← Back to Library
FDA LABEL
GENERIC: Menthol MFR: V2 Pharma LLC
Menthol 0.06 Mg/mg Topical Gel
Lidocaine Patch 5% & Menthol Roll-on Gel
Rx Only
Relivyx Plus is a kit containing:
Lidocaine 5% Patches (30 count)
Menthol Gel
DESCRIPTION
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 x 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:
Each adhesive patch contains 700 mg of lidocaine (50 mg per gram adhesive) in an aqueous base. It also contains the following inactive ingredients: purified water, glycerin, sorbitol, polyacrylic acid, sodium carboxymethylcellulose, sodium polyacrylate, propylene glycol, urea, kaolin, tartaric acid, gelatin, polyvinyl alcohol, dihydroxyaluminum aminoacetate, edetate disodium, methylparaben, and propylparaben.
CLINICAL PHARMACOLOGY
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 a lidocaine patch 5% is sufficient
to produce an analgesic effect, but less than the amount necessary
to produce a complete sensory block.
Absorption
The amount of lidocaine systemically absorbed from lidocaine patch 5% is directly related to both the duration of application and the surface area over which it is applied. In a pharmacokinetic study, three lidocaine patches were applied over an area of 420 cm 2 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 Blood samples were withdrawn for determination of lidocaine concentration during the application and for 12 hours after removal of patches.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 Lidocaine Patch 5%
|
Lidocaine Patch 5%
|
Application Site
|
Area
(cm 2)
|
Dose
Absorbed
(mg)
|
C max
(mcg/mL)
|
T max
(hr)
|
3 patches
(2100 mg) |
Back |
420 |
64 ± 32 |
0.13 ± 0.06 |
11 hr |
|
|
|
|
|
|
When lidocaine patch 5% 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 mcg/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 lidocaine patches simultaneously for 12 hours per day in healthy volunteers (n = 15).
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 lidocaine patch 5%, lidocaine is approximately 70% bound to plasma proteins, primarily alpha-1-acid glycoprotein. At much higher plasma concentrations (1 to 4 mcg/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 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
Single-dose treatment with lidocaine patch
5% 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. Lidocaine
patch 5% performed statistically better than vehicle patch in terms
of pain intensity from 4 to 12 hours.
Multiple-dose, two-week treatment with lidocaine
patch 5%, 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 lidocaine patch 5% prior to the study. The constant type of pain
was evaluated but not the pain induced by sensory stimuli (dysesthesia).
Statistically significant differences favoring lidocaine patch 5%
were observed in terms of time to exit from the trial (14 versus 3.8
days at p-value <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
Lidocaine patch 5% is indicated for relief
of pain associated with post-herpetic neuralgia. It should be applied
only to
intact skin.
CONTRAINDICATIONS
Lidocaine patch 5% 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
Risk of Methemoglobinemia
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 lidocaine patch 5% 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 oxygen.
Accidental Exposure in Children
Even a
used lidocaine patch 5% 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 lidocaine
patch 5%, although the risk with this formulation has not been evaluated.
It is important for patients
to store
and dispose
of lidocaine patch 5% out of the reach of children, pets,
and others
(see HANDLING AND DISPOSAL).
Excessive Dosing
Excessive dosing by applying lidocaine patch
5% 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 mcg/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 lidocaine patch 5%, the average peak blood concentration
is about 0.13 mcg/mL, but concentrations higher than 0.25 mcg/mL have
been observed in some individuals.
PREGNANCY
PRECAUTIONS
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,
lidocaine patch 5% 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. Lidocaine patch 5% is only recommended
for use on intact skin.
External Heat Sources
Placement of external heat sources, such as
heating pads or electric blankets, over lidocaine patch 5% is not
recommended as this has not been evaluated and may increase plasma
lidocaine levels.
Eye Exposure
The contact of lidocaine patch 5% 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.
Information
for Patients
Methemoglobinemia
Inform patients that use of local anesthetics
may cause methemoglobinemia, a serious condition that must be treated
promptly. Advise patients or caregivers to stop use and seek immediate
medical attention if they or someone in their care experience the
following signs or symptoms: pale, gray, or blue colored skin (cyanosis);
headache; rapid heart rate; shortness of breath; lightheadedness;
or fatigue.
DRUG INTERACTIONS
Antiarrhythmic Drugs
Lidocaine patch 5% 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 lidocaine patch 5% is used concomitantly
with other products containing local anesthetic agents, the amount
absorbed from all formulations must be considered.
Drugs That May Cause
Methemoglobinemia When Used with Lidocaine Patch 5%
Patients who
are administered local anesthetics are at increased risk of developing
methemoglobinemia when concurrently exposed to the following drugs,
which could include other local anesthetics:
Examples of Drugs Associated
with Methemoglobinemia:
| Class |
Examples |
| Nitrates/Nitrites |
nitric oxide, nitroglycerin,
nitroprusside, nitrous oxide |
| Local anesthetics |
articaine, benzocaine, bupivacaine,
lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine |
| Antineoplastic agents |
cyclophosphamide, flutamide,
hydroxyurea, ifosfamide, rasburicase |
| Antibiotics |
dapsone, nitrofurantoin, para-aminosalicylic
acid, sulfonamides |
| Antimalarials |
chloroquine, primaquine |
| Anticonvulsants |
Phenobarbital, phenytoin, sodium
valproate |
| Other drugs |
acetaminophen, metoclopramide,
quinine, sulfasalazine |
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 lidocaine patch
5%.
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 lidocaine patch 5% on fertility
has not been studied.
USE IN SPECIFIC POPULATIONS
Teratogenic Effects
Pregnancy
Category B.
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,
lidocaine patch 5% should be used during pregnancy only if clearly
needed.
Lidocaine patch 5% has not been studied in
labor and delivery. Lidocaine is not contraindicated in labor and
delivery. Should lidocaine patch 5% be used concomitantly with other
products containing lidocaine, total doses contributed by all formulations
must be considered.
Lidocaine patch 5% 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 lidocaine
patch 5% is administered to a nursing woman.
Safety and effectiveness in pediatric patients
have not been established.
ADVERSE REACTIONS
Application Site Reactions
During or immediately after treatment
with 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 lidocaine patch 5% 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 (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).
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
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 LD
50 of lidocaine HCl is 459 (346 to 773) mg/kg (as the salt) in non-fasted
female rats and 214 (159 to 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
Apply lidocaine patch 5% to intact skin to
cover the most painful area. Apply the prescribed number of patches
(maximum of 3), 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 lidocaine patch 5% is used concomitantly
with other products containing local anesthetic agents, the amount
absorbed from all formulations must be considered.
Lidocaine patch 5% may not stick if it gets
wet. Avoid contact with water, such as bathing, swimming, or showering.
HOW SUPPLIED/STORAGE AND HANDLING
Lidocaine patch 5% is available as the following:
Carton of 30 patches...........................................................................................NDC 82347-0505-5
(packaged in individual child-resistant envelopes)
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
For more information, call YARAL Pharma, Inc. at 1-866-218-9009.
Marketed by:
YARAL Pharma, Inc.
Pasippany, NJ 07054, USA
Manufactured by:
Altergon Italia Srl
Zona Industriale ASI, Morra de Sanctis
Avellino, 83040, Italy
Revised 12/2022
Lidocaine 5% Patch Packaging
Hands should be washed after the handling of lidocaine patch 5%, and eye contact with lidocaine patch 5% 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. Lidocaine patch 5% should be kept out of the reach of children.
Menthol Gel
Active Ingredient
Menthol 6%
When using this product avoid contacts with the eyes or mucous membranes. do not apply to wounds or damaged skin. do not apply to irritated skin. do not bandage. wash hands after use with cool water. do not use with heating pad or device.
Menthol 6%------------------------------------------------------------Topical Analgesic
WARNINGS
For external use only.
Stop use and ask doctor if condition worsens, or if symtoms persist for more than 7 days, or clean up and reoccur again within a few days.
keep out of reach of children if swallowed,get medical help or contact a poson Control Center Immediately.
Inactive Ingredient
Aloe Barbadensis Leaf Juice
Arctium Lappa Root Extract
Arnica Montana Flower Extract
Boswellia Carterii resin Extract
Calendula Officinalis Extract
Camellia Sinensis Leaf Extract
Camphor
Carbomer
FD & C Blue #1
FD & C Yellow #5
Glycerin
Isopropyl Alcohol
Isopropyl Myristate
llex Paraguariensis Leaf Extract
Melissa Officinalis Leaf Extract
Phenoxyethanol
Silicon dioxide
Tocopheryl Acetate
Triethanolamine
Water
DOSAGE AND ADMINISTRATION
Direction: Apply to affectered area not more that 3 to 4 times daily.
INDICATIONS AND USAGE
PRINCIPAL DISPLAY PANEL
The packaging for Relivyx Plus is shown below: