Capsaicin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Cream, topical:

Capzasin-HP: 0.1% (42.5 g) [contains benzyl alcohol]

Capzasin-P: 0.035% (42.5 g) [contains benzyl alcohol]

Capzix: 0.1% (56.6 g) [contains benzyl alcohol, cetyl alcohol]

Sure Result SR Relief: 0.025% (118 mL)

Trixaicin: 0.025% (60 g [DSC]) [contains benzyl alcohol]

Trixaicin HP: 0.075% (60 g) [contains benzyl alcohol]

Zostrix HP: 0.1% (60 g) [contains benzyl alcohol]

Zostrix Maximum Strength Natural Pain Relief: 0.1% (56.6 g) [contains benzyl alcohol]

Zostrix Maximum Strength Natural Foot Pain Relief: 0.1% (56.6 g) [contains benzyl alcohol]

Zostrix Original Strength Natural Pain Relief: 0.033% (56.6 g) [contains benzyl alcohol]

Generic: 0.025% (25 g, 50 g, 60 g, 120 g)

Gel, topical:

Capzasin-P: 0.025% (42.5 g) [contains menthol]

Liquid, topical:

Capzasin-P: 0.15% (29.5 mL)

Lotion, topical:

DiabetAid Pain and Tingling Relief: 0.025% (120 mL)

Patch, topical:

Allevess: 0.05% (15s) [contains menthol 5%]

Captracin: 0.0375% (15s [DSC]) [contains menthol 5%]

Flexin: 0.0375% (15s) [contains menthol 5%]

Levatio: 0.03% (15s) [contains menthol 5%]

MaC Patch: 0.0375% (15s) [contains menthol 5%] [DSC]

MenCaps: 0.0225% (15s) [contains menthol 4.5%]

Neuvaxin: 0.0375% (15s [DSC]) [contains menthol 5%]

Qutenza: 8% (1s, 2s) [contains metal; supplied with cleansing gel]

Releevia: 0.0375% (15s [DSC]) [contains menthol 5%]

Releevia MC: 0.0375% (15s [DSC]) [contains menthol 5%]

Renovo: 0.0375% (15s) [contains menthol 5%]

Sinelee: 0.0375%, 0.05% (15s [DSC]) [contains menthol 5%]

Salonpas Gel-Patch Hot: 0.025% (3s, 6s) [contains menthol]

Salonpas Hot: 0.025% (1s [DSC]) [contains natural rubber/natural latex in packaging]

Pharmacology

Mechanism of Action

Capsaicin, a transient receptor potential vanilloid 1 receptor (TRPV1) agonist, activates TRPV1 ligand-gated cation channels on nociceptive nerve fibers, resulting in depolarization, initiation of action potential, and pain signal transmission to the spinal cord; capsaicin exposure results in subsequent desensitization of the sensory axons and inhibition of pain transmission initiation. In arthritis, capsaicin induces release of substance P, the principal chemomediator of pain impulses from the periphery to the CNS, from peripheral sensory neurons; after repeated application, capsaicin depletes the neuron of substance P and prevents reaccumulation. The functional link between substance P and the capsaicin receptor, TRPV1, is not well understood.

Pharmacokinetics/Pharmacodynamics

Absorption

Topical patch (capsaicin 8%): Systemic absorption is transient and low (<5 ng/mL) in approximately one-third of patients when measured following 60-minute application. In patients with quantifiable concentrations, most fell below the limit of quantitation at 3 to 6 hours post application.

Onset of Action

OTC products (capsaicin 0.025% to 0.1%): 2 to 4 weeks of continuous therapy; Qutenza patch: 1 week after application

Half-Life Elimination

Topical patch (capsaicin 8%): 1.64 hours (Babbar 2009)

Use: Labeled Indications

Muscle/Joint pain: Temporary relief of minor aches and pain of muscles and joints associated with backache, strains, sprains, arthritis, bruises, cramps, or muscle stiffness or soreness.

Neuropathic pain: Management of neuropathic pain associated with diabetic neuropathy or postherpetic neuralgia.

Use: Off Label

Burning mouth syndrome (topical)c

Data from a prospective, double-blinded, placebo-controlled, randomized cross-over study in patients with burning mouth syndrome suggests that capsaicin 0.02% oral rinse (unavailable in the US) may be beneficial for the treatment of this condition (Silvestre 2012). In addition, data from a limited number of patients studied (single case report) suggest that topical capsaicin (Tobasco sauce diluted in water), may be beneficial for the treatment of burning mouth syndrome (Spice 2004). Data from a prospective, triple-blind, randomized, placebo-controlled study demonstrated that the use of systemic capsaicin 0.25% capsules (unavailable in the US) is effective for the short-term treatment of burning mouth syndrome but significant gastrointestinal side effects were seen (Petruzzi, 2004). Because of the side effects seen with systemic capsaicin, some authors do not recommend the use of capsaicin for this condition. Instead, other treatments are recommended (eg, topical clonazepam) (Minquez Serra 2007). Additional data may be necessary to further define the role of capsaicin in treatment of burning mouth syndrome. Optimal dosing has yet to be established.

Diabetic neuropathyyes

Based on the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation guidelines for the treatment of painful diabetic neuropathy, capsaicin 0.075% given for diabetic neuropathy is probably effective and recommended in the management of this condition.

Pain associated with psoriasis and intractable pruritusb

Data from two double-blind randomized clinical trials in patients with pruritic psoriasis suggest that capsaicin cream may be beneficial for the treatment of pain associated with psoriasis and intractable pruritus (Bernstein, 1986; Ellis, 1993). Additional trials may be necessary to further define the role of capsaicin in this condition.

Contraindications

Hypersensitivity to capsaicin, menthol, or any component of the formulation.

OTC labeling: When used for self-medication, do not use on wounds, damaged, broken, or irritated skin; do not cover with bandage; do not use in combination with external heat source (eg, heating pad).

Dosage and Administration

Dosing: Adult

Muscle/joint pain: Topical:

Cream, gel, liquid, lotion: Apply thin film to affected areas 3 to 4 times daily.

Patch: 0.025%, 0.03%, 0.0375%, 0.05% (Sinelee only): Apply 1 patch to affected area for up to 8 hours (maximum: 4 patches/day); do not use for >5 consecutive days (product specific)

Neuropathic pain: Topical: Patch (Qutenza): Apply patch to most painful area for 60 minutes. Up to 4 patches may be applied in a single application. Treatment may be repeated ≥3 months as needed for return of pain (do not apply more frequently than every 3 months). Area should be pretreated with a topical anesthetic prior to patch application.

Diabetic neuropathy (off-label use): Topical: Cream (0.075%): Apply 4 times/day (Bril 2011)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Muscle ache and joint pain, minor: Topical:

Lotion 0.025% (DiabetAid Tingling and Pain Relief) Children ≥2 years and Adolescents: Topical: Apply to affected area not more than 3 to 4 times/day

Patch: Note: With OTC products, approved ages and uses may vary; consult product specific labeling.

Product strength <0.05%: Adolescents ≥12 years: Topical:

Flexin (0.0375%): Apply 1 patch to affected area; may change 2 to 3 times/day; maximum daily dose: 3 patches/day

Levatio (0.03%): Apply 1 patch to affected area for up to 8 hours; change patch 1 to 2 times daily; maximum daily dose: 4 patches/day; do not use for >5 consecutive days

MaC (0.0375%): Apply 1 patch to affected area for up to 8 hours; change patch 2 to 3 times/day; maximum daily dose: 4 patches/24 hours

MenCaps (0.0225%): Apply 1 patch to affected area for up to 8 hours; may change patch up to 3 times daily

Releevia MC (0.0375%), Renovo (0.0375%): Apply 1 patch to affected area; may change patch 1 to 2 times daily; maximum daily dose: 3 patches/day

Salonpas Pain Relieving Hot Patch (0.025%): Apply 1 patch to affected area for up to 8 hours; may change patch up to 3 to 4 times daily

Product strength 0.05%: Adolescents ≥16 years: Topical: Allevess patch: Apply 1 patch to affected area; may change patch 1 to 2 times daily

Administration

Topical products (cream, gel, liquid, lotion): Gently rub into painful area until thoroughly absorbed. Wash hands with soap and water immediately after applying (unless hands are part of the treatment area). If applying cream to hands, wait 30 minutes before washing hands.

Topical patch: Apply patch externally to clean and dry affected area. Remove protective film prior to application. May cut patch to desired size prior to removing the film (product specific). Do not use within 1 hour prior to a bath or immediately after bathing. Do not use with a heating pad.

Topical patch (Qutenza): Patch should only be applied by a health care provider. The treatment area must be identified and marked by a physician. May cut patch to match size/shape of treatment area. If necessary, excessive hair present on and surrounding the treatment area, may be clipped (not shaved). Prior to application, the treatment area should be cleansed with mild soap and water and dried thoroughly. The treatment area and surrounding 1 to 2 cm should be anesthetized with a topical anesthetic prior to patch application; keep the local anesthetic in place until the skin is anesthetized and then remove with a dry wipe; cleanse area again with soap/water, and dry thoroughly. Patch may then be applied to dry, intact skin within 2 hours of opening the patch; apply patch using nitrile gloves (latex gloves should not be used). During application, slowly peel back the release liner under the patch. Patch should remain in place for 60 minutes. Remove patches gently and slowly. Following patch removal, apply cleansing gel to the treatment area and leave in place for at least 1 minute. Remove cleansing gel with a dry wipe and gently wash the area with mild soap and water and dry thoroughly. All treatment materials should be disposed of according to biomedical waste procedures.

Storage

Store at room temperature; protect from light.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

The following adverse events occurred with topical patch administration.

>10%: Local: Localized erythema (63%), local pain (42%)

1% to 10%:

Cardiovascular: Hypertension (2%; transient)

Dermatologic: Papule (6%), local dryness (2%), pruritus (2%)

Gastrointestinal: Nausea (5%), vomiting (3%)

Local: Local pruritus (6%), localized edema (4%), local swelling (2%)

Respiratory: Nasopharyngitis (4%), sinusitis (3%), bronchitis (2%)

<1%, postmarketing, and/or case reports: Abnormal skin odor, application site reactions (includes bruise, dermatitis, desquamation, excoriation, hyperesthesia, inflammation, paresthesia, urticaria), burning sensation of skin, cough, dizziness, dysgeusia, headache, hypoesthesia, peripheral edema, peripheral sensory neuropathy, throat irritation

Warnings/Precautions

Concerns related to adverse effects:

• Burns: May cause serious burns (eg, first- to third-degree chemical burns) at the application site. In some cases, hospitalization has been required. Discontinue use and seek medical attention if signs of skin injury (eg, pain, swelling, or blistering) occur following application (FDA Drug Safety Communication, 2012).
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with uncontrolled hypertension or a history of cardiovascular events; transient increases in blood pressure due to treatment-related pain have occurred during and after application of RX patch.
• Cerebrovascular disease: Use with caution in patients with a history of cerebrovascular events; transient increases in blood pressure due to treatment-related pain have occurred during and after application of RX patch.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.
• Patch: Avoid inhaling airborne material from dried residue. Remove patches gently and slowly to decrease risk of aerosolization; inhalation of airborne capsaicin may result in coughing or sneezing.
• Qutenza: If skin not intended to be treated comes in contact with capsaicin, apply provided cleansing gel for one minute and wipe off with dry gauze; then wash the area with soap and water. Post-application pain should be treated with local cooling methods (ice pack) and/or analgesics.

Other warnings/precautions:

• Appropriate use: For external use only; avoid contact with eyes, mouth, genitals, or any or other mucous membranes. Do not use immediately before or after activities such as bathing, swimming, showering, sun bathing, strenuous exercise, steam bath, sauna, or other heat or sunlight exposure to the treated area. Stop use and consult a healthcare provider if excessive redness, blistering burning or irritation develops, symptoms get worse, symptoms persist for >7 days, symptoms resolve and then recur, or if difficulty breathing or swallowing occurs. Do not handle contact lenses for 1 hour after handling, applying, or removing capsaicin (product specific).
• OTC labeling: Transient burning may occur and generally disappears after several days.
• RX labeling: Do not cover with bandage or compression. Use only on intact skin; do not use on wounds, damaged, broken, infected, sensitive or inflamed skin. Do not apply to face or scalp. Do not use concurrently with other external pain-relieving products.

Pregnancy

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies with capsaicin patch or liquid. Systemic absorption is limited following topical administration of the patch; plasma concentrations are below the limit of detection 3 to 6 hours after the patch is removed.

Patient Education

What is this drug used for?

• It is used to ease muscle and joint aches and pain.
• It is used to help diabetic nerve pain.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Skin irritation
• Burning or stinging feeling
• Application site pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe headache
• Severe dizziness
• Passing out
• Vision changes
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.