Trubrexa Patch
FDA Label NDC 76420-644

Trubrexa ^TMTransdermal Patch

Extended Time Release

Lidocaine 4.75%

Capsaicin 0.025%

Rx Only

Relabeled by:

Enovachem PHARMACEUTICALS

Torrance, CA 90501

Trubrexa ^TMTransdermal Patch is indicated in adults over the age of 12 years old for the treatment of acute and chronic pain in muscles and joints associated with muscle soreness, strains, sprains, arthritis, simple backache, muscle stiffness, and more.

2.1 Important Dosage and Administration Instructions

• Unintended exposure to capsaicin can cause severe irritation of the eyes, mucous membranes, respiratory tract, and skin in healthcare providers and others.
• Because unintended exposure to capsaicin can cause severe irritation of eyes, mucous membranes, respiratory tract, and skin, when administering Trubrexa ^TMTransdermal Patch it is important to follow these procedures:
  • Keep Trubrexa ^TMTransdermal Patch in the sealed pouch until immediately before use.
  • Use Trubrexa ^TMTransdermal Patch only on dry, intact (unbroken) skin.
  • During administration, avoid unnecessary contact with any items in the room, including items that the patient may later have contact with, such as horizontal surfaces and bedsheets.
  • Immediately after use, clean all areas of skin that had contact with Trubrexa ^TMTransdermal Patch.
  • Ensure all used and unused pieces Trubrexa ^TMTransdermal Patch are properly disposed of.

  2.2 Dosing and Instructions for Use

  • Tear open pouch bag and remove one patch. Place remaining patches back in pouch bag and seal the pouch bag closed.
  • Peel the clear plastic film away and apply Trubrexa ^TMTransdermal Patch to intact skin to cover the most painful area. Apply one patch per day for up to 12 hours within a 24 hour period (12 on, 12 off). One single Trubrexa ^TMTransdermal Patch may be used twice per day. To re-use after first application, place the clear plastic film back on to medicated hydrogel pad.
  • Clothing may be worn over the area of application.
  • Wash hands with soap and water after handling the patch.
  • If irritation or a burning sensation occurs during application, remove the patch and do not reapply until the irritation subsides.
  • When Trubrexa ^TMTransdermal Patch is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered.

Trubrexa ^TMTransdermal Patch contains 4.75% lidocaine and 0.025% capsaicin. Each patch is 2 in x 2 in (5.08 cm x 5.08 cm) and consists of an adhesive side containing the active/inactive ingredients and an outer surface backing layer. The adhesive side is covered with a removable, clear, unprinted, plastic film. The outer surface of the backing layer is imprinted with the Trubrexa ^TMTransdermal Patch logo.

Trubrexa ^TMTransdermal Patch 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.

5.1 Risk of 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; fatigue; or lightheadedness.

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 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 Trubrexa ^TMTransdermal Patch 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, etc. A more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

5.2 Excessive Dosing

Excessive dosing by applying Trubrexa ^TMTransdermal Patch to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine and capsaicin and high blood concentrations. Lidocaine toxicity could b e 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 and capsaicin.

5.3 Severe Irritation with Unintended Capsaicin Exposure

Unintended exposure to capsaicin can cause severe irritation of eyes, mucous membranes, respiratory tract, and skin.

Eye and Mucous Membrane Exposure

• Do not apply Trubrexa ^TMTransdermal Patch to the face, eyes, mouth, nose, or scalp to avoid risk of exposure to eyes or mucous membranes.
• Accidental exposure to the eyes and mucous membranes can occur from touching Trubrexa ^TMTransdermal Patch or items exposed to capsaicin, then touching the eyes and mucous membranes.
• If irritation of eyes or mucous membranes occurs, remove the affected individual from the vicinity of Trubrexa ^TMTransdermal Patch and flush eyes and mucous membranes with cool water.

Respiratory Tract Exposure

• Inhalation of airborne capsaicin can result in coughing or sneezing. If irritation of airways occurs, remove the affected individual from the vicinity of Trubrexa ^TMTransdermal Patch. Provide supportive medical care if shortness of breath develops.

Skin Exposure

• Thoroughly clean all areas that had contact with Trubrexa ^TMTransdermal Patch and properly dispose of all patch components.

5.4 Application-Associated Pain

During or immediately after treatment with Trubrexa ^TMTransdermal 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.

5.5 Increase in Blood Pressure

Patient with unstable or poorly controlled hypertension, or a recent history of cardiovascular or cerebrovascular events, may be at increased risk of adverse cardiovascular effects. Consider these factors prior to initiating Trubrexa ^TMTransdermal Patch treatment. Monitor blood pressure periodically during and following the treatment procedure and provide adequate support for treatment-related pain.

5.6 Sensory Function

Decreases in sensory functions are generally minor and temporary (including to thermal and other harmful stimuli). All patients with pre-existing sensory deficits should be clinically assessed for signs of sensory deterioration or loss prior to each prescription of Trubrexa ^TMTransdermal Patch. If sensory deterioration or loss is detected or pre-existing sensory deficit worsens, continued use of Trubrexa ^TMTransdermal Patch treatment should be reconsidered.

5.7 Precautions

Allergic Reactions

Allergic and anaphylactoid reactions associated with lidocaine can occur. They are characterized by angioedema, bronchospasm, dermatitis, dyspnea, hypersensitivity, laryngospasm, pruritus, chock, and urticaria. If they occur, they should be managed by conventional means. Patients allergic to para-aminobenzoic acid derivates (procaine, tetracaine, benzocaine, etc.) have not shown cross-sensitivity to lidocaine. However, Trubrexa ^TMTransdermal Patch should be used with caution in patients with a history of drug sensitivities, especially if the etiologic agent is uncertain.

External Heat Sources

Placement of external heat sources, such as heating pads or electric blankets, over Trubrexa ^TMTransdermal Patch is not recommended.

Eye Exposure

The contact of Trubrexa ^TMTransdermal Patch with eyes should be avoided based on finding from previous studies with use of similar products. If eye contact occurs, immediately wash out the eye with water and saline and protect the eye until sensation returns.

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.

Non-Intact Skin

Trubrexa ^TMTransdermal Patch is only recommended for use on intact skin. Application to broken or inflamed skin may result in increased irritation and/or increased absorption of ingredients.

5.8 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.

5.9 Systemic (Dose-Related) Reactions

Systemic adverse reactions following appropriate use of Trubrexa ^TMTransdermal Patch are unlikely due to the small dose absorbed. 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 manifestations may include bradycardia, hypotension, and cardiovascular collapse leading to arrest.

Antiarrhythmic Drugs

Trubrexa ^TMTransdermal Patch 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 Trubrexa ^TMTransdermal Patch is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered.

Drugs That May Cause Methemoglobinemia

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:

Nitrates/Nitrites(nitric oxide, nitroglycerin, nitroprusside, nitrous oxide)

Local anesthetics(benzocaine, bupivacaine, lidocaine, prilocaine, procaine, 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)

7.1 Pregnancy

Trubrexa ^TMTransdermal Patch has not been studied in pregnancy. Maternal use is not expected to result in fetal exposure. Animal studies have shown no adverse effects when lidocaine and capsaicin are administered and absorbed. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Trubrexa ^TMTransdermal Patch should only be used during pregnancy if clearly needed or advised by a healthcare professional. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

7.2 Lactation

Trubrexa ^TMTransdermal Patch has not been studied in nursing mothers. Lidocaine is excreted in human milk, and the milk:plasma ration of lidocaine is 0.4. Capsaicin is negligibly absorbed systemically by the mother following topical administration of Trubrexa ^TMTransdermal Patch. Caution should be exercised when Trubrexa ^TMTransdermal Patch is administered to a nursing woman. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Trubrexa ^TMTransdermal Patch and any potential adverse effects on the breastfed infant.

7.3 Pediatric Use

Safety and effectiveness in pediatric patients under the age of 12 have not been studied or established.

7.4 Geriatric Use

Safety and effectiveness are similar in geriatric patients and younger patients. No dose adjustments are required in geriatric patients.

Lidocaine overdose from cutaneous absorption is rare but could occur. If there is any suspicion of lidocaine 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. 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. There is no specific antidote for overdose with capsaicin. In case of suspected overdose, remove Trubrexa ^TMTransdermal Patch and gently wash the area with soap and water. Use supportive measures and treat symptoms as clinically warranted.

Trubrexa ^TMTransdermal Patch is comprised of an adhesive material containing 4.75% lidocaine and 0.025% capsaicin. Each patch is 2 in x 2 in (5.08 cm x 5.08 cm) and consists of an adhesive side containing the active/inactive ingredients and an outer surface backing layer with breathable fabric. The adhesive side is covered with a removable, clear, unprinted, plastic film. The outer surface of the backing layer is imprinted with the Trubrexa ^TMTransdermal Patch logo. 4 patches are included in each pouch bag. The inactive ingredients include: Arnica, Magnesium, Polyacrylate, Vegan Glycerol, and Water. Trubrexa ^TMTransdermal Patch is Latex Free, Paraben Free, and Vegan.

10.1 Pharmacodynamics

Lidocaine is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl), has an octanol:water partition ratio of 43 at pH 7.4. Capsaicin is soluble in alcohol, acetone, and ethyl acetate and very slightly soluble in water. 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 Trubrexa ^TMTransdermal Patch is sufficient to produce an analgesic effect, but less than the amount necessary to produce a complete sensory block. Capsaicin is an agonist for the transient receptor potential vanilloid 1 receptor (TRPV1), which is an ion channel-receptor complex expressed on nociceptive nerve fibers in the skin. Topical administration of capsaicin causes an initial enhanced stimulation of the TRPV1-expressing cutaneous nociceptors that may be associated with painful sensations. This is followed by pain relief thought to be mediated by a reduction in TRPV1-expressing nociceptive nerve endings.

10.2 Pharmacokinetics

The amount of lidocaine and capsaicin systemically absorbed from Trubrexa ^TMTransdermal Patch is directly related to both the duration of application and the surface area over which it is applied. Systemic exposure decreases upon removal of Trubrexa ^TMTransdermal Patch. Lidocaine crosses the placental and blood brain barriers, presumably by passive diffusion. 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. Lidocaine and its metabolites are excreted by the kidneys.

11.1 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 Trubrexa ^TMTransdermal Patch.

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 Trubrexa ^TMTransdermal Patch on fertility has not been studied.

12.1 How Supplied

Trubrexa ^TMTransdermal Patch comes in a sealed pouch bag. Each patch is 2 in x 2 in (5.08 cm x 5.08 cm) and consists of an adhesive side containing the active/inactive ingredients and an outer surface backing layer. The adhesive side is covered with a removable, clear, unprinted, plastic film. The outer surface of the backing layer is imprinted with the Trubrexa ^TMTransdermal Patch logo.

Trubrexa ^TMTransdermal Patch is available as a unit box containing 32 patches (8 pouch bags). NDC 76420-644-32 (relabeled from NDC 83295-4000-1)

12.2 Storage

Store unit box between 68 ^o-77 ^oF (20 ^o-25 ^oC). Excursions between 15 ^o-30 ^oC (59 ^o-86 ^oF) are allowed. Keep Trubrexa ^TMTransdermal Patch in the sealed pouch bags until immediately before use.

12.3 Handling and Disposal

Unintended exposure to capsaicin can cause severe irritation of eyes, skin, respiratory tract, and mucous membranes. Avoid contact with your eyes, nose, or mouth. Keep used and unused patches out of the reach of children and pets. Pouch bags are not child resistant. Wash hands with soap and water after handling the patch. If irritation or a burning sensation occurs during application, remove the patch and do not reapply until the irritation subsides. After use, fold patches so that the adhesive side sticks to itself, then safely discard used patches where children and pets cannot get to them.

• Inform patients that accidental exposure to capsaicin from touching Trubrexa ^TMTransdermal Patch can cause severe irritation of eyes, mucous membranes, respiratory tract, and skin. If this occurs, patient should notify a healthcare professional immediately.
• Inform patients that the treated area may be sensitive to heat (e.g., hot showers/bath, direct sunlight, vigorous exercise) for a few days following treatment.
• Inform patients that as a result of treatment-related increases in pain, small transient increases in blood pressure may occur during and shortly after Trubrexa ^TMTransdermal Patch treatment and that blood pressure will be monitored during the treatment process. If any cardiovascular event occurs, patient should notify a healthcare professional immediately.