Trubrexa Patch ER

Trubrexa TM Transdermal 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 TM Transdermal Patch it is important to follow these procedures: Keep Trubrexa TM Transdermal Patch in the sealed pouch until immediately before use. Use Trubrexa TM Transdermal 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 TM Transdermal Patch. Ensure all used and unused pieces Trubrexa TM Transdermal 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 TM Transdermal 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 TM Transdermal 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 TM Transdermal Patch is used concomitantly with other products containing local anesthetic agents, the amount absorbed from all formulations must be considered.

Trubrexa TM Transdermal 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 TM Transdermal 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 TM Transdermal 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 TM Transdermal 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 TM Transdermal 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 TM Transdermal 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 TM Transdermal Patch. Provide supportive medical care if shortness of breath develops. Skin Exposure Thoroughly clean all areas that had contact with Trubrexa TM Transdermal Patch and properly dispose of all patch components. 5.4 Application-Associated Pain During or immediately after treatment with Trubrexa TM Transdermal 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 TM Transdermal 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 TM Transdermal Patch. If sensory deterioration or loss is detected or pre-existing sensory deficit worsens, continued use of Trubrexa TM Transdermal 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 TM Transdermal 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 TM Transdermal Patch is not recommended. Eye Exposure The contact of Trubrexa TM Transdermal 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 TM Transdermal 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 TM Transdermal 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 TM Transdermal 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 TM Transdermal 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)

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 TM Transdermal 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 TM Transdermal 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 TM Transdermal 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 TM Transdermal 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 TM Transdermal 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 TM Transdermal Patch. Provide supportive medical care if shortness of breath develops. Skin Exposure Thoroughly clean all areas that had contact with Trubrexa TM Transdermal Patch and properly dispose of all patch components. 5.4 Application-Associated Pain During or immediately after treatment with Trubrexa TM Transdermal 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 TM Transdermal 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 TM Transdermal Patch. If sensory deterioration or loss is detected or pre-existing sensory deficit worsens, continued use of Trubrexa TM Transdermal 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 TM Transdermal 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 TM Transdermal Patch is not recommended. Eye Exposure The contact of Trubrexa TM Transdermal 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 TM Transdermal 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 TM Transdermal 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.

7.1 Pregnancy Trubrexa TM Transdermal 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 TM Transdermal 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 TM Transdermal 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 TM Transdermal Patch. Caution should be exercised when Trubrexa TM Transdermal 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 TM Transdermal 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.