CAPSAICIN: 1,719 Adverse Event Reports & Safety Profile

QUTENZA (capsaicin) 8% topical system contains capsaicin in a localized dermal delivery system. The capsaicin in QUTENZA is a synthetic equivalent of the naturally occurring compound found in chili peppers. Capsaicin is soluble in alcohol, acetone, and ethyl acetate and very slightly soluble in water. QUTENZA is a single-use topical system stored in a foil pouch. Each QUTENZA is 14 cm x 20 cm (280 cm 2 ) and consists of a polyester backing film coated with a drug-containing silicone adhesive mixture and covered with a removable polyester release liner. The backing film is imprinted with “capsaicin 8%”. Each QUTENZA contains a total of 179 mg of capsaicin (8% in adhesive, 80 mg per gram of adhesive) or 640 micrograms (mcg) of capsaicin per square cm of topical system. The empirical formula is C 18 H 27 NO 3 , with a molecular weight of 305.42. The chemical compound capsaicin [(E)-8-methyl-N-vanillyl-6-nonenamide] is an activating ligand for transient receptor potential vanilloid 1 receptor (TRPV1) and it has the following structure: FIGURE 1: Structural Formula of Capsaicin QUTENZA contains the following inactive ingredients: diethylene glycol monoethyl ether, dimethicone, ethyl cellulose, polyester film, silicone adhesive, and white ink. QUTENZA is supplied with a Cleansing Gel which is used to remove residual capsaicin from the skin after treatment.

Cleansing

Gel consists of the following ingredients: butylated hydroxyanisole, carbomer copolymer, edetate disodium, polyethylene glycol, purified water, and sodium hydroxide.

Structural

Formula of Capsaicin

Directions Uses For temporary relief of minor aches & pains of muscles & joints associated with: simple backache arthritis strains bruises sprains Adult and children 12 years of age and over: clean and dry affected area remove film from patch and apply to the skin (see illustration) apply 1 patch at a time to affected area, not more than 3 to 4 times daily remove patch from the skin after at most 8-hour apolication Children under 12 years of age: consult a doctor

AND ADMINISTRATION Only physicians or health care professionals are to administer QUTENZA. ( 2.1 ) Administer QUTENZA in a well-ventilated treatment area. ( 2.1 ) Wear nitrile (not latex) gloves when handling QUTENZA and when cleaning treatment areas. ( 2.1 ) Use of a face mask and protective glasses is advisable for healthcare professionals. ( 2.1 ) Do not use QUTENZA on broken skin. ( 2.1 ) PHN: Apply up to four topical systems for 60 minutes. ( 2.2 ) DPN: Apply up to four topical systems for 30 minutes on the feet. ( 2.2 ) Repeat every 3 months or as warranted by the return of pain (not more frequently than every three months). ( 2.2 )

See

Dosage and Administration, Instructions for Use, for detailed instructions on QUTENZA administration. ( 2.3 )

2.1 Important Dosage and Administration Instructions Do not dispense QUTENZA to patients for self-administration or handling. Only physicians or healthcare professionals are to administer and handle QUTENZA. Unintended exposure to capsaicin can cause severe irritation of eyes, mucous membranes, respiratory tract, and skin in healthcare professionals, patients and others <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 )]</span> . Because unintended exposure to capsaicin can cause severe irritation of eyes, mucous membranes, respiratory tract, and skin, when administering QUTENZA, it is important to follow these procedures: − Administer QUTENZA in a well-ventilated treatment area. − Wear only nitrile gloves when handling QUTENZA or any item that makes contact with QUTENZA, and when cleaning capsaicin residue from the skin. Do not use latex gloves as they do not provide adequate protection. − Use of a face mask and protective glasses is advisable for healthcare professionals. − Keep QUTENZA in the sealed pouch until immediately before use. − Use QUTENZA only on dry, intact (unbroken) skin. − In patients treated for neuropathic pain associated with diabetic peripheral neuropathy, a careful examination of the feet should be undertaken prior to each application of QUTENZA to detect skin lesions related to underlying neuropathy or vascular insufficiency. <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.4 )]</span> . − 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. − Aerosolization of capsaicin can occur upon rapid removal of QUTENZA. Therefore, remove QUTENZA gently and slowly by rolling the adhesive side inward <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 )]</span> . − Immediately after use, 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. − If QUTENZA is cut, ensure unused pieces are properly disposed of.

2.2 Dosing The recommended dose of QUTENZA for neuropathic pain associated with postherpetic neuralgia is a single, 60-minute application of up to four topical systems. The recommended dose of QUTENZA for neuropathic pain associated with diabetic peripheral neuropathy is a single, 30-minute application on the feet of up to four topical systems. Treatment with QUTENZA may be repeated every three months or as warranted by the return of pain (not more frequently than every three months).

2.3 Instructions for Use USE IN NEUROPATHIC PAIN ASSOCIATED WITH POSTHERPETIC NEURALGIA (60-MINUTE APPLICATION TIME)

Prepare

Administer QUTENZA in a well-ventilated treatment area. Put on nitrile (not latex) gloves. Use of a face mask and protective glasses is advisable for healthcare professionals. Inspect the pouch. Do not use if the pouch has been torn or damaged.

Identify

The treatment area (painful area including areas of hypersensitivity and allodynia) must be identified by a physician or healthcare professional and marked on the skin. If necessary, clip hair (do not shave) in and around the identified treatment area to promote QUTENZA adherence. QUTENZA can be cut to match the size and shape of the treatment area. Gently wash the treatment area with mild soap and water, and dry thoroughly. Anesthetize (optional) The treatment area may be pretreated with a topical anesthetic to potentially reduce discomfort associated with the application of QUTENZA. Apply topical anesthetic to the entire treatment area and surrounding 1 to 2 cm, and keep the local anesthetic in place until the skin is anesthetized prior to the application of QUTENZA. Remove the topical anesthetic with a dry wipe. Gently wash the treatment area with mild soap and water, and dry thoroughly.

Apply

Tear open the pouch along the three dashed lines and remove QUTENZA. Inspect QUTENZA and identify the outer surface backing layer with the printing on one side and the capsaicin-containing adhesive on the other side. The adhesive side of QUTENZA is covered by a clear, unprinted, diagonally cut release liner. Cut QUTENZA before removing the protective release liner. Ensure that unused pieces do not make contact with other objects and are disposed of appropriately. The diagonal cut in the release liner is to aid in its removal. Peel a small section of the release liner back and place the adhesive side of QUTENZA on the treatment area. While you slowly peel back the release liner from under the QUTENZA with one hand, use your other hand to smooth QUTENZA down onto the skin. Once QUTENZA is applied, leave in place for 60 minutes (PHN). To ensure QUTENZA maintains contact with the treatment area, a dressing, such as rolled gauze, may be used. Remove the nitrile gloves after the application. Instruct the patient not to touch QUTENZA or the treatment area.

Remove

Put on nitrile (not latex) gloves. Remove QUTENZA by gently and slowly rolling inward.

Cleanse

After removal of QUTENZA, generously apply Cleansing Gel to the treatment area and leave on for at least one minute.

Remove Cleansing

Gel with a dry wipe and gently wash the area with mild soap and water. Dry thoroughly. Dispose of all treatment materials as described [see Dosage and Administration ( 2.1 )] . Inform the patient that the treated area may be sensitive for a few days to heat (e.g., hot showers/baths, direct sunlight, vigorous exercise). USE IN NEUROPATHIC PAIN ASSOCIATED WITH DIABETIC PERIPHERAL NEUROPATHY (30-MINUTE APPLICATION TIME ON THE FEET)

Prepare

Administer QUTENZA in a well-ventilated treatment area. Put on nitrile (not latex) gloves. Use of a face mask and protective glasses is advisable for healthcare professionals. Inspect the pouch. Do not use if the pouch has been torn or damaged.

Identify

The treatment area (painful area including areas of hypersensitivity and allodynia) must be identified by a physician or healthcare professional and marked on the skin. Examine the feet prior to application of QUTENZA to detect skin lesions related to underlying neuropathy or vascular insufficiency. If necessary, clip hair (do not shave) in and around the identified treatment area to promote QUTENZA adherence. QUTENZA can be cut to match the size and shape of the treatment area. Gently wash the treatment area with mild soap and water, and dry thoroughly. Anesthetize (optional) The treatment area may be pretreated with a topical anesthetic to potentially reduce discomfort associated with the application of QUTENZA. Apply topical anesthetic to the entire treatment area and surrounding 1 to 2 cm, and keep the local anesthetic in place until the skin is anesthetized prior to the application of QUTENZA. Remove the topical anesthetic with a dry wipe. Gently wash the treatment area with mild soap and water, and dry thoroughly.

Apply

Tear open the pouch along the three dashed lines and remove QUTENZA. Inspect QUTENZA and identify the outer surface backing layer with the printing on one side and the capsaicin-containing adhesive on the other side. The adhesive side of QUTENZA is covered by a clear, unprinted, diagonally cut release liner. Cut QUTENZA before removing the protective release liner. Ensure that unused pieces do not make contact with other objects and are disposed of appropriately. The diagonal cut in the release liner is to aid in its removal. Peel a small section of the release liner back and place the adhesive side of QUTENZA on the treatment area. While you slowly peel back the release liner from under the QUTENZA with one hand, use your other hand to smooth QUTENZA down onto the skin. QUTENZA can be wrapped around the dorsal, lateral, and plantar surfaces of each foot to completely cover the treatment area. Once QUTENZA is applied, leave in place for 30 minutes on the feet (DPN). To ensure QUTENZA maintains contact with the treatment area, a dressing, such as rolled gauze, may be used. Remove the nitrile gloves after the application. Instruct the patient not to touch QUTENZA or the treatment area.

Remove

Put on nitrile (not latex) gloves. Remove QUTENZA by gently and slowly rolling inward.

Cleanse

After removal of QUTENZA, generously apply Cleansing Gel to the treatment area and leave on for at least one minute.

Remove Cleansing

Gel with a dry wipe and gently wash the area with mild soap and water. Dry thoroughly. Dispose of all treatment materials as described [see Dosage and Administration ( 2.1 )] . Inform the patient that the treated area may be sensitive for a few days to heat (e.g., hot showers/baths, direct sunlight, vigorous exercise).

Figure

2.3-1 Figure 2.3-2 Figure 2.3-3 Figure 2.3-4 Figure 2.3-5 Figure 2.3-6 Figure 2.3-7 Figure 2.3-8 Figure 2.3-9 Figure 2.3-10

4.

Contraindications

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.

5. 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.

6.

Drug Interactions

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)

Active Ingredients Purpose Menthol 4% .................................................Topical Analgesic Capsaicin 0.025% .........................................Topical Analgesic Active Ingredient Section

Inactive ingredients: Aloe Barbadensis (Aloe Vera)

Leaf

Juice, Aqua (Purified Water), Arnica Montana (Arnica)

Flower

Extract, Beta-Sitosterol, Bisabolol, C12-15 Alkyl Benzoate, C13-14 Isoparaffin, Calcium Pantothenate (Vitamin B5), Calendula Officinalis (Calendula)

Flower

Extract, Carthamus Tinctorius (Safflower) Oleosomes, Cetearyl Alcohol, Chamomilla Recutita (Matricaria)

Flower

Extract, Dimethicone, DL-Alpha-Tocopheryl Acetate (Vitamin E), Escin, Ginkgo Biloba (Ginkgo)

Leaf

Extract, Glycerin, Glyceryl Stearate, Imidazolidinyl Urea, Isopropyl Myristate, Laureth-7, Lecithin, Maltodextrin, Myristyl Myristate, Niacinamide (Vitamin B3), Nylon-12, PEG-100 Stearate, Peucedanum Ostruthium (Masterwort)

Leaf

Extract, Phenoxyethanol, Polyacrylamide, Pyridoxine HCl (Vitamin B6), Silica, Sodium Ascorbyl Phosphate (Vitamin C), Sodium Hyaluronate, Sodium Starch Octenylsuccinate, Zingiber Officinale (Ginger)

Root

Extract.