Capsaicin is an external analgesic. As the major pungent ingredient of hot chile peppers and other botanicals, capsicum preparations (e.g., capsaicin, capsicum, and capsicum oleoresin) can be derived from the fruit of various species of plants of the Solanaceae (i.e., nightshade) family or synthetically. Capsaicin is available as a topical solution, creams, and transdermal patches are available over-the-counter for the temporary relief of pain from arthritis, myalgias, arthralgias, and neuralgias. The FDA has granted capsaicin orphan drug status in the treatment of postherpetic neuralgia, intermetatarsal neuroma, erythromelalgia, and HIV-associated neuropathy. The prescription-only capsaicin 8% patch is approved for the management of neuropathic pain associated with postherpetic neuralgia (PHN) and for the management of diabetic neuropathy of the feet.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
-Do not apply to open wounds, infections, or irritated skin.
-Do not apply external heat or occlusive dressings to treated areas.
-Avoid contact with eyes and mucous membranes. If eye contact occurs, immediately wash out the eye with water or saline, and consult a physician if irritation persists.
Cream/Ointment/Lotion Formulations
-Apply sparingly; rub well into the affected area until thoroughly absorbed.
-Wash hands with soap or water after applying to avoid getting into eyes or other sensitive areas of the body. However, if used on arthritic hands, do not wash hands for at least 30 minutes after application.
-The capsaicin 0.025% and 0.05% DermacinRx cream formulations are flammable. Avoid heat, flame, or smoking during and immediately following application of the foam.
Transdermal Patch Formulations
Capsaicin low-concentration (0.025%, 0.075%, and 0.25%) transdermal patch:
-Clean and dry intended treatment area prior to patch application.
-Apply patch according to package instructions.
-Wash hands with soap or water after applying to avoid getting into eyes or other sensitive areas of the body.
Capsaicin high-concentration (8%) transdermal patch:
-Do not allow patients to self-administer capsaicin 8% topical patch; administration must only be undertaken by a health care professional familiar with proper dosing, handling, and disposal of the product.
-Administer the patch in a well ventilated area.
-Use nitrile gloves at all times while handling and disposing of capsaicin topical patch and while in contact with treatment area(s); do not use latex gloves as latex gloves do not provide full protection. It is advisable for health care professionals to utilize a face mask and protective glasses.
-Avoid unnecessary contact with items in the room, including items that the patient may later have contact with, such as horizontal surfaces and bedsheets.
-Do not hold medicated patch near eyes, nose, or mouth. Avoid application to the face, eyes, nose, or scalp to avoid exposure risk to the eyes or mucous membranes.
-Treatment location must be identified and marked on the skin by the treating physician. When used for diabetic neuropathy, examine the feet prior to patch application to detect skin lesions related to underlying neuropathy or vascular insufficiency.
-Trim capsaicin topical patch to fit the size and shape of the treatment area as needed.
-Prepare skin for treatment by clipping hair (do not shave) within the area and gently washing with mild soap. Next, apply a topical anesthetic prior to patch application in an effort to reduce capsaicin-induced discomfort. Apply the anesthetic to the entire treatment area, including the 1 to 2 cm surrounding the treatment area. Once the skin is anesthetized, remove the anesthetic with a dry wipe. Wash the treatment area with mild soap and water; dry thoroughly.
-Apply the patch(es) by aligning the patch(es) with the treatment area(s), then slowly removing capsaicin release liner while smoothing patch down on to the skin. Patches can be wrapped around the dorsal, lateral, and plantar foot surfaces of each foot to completely cover the treatment area. Use a 30-minute application time for diabetic neuropathy and a 60-minute application time for postherpetic neuralgia.
-A dressing, such as rolled gauze, may be used to maintain patch contact with skin.
-Instruct patients to avoid touching the patch or treatment area during treatment.
-Remove patch(es) by gently rolling inward after treatment is complete.
-Clean treatment area with the supplied cleansing gel. Apply gel over the entire area, leave the gel on for 1 minute, then gently remove gel with a dry wipe and wash area with mild soap and water.
-Thoroughly clean all areas that had contact with the patch and dispose of used and unused cleansing gel, patch(es), and other treatment materials in accordance with local biomedical waste procedures.
Other Topical Formulations
Topical Solution Formulations:
-Massage into the affected area until thoroughly absorbed.
-Avoid taking a bath or shower within 1 hour before or after application.
The most common adverse effect associated with the use of capsaicin is transient skin irritation and/or paresthesias (e.g., burning, stinging, warm sensation) at the site of application; the severity of this effect appears to be dose-related. With the use of capsaicin 0.025% or 0.075% cream, this sensation usually disappears after the first several days of continuous treatment; however, it may persist for 2 to 4 weeks or longer. Factors such as exposure of the treated area to heat or humidity, direct sunlight, wrappings (e.g., clothing or bandages), bathing in warm water, or sweating may intensify the sensation. The burning or stinging sensation produced during initial administration may be prolonged if capsaicin cream is applied less than 3 to 4 times per day. During clinical trials, the use of the capsaicin 8% topical patch in patients with postherpetic neuralgia was associated with application site reactions including erythema (63%), pain (42%), pruritus (6%), papules or maculopapular rash (6%), edema (4%), swelling (2%), and dryness or xerosis (2%). In a clinical trial of the patch in patients with diabetic neuropathy (n = 186), application site reactions included burning sensation (14%), pain (10%), and erythema (2%). The majority of reactions were considered mild to moderate. Reactions may necessitate local anesthetic pretreatment; even with such pretreatment, application site reactions may still occur. Increases in pain with capsaicin 8% patch therapy were considered transient, on average starting during patch application, beginning to resolve after patch removal, and returning to baseline by the end of treatment day. However, 3% of patients reported a sustained increase in pain level. Other application site reactions reported following treatment with capsaicin 8% topical patch in postherpetic neuralgia trials include contact dermatitis, urticaria, ecchymosis (bruising), exfoliation, inflammation, anesthesia, site warmth, excoriation, and hyperesthesia. Excoriation (2%) and blisters (less than 1%) were reported is the diabetic neuropathy trial. Second-degree burn and scarring have been reported with postmarketing use of the capsaicin patch. Generalized pruritus (2%) and drug-induced body odor (abnormal skin odor) have also occurred. Skin irritation is related to the initial excitatory effect of capsaicin on type C fibers and their release of substance P. In clinical trials of capsaicin cream, patients with arthritis or postmastectomy pain generally experience less intense burning than do patients with peripheral neuropathies. Although the reason(s) for this difference is unclear, it may be related to the differences in etiology or pathogenesis of the pain syndromes. The FDA has warned healthcare providers and consumers about the rare risk of serious skin injuries, including first- to third-degree burns, with the use of over the counter topical analgesics used for mild muscle and joint pain. Postmarketing surveillance and medical literature review detected 43 cases of burns on application sites with the use of topical analgesic patches, balms, and creams. Few cases have been reported with capsaicin containing products. Many burns appeared in areas where the product was applied following 1 application, with severe burning or blistering occurring within 24 hours. Some burns resulted in hospitalization. Patients should not apply topical analgesics such as capsaicin to wounds or broken, irritated skin, and the area should not be tightly wrapped or bandaged. Contact with mucous membranes and application of heat to the affected area should be avoided. Items such as heating pads, lamps, or hot water bags and bottles may increase the risk of burns. Discuss the risk of burns with patients, as warnings on over the counter topical analgesics for joint or muscle pain are not required. Patients who experience pain, skin blistering, or swelling should stop use and contact their healthcare provider for treatment.
Capsaicin is a known respiratory irritant. Cough, sneezing, nasal irritation, and throat irritation have been reported in patients treated with capsaicin. In a clinical trial of the capsaicin 8% topical patch in patients with diabetic neuropathy (n = 186), upper respiratory tract infection (4%) and cough (2%) were reported. Do not hold capsaicin products or any treatment materials near the face. Infections that have been reported during capsaicin patch use in postherpetic neuralgia include bronchitis (2%), naso-pharyngitis (4%), and sinusitis (3%).
Use of capsaicin 8% topical patch is associated with a transient increase in blood pressure related to treatment-induced increases in pain. Hypertension was reported in 2% of patients with postherpetic neuralgia treated with capsaicin 8% patch (n = 622) and 1% of patients treated with a control patch (contained a low concentration of capsaicin 0.04% to maintain blinding) (n = 495). In a clinical trial of the capsaicin 8% topical patch in patients with diabetic neuropathy (n = 186), hypertension was reported in 2% of patients treated with the patch. In clinical trials, blood pressure elevations averaged less than 10 mmHg and returned to baseline within two hours of patch removal; no lasting effect was measured at the 4, 8, or 12-week follow-up visits. Appropriate pain management during treatment may minimize risk.
Nausea (5%) and vomiting (3%) has been reported following treatment with capsaicin 8% topical patch.
In a clinical trial of the capsaicin 8% topical patch in patients with diabetic neuropathy (n = 186), pain in the extremity occurred in 11% of patients. Peripheral edema has been reported in patients following treatment with capsaicin 8% topical patch; the causality was not determined.
Screen patients with pre-existing sensory deficits for signs of sensory deterioration or loss prior to each application of capsaicin. Reductions in sensory function have been reported following the administration of the capsaicin 8% topical patch. If sensory deterioration or loss is detected or pre-existing sensory deficit worsens, continued use of capsaicin treatment should be reconsidered. In clinical trials involving patients with postherpetic neuralgia using the capsaicin 8% patch, reported CNS effects included headache, burning sensation, peripheral neuropathy (specifically peripheral sensory neuropathy), dizziness, dysgeusia, hyperesthesia, and hypoesthesia. In a clinical trial of the capsaicin 8% topical patch in patients with diabetic neuropathy (n = 186), headache (3%), dizziness (less than 1%), and dysesthesia (less than 1%) were reported.
Capsaicin should not be used in patients who are known to be sensitive to the fruits of capsicum plants (e.g., hot peppers).
Capsaicin should not be applied to areas with skin abrasion, irritation, infection, or inflammation. Due to the potential for enhanced absorption, do not apply capsaicin within 1 hour before or after a bath, shower, hot tub, sauna, or strenuous exercise. Do not use capsaicin with a heating pad, hot water bottle, or other sources of heat due to increased burn risk. Do not tightly wrap or bandage the treated area. Treated areas may be sensitive to heat, including hot showers or bath, direct sunlight (UV) exposure, or vigorous exercise for a few days after treatment. If condition worsens or symptoms persist for more than 7 days, or clear up and occur again within a few days, therapy should be discontinued and a physician should be consulted. Patients should discontinue capsaicin and seek immediate medical attention if experience burning, pain, swelling, or blistering of the skin. Screen patients with pre-existing sensory deficits for signs of sensory deterioration or loss prior to each application of capsaicin. Reductions in sensory function have been reported following the administration of the capsaicin 8% patch. If sensory deterioration or loss is detected or pre-existing sensory deficit worsens, continued use of capsaicin treatment should be reconsidered.
Generally, use of capsaicin topical cream is not recommended in children, except under the direction of a physician. The manufacturers of some over-the-counter capsaicin 0.25% products include directions for use in children as young as 10 years of age; refer to specific package directions. The safety and efficacy of capsaicin 8% topical patch has not been established in patients less than 18 years of age. Capsacian may cause skin irritation in infants and neonates, so they generally should not come in contact with the products.
Adequate and well-controlled studies of capsaicin in women during pregnancy have not been conducted. Capsaicin is negligibly absorbed systemically following topical administration of the patch, and maternal use is not expected to result in fetal exposure. No malformations were observed when capsaicin was administered daily by the topical route to pregnant rats (patch) and rabbits (liquid) during the period of organogenesis at doses of up to 11 and 37 times, respectively, the maximum recommended human dose (MRHD) of the capsaicin 8% topical patch at 716 mg capsaicin per day (4 patches containing 179 mg/patch). No adverse effects were observed when the capsaicin patch was applied for 3-hours, once daily to rats during gestation and lactation at doses of up to 11 times the MRHD. The effects of capsaicin during labor and obstetric delivery are unknown.
Capsaicin is negligibly absorbed systemically by the mother following topical administration of the capsaicin patch, and breast-feeding is not expected to result in exposure of the infant to capsaicin. There are no data on the effects of capsaicin on milk production. Manufacturer recommendations for breast-feeding mothers are not available for less potent, non-prescription capsaicin formulations. Adequate studies have not been conducted in infants exposed to capsaicin, a component of cayenne peppers, via breast milk or direct administration. Adverse effects, including erythematous rash with desquamation, have been reported in nursing infants whose mothers ingested foods flavored with red pepper. Since mild to severe skin irritation may occur following topical application of capsaicin, the infant's skin should not come into direct contact with areas of the mother's skin that have been treated. Avoid applying capsaicin directly to the nipple and areola to minimize potential direct exposure to the infant. Consider the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for capsaicin and any potential adverse effects on the breastfed infant from capsaicin or from the underlying maternal condition.
Unintended exposure to capsaicin can cause severe irritation of eyes, mucous membranes, respiratory tract, and skin. Avoid mucous membrane and ocular exposure to capsaicin. Do not apply the capsaicin patch to the face, eyes, mouth, nose, or scalp. If capsaicin comes in contact with the eyes, rinse well with water; advise patients to seek medical help if irritation persists. Handle capsaicin products with care, using appropriate precautions to avoid accidental exposure to non-treatment areas of skin. Aerosolization of capsaicin from the 8% patch is possible if the patches are rapidly removed; take care to remove patches gently by slowly rolling the adhesive side inward. Accidental exposure to the eyes and mucus membrane can occur from touching the patch or items exposed to capsaicin and then touching the eyes and mucus membranes. Do not dispense capsaicin 8% topical patch for self-administration; administration must be undertaken only by physicians or other health care professionals, under the supervision of the treating physician, who are familiar with the administration, handling, and disposal of the capsaicin 8% topical patch. Administration of the 8% patch should be done in a well-ventilated area. If irritation of eyes or mucous membranes occurs, remove the affected individual from the vicinity of the patch and flush eyes and mucous membranes with cool water. Inhalation of airborne capsaicin can result in coughing or sneezing. If irritation of airways occurs, remove the affected individual from the vicinity of the patch. Provide supportive medical care if shortness of breath develops. If respiratory irritation worsens or does not resolve, do not re-expose the affected health care professional or patient to the patch. If skin not intended to be treated is exposed to the patch, apply the supplied cleansing gel for 1 minute and wipe off with dry gauze. After the cleansing gel has been wiped off, wash the area with soap and water.
When treated with topical products that contain 8% capsaicin patients may experience substantial procedural pain, even after use of a local anesthetic; acute pain should be treated with local cooling and appropriate analgesic medications. During the procedure, some patients experienced an elevation in blood pressure, likely induced by pain. Patients with poorly controlled hypertension, a recent cardiovascular event (e.g., myocardial infarction), or a recent cerebrovascular event (e.g., stroke) may be at an increased risk for an adverse cardiovascular event during treatment with capsaicin 8% topical patch because of the associated transient increase in blood pressure. In clinical trials, blood pressure elevations averaged less than 10 mmHg and appeared to be related to treatment-related increases in pain and not to pretreatment blood pressure. Further, blood pressure returned to baseline within two hours of patch removal with no lasting effect measured at the 4, 8, or 12 week follow-up visits. Monitor blood pressure and manage pain during treatment.
The capsaicin 0.025% and 0.05% DermacinRx cream formulations are flammable. Avoid use of the cream near a fire or flame, including tobacco smoking, during or immediately after application.
For the treatment of mild pain or moderate pain, including due to osteoarthritis, rheumatoid arthritis, or postmastectomy:
-for self-medication of pain associated with osteoarthritis or rheumatoid arthritis:
Topical dosage (cream, lotion, or solution):
Adults: Apply topically to affected joints 3 to 4 times daily; for best results use 3 to 4 times daily continuously.
-for self-medication of myalgia or arthralgia associated with bruises, simple backache, sprains, or strains:
Topical dosage (cream, lotion, or solution):
Adults: Apply topically to affected area(s) 3 to 4 times daily; for best results use 3 to 4 times daily continuously.
Topical dosage (0.025% topical patch):
Adults, Adolescents, and Children 12 years and Older: Apply topically to affected area 3 to 4 times daily for up to 7 days; remove patch within 8 hours.
-for pain associated with postmastectomy pain syndrome*:
Topical dosage (0.025% or 0.075% cream):
Adults: Fourteen patients applied capsaicin 0.025% topically 4 to 5 times per day for 4 weeks. A few patients who did not respond to the 0.025% cream were switched to 0.075% capsaicin applied 4 to 5 times per day. Of those completing the study, 8 patients were either pain free or had only mild pain. At least 50% improvement was observed in 12 of 14 patients. Burning upon initial application of capsaicin was reported to be insignificant.
For the treatment of neuropathic pain, including diabetic neuropathy and postherpetic neuralgia:
-for the treatment of diabetic neuropathy, including diabetic foot pain:
Topical dosage (capsaicin 8% dermal patch):
Adults: Apply up to 4 patches per application; patches should be applied for 30 minutes and repeated no more frequently than every 3 months as needed.
Topical dosage (Zostrix Neuropathy Cream 0.25%)*:
Adults, Adolescents, and Children 10 years and Older: Apply to the affected areas topically 2 to 4 times daily.
Topical dosage (0.075% products)*:
Adults: Several controlled studies have shown topical capsaicin 0.075% to be significantly more effective than vehicle cream in reducing neuropathic pain in patients with diabetic neuropathy who were unresponsive or intolerant to conventional therapy. In these studies, capsaicin 0.075% was applied topically to painful areas 4 times per day.
-for the treatment of postherpetic neuralgia:
Topical dosage (capsaicin 8% dermal patch):
Adults: Apply up to 4 patches per application; patches should be applied for 60 minutes and repeated no more frequently than every 3 months as needed.
Topical dosage (0.025% to 0.075% cream)*:
Adults: Apply 3 to 4 times daily to the affected areas topically for 4 to 6 weeks to achieve the desired effect on nociceptors.
Maximum Dosage Limits:
-Adults
Capsaicin 8% patch: up to 4 patches/treatment, wait a minimum of 3 months before repeat application. Solutions, lotions, and creams: 4 applications/day; the 0.025% and 0.075% concentrations have been used off-label up to 5 times/day for neuropathic pain and postmastectomy pain syndrome.
-Geriatric
Capsaicin 8% patch: up to 4 patches/treatment, wait a minimum of 3 months before repeat application. Solutions, lotions, and creams: 4 applications/day; the 0.025% and 0.075% concentrations have been used off-label up to 5 times/day for neuropathic pain and postmastectomy pain syndrome.
-Adolescents
Capsaicin 0.025%, 0.075%, and 0.25%: 4 topical applications/day; capsaicin 8% patch: safety and efficacy have not been established.
-Children
10 years and older: 4 topical applications/day of 0.25% capsaicin; 4 topical applications/day of 0.025% and 0.075% capsaicin has been suggested; safety and efficacy of capsaicin 8% patch have not been established.
3 to 9 years: 4 topical applications/day of 0.025% and 0.075% capsaicin has been suggested; safety and efficacy of capsaicin 0.25% and capsaicin 8% patch have not been established.
1 to 2 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Capsaicin products.
Capsaicin depletes and prevents reaccumulation of substance P in peripheral sensory neurons. Substance P is found in slow-conducting, unmyelinated type C neurons that innervate the dermis and epidermis. Substance P is thought to be the primary chemical mediator of pain impulses from the periphery to the central nervous system. It can also be released into joint tissues, where it activates inflammatory substances involved in the development of rheumatoid arthritis. By depleting substance P, capsaicin renders skin and joints insensitive to pain since local pain impulses cannot be transmitted to the brain. When capsaicin therapy is discontinued, substance P reaccumulates and neuronal sensitivity returns to normal.
Capsaicin is administered topically. Capsaicin binds to the TRPV1 proteins located on pain and heat neurons. Capsaicin is metabolized by CYP450 enzymes and carboxyesterase class enzymes; metabolites possess less potential at VR1 receptors.
Affected cytochrome P450 isoenzymes (Capsaicin): CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4
Capsaicin is extensively metabolized by CYP450 isoenzymes; however, clinically significant drug interactions are not expected.
-Route-Specific Pharmacokinetics
Topical Route
Following the topical application of capsaicin, systemic exposure is minimal. Application of a single capsaicin 8% topical patch resulted in low systemic exposure to capsaicin in one-third of an unstated number of studied patients; Cmax was less than 5 ng/mL in all patients and occurred at 60 minutes after patch application. The capsaicin plasma concentration of most patients was undetectable within 3 to 6 hours following patch removal. Use of a single 60 minute patch results in >= 30% relief of postherpetic neuralgia in as soon as 1 week and persisting for up to 12 weeks following application.