as maternal hypotension or
fetal
bradycardia,
the parturient should be maintained in the left lateral decubitus position if
possible
or manual displacement of the uterus off the great vessels be accomplished.
Elevating
the patient’s legs will also help prevent decreases in blood pressure. The
fetal heart
rate
also should be monitored continuously, and electronic fetal monitoring is
highly advisable.
Labor
or delivery
Local
anesthetics rapidly cross the placenta and can cause varying degrees of
maternal, fetal
and
neonatal toxicity [see Clinical Pharmacology (12.3)]. The incidence and
degree of toxicity
depend
upon the procedure performed, the type and amount of drug used, and the
technique
of
drug administration. Adverse reactions in the parturient, fetus and neonate
involve
alterations
of the central nervous system, peripheral vascular tone, and cardiac function.
However,
dosage recommendations for local anesthesia are much lower than dosage
recommendations
for other major blocks.
Data
Animal
Data
Reproduction
studies for lidocaine have been performed in both rats and rabbits. There was
no
evidence
of harm to the fetus when pregnant rats were given subcutaneous doses of up to
50
mg/kg
lidocaine (approximately 0.8 times the MRHD of 600 mg based on body surface
area
(BSA)
comparison) during the period of organogenesis. In addition, there was no
evidence of
harm to the fetus when pregnant rabbits were given a subcutaneous
dose of 5 mg/kg
(approximately
0.16 times the MRHD based on BSA comparison) during the period of
organogenesis.
Treatment of pregnant rabbits with 25 mg/kg (approximately 0.8 times the
MRHD
based on BSA comparison) 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 (approximately 0.03,
0.16,
and
0.8 times, respectively, the MRHD based on BSA comparison) from Day 15 of
pregnancy
and
up to 20 days postpartum. No signs of adverse effects were seen either in dams
or in the
pups
up to and including the dose of 10 mg/kg; however, the number of surviving pups
was
reduced
at 50 mg/kg, 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.
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 (approximately 0.8 and 1.6 times,
respectively, the
MRHD
based on BSA comparison). 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 periods.
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
8 times the MRHD based on BSA comparison) in the absence of maternal
toxicity.
8.2 Lactation
PLLR conversion:
Risk
Summary
Published
data report the presence of lidocaine and its metabolites in human milk in low
amounts,
along with poor oral bioavailability. There are no data on the effect of
lidocaine on
the
breastfed infant or the effect on milk production.
The
developmental and health benefits of breastfeeding should be considered along
with the
mother’s
clinical need for Xylocaine Jelly and any potential adverse effects on the
breastfed
child
from Xylocaine Jelly or from the underlying maternal condition.
8.5 Geriatric Use
Additions and/or
revisions underlined:
Elderly patients should be given reduced doses
commensurate with their age and physical
condition.
8.6 Hepatic
Impairment
Additions and/or
revisions underlined:
Amide-type local anesthetics such as lidocaine are
metabolized by the liver. Patients with
severe hepatic impairment, because of their
inability to metabolize local anesthetics normally,
are at greater risk of developing toxic plasma
concentrations and potentially local anesthetic
systemic toxicity. Therefore, consider reduced
dosing and increased monitoring for local
anesthetic systemic toxicity in patients with
hepatic impairment treated with Xylocaine jelly
especially with repeat doses [see Warnings and
Precautions (5.6)]
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