{"active_ingredient":["Lidocaine HCL 4.00% Menthol 1.00%"],"dosage_and_administration":["clean and dry affected area remove patch from backing and apply to affected area use only one patch at a time, and maximum of four patches/day leave patch on affected area for up to 8 hours do not use patches for longer than five consecutive days children under 12 should consult physician prior to use"],"effective_time":"20150708","id":"64ed7031-1c18-4c9a-be78-e002c09b721d","inactive_ingredient":["aloe barbadensis leaf, water, arnica montan extract, boswella serrata extract, camelia sinensis leaf extract, carbomer, ethylhexylglycerine, glycerine, isopropyl myristate, PEG 8, phenoxyethanol, polysorbate 80, sodium lauryl sulfate, triethanolamine, fd&c blue #1, fd&c yellow #5"],"indications_and_usage":["Temporary relief of pain associated with minor cuts, scrapes and minor skin irritations"],"keep_out_of_reach_of_children":["Keep out of reach of children"],"openfda":{},"package_label_principal_display_panel":["box image"],"patient_medication_information":["DESCRIPTION: Lidodextrapine (Lidocaine HCl 4%/Menthol 1%) is comprised of an adhesive material containing Lidocaine HCl 4% and Menthol 1% which is applied to a woven polyester backing and covered with a PET film release line. The release liner is removed prior to application to the skin. The size of the patch is 12.5 cm x 8.5cm. Lidocaine HCl is chemically designated as 2-(diethylamino)-N-(2,6-dimethylphenyl), has an octanol: water partition ration of 43 at pH 7.4, and has the following structure: Menthol is chemically designated as 2-Isopropyl-5-methylcyclohexanol. It is colorless, hexagonal crystals, usually needle-like; fused masses or crystalline powder with a pleasant, peppermint-like odor. It has a melting point between 31°C to 36° C. Each adhesive patch contains 68 mg of Lidocaine HCl and 17mg of Menthol. It also contains the following inactive ingredients: Aloe Barbadensis Leaf (Aloe Vera Juice) Gel, Aqua (Deionized Water), Arnica Montana Extract, Boswella Serrata Extract, Camellia Sinensis Leaf (Green Tea) Extract, Carbomer, Ethylhexylglycerin, Glycerin, Isopropyl Myristate, PEG-8, Phenoxyethanol, Polysorbate-80, Sodium Lauryl Sulfate, Triethanolamine, FD&C Blue #1, FD&C Yellow #5. CLINICAL PHARMACOLOGY: Pharmacodynamics Menthol works by targeting th k-opiod receptior on the TRPM8 neuron. THe TRPM8 neuron is normally activated at temperatures between (8° - 28° C). Menthol causes the neuron to fire at temperatures above normal activation which triggers the characteristic cooling sensation. Also because of menthol's specific targeting of the k-opioid receptor, it is endowed with analgesic properties.. Lidocaine HCl 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 HCl into intact skin after application of patch 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 HCl and menthol systemically absorbed is directly related to both the duration of application and the surface area over which it is applied. In a pharmacokinetic study, three Lidocaine HCl 5% 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 a determination of Lidocaine HCl concentration during the application and for 12 hours after removal of patches. the results are summarized in table 1. Table 1 Absorption of Lidocaine HCl Normal volunteers (n=15, 12-hour wearing time) 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 Lidocaine HCl 5% patch 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 HCl will remain in a used patch. Mean peak blood concentration of Lidocaine HCl is about 0.13 µg/mL (about 1/10 of the therapeutic concentration required to treat cardiac arrhythmias). Repeated application of three days, indicated that the Lidocaine HCl concentration does not increase with daily use. In a pharmacokinetic study, a single-dose, three-treatment crossover study to evaluate the percutaneous absorption of menthol from patch (study drug) and two reference menthol ointments (1.25% and 16%) was performed. The study was to show that the systemic absorption of the active ingredients in patch did not fall outside the bioavailability of the menthol associated with the lower and upper ointment limits. The results are summarized in table 2. The data showed that patch did not deliver systemic drug levels in excess of those levels associated with the 16% menthol ointment preparation. the Clinical Overview concluded that patch will not be associated with systemic safety concerns. Table 2. Metabolism It is not known if Lidocaine HCl is metablized in the skin. Lidocaine HCl is metablized rapily by the liver to a number of metabolites, including menoethylglycinexylidie (MEGX) and glycinexylidide (GX), both of which have pharmacologic activity silimar to, but less potent than that of Lidocaine HCl. 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 HCl 5% patch. Following intravenous administration, MEGX and GX concentrations in serum range from 11 to 36% and from 5 to 11% of Lidocaine HCl concentrations, respectively. Menthol is rapidly metabolized in human bodies into metabolites such as polyols and hydroxy acids that are subsequently excreted as such or, most predominantly, as glucuronide conjugates. Excretion Lidocaine HCl and its metabolites are excreted by the kidneys. Less than 10% of Lidocaine HCl is excreted unchanged. The half-life of Lidocaine HCl elimination from 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). INDICATIONS AND USAGE Lidodextrapine is indicated for the temporary relief of pain associated with minor cuts, scrapes and minor skin irritations. CONTRAINDICATIONS Lidodextrapine 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 Accidental Exposure in Children Even a used Lidodextrapine patch contains a large amount of Lidocaine HCl. The potential exists for a small child or a pet to suffer serious adverse effects from chewing or ingesting a new or used Lidodextrapine patch, although the risk with this formulation has not been evaluated. it is important for patients to store and dispose of Lidodextrapine out of the reach of children, pets and others. (See HANDLING AND DISPOSAL) Excessive Dosing Excessive dosing by applying Lidodextrapine to larger areas for longer than the recommended wearing time could result in increased absorption of Lidocaine HCl and high blood concentrations, leading to serious adverse effects. Lidocaine HCl toxicity could be expected at Lidocaine HCl blood concentrations above 5 µg/mL. The blood concentration of Lidocaine HCl 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 HCl. With recommended dosing of Lidodextrapine, the average blood concentration is about 0.13 µg/mL, but concentration higher than 0.25 µg/mL have been observed in some patients. PRECAUTIONS General Hepatic Disease Patients with severe hepatic disease are at greater risk of developing toxic blood concentrations of Lidocaine HCl, because of their inability to metabolize Lidocaine HCl normally. Allergic Reactions Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to Lidocaine HCl. However, Lidodextrapine 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 HCl from increased absorption. Lidodextrapine is only recommended for use on intact skin. Eye Exposure The contact of Lidodextrapine with eyes, although not studied, should be avoided based on the findings of severe eye irritations 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 Lidodextrapine should be used with caution in patients receiving Class 1 antiarrhythmic drugs (such as tocainide and mexiletine) since the toxic effects are additive and potentially synergistic. Local Anesthetics When Lidodextrapine is used concomitantly with other products containing local anesthetic agents the amount absorbed from all formulations must be considered. Pregnancy Teratogenic Effects Pregnancy Category B Lidodextrapine (Lidocaine HCl 4%/Menthol 1% patch) has not been studied in pregnancy. Reproduction studies with Lidocaine HCl have been performed in rats at doses up to 30 mg/kg subcutaneously and have revealed no evidence if harm to the fetus due to Lidocaine HCl. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Lidodextrapine should be used during pregnancy only if clearly needed. Nursing Mothers Lidodextrapine has not been studied in nursing mothers. Lidocaine HCl is excreted in human milk, and the milk: plasma ration of Lidocaine HCl is 0.4. Caution should be exercised when Lidodextrapine is administered to a nursing mother. Pediatric Use Safety and effectiveness in pediatric patients have not been established. ADVERSE REACTIONS Application Site Reactions During or immediately after treatment with Lidodextrapine (Lidocaine HCl 4%/Menthol 1% patch), 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 HCl, although rare, can occur. They are characterized by angioedema, bronchospasm, dermatits, 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. OVERDOSAGE Lidocaine HCl overdose from cutaneous absorption is rare, but could occur. If there is any suspicion of Lidocaine HCl overdose, 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 HCl. 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 over dosage from other sources of Lidocaine HCl or other local anesthetics. The oral LD50 of Lidocaine HCl HCl is 459 (346-773) mg/kg (as the salt) in non-fasted female rats and 214 (154-324) 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 Lidodextrapine to intact skin to cover the most painful area. Apply up to four patches per day. Each patch should not be applied for more than 8 hours in a given 24- hour period. Patches may be cut into smaller sizes with scissors prior to removal of the release liner. 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 and do not reapply until the irritation subsides. When Lidodextrapine is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered. HANDLING AND DISPOSAL Hands should be washed after handling of Lidodextrapine, and eye contact with Lidodextrapine should be avoided. Do not store patch outside the sealed envelope. Apply immediately after removal from the protective envelope. Fold use 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. Lidodextrapine should be kept out of reach of children. HOW SUPPLIED Lidodextrapine (Lidocaine HCl 4%/Menthol 1% patch) is available as the following: Box of 15 patches, packaged into 3 child-resistant envelopes (5 patches/envelope) NDC 49430-046-15 Store below 25°C (77° F); excursion permitted to 15°-30°C (59°-86° F). [See USP Controlled Room Temperature]. Manufactured for: Pharmaceutics Corporation Glendale, CA 91205 August 2014"],"purpose":["Topical anesthetic External analgesic"],"set_id":"51e53cf0-66db-41ae-94ad-237516c5efd6","spl_product_data_elements":["Lidodextrapine Lidocaine, Menthol LIDOCAINE HYDROCHLORIDE LIDOCAINE LIDOCAINE HYDROCHLORIDE ANHYDROUS MENTHOL MENTHOL WATER GLYCERIN ARNICA MONTANA POLYSORBATE 80 ALOE VERA LEAF BOSWELLIA SACRA WHOLE GREEN TEA LEAF CARBOMER 1342 ETHYLHEXYLGLYCERIN ISOPROPYL MYRISTATE PEG-8 GLYCERYL ISOSTEARATE PHENOXYETHANOL SODIUM LAURYL SULFATE TRIETHANOLAMINE BENZOATE FD&C BLUE NO. 1 FD&C YELLOW NO. 5"],"version":"3","warnings_and_cautions":["Warnings For external use only Avoid contact with eyes Do not applly to open wounds or damaged skin If symptoms persist for more than seven days, discontinue use and consult physician If swallowed, consult physician Do not bandage tightly If pregnant or breast feeding, contact physician prior to use Do not use in large quantities, particularly over raw surfaces or blistered areas"]}