Can Capsaicin cause application site erythema?

ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Severe Irritation Due to Accidental Exposure of Eyes, Skin, Respiratory Tract, and Mucous Membranes [see Warning and Precautions ( 5.1 )] Application-Associated Pain [see Warnings and Precautions ( 5.2 )] Increase in Blood Pressure [see Warnings and Precautions ( 5.3 )] Sensory Function Reduction [see Warning and Precautions ( 5.4 )] Severe Application Site Burns ​[see Warning and Precautions ( 5.5 )] The most common adverse reactions (≥5% and greater than control) in all controlled clinical trials are application site erythema, application site pain, and application site pruritus. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Averitas Pharma at 1-877-900-6479 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in clinical practice. Across all controlled and uncontrolled clinical trials, 2848 patients have received QUTENZA. A total of 924 patients received more than one treatment application and 732 patients were followed for 48 weeks or longer. A total of 590 DPN patients and 1112 PHN patients have received QUTENZA across all controlled and uncontrolled clinical trials. Among patients treated with QUTENZA, 1% discontinued prematurely due to an adverse event. Most Common Adverse Reactions in all Controlled Clinical Trials In all controlled clinical trials, adverse reactions occurring in ≥5% of patients in the QUTENZA group and at an incidence at least 1% greater than in the control group were application site erythema, application site pain, and application site pruritus. The majority of application site reactions were transient and self-limited. Transient increases in pain were commonly observed on the day of treatment in patients treated with QUTENZA. Pain increases occurring during QUTENZA application usually began to resolve after QUTENZA removal. On average, pain scores returned to baseline by the end of the treatment day and then remained at or below baseline levels. A majority of QUTENZA-treated patients in clinical trials had adverse reactions with a maximum intensity of "mild" or "moderate". Postherpetic Neuralgia (PHN) Table 1 summarizes all adverse reactions, regardless of causality, occurring in >1% of patients with PHN in the QUTENZA group for which the incidence was at least 1% greater than in the control group. TABLE 1: Adverse Reaction Incidence (%) in Controlled Double-blind Trials in Postherpetic Neuralgia (Events in >1% of QUTENZA-treated Patients and at Least 1% Greater in the QUTENZA Group than in the Control Group) Body System Preferred Term QUTENZA 60 minutes (N=622) % Control 60 minutes (N=495) % General Disorders and Administration Site Conditions Application site erythema 63 54 Application site pain 42 21 Application site pruritus 6 4 Application site papules 6 3 Application site edema 4 1 Application site swelling 2 1 Application site dryness 2 1 Infections and Infestations Nasopharyngitis 4 2 Bronchitis 2 1 Sinusitis 3 1 Gastrointestinal Disorders Nausea 5 2 Vomiting 3 1 Skin and Subcutaneous Tissue Disorder Pruritus 2 < 1 Vascular Disorders Hypertension 2 1 Less common adverse reactions (<1%) with QUTENZA observed during PHN clinical trials included: palpitations, tachycardia, eye pruritus, application site reactions (such as urticaria, paresthesia, dermatitis, hyperesthesia). Neuropathic Pain Associated with Diabetic Peripheral Neuropathy (DPN) Table 2 summarizes all adverse reactions, regardless of causality, occurring in >1% of patients with DPN in the QUTENZA group for which the incidence was at least 1% greater than in the control group. TABLE 2: Adverse Reaction Incidence (%) in Double-blind Controlled Trials in Neuropathic Pain Associated with Diabetic Peripheral Neuropathy (Events in >1% of QUTENZA-treated Patients and at Least 1% Greater in the QUTENZA Group than in the Control Group) Body System Preferred Term QUTENZA 30 minutes (N=186) % Control 30 minutes (N=183) % General Disorders and Administration Site Conditions Application site reactions Burning sensation 14 3 Application site pain 10 2 Erythema 2 0 Injury, Poisoning and Procedural Complications Excoriation 2 0 Musculoskeletal and Connective Tissue Disorders Pain in extremity 11 6 Nervous System Disorders Headache 3 2 Respiratory, Thoracic and Mediastinal Disorders Upper respiratory symptoms Upper respiratory tract infection 4 < 1 Cough 2 < 1 Vascular Disorders Hypertension 2 < 1 Less common adverse reactions (<1%) with QUTENZA observed during DPN clinical trials included: dizziness, dysesthesia, blister. 6.2 Postmarketing Experience Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during post approval use of QUTENZA: deep partial-thickness (second-degree) and full-thickness (third-degree) burns and scarring; accidental exposure (including eye pain, cough, eye and throat irritation) ​[see Warnings and Precautions ( 5.1 , 5.5 )].

WARNINGS AND PRECAUTIONS Severe Irritation with Unintended Capsaicin Exposure: Capsaicin can cause severe irritation of eyes, mucous membranes, respiratory tract, and skin to the healthcare professional, patients, and others. (See Full Prescribing Information for detailed instructions on how to manage this risk. ( 2.1 , 5.1 ) Application-Associated Pain: Patients may experience substantial procedural pain and burning upon application of QUTENZA and following removal of QUTENZA. Prepare to treat acute pain during and following the application procedure with local cooling and/or appropriate analgesic medication. ( 5.2 ) Increase in Blood Pressure: Transient increases in blood pressure may occur with QUTENZA treatment. Monitor blood pressure during and following the treatment procedure. ( 5.3 ) Sensory Function: Reductions in sensory function, which were generally minor and temporary, have been reported following administration of QUTENZA. Assess for signs of sensory deterioration or loss prior to each application of QUTENZA. If sensory loss occurs, treatment should be reconsidered. ( 5.4 ) Severe Application Site Burns: Full-thickness (third-degree) and deep partial-thickness (second-degree) burns have been reported following administration of QUTENZA. Ensure that dosage and administration recommendations are followed. ( 5.5 ) 5.1 Severe Irritation with Unintended Capsaicin Exposure Unintended exposure to capsaicin can cause severe irritation of eyes, mucous membranes, respiratory tract, and skin in healthcare professionals, patients, and others. Ensure that the recommended procedures and protective measures are used when administering QUTENZA [see Dosage and Administration ( 2.1 )] . Eye and Mucous Membrane Exposure • For healthcare professionals: ○ Wear nitrile gloves when administering QUTENZA and avoid unnecessary contact with items in the room, including items that the patient may later have contact with, such as horizontal surfaces and bedsheets. ○ Use of a face mask and protective glasses is advisable. • Do not apply QUTENZA to the patient’s 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 QUTENZA or items exposed to capsaicin and then touching the eyes and mucous membranes. • If irritation of eyes or mucous membranes occurs, flush eyes and mucous membranes with cool water. Remove the affected individual (healthcare professional or patient) from the vicinity of QUTENZA. Respiratory Tract Exposure Aerosolization of capsaicin can occur upon rapid removal of QUTENZA. Therefore, remove QUTENZA gently and slowly by rolling the adhesive side inward [see Dosage and Administration ( 2.1 , 2.3 )] . Inhalation of airborne capsaicin can result in coughing or sneezing. Administer QUTENZA in a well-ventilated treatment area. Provide supportive medical care if shortness of breath develops. If irritation of airways occurs, remove the affected individual (healthcare professional or patient) from the vicinity of QUTENZA. If respiratory irritation worsens or does not resolve, do not re-expose the affected healthcare professional or patient to QUTENZA [see Adverse Reactions ( 6.2 )] . Skin Exposure If skin not intended to be treated is exposed to QUTENZA, apply Cleansing Gel for one minute and wipe off with dry gauze. After the Cleansing Gel has been wiped off, wash the area with soap and water. Thoroughly clean all areas that had contact with QUTENZA and properly dispose of QUTENZA, associated packaging, Cleansing Gel, gloves, and other treatment materials in accordance with local biomedical waste procedures [see Dosage and Administration ( 2.1 , 2.3 )] . 5.2 Application-Associated Pain Even following use of a local anesthetic prior to administration of QUTENZA, patients may experience substantial procedural pain and burning upon application of QUTENZA and following removal of QUTENZA. Prepare to treat acute pain during and following the application procedure with local cooling and/or appropriate analgesic medication. 5.3 Increase in Blood Pressure In clinical trials, transient increases in blood pressure occurred during or shortly after exposure to QUTENZA. The changes averaged less than 10 mm Hg, although some patients had greater increases and these changes lasted for approximately two hours after QUTENZA removal. Increases in blood pressure were unrelated to the pretreatment blood pressure but were related to treatment-related increases in pain. Monitor blood pressure periodically during and following the treatment procedure and provide adequate support for treatment-related pain. Patients with unstable or poorly controlled hypertension, or a recent history of cardiovascular or cerebrovascular events, may be at an increased risk of adverse cardiovascular effects. Consider these factors prior to initiating QUTENZA treatment. 5.4 Sensory Function Reductions in sensory function have been reported following administration of QUTENZA. 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 application of QUTENZA. If sensory deterioration or loss is detected or pre-existing sensory deficit worsens, continued use of QUTENZA treatment should be reconsidered. 5.5 Severe Application Site Burns Cases of full-thickness (third-degree) and deep partial-thickness (second-degree) burns have been reported following administration of QUTENZA. Cases of full-thickness (third-degree) burns, requiring hospitalization and skin grafting have been reported in patients who received QUTENZA for an unapproved indication and/or frequency of dosing at an application site where there had been prior skin trauma ​[see Adverse Reactions ( 6.2 )]. ​Ensure that dosage and administration recommendations are followed ​[see Dosage and Administration ( 2 )]. ​