Capsaicin and menthol are used together in an external preparation for the temporary relief of minor aches and pains associated with arthritis, simple backache, strains, bruises, and sprains. Capsaicin and menthol, known for their characteristic heating and cooling effects, respectively, work synergistically to diminish pain. Capsaicin; menthol products are over the counter preparations and have not been reviewed or approved by the FDA.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
Cream/Ointment/Lotion Formulations
Gel and Solution
-Squeeze desired amount of gel onto affected area.
-Using the sponge-top applicator, massage dispensed gel into painful area until thoroughly absorbed.
-Avoid contact with eyes and mucous membranes.
-Do not bandage tightly or use with a heating pad.
-Do not apply to wounds or damaged, broken or irritated skin.
-Do not expose the area treated with product to heat or direct sunlight.
Transdermal Patch Formulations
-Clean and dry the affected area.
-Remove any protective film and apply to the affected area.
-Wash hands with soap and water after handling the patch.
-Discontinue use at least 1 hours before a bath or shower. Do not use immediately following a bath or shower.
-Storage: Reseal pouch containing unused patches after each use. Do not store the patch outside the sealed envelope.
-Disposal: Fold used patches so the adhesive side sticks to itself. Discard in a place that children and pets cannot access.
The most common adverse effect associated with use of capsaicin; menthol is transient skin irritation, application site reactions including dermatitis, pruritus (greater than or equal to 10% of patients), scaling (greater than or equal to 10% of patients), erythema (greater than or equal to 10% of patients) and/or paresthesias (e.g., burning, stinging, warm sensation) at the site of application; the severity of this effect appears to be dose related. During clinical trials, the use of the capsaicin 8% topical patch 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%). 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.
In September 2012, the FDA 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. Post-marketing 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 or menthol 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 has been reported rarely upon removal of clothing or bed sheets that have covered the site of application. This effect has been attributed to respiratory irritation from inhalation of the residue of the dried cream. In addition, cough, sneezing, nasal irritation, and throat irritation have been reported in patients treated with capsaicin. Do not hold capsaicin products or any treatment materials near the face. Infections that have been reported during use include bronchitis, naso-pharyngitis, and sinusitis.
Capsaicin and capsaicin-containing products should not be used in patients who are known to be sensitive to the fruits of capsicum plants (e.g., hot peppers) or other components of the preparation.
Capsaicin; menthol should not be applied to areas with skin abrasion, irritation, infection, or inflammation. Due to the potential for enhanced absorption, capsaicin and capsaicin-containing preparations should not be used with a heating pad, applied after strenuous exercise, or be tightly bandaged. In the days following treatment, treated areas may become more heat sensitive; patients may wish to avoid external heat from heating pads, hot baths or showers, artifical or natural sunlight (UV) exposure, and strenuous exercise until sensitivity resolves. When used for self-medication, if a person's condition worsens or if 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.
Capsaicin and menthol are both irritants; avoid mucous membrane, genital, and ocular exposure to drug product, dried residue, or any treatment materials. Do not hold capsaicin; menthol products or treatment materials near the face. If capsaicin; menthol comes in contact with the eyes, rinse well with water; advise patients to seek medical help if irritation persists. Handle all capsaicin; menthol products with care, using appropriate precaution to avoid accidental exposure to non-treatment areas of skin.
Adequate and well-controlled studies of capsaicin; menthol in pregnant women have not been conducted. No evidence of fetal teratogenicity was demonstrated in rats using capsaicin patches at doses of up to 11 times the recommended human maximum dose or in rabbits using capsaicin liquid at doses of up to 37 times the recommended human maximum dose. During use of capsaicin patches in pregnant rats, there were no adverse effects observed on survival, growth, learning and memory tests, sexual maturation, mating, pregnancy, or fetal development. Because animal studies are not always predictive of human response, capsaicin topical products should be used during pregnancy only when clearly indicated. The effects of capsaicin during labor and obstetric delivery are unknown. Adequate and well controlled studies of topical menthol use during pregnancy have not been conducted. Consider the potential for risks and benefits to both mother and fetus.
It is not known if capsaicin is excreted in human milk. Adequate study has not been conducted in infants exposed to capsaicin, a natural component of 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. Because 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.
Adequate and well controlled study of topical menthol use during pregnancy has not been conducted. The American Academy of Pediatrics has not made a determination regarding the use of menthol and breast-feeding. Do not use menthol on or near the breast where baby might ingest it during breast-feeding, and use care not to make contact with the skin of an infant or very young child. There have been cases where the direct application of menthol topical products to an infant's skin resulted in severe breathing difficulties.
Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
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.
For the treatment of mild pain to moderate pain associated with arthritis, simple backache, muscle strains, sprains, bruises, or cramps:
Topical dosage (Capzasin Quick Relief Gel or Absorbine Jr. Arthritis Extra Strength Topical Solution):
Adults 18 years of age and older: Apply to affected area as needed, not to exceed 3 to 4 times per day.
Transdermal dosage (e.g., RelyyT, Sinelee, Capsiderm, MaC):
Adults, Adolescents, and Children 12 years of age and older: Apply 1 patch to affected area of intact skin every 8 hours as needed. If irritation occurs, remove the patch and do not reapply until the irritation subsides.
Maximum Dosage Limits:
-Adults
Topical gel or topical solution: 4 applications per day.
Transdermal patch: 3 applications per day.
-Geriatric
Topical gel or topical solution: 4 applications per day.
Transdermal patch: 3 applications per day.
-Adolescents
Topical gel or topical solution: Safety and efficacy have not been established.
Transdermal patch: 3 applications per day.
-Children
Topical gel or topical solution: Safety and efficacy have not been established in children.
Transdermal patch:
Children 12 years of age and older: 3 applications per day.
Children less than 12 years of age: 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; Menthol products.
Mechanism of Action:-Capsaicin: 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 not a traditional counterirritant since it does not produce vasodilation.
-Menthol: Local effects including mild analgesia, cooling sensation, irritant/counter-irritant effect, and vasodilation have been attributed to topical menthol application. The exact mechanism of these actions is not well defined and primarily based on observation. Analgesia may occur directly through interaction with kappa-opioid receptors or indirectly through nociceptor activation and resultant counter-irritant effect.
Capsaicin; menthol is administered topically. Menthol targets the kappa opioid receptor on the TRPM8 neuron. Menthol is rapidly metabolized to polyols and hydroxy acids that are excreted in these forms or as glucuronide conjugates. 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: 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
-Capsaicin: Following the topical application of capsaicin, the duration of action is 4 to 6 hours; maximal relief of neuropathic and arthritic pain is usually noted with 2 weeks of continuous therapy, although may not be observed for 4 to 6 weeks. Application of a single capsaicin 8% topical patch resulted in systemic exposure to capsaicin in 1/3 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 greater than or equal to 30% relief of postherpetic neuralgia in as soon as 1 week and persisting for up to 12 weeks following application.
-Menthol: Limited pharmacokinetic study has been conducted with cutaneous menthol. However, low levels of systemic exposure have been demonstrated following the use of menthol; camphor; methyl salicylate combination topical patches. Eight hour application of various numbers of patches resulted in menthol systemic exposure in all study patients. Average maximum menthol plasma concentrations of 7.6 +/- 2.6 ng/mL, 19 +/- 5.4 ng/mL, and 31.9 +/- 8.8 ng/mL were measured following the use of 74.88 mg, 149.76 mg, and 299.52 mg of menthol. Menthol was no longer detectable 8 to 12 hours after patch removal following the use of 74.88 mg of menthol, a normal dose for this product. Based on data from each of the 3 administered doses, a menthol terminal half-life of 3 to 6 hours was estimated.