LIDODERM is indicated for relief of pain associated with post-herpetic neuralgia. It should be applied only to intact skin .
Dosage and administration
Apply LIDODERM to intact skin to cover the most painful area. Apply up to three patches, only once for up to 12 hours within a 24-hour period. Patches may be cut into smaller sizes with scissors prior to removal of the release liner. (See HANDLING AND DISPOSAL ) Clothing may be worn over the area of application. Smaller areas of treatment are recommended in a debilitated patient, or a patient with impaired elimina...
LIDODERM (lidocaine patch 5%) is comprised of an adhesive
material containing 5% lidocaine, which is applied to a non-woven polyester felt
backing and covered with a polyethylene terephthalate (PET) film release liner.
The release liner is removed prior to application to the skin. The size of the
patch is 10 cm × 14 cm.
Lidocaine is chemically designated as acetamide,
2-(diethylamino)-N-(2,6-dimethylphenyl), has an octanol: water partition ratio
of 43 at pH 7.4, and has the following structure:
image of chemical structure
Each adhesive patch contains 700 mg of lidocaine (50 mg per gram adhesive) in an
aqueous base. It also contains the following inactive ingredients:
dihydroxyaluminum aminoacetate, disodium edetate, gelatin, glycerin, kaolin,
methylparaben, polyacrylic acid, polyvinyl alcohol, propylene glycol,
propylparaben, sodium carboxymethylcellulose, sodium polyacrylate, D-sorbitol,
tartaric acid, and urea.
CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
Pharmacodynamics
Lidocaine is an amide-type local anesthetic agent and is
suggested to stabilize neuronal membranes by inhibiting the ionic fluxes
required for the initiation and conduction of impulses.
The penetration of lidocaine into intact skin after application of LIDODERM
is sufficient to produce an analgesic effect, but less than the amount necessary
to produce a complete sensory block.
Pharmacokinetics
Absorption: The amount of
lidocaine systemically absorbed from LIDODERM is directly related to both the
duration of application and the surface area over which it is applied. In a
pharmacokinetic study, three LIDODERM patches were applied over an area of 420
cm2 of intact skin on the back of normal volunteers for
12 hours. Blood samples were withdrawn for determination of lidocaine
concentration during the application and for 12 hours after removal of patches.
The results are summarized in Table 1.
Table 1 Absorption of lidocaine from LIDODERM
Normal volunteers (n = 15, 12-hour wearing
time)
LIDODERM Patch
Application Site
Area (cm2)
Dose Absorbed (mg)
Cmax (µg/mL)
Tmax (hr)
3 patches (2100 mg)
Back
420
64 ± 32
0.13 ± 0.06
11
hr
When LIDODERM is used according to the recommended dosing instructions, only
3 ± 2% of the dose applied is expected to be absorbed. At least 95% (665 mg) of
lidocaine will remain in a used patch. Mean peak blood concentration of
lidocaine is about 0.13 µg/mL (about 1/10 of the therapeutic concentration
required to treat cardiac arrhythmias). Repeated application of three patches
simultaneously for 12 hours (recommended maximum daily dose), once per day for
three days, indicated that the lidocaine concentration does not increase with
daily use. The mean plasma pharmacokinetic profile for the 15 healthy volunteers
is shown in Figure 1.
Figure 1 Mean lidocaine blood concentrations after
three consecutive daily applications of three LIDODERM patches simultaneously
for 12 hours per day in healthy volunteers (n = 15).
image of figure 1
Distribution: When lidocaine is
administered intravenously to healthy volunteers, the volume of distribution is
0.7 to 2.7 L/kg (mean 1.5 ± 0.6 SD, n = 15). At concentrations produced by
application of LIDODERM, lidocaine is approximately 70% bound to plasma
proteins, primarily alpha-1-acid glycoprotein. At much higher plasma
concentrations (1 to 4 µg/mL of free base), the plasma protein binding of
lidocaine is concentration dependent. Lidocaine crosses the placental and blood
brain barriers, presumably by passive diffusion.
Metabolism: It is not known if
lidocaine is metabolized in the skin. Lidocaine is metabolized rapidly by the
liver to a number of metabolites, including monoethylglycinexylidide (MEGX) and
glycinexylidide (GX), both of which have pharmacologic activity similar to, but
less potent than that of lidocaine. A minor metabolite, 2,6-xylidine, has
unknown pharmacologic activity but is carcinogenic in rats. The blood
concentration of this metabolite is negligible following application of LIDODERM
(lidocaine patch 5%). Following intravenous administration, MEGX and GX
concentrations in serum range from 11 to 36% and from 5 to 11% of lidocaine
concentrations, respectively.
Excretion: Lidocaine and its
metabolites are excreted by the kidneys. Less than 10% of lidocaine is excreted
unchanged. The half-life of lidocaine elimination from the plasma following IV
administration is 81 to 149 minutes (mean 107 ± 22 SD, n = 15). The systemic
clearance is 0.33 to 0.90 L/min (mean 0.64 ± 0.18 SD, n = 15).
CLINICAL STUDIES
CLINICAL STUDIES SECTION
Single-dose treatment with LIDODERM was compared to treatment
with vehicle patch (without lidocaine), and to no treatment (observation only)
in a double-blind, crossover clinical trial with 35 post-herpetic neuralgia
patients. Pain intensity and pain relief scores were evaluated periodically for
12 hours. LIDODERM performed statistically better than vehicle patch in terms of
pain intensity from 4 to 12 hours.
Multiple-dose, two-week treatment with LIDODERM was compared to vehicle patch
(without lidocaine) in a double-blind, crossover clinical trial of
withdrawal-type design conducted in 32 patients, who were considered as
responders to the open-label use of LIDODERM prior to the study. The constant
type of pain was evaluated but not the pain induced by sensory stimuli
(dysesthesia). Statistically significant differences favoring LIDODERM were
observed in terms of time to exit from the trial (14 versus 3.8 days at p-value
less than 0.001), daily average pain relief, and patient's preference of treatment.
About half of the patients also took oral medication commonly used in the
treatment of post-herpetic neuralgia. The extent of use of concomitant
medication was similar in the two treatment groups.
INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
LIDODERM is indicated for relief of pain associated with post-herpetic
neuralgia. It should be applied only to intact skin.
CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
LIDODERM is contraindicated in patients with a known history of sensitivity to
local anesthetics of the amide type, or to any other component of the product.
WARNINGS
WARNINGS SECTION
Accidental Exposure in Children
Even a used LIDODERM patch contains a
large amount of lidocaine (at least 665 mg). The potential exists for a small
child or a pet to suffer serious adverse effects from chewing or ingesting a new
or used LIDODERM patch, although the risk with this formulation has not been
evaluated. It is important for patients to store and dispose of LIDODERM out of the reach of children,
pets and others. (See HANDLING AND
DISPOSAL)
Excessive Dosing
Excessive dosing by applying LIDODERM to larger areas or for
longer than the recommended wearing time could result in increased absorption of
lidocaine and high blood concentrations, leading to serious adverse effects (see
ADVERSE REACTIONS, Systemic Reactions).
Lidocaine toxicity could be expected at lidocaine blood concentrations above 5
µg/mL. The blood concentration of lidocaine is determined by the rate of
systemic absorption and elimination. Longer duration of application, application
of more than the recommended number of patches, smaller patients, or impaired
elimination may all contribute to increasing the blood concentration of
lidocaine. With recommended dosing of LIDODERM, the average peak blood
concentration is about 0.13 µg/mL, but concentrations higher than 0.25 µg/mL
have been observed in some individuals.
PRECAUTIONS
PRECAUTIONS SECTION
General
Hepatic Disease: Patients with
severe hepatic disease are at greater risk of developing toxic blood
concentrations of lidocaine, because of their inability to metabolize lidocaine
normally.
Allergic Reactions: Patients
allergic to para-aminobenzoic acid derivatives (procaine, tetracaine,
benzocaine, etc.) have not shown cross sensitivity to lidocaine. However,
LIDODERM should be used with caution in patients with a history of drug
sensitivities, especially if the etiologic agent is uncertain.
Non-intact Skin: Application to
broken or inflamed skin, although not tested, may result in higher blood
concentrations of lidocaine from increased absorption. LIDODERM is only
recommended for use on intact skin.
External Heat Sources: Placement
of external heat sources, such as heating pads or electric blankets, over
LIDODERM patches is not recommended as this has not been evaluated and may
increase plasma lidocaine levels.
Eye Exposure: The contact of
LIDODERM with eyes, although not studied, should be avoided based on the
findings of severe eye irritation with the use of similar products in animals.
If eye contact occurs, immediately wash out the eye with water or saline and
protect the eye until sensation returns.
Drug Interactions
Antiarrhythmic Drugs: LIDODERM
should be used with caution in patients receiving Class I antiarrhythmic drugs
(such as tocainide and mexiletine) since the toxic effects are additive and
potentially synergistic.
Local Anesthetics: When LIDODERM
is used concomitantly with other products containing local anesthetic agents,
the amount absorbed from all formulations must be considered.
Carcinogenesis, Mutagenesis, Impairment of
Fertility
Carcinogenesis: A minor
metabolite, 2,6-xylidine, has been found to be carcinogenic in rats. The blood
concentration of this metabolite is negligible following application of
LIDODERM.
Mutagenesis: Lidocaine HCl is not
mutagenic in Salmonella/mammalian microsome test nor clastogenic in chromosome
aberration assay with human lymphocytes and mouse micronucleus test.
Impairment of Fertility: The
effect of LIDODERM on fertility has not been studied.
Pregnancy
Teratogenic Effects: Pregnancy Category
B. LIDODERM (lidocaine patch 5%) has not been studied in pregnancy.
Reproduction studies with lidocaine have been performed in rats at doses up to
30 mg/kg subcutaneously and have revealed no evidence of harm to the fetus due
to lidocaine. There are, however, no adequate and well-controlled studies in
pregnant women. Because animal reproduction studies are not always predictive of
human response, LIDODERM should be used during pregnancy only if clearly
needed.
Labor and Delivery
LIDODERM has not been studied in labor and delivery. Lidocaine is
not contraindicated in labor and delivery. Should LIDODERM be used concomitantly
with other products containing lidocaine, total doses contributed by all
formulations must be considered.
Nursing Mothers
LIDODERM has not been studied in nursing mothers. Lidocaine is
excreted in human milk, and the milk:plasma ratio of lidocaine is 0.4. Caution
should be exercised when LIDODERM is administered to a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients have not been
established.
ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
Application Site Reactions
During or immediately after treatment with LIDODERM (lidocaine
patch 5%), 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.
Allergic Reactions
Allergic and anaphylactoid reactions associated with lidocaine,
although rare, can occur. They are characterized by angioedema, bronchospasm,
dermatitis, dyspnea, hypersensitivity, laryngospasm, pruritus, shock, and
urticaria. If they occur, they should be managed by conventional means. The
detection of sensitivity by skin testing is of doubtful value.
Other Adverse Events
Due to the nature and limitation of spontaneous reports in
postmarketing surveillance, causality has not been established for additional
reported adverse events including:
Asthenia, confusion, disorientation, dizziness, headache, hyperesthesia,
hypoesthesia, lightheadedness, metallic taste, nausea, nervousness, pain
exacerbated, paresthesia, somnolence, taste alteration, vomiting, visual
disturbances such as blurred vision, flushing, tinnitus, and tremor.
Systemic (Dose-Related) Reactions
Systemic adverse reactions following appropriate use of LIDODERM
are unlikely, due to the small dose absorbed (see CLINICAL PHARMACOLOGY, Pharmacokinetics). Systemic
adverse effects of lidocaine are similar in nature to those observed with other
amide local anesthetic agents, including CNS excitation and/or depression (light
headedness, 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). Excitatory CNS reactions may be brief or not occur at
all, in which case the first manifestation may be drowsiness merging into
unconsciousness. Cardiovascular manifestations may include bradycardia,
hypotension and cardiovascular collapse leading to arrest.
OVERDOSAGE
OVERDOSAGE SECTION
Lidocaine overdose from cutaneous absorption is rare, but could
occur. If there is any suspicion of lidocaine overdose (see ADVERSE REACTIONS, Systemic Reactions), drug
blood concentration should be checked. The management of overdose includes close
monitoring, supportive care, and symptomatic treatment. Dialysis is of
negligible value in the treatment of acute overdose with lidocaine.
In the absence of massive topical overdose or oral ingestion, evaluation of
symptoms of toxicity should include consideration of other etiologies for the
clinical effects, or overdosage from other sources of lidocaine or other local
anesthetics.
The oral LD50 of lidocaine HCl is 459 (346-773) mg/kg
(as the salt) in non-fasted female rats and 214 (159-324) mg/kg (as the salt) in
fasted female rats, which are equivalent to roughly 4000 mg and 2000 mg,
respectively, in a 60 to 70 kg man based on the equivalent surface area dosage
conversion factors between species.
DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
Apply LIDODERM to intact skin to cover the most painful area.
Apply up to three patches, only once for up to 12 hours within a 24-hour period.
Patches may be cut into smaller sizes with scissors prior to removal of the
release liner. (See HANDLING AND DISPOSAL)
Clothing may be worn over the area of application. Smaller areas of treatment
are recommended in a debilitated patient, or a patient with impaired
elimination.
If irritation or a burning sensation occurs during application, remove the
patch(es) and do not reapply until the irritation subsides.
When LIDODERM is used concomitantly with other products containing local
anesthetic agents, the amount absorbed from all formulations must be considered.
HANDLING AND DISPOSAL
SPL UNCLASSIFIED SECTION
Hands should be washed after the handling of LIDODERM, and eye contact with
LIDODERM should be avoided. Do not store patch outside the sealed envelope.
Apply immediately after removal from the protective envelope. Fold used patches
so that the adhesive side sticks to itself and safely discard used patches or
pieces of cut patches where children and pets cannot get to them. LIDODERM
should be kept out of the reach of children.
HOW SUPPLIED
HOW SUPPLIED SECTION
LIDODERM (lidocaine patch 5%) is available as the following:
Carton of 30 patches, packaged into individual child-resistant envelopes.
NDC 54868-4146-0
3 Cartons of 30 patches, packaged into individual child-resistant envelopes. NDC 54868-4146-1
Store at 25°C (77°F); excursions permitted to 15°-30°C
(59°-86°F). [See USP Controlled Room Temperature].
Manufactured for: Endo Pharmaceuticals
Inc. Chadds Ford, Pennsylvania 19317
LIDODERM® is a Registered Trademark of Hind Health
Care, Inc.
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