Included as part of the PRECAUTIONS section.
Do not use around the eyes.
Do not use ZINGO on body orifices, mucous membranes, or
on areas with a compromised skin barrier. Only use ZINGO on skin locations
where an adequate seal can be maintained.
Patients with severe hepatic disease or
pseudocholinesterase deficiency, because of their inability to metabolize local
anesthetics normally, are at a greater risk of developing toxic plasma
concentrations of lidocaine.
Patients with bleeding tendencies or platelet disorders
could have a higher risk of superficial dermal bleeding.
Cases of methemoglobinemia have been reported in
association with local anesthetic use. Although all patients are at risk for methemoglobinemia,
patients with glucose-6-phosphate dehydrogenase deficiency, congenital or
idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6
months of age, and concurrent exposure to oxidizing agents or their metabolites
are more susceptible to developing clinical manifestations of the condition. If
local anesthetics must be used in these patients, close monitoring for symptoms
and signs of methemoglobinemia is recommended.
Signs of methemoglobinemia may occur immediately or may
be delayed some hours after exposure, and are characterized by a cyanotic skin
discoloration and/or abnormal coloration of the blood. Methemoglobin levels may
continue to rise; therefore, immediate treatment is required to avert more
serious central nervous system and cardiovascular adverse effects, including seizures,
coma, arrhythmias, and death. Discontinue ZINGO and any other oxidizing agents.
Depending on the severity of the signs and symptoms, patients may respond to
supportive care, i.e., oxygen therapy, hydration. A more severe clinical presentation
may require treatment with methylene blue, exchange transfusion, or hyperbaric
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals have not been performed to
evaluate the carcinogenic potential of lidocaine.
No mutagenic potential of lidocaine was demonstrated in
the in vitro Ames Bacterial Reverse Mutation Assay, the in vitro chromosome
aberration assay using Chinese hamster ovary cells, and the in vivo mouse
Impairment Of Fertility
ZINGO was not formally evaluated for effects on
fertility. Significant systemic exposure to lidocaine is not expected under recommended
conditions of use of ZINGO, as lidocaine levels were below the limit of
detection in human studies. Lidocaine has been previously tested in animal
studies for effects on fertility, however. The following ratios are based on
the assumption that the applied dose is completely absorbed through the skin.
Lidocaine did not affect fertility in female rats when
given via continuous subcutaneous infusion via osmotic minipumps up to doses of
250 mg/kg/day [1500 mg/m² or 5000-fold higher than the SDA of 0.5 mg lidocaine
in a 60 kg individual (0.3 mg/m²)]. Although lidocaine treatment of male rats
increased the copulatory interval and led to a dose-related decreased homogenization
resistant sperm head count, daily sperm production, and spermatogenic
efficiency, the treatment did not affect overall fertility in male rats when
given subcutaneous doses up to 60 mg/kg (360 mg/m² or 1200-fold the SDA).
Use In Specific Populations
ZINGO was not formally evaluated for effects on
reproduction. Significant systemic exposure to lidocaine is not expected under recommended
conditions of use of ZINGO as lidocaine levels were below the limit of
detection in human studies. Lidocaine has been previously tested for
reproductive toxicity in animal studies, however. The following ratios are
based on the assumption that the applied dose is completely absorbed through
Pregnancy Category B
Lidocaine was not teratogenic in rats given subcutaneous
doses up to 60 mg/kg [360 mg/m² or 1200- fold the single dermal administration
(SDA) of 0.5 mg lidocaine in a 60 kg individual (0.3 mg/m²)] or in rabbits up
to 15 mg/kg (180 mg/m² or 600-fold the SDA).
There are, however, no adequate and well-controlled
studies in pregnant women. Because animal reproduction studies are not always
predictive of human response, ZINGO should be used during pregnancy only if
Lidocaine, containing 1:100,000 epinephrine, at a dose of
6 mg/kg (36 mg/m² or 120-fold the SDA) injected into the masseter muscle of the
jaw or into the gum of the lower jaw of Long-Evans hooded pregnant rats on
gestation day 11 led to developmental delays in neonatal behavior among
offspring. 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 the animal data is uncertain. No adequate and well–controlled studies have
been conducted in pregnant women. Because animal studies are not always
predictive of human response, ZINGO should be used during pregnancy only if the
potential benefit justifies risk to the fetus.
Labor And Delivery
Lidocaine is not contraindicated in labor and delivery.
In humans, the use of lidocaine for labor conduction analgesia has not been
associated with an increased incidence of adverse fetal effects either during
delivery or during the neonatal period. Should ZINGO be used concomitantly with
other products containing lidocaine, total doses contributed by all
formulations must be considered.
Lidocaine is excreted into human milk; therefore, caution
should be exercised when ZINGO is administered to a nursing mother. Because no
plasma concentrations of lidocaine are detected after topical administration of
ZINGO in recommended doses, the small amount of lidocaine that would be
ingested orally by a suckling infant is unlikely to cause adverse effects.
Safety and effectiveness in pediatric patients below the
age of 3 years have not been established.
Of the 693 patients evaluated in a Phase 3 randomized,
double blind, sham-placebo-controlled trial in adults, 17% were of 65 and over.
The safety and effectiveness of ZINGO in geriatric patients were similar to
that of ZINGO in adults under 65 years of age.