TRUBREXA

WARNINGS, PRECAUTIONS & ADVERSE REACTIONS 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.