CLASSES

Topical Counterirritants (selected)

DEA CLASS

OTC, Rx

DESCRIPTION

External topical analgesic
Available over-the-counter for the temporary relief of pain from arthritis, myalgias, arthralgias, and neuralgias; prescription only patch approved for postherpetic neuralgia and diabetic neuropathy of the feet
Most common adverse effect 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

COMMON BRAND NAMES

Arthricare for Women, Arthritis Pain Relieving, Capzasin-HP, Castiva Warming, Circatrix, DermacinRx, DermacinRx Circata, DermacinRx Penetral, DiabetAid, Qutenza, Zostrix, Zostrix HP, Zostrix Neuropathy

HOW SUPPLIED

Arthricare for Women/Arthritis Pain Relieving/Capsaicin/Capzasin-HP/Circatrix/DermacinRx/DermacinRx Circata/DermacinRx Penetral/Zostrix/Zostrix HP/Zostrix Neuropathy Topical Cream: 0.025%, 0.05%, 0.075%, 0.1%, 0.25%
Capsaicin/Castiva Warming/DiabetAid Topical Lotion: 0.025%, 0.035%
Capsaicin/Qutenza Topical Film: 0.025%, 8%

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

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.

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.

Capsaicin 0.025%, 0.075%, and 0.25%: 4 topical applications/day; capsaicin 8% patch: safety and efficacy have not been established.

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.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

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.

STORAGE

Generic:
- Store at room temperature (between 59 to 86 degrees F)
Arthricare for Women:
- Store at room temperature (between 59 to 86 degrees F)
Arthritis Pain Relieving:
- Store at room temperature (between 59 to 86 degrees F)
Capzasin-HP:
- Store at room temperature (between 59 to 86 degrees F)
Capzasin-P:
- Storage information not listed
Castiva Warming:
- Storage information not listed
Circatrix:
- Avoid excessive heat (above 104 degrees F)
- Flammable, keep away from heat and flame
- Store at controlled room temperature (between 68 and 77 degrees F)
DermacinRx:
- Store at room temperature (between 59 to 86 degrees F)
DermacinRx Circata:
- Avoid excessive heat (above 104 degrees F)
- Flammable, keep away from heat and flame
- Store at controlled room temperature (between 68 and 77 degrees F)
DermacinRx Penetral:
- Store at room temperature (between 59 to 86 degrees F)
DiabetAid:
- Store between 59 to 77 degrees F
Qutenza:
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
- Store in original package until time of use
Zostrix:
- Store at room temperature (between 59 to 86 degrees F)
Zostrix HP:
- Store at room temperature (between 59 to 86 degrees F)
Zostrix Neuropathy:
- Store at room temperature (between 59 to 86 degrees F)

CONTRAINDICATIONS / PRECAUTIONS

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.[37523] [51397]

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.

ADVERSE REACTIONS

erythema / Early / 2.0-63.0
edema / Delayed / 4.0-4.0
hypertension / Early / 2.0-2.0
burns / Early / 0-0.5
hyperesthesia / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known

maculopapular rash / Early / 6.0-6.0
pruritus / Rapid / 2.0-6.0
nausea / Early / 5.0-5.0
infection / Delayed / 4.0-4.0
vomiting / Early / 3.0-3.0
headache / Early / 3.0-3.0
xerosis / Delayed / 2.0-2.0
cough / Delayed / 2.0-2.0
throat irritation / Early / 0-1.0
dizziness / Early / 0-1.0
dysesthesia / Delayed / 0-1.0
ecchymosis / Delayed / Incidence not known
drug-induced body odor / Delayed / Incidence not known
skin irritation / Early / Incidence not known
paresthesias / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
pharyngitis / Delayed / Incidence not known
sinusitis / Delayed / Incidence not known
nasal irritation / Early / Incidence not known
sneezing / Early / Incidence not known
dysgeusia / Early / Incidence not known
hypoesthesia / Delayed / Incidence not known

DRUG INTERACTIONS

There are no drug interactions associated with Capsaicin products.

PREGNANCY AND LACTATION

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.

MECHANISM OF ACTION

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.

PHARMACOKINETICS

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.