Capsaicin (Topical)


VA CLASSIFICATION
Primary: DE900

Commonly used brand name(s): Zostrix; Zostrix–HP.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Analgesic, specific pain syndromes (topical)—

antineuralgic, specific pain syndromes (topical)—

antipruritic (topical)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Neuralgia (treatment)—Capsaicin is indicated for the treatment of neuralgias, such as the pain following herpes zoster (shingles) and painful diabetic neuropathy {01} {03} {05} {11} {12} {13} {14} {15} {16} {17} {19} {21} {22} {43} {44} {46} {52} {53} {54} {55} {56} {58} {73}.

Osteoarthritis (treatment); or
Rheumatoid arthritis (treatment)—Capsaicin is indicated for the treatment of pain from osteoarthritis and rheumatoid arthritis {01} {03} {05} {15} {57}.

[Pain, neurogenic, other (treatment)]—Capsaicin is used to treat the pain associated with postmastectomy pain syndrome (PMPS) and reflex sympathetic dystrophy syndrome (RSDS, causalgia) {03} {15} {23} {45}.

[Pruritus, aquagenic (treatment) or {70} {74} ]
[Pruritus, hemodialysis-induced (treatment) {68} {74} ]—Capsaicin is used in the treatment of pruritus associated with hemodialysis and exposure to water (aquagenic).

Acceptance not established
Preliminary studies suggest capsaicin may be used to treat pruritus associated with psoriasis {67} {69} {74} . However, there are currently insufficient data to establish the safety and efficacy of capsaicin for this indication.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Capsaicin is a naturally occurring substance in plants of the Solanaceae family {01} {11} {15}.
Molecular weight—
    305.4 {01} {03}

Mechanism of action/Effect:

The precise mechanism of action has not been fully elucidated. Capsaicin is a neuropeptide-active agent that affects the synthesis, storage, transport, and release of substance P. Substance P is thought to be the principal chemical mediator of pain impulses from the periphery to the central nervous system. In addition, substance P has been shown to be released into joint tissues where it activates inflammatory intermediates that are involved with the development of rheumatoid arthritis. Capsaicin renders skin and joints insensitive to pain by depleting and preventing reaccumulation of substance P in peripheral sensory neurons. With the depletion of substance P in the nerve endings, local pain impulses cannot be transmitted to the brain. {01} {03} {05} {09} {10} {11} {15} {24} {48} {49} {50} {51} {56}

Note: Capsaicin is not a local anesthetic, since it only blocks the conduction of painful impulses carried by the type-C fibers, whereas local anesthetics block the conduction of impulses in all afferent neurons, which impairs all sensations including touch, pressure, heat, and vibration {03} {09} {40} {54}.
Capsaicin is not a traditional counterirritant, since it does not produce vasodilation {03} {65}.



Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Problems in humans have not been documented {01} {05}.

Breast-feeding

It is not known whether capsaicin, applied topically, is distributed into breast milk. However, problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of capsaicin have not been performed in infants and children up to 2 years of age {01} {05}. However, use in infants and children up to 2 years of age is not recommended.


Geriatrics


Appropriate studies on the relationship of age to the effects of capsaicin have not been performed in the geriatric population {03} {15}. However, geriatrics-specific problems that would limit the usefulness of this medication in the elderly are not expected {03} {15}.

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Broken or irritated skin on area to be treated{01}{03}{11}{65}    (will cause pain and further irritation of skin)


Risk-benefit should be considered when the following medical problem exists
Sensitivity to capsaicin{11}{18}{20} or to the fruits of Capsicum plants (e.g., hot peppers){47}


Side/Adverse Effects

Note: Capsaicin has no known systemic side effects {03}.
Patients may experience a warm, stinging, or burning sensation at the site of application, especially during the initial few days of use. Although this sensation frequently disappears after the first several days of treatment, it may persist for 2 to 4 weeks or longer. This effect is related to the initial excitatory effect of capsaicin on type-C fibers and their release of substance P. The burning usually decreases in frequency and intensity with continued administration of capsaicin. However, application schedules of capsaicin of less than 3 or 4 times daily may prolong the burning sensation while not providing optimum pain relief. Environmental factors, such as heat or humidity; wrappings, such as clothing or bandages; bathing in warm water; or sweating may intensify the sensation. The incidence of the burning sensation has been variable in different studies. This may be related to the etiology and pathogenesis of the pain syndrome in different persons. For example, patients with arthritis generally experience less intense burning than do patients with peripheral neuropathies. {01} {03} {11} {14} {15} {26}
Removal of clothing or bedsheets that have covered the area of topical capsaicin application has been associated rarely with respiratory irritation, such as coughing, in the patient and bystanders who were present at the time. This has been attributed to the inhalation of the residue of the dried cream. {11} {18} {20} {65} {66}
There is some concern that capsaicin may be potentially neurotoxic, although animal and clinical studies with topical capsaicin {65} have not shown this to occur. Capsaicin is thought to be capable of elevating the heat-pain threshold in the treated skin areas, especially in patients with diabetic neuropathy; these patients often already have an elevated threshold for heat and pain. {09} {11} {16} {27} {28} {29} {30} {31} {32} {33} {34} {35} {36} {37} {38} {39} {40} {41} {53} {54}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Warm, stinging, or burning sensation at the site of application{01}{03}{11}{15}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Capsaicin (Topical) .


In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to capsaicin or to the fruits of Capsicum plants (e.g., hot peppers)





Use in children—Not recommended in infants and children up to 2 years of age, except under the direction of a physician

Other medical problems, especially broken or irritated skin on area to be treated

Proper use of this medication
If using capsaicin for treatment of neuralgia due to herpes zoster, not applying medicine until after zoster sores have healed

Washing areas to be treated will not cause harm, but is not necessary

Rubbing cream into the affected area well so that little or no cream is left on surface of skin

Washing hands with soap and water after applying capsaicin to avoid getting medicine in eyes or on other sensitive areas of body; however, if medication used on arthritic hands, not washing hands for at least 30 minutes after application

If bandage is being used, not applying tightly

Warm, stinging, or burning sensation may occur and is related to the action of capsaicin on the skin; usually disappears after first several days of treatment, however, may last 2 to 4 weeks or longer {11}; heat, humidity, clothing, bathing in warm water, or sweating may increase sensation; sensation usually lessens in frequency and intensity the longer medication is used; reducing number of daily doses of capsaicin will not lessen sensation, and may prolong period of time that sensation occurs; reducing number of doses also will reduce amount of pain relief obtained

Relief from pain may {65} not occur right away; also, time it takes for capsaicin to work differs depending on type of pain; with arthritis, pain relief usually begins within 1 or 2 weeks; with neuralgia, pain relief usually begins within 2 to 4 weeks; with head and neck neuralgias, pain relief may take 4 to 6 weeks

Using capsaicin 3 or 4 times a day or as directed by doctor; pain relief will last only as long as capsaicin is used regularly; if medicine is discontinued and pain recurs, capsaicin treatment may be restarted

» Proper dosage
Missed dose: Using as soon as possible; if almost time for next dose, skipping missed dose and returning to regular dosing schedule; not doubling doses

» Proper storage

Precautions while using this medication
If capsaicin gets into eyes, flushing with water; if capsaicin gets on other sensitive areas of body, washing with warm (not hot) soapy water {65}

If condition worsens, or does not improve after 1 month, discontinuing use and checking with physician


General Dosing Information
The cream should be applied sparingly {65} and rubbed well into the affected area so that little or no cream is left on the surface of the skin {04}.

During the first 1 or 2 weeks of treatment, application of a topical lidocaine product before capsaicin application may reduce initial discomfort {03} {11} {21}.

A therapeutic pain response is usually achieved within 2 to 4 weeks. Most patients with arthritis notice an initial response within 1 or 2 weeks {03} {15}. Most patients with neuralgia pain begin to respond within 2 to 4 weeks, although patients with pain from head and neck neuralgias may take 4 to 6 weeks to respond {03} {15}.

Continued application of capsaicin 3 or 4 times daily is necessary to sustain pain relief {03} {15}. If the medicine is discontinued and pain recurs, capsaicin treatment may be restarted {03} {15}.

Persons using capsaicin to treat arthritis in their hands should avoid washing their hands for at least 30 minutes after application {03}.

When capsaicin is used for the treatment of neuralgia due to herpes zoster, it should not be applied to the skin until after the zoster lesions have healed {01}.

If a bandage is being used on the treated area, it should not be applied tightly {01}.


Topical Dosage Forms

CAPSAICIN CREAM

Usual adult and adolescent dose
Topical, to the affected area, three or four times a day {01}.

Usual pediatric dose
Infants and children up to 2 years of age—Use is not recommended {65}.

Children 2 years of age and older—See Usual adult and adolescent dose {01}.

Strength(s) usually available
U.S.—


0.025% (OTC) [Zostrix (benzyl alcohol) (cetyl alcohol)]{01}


0.075% (OTC) [Zostrix–HP (benzyl alcohol) (cetyl alcohol)]{01}

Canada—


0.025% (OTC) [Zostrix{05}]


0.075% (OTC) [Zostrix–HP{05}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing. {01}

Auxiliary labeling:
   • For external use only.
   • Avoid contact with eyes. {01}



Revised: 05/01/1998



References
  1. Zostrix Cream 0.025% and Zostrix-HP Cream 0.075% (GenDerm—US). In: PDR Physicians' desk reference. 50th ed. 1996. Montvale, NJ: Medical Economics Data, 1996. p. 1056.
  1. HOLD
  1. Zostrix Cream 0.025 and Zostrix-HP Cream 0.075% manufacturer's drug monograph, GenDerm (US). Received 2/92.
  1. Zostrix Cream 0.025% and Zostrix-HP Cream 0.075% patient package insert (GenDerm—US), Rev 11/95, Rec 12/95.
  1. Zostrix Cream 0.025% (GenDerm) In: Krogh CME editor. CPS compendium of pharmaceuticals and specialties. 30th ed. Ottawa: Canadian Pharmaceutical Association, 1997. p. 1811.
  1. HOLD
  1. HOLD
  1. HOLD
  1. Fitzgerald M. Capsaicin and sensory neurons [review]. Pain 1983; 15: 109-30.
  1. Lynn B. Capsaicin: actions on nociceptive C-fibres and therapeutic potential [review]. Pain 1990 Apr; 41(1): 61-9.
  1. Rumsfield JA, West DP. Topical capsaicin in dermatologic and peripheral pain disorders. DICP 1991 Apr; 25: 381-7.
  1. Bernstein JE, et al. Topical capsaicin treatment of chronic postherpetic neuralgia. J Am Acad Dermatol 1989 Aug; 21(2 Part 1): 265-70.
  1. Ross DR, Varipapa RJ. Letter to the Editor. Treatment of painful diabetic neuropathy with topical capsaicin. N Engl J Med 1989 Aug 17; 321(7): 474-5.
  1. Donofrio P, et al. Capsaicin Study Group. Treatment of painful diabetic neuropathy with topical capsaicin. Arch Intern Med 1991; 151: 2225-9.
  1. Deal CL, et al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clinical Therapeutics 1991; 13(3): 383-95.
  1. Levy DM, et al. Topical capsaicin in the treatment of painful diabetic neuropathy [letter]. N Engl J Med 1991 Mar 14; 324(11): 776-7.
  1. Westerman RA, et al. Effects of topical capsaicin on normal skin and affected dermatomes in herpes zoster [abstract]. Clin Exp Neurol 1988; 25: 71-84.
  1. Choudry NB, et al. Separation of cough and reflex bronchoconstriction by inhaled local anaesthetics [abstract]. Eur Respir J 1990 May; 3(5): 579-83.
  1. Campbell RK, et al. New drug update: capsaicin. Diabetes Educ 1990 Jul-Aug; 16(4): 313-16.
  1. Hakas JF Jr. Letter. Topical capsaicin induces cough in patient receiving ACE inhibitor. Ann Allerg 1990 Oct; 65(4): 322.
  1. Watson CPN, et al. Postherpetic neuralgia and topical capsaicin [abstract]. Pain 1988 Jun; 33(3): 333-40.
  1. Bernstein JE, et al. Treatment of chronic postherpetic neuralgia with topical capsaicin. A preliminary study [abstract]. J Am Acad Dermatol 1987 Jul; 17(1): 93-6.
  1. Watson CPN, et al. The post-mastectomy pain syndrome and the effect of topical capsaicin [abstract]. Pain 1989 Aug; 38(2): 177-86.
  1. Jessell TM, et al. Capsaicin-induced depletion of substance P from primary sensory neurons. Brain Res 1978; 152: 183-8.
  1. Inman RD, et al. Neuromodulation of synovitis; Capsaicin effect on severity of experimental arthritic. J Neuroimmunol 1989; 24: 17-22.
  1. Brorson JR, et al. Capsaicin reduces voltage-gated calcium currents in sensory neurons. Neurology 1990; 40: 232.
  1. Jancso G, et al. Possible use of capsaicin in pain therapy. Clin J Pain 1987; 3: 123-6.
  1. Jancso G, et al. Neurotoxic effects of capsaicin in mammals. Acta Physiol Hung 1987; 69: 295-313.
  1. Welk E, et al. Afferent C-fibres in rats after neonatal capsaicin treatment. Fflugers Arch 1984; 400: 66-71.
  1. Szolcsanyi J. Capsaicin and nociception. Acta Physiol Hung 1987; 69: 323-32.
  1. Szolcsanyi J, et al. Functional and fine structural characteristics of the sensory neuron blocking effect of capsaicin. Naunyn Schmiedebergs Arch Pharmacol 1975; 287: 157-69.
  1. Miller MS, et al. Regulation of substance P by nerve growth factor; disruption by capsaicin. Brain Res 1982; 250: 193-6.
  1. Winter J, et al. Nerve growth factor (NGF) regulates adult rat cultured dorsal root ganglion neuron responses to the excitotoxin capsaicin. Neuron 1988; 1: 973-81.
  1. Lindsay RM, et al. Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature 1989; 337: 362-4.
  1. Fowler CJ, et al. The conduction velocities of peripheral nerve fibres conveying sensations of warming and cooling. J Neurol Neurosurg Psychiatry 1988; 51: 1164-70.
  1. Carpenter SE, et al. Vascular and sensory responses of human skin to mild injury after topical treatment with capsaicin. Br J Pharmacol 1981; 73: 755-8.
  1. McMahon S, et al. The consequences of long-term topical capsaicin application in the rat. Pain 1991; 44: 301-10.
  1. Levy D, et al. A comparison of two methods for measuring thermal thresholds in diabetic neuropathy. J Neurol Neurosurg Psychiatry 1989; 52: 1072-7.
  1. Walker FO, et al. Somesthetic and electrophysiologic effects of topical 0.025% capsaicin in man [abstract]. Reg Anesth 1990 Mar-Apr; 15(2): 61-6.
  1. Simone D, et al. Early and late effects of prolonged topical capsaicin on cutaneous sensibility and neurogenic vasodilation in humans. Pain 1991; 47: 285-94.
  1. Tandan R, et al. Topical capsaicin in painful diabetic polyneuropathy. Neurology 1990; 40(Suppl 1): 380.
  1. Geppetti P, et al. Secretion, pain, and sneezing induced by the application of capsaicin to the nasal mucosa in man [abstract]. Br J Pharmacol 1988 Mar; 93(3): 509-14.
  1. Bucci FA Jr, et al. Successful treatment of postherpetic neuralgia with capsaicin. Am J Ophthalmol 1988 Dec 15; 106(6): 758-9.
  1. Watson CP, et al. Post-herpetic neuralgia: 208 cases [abstract]. Pain 1988 Dec; 35(3): 289-97.
  1. Cheshire WP, et al. Treatment of reflex sympathetic dystrophy with topical capsaicin [abstract]. Pain 1990 Sep; 42(3): 307-11.
  1. Watson CP. Postherpetic neuralgia [abstract]. Neurol Clin 1989 May; 7(2): 231-48.
  1. Carter RB. Topical capsaicin in the treatment of cutaneous disorders [review]. Drug Development Research 1991; 22: 109-23.
  1. Buck SH, et al. The neuropharmacology of capsaicin: review of some recent observations [review]. Pharmacological Reviews 1986; 38(3): 179-226.
  1. Maggi CA, et al. The sensory-efferent function of capsaicin-sensitive sensory neurons [review]. Gen Pharmac 1988; 19(1): 1-43.
  1. Holzer P. Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide, and other neuropeptides [commentary]. Neuroscience 1988; 24(3): 739-68.
  1. Szolcsanyi J. Capsaicin, irritation, and desensitization—Neurophysiological basis and future prospectives. In: Green BG, et al, editors. Chemical senses: Volume 2 Irritation. New York: Marcel Dekker; 1990. p. 141-69.
  1. Scheffler NM, et al. Treatment of painful diabetic neuropathy with capsaicin 0.075%. Journal American Podiatric Medical Association 1991 Jun; 81(6): 288-93.
  1. Tandan R, et al. Topical capsaicin in painful diabetic neuropathy—Controlled study with long-term follow-up. Diabetics Care 1992 Jan; 15 (1): 8-14.
  1. Tandan R, et al. Topical capsaicin in painful diabetic neuropathy—Effect on sensory function. Diabetics Care 1992 Jan; 15(1): 15-18.
  1. Dailey GE, et al. Capsaicin Study Group. Effect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Diabetics Care 1992 Feb; 15(2): 159-165.
  1. Dubner R. Topical capsaicin therapy for neuropathic pain [Editorial Comment]. Pain 1991; 47: 247-8.
  1. McCarthy GM, et al. Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. J Rheumatol 1992 Apr; 19 (4): 604-607.
  1. Peikert A, et al. Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response, and long-term course. J Neurol 1991; 238: 452-6.
  1. Anand P, et al. Topical capsaicin pretreatment inhibits axon reflex vasodilation caused by somostatin and vasoactive intestinal peptide in human skin. Br J Pharmacol 1983; 78: 665-9.
  1. Toth-Kasa I, et al. Capsaicin prevents histamine-induced itching. Int J Clin Pharmacol Res 1986; 6: 163-9.
  1. Kurkcuoglu N, et al. Topical capsaicin for psoriasis. Br J Dermatol 1990; 123: 549-50.
  1. Berberian B, et al. Double-blind evaluation of capsaicin cream in pruritic psoriasis. J Invest Dermatol 1990; 94: 506.
  1. Wallengren J. Treatment of notalgia paresthetica with topical capsaicin. J Amer Acad Dermatol 1991; 24: 286-8.
  1. Breneman DL, et al. Topical capsaicin for treatment of hemodialysis-related pruritis. J Am Acad Dermatol 1992; 26: 91-4.
  1. Panel comments, 5/12/92.
  1. Lefebvre J, et al. Prospective trial on captopril-related cough. Ann Pharmacother 1992 Feb; 26: 161-4.
  1. Ellis CN, Berberian B, Sulica V. A double-blind evaluation of topical capsaicin in pruritic psoriasis. J Am Acad Dermatol 1993; 29: 438-42.
  1. Tarng DC, Cho YL, Lui TP. Hemodialysis-related pruritus a double-blind, placebo-controlled, crossover study of capsaicin 0.025% cream. Nephron 1996; 72: 617-22.
  1. Bernstein JE, Parish LC, Rapaport M, et al. Effects of topically applied capsaicin on moderate and severe vulgaris. J Am Acad Dermatol 15: 504-7.
  1. Lotti T, Teofoli P, Tsampau. Treatment of aquagenic pruritus with topical capsaicin cream. J Am Acad Dermatol 1994; 30: 232-5.
  1. Sicuteri F, Fusco BM, Marabibi S, et al. Beneficial effect of capsaicin application to the nasal mucosa in cluster headache. Clin J Pain 1989; 5: 49-53.
  1. Fusco BM, Marabini S, Maggi CA. Preventative effect of repeated nasal applications of capsaicin in cluster headache. Pain 1994; 59: 321-5
  1. Kost R, Straus S. Postherpetic neuralgia—pathogenesis, treatment, and prevention. NEJM 1996; 335: 32-42.
  1. Reviewer's consensus on monograph revision of 4/98.
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