{"active_ingredient":["Menthol 5.00% Capsaicin 0.0375%"],"dosage_and_administration":["Adults and children 12 years and to apply to affected area; change patch 1 to 2 times daily Children under 12 years, consult physician before use How to apply clean and dry affected area cut open pouch and remove patch remove protective fim and apply directly to area of pain apply to affected area not more than 3 times daily wash hands with soap after applying patch reseal pouch containing unused patches"],"effective_time":"20150708","id":"6bc49d4a-0bad-4563-8744-b04eb8a84287","inactive_ingredient":["Water, glycerine, sodium polyacrylate, polysorbate 80, aloe vera gel juice, EDTA disodium salt, diazolidinyl urea, methylparaben, iodoproynyl butylcabamate, proylparaben"],"indications_and_usage":["Use for the temporary relief of minor aches and muscle pains associated wit harthritis, simple bachache, strains, muscle soreness and stiffness."],"keep_out_of_reach_of_children":["Keep out of reach of children"],"openfda":{},"package_label_principal_display_panel":["box image"],"patient_medication_information":["DESCRIPTION: Neuvaxin (Menthol 5%/Capsaicin 0.0375%) is comprised of an adhesive material containing Menthol and Capsaicin 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. Menthol is checmically designated as 2-Isopropyl-5- methylcyclohexanol. It is colourless, hexagonal crystals, usually needle-like; fused masses or crystalline powder with a pleasant, peppermint-like odour. If has a melting point between 31°C to 36° C. Capsaicin is chemically designated as (6E)-N-(4-Hydroxy-3- methoxybenzyl)-8-methyl-6-nonenamide. It is a crystalline white powder. It has a melting point of 65° C. Each adhesive patch contains 850 mg of Menthol and 6.375 mg of Capsaicin. It also contains the following inactive ingredients: Water, Glcerin, Sodium Polyacrylate (250000MV), Polysorbate 80, Aloe Vera Leaf, Edetate Disodium, Diazolidinyl Urea, Methylparaben, Iodopropynyl, Butylcarbamate and Propylparaben. CLINICAL PHARMACOLOGY: Pharmacodynamics Menthol works by targeting th k-opiod receptor 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. Capsaicin is a naturally occurring compound. It is found in chili peppers and is what gives is \"heat\". Capsaicin has been found to be effective in reducing inflammation and pain. When Capsaicin enters the body it binds with the protein TRPV1 which is located on pain and heat neurons. When the TRPV1 proton is activated (between 37° - 45° C) it opens the calcium ion channel and give the sensation of pain and heat. When Capsaicin binds to the TRPV1 proton it forces the ion channel to open below its normal activation temperature which is why it gives the distinct heating sensation. It is thought that prolonged activation of these neurons by Capsaicin depletes substance P, a neurotransmitter for pain and heat. The end result appears that the nerves are overwhelmed by the influx and unable to report pain for an extended period of time. Pharmacokinetics Absorption The amount of Menthol and Capsaicin systemically absorbed is directly related to both the duration of application and the surface area over which it is applied. 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 1. 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. Metabolism 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. Capsaicin is metabolized extensively by the liver CYP450 enzymes and Carboxyesterase class enzymes and yield numerous byproducts via alkyl, aromatic, and amide metabolic pathways. Due to metabolic changes to the vanilliod ring and capsaicin's hydrophobic alkyl side chain, the metabolites possess less potential at the VR1 receptor. Capsaicin also possess numerous electrophile metabolites that can bind to liver enzymes and proteins via a reactive arene oxide or quinone methide group. INDICATIONS AND USAGE Neuvaxin is indicated for the temporary relief of minor aches and muscle pains associated with arthritis, simple backache, strains, muscles soreness and stiffness. CONTRAINDICATIONS Neuvaxin is contraindicated in patients with a known history of sensitivity to any component of the product. WARNINGS Accidental Exposure in Children The potential exists for a small child or a pet to suffer serious adverse effect from chewing or ingesting a new or used Neuvaxin patch, although the risk with this formulation has not been evaluated. It is important for patients to store and dispose of Neuvaxin out of the reach of children, pets and others. (See HANDLING AND DISPOSAL) Excessive Dosing Excessive dosing by applying Neuvaxin to larger areas for longer than the recommended wearing time could result in increased absorption and higher blood concentrations. 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. PRECAUTIONS General Allergic Reactions Patients allergic to Menthol or Capsaicin or any other ingredient in Neuvaxin should not use Neuvaxin. Non-intact Skin Application to broken or inflamed skin, although not tested, may result in higher blood concentrations from increased absorption. Neuvaxin is only recommended for use on intact skin. Eye Exposure The contact of Neuvaxin with eyes, although not studied, should be avoided based on the findings of sever eye irritations with the use of similar products in animals. If eye contact occurs, immediately wash out the eye with water or saline. Pregnancy Nursing Mothers Neuvaxin has not been studied in nursing mothers. Caution should be exercised when Neuvaxin is administered to a nursing mother. Pediatric Use Safety and effectiveness in pediatric patients have not been established. DOSAGE AND ADMINISTRATION Apply Neuvaxin 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 Neuvaxin is used concomitantly with other products containing same or similar agents, the amount absorbed from all formulations must be considered. HANDLING AND DISPOSAL Hands should be washed after handling of Neuvaxin, and eye contact with Neuvaxin 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. Neuvaxin should be kept out of reach of children. HOW SUPPLIED Neuvaxin (Menthol 5%/Capsaicin 0.0375% patch) is available as the following: Box of 15 patches, packaged into 3 child-resistant envelopes (5 patches/envelope) NDC 49430-049-15 Store below 25°C (77° F); excursion permitted to 15°-30°C (59°-86° F). [See USP Controlled Room Temperature]. Manufactured for: Pharmaceutics Corporation, Inc. Glendale, CA 91205 January 2015"],"purpose":["Analgesic/counterirritant External analgesic"],"set_id":"c5a415a9-d9ae-47d7-9838-5a34bbc50e50","spl_product_data_elements":["Neuvaxin Patch Menthol, Capsaicin CAPSAICIN CAPSAICIN MENTHOL MENTHOL WATER GLYCERIN POLYSORBATE 80 ALOE VERA LEAF EDETATE DISODIUM DIAZOLIDINYL UREA METHYLPARABEN IODOPROPYNYL BUTYLCARBAMATE PROPYLPARABEN"],"version":"2","warnings_and_cautions":["Warnings For external use only Use only as directed Avoid contact with eyes and mucus membranes Do not use on wounds or damaged skin Stop use and ask a doctor if symptoms persist for more than seven days, or clear up and occur again within a few days, or rash, itching or excessive skin irritation occurs Do not cover with bandage Do not use if you are allergic to Menthol Consult phsyciain for children under 12"]}