Capsaicin

Capsaicin
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [4]

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Overview

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Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

• For the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, strains and sprains

• For use in treating neuralgias, consult a physician

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Indications and Dosage

• Arthritis - Pain: TOPICAL, apply thin film to the affected area 3 to 4 times per day.
• Musculoskeletal pain: TOPICAL, apply thin film to the affected area 3 to 4 times per day.
• Neuropathic pain, associated with postherpetic neuralgia: (patch) a single 60-minute application of up to 4 patches every 3 months as needed; do not apply more frequently than every 3 months>
• Psoriasis: apply cream 6 times/day for 3 days, then 4 times/day

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Capsaicin in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Capsaicin FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

• Safety and effectiveness of capsaicin 8% patch (Qutenza(R)) not established in pediatric patients [3]; consult a physician before using capsaicin cream on patients under 18 years of age [

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Capsaicin in pediatric patients.

Contraindications

There is limited information regarding Capsaicin Contraindications in the drug label.

Warnings

For external use only.

Do not apply to wounds or to damaged or irritated skin.

When using this product

• You may experience a burning sensation which is normal and related to the way the product works. With regular use, this sensation generally disappears within several days.

• Do not get it on mucous membranes, into eyes, or on contract lenses. If this occurs, rinse the affected area thoroughly with water.

• Do not apply immediately before or after activities such as bathing, swimming, sun bathing, or strenuous exercise.

• Do not apply heat to the treated areas immediately before or after use.

• Do not tightly wrap or bandage the treated area.

• Avoid inhaling airborne material from dried residue. This can result in coughing, sneezing, tearing, throat or respiratory irritation.

Stop use and ask a doctor if

• Condition worsens or does not improve after regular use.

• Blistering occurs.

• Difficulty breathing or swallowing occurs.

• Severe burning persists.

Keep out of reach of children.

• If swallowed, get medical help or contact a Poison Control Center immediately.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Capsaicin Clinical Trials Experience in the drug label.

Postmarketing Experience

Common

• Dermatologic: Application site erythema (63% ), application site pain (42% ), application site rash (6% ), pruritus, application Site (6% )

• Gastrointestinal: Nausea (5% )

• Respiratory: Nasopharyngitis (4% )

• Cardiovascular: Hypertension (2% )Serious'

Drug Interactions

There is limited information regarding Capsaicin Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Capsaicin in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Capsaicin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Capsaicin during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Capsaicin in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Capsaicin in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Capsaicin in geriatric settings.

Gender

There is no FDA guidance on the use of Capsaicin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Capsaicin with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Capsaicin in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Capsaicin in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Capsaicin in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Capsaicin in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Capsaicin Administration in the drug label.

Monitoring

There is limited information regarding Capsaicin Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Capsaicin and IV administrations.

Overdosage

There is limited information regarding Capsaicin overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Capsaicin Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Capsaicin Mechanism of Action in the drug label.

Structure

There is limited information regarding Capsaicin Structure in the drug label.

Pharmacodynamics

There is limited information regarding Capsaicin Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Capsaicin Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Capsaicin Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Capsaicin Clinical Studies in the drug label.

How Supplied

There is limited information regarding Capsaicin How Supplied in the drug label.

Storage

Store at 15° - 30°C (59° - 86°F)

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

• For persons under 18 years of age, ask a doctor before using.

• To avoid getting cream on hands use applicator pad to apply a thin film of cream to the affected area and gently rub in until fully absorbed. Discard applicator pad after use.

• For optimum relief, apply 3 to 4 times daily.

• Best results typically occur after 2 to 4 weeks of continuous use.

• Unless treating hands, wash hands thoroughly with soap and water immediately after use.

• See package insert for more information.

Precautions with Alcohol

Alcohol-Capsaicin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Capsaicin Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Capsaicin Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Capsaicin Template:IPA (8-methyl-N-vanillyl-6-nonenamide) is the active component of chilli peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact. Capsaicin and several related compounds are called capsaicinoids and are produced as a secondary metabolite by chilli peppers, probably as deterrents against herbivores. Pure capsaicin is a hydrophobic, colorless, odorless, crystalline to waxy compound.

History

The molecule was first isolated in 1816 in crystalline form by P. A. Buchtholz and again 30 years later by L. T. Tresh, who gave it the name capsaicin. In 1878, the Hungarian doctor Endre Hogyes (calling it capsicol) isolated it and proved that it not only caused the burning feeling when in contact with mucous membranes but also increased secretion of gastric juice. Capsaicin was first synthesized in 1930 by E. Spath and F. S. Darling. In 1964, similar substances were isolated from chilli peppers by the Japanese chemists S. Kosuge and Y. Inagaki, who named them capsaicinoids.

Capsaicinoids

Capsaicin is the main capsaicinoid in chilli peppers, followed by dihydrocapsaicin. These two compounds are also about twice as potent to the taste and nerves as the minor capsaicinoids nordihydrocapsaicin, homodihydrocapsaicin, and homocapsaicin. Dilute solutions of pure capsaicinoids produced different types of pungency; however, these differences were not noted using more concentrated solutions.

Capsaicin is believed to be synthesized in the interlocular septa of chilli peppers by addition of a branched-chain fatty acid to vanillylamine. Biosynthesis depends on the gene AT3, which resides at the pun1 locus, and which encodes a putative acyltransferase.

Besides six natural capsaicinoids also one synthetic member capsaicinoid exists. It is vanillylamide of n-nonanoic acid (VNA) and it is used as a reference substance for determining capsaicinoids relative pungency.

Capsaicinoid name	Abbrev.	Typical relative amount	Scoville heat units	Chemical structure
Capsaicin	C	69%	15,000,000	Chemical structure of capsaicin
Dihydrocapsaicin	DHC	22%	15,000,000	Chemical structure of dihydrocapsaicin
Nordihydrocapsaicin	NDHC	7%	9,100,000	Chemical structure of nordihydrocapsaicin
Homodihydrocapsaicin	HDHC	1%	8,600,000	Chemical structure of homodihydrocapsaicin
Homocapsaicin	HC	1%	8,600,000	Chemical structure of homocapsaicin
Nonivamide	PAVA			Chemical structure of nonivamide

Natural function

Capsaicin is present in large quantities in the placental tissue which holds the seeds, the internal membranes and to a lesser extent in the other fleshy parts of the fruits of plants in the genus Capsicum. Despite popular belief, the seeds do not produce any capsaicin. Unlike many such fruits which have evolved to aid in seed dispersal by attracting animals, which consume the fruits and swallow the seeds, which pass through the digestive tract and are subsequently deposited elsewhere, the seeds of Capsicum plants are predominantly dispersed by birds, in which capsaicin has analgesic properties rather than acting as an irritant. Chilli pepper seeds consumed by birds pass through the digestive tract unharmed, whereas those consumed by mammals do not germinate at all. The presence of capsaicin in the fruits therefore protects them from being consumed by mammals.

It was recently discovered that the same pathway of pain utilized by capsaicin is a component of tarantula venom, becoming the first demonstrated shared target between plant and animal in defense from mammals.

Uses

Food

Because of the burning sensation caused by capsaicin when it comes in contact with human mucous membranes as found in the eye or the mouth, it is commonly used in food products to give them added spice or "heat" (pungency). The degree of heat found within a food is often measured on the Scoville scale, although the high performance liquid chromatography method is now preferred . Typically the capsaicin is obtained from chilli peppers. Hot sauce is an example of a product customarily containing large amounts of capsaicin and may contain chilli peppers or pure capsaicin.

Cooling and mechanical stimulation are the only proven methods to relieve the pain, however many questionable tips are widely perpetuated, including oil and oily food (probably because capsaicin in its pure state is poorly soluble in water but soluble in oil). However, the burning sensation will slowly fade away without any measure taken. Milk is the most popular form of relief; molecularly it attracts the burning ligands away from taste receptors (Dustrophsky, 2006).

Medical

Capsaicin is currently used in topical ointments to relieve the pain of peripheral neuropathy such as post-herpetic neuralgia caused by shingles. It may be used in concentrations of between 0.025% and 0.075%.

It may also be used as a cream for the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, strains and sprains. The treatment typically involves the application of a topical anesthetic until the area is numb. Then the capsaicin is applied by a therapist wearing rubber gloves and a face mask. The capsaicin remains on the skin until the patient starts to feel the "heat", at which point it is promptly removed. Capsaicin is also available in large adhesive bandages that can be applied to the back.

The result appears to be that the nerves are overwhelmed from the burning sensation and are unable to report pain for an extended period of time. With chronic exposure to capsaicin, neurons are depleted of neurotransmitters and it leads to reduction in sensation of pain and blockade of neurogenic inflammation. If capsaicin is removed, the neurons recover.

Capsaicin is being explored as a possible cure for diabetes by researchers in Toronto, Canada. Early work curing diabetic mice looks promising. Capsaicin was injected into pancreatic sensory nerves of mice with Type 1 diabetes because of a suspected link between the nerves and diabetes.

The American Association for Cancer Research reports studies suggesting capsaicin is able to kill prostate cancer cells by causing them to undergo apoptosis. The studies were performed on tumors formed by human prostate cancer cell cultures grown in mouse models, and showed tumors treated with capsaicin were about one-fifth the size of the untreated tumors. It has long been noted that in Thailand, where lots of spicy food is consumed, there is very low incidence of gastrointestinal cancers, including colorectal, stomach, cancers, compared to the rest of Asia, including Japan and China. Mexico also has low rates of the same cancers compared to the USA.

Another study carried out at the University of Nottingham suggests capsaicin is able to trigger apoptosis in human lung cancer cells as well.

Capsaicin is also the key ingredient in the experimental drug Adlea, which is in Phase 2 trials as a long-acting analgesic to treat post-surgical and osteoarthritis pain for weeks to months after a single injection to the site of pain.

Non-lethal force

Capsaicin is also the active ingredient in the chemical riot control agent pepper spray. When the spray comes in contact with skin, especially eyes or mucous membranes, it is very painful. Refer to the Scoville scale for a comparison of pepper spray to other sources of capsaicin.

In large quantities, capsaicin can cause death. Symptoms of overdose include difficulty breathing, blue skin, and convulsions. The large amount needed to kill an adult human and the low concentration of capsaicin in chillis make accidental poisoning by chilli consumption exceedingly unlikely.

Possible drug abuse deterrent

Clifford Woolf, the Richard J. Kitz Professor of Anesthesia Research at Harvard Medical School, has suggested using capsaicin to deter abuse of certain extended-release drugs such as OxyContin and Ritalin. When taken as prescribed, opioid prescription drugs such as OxyContin or stimulant drugs such as Adderall XR release their active chemical over time, but when crushed and snorted, taken as a suppository, chewed, or injected, the larger than normal dosage is absorbed all at once and a much stronger effect is produced that can be highly addictive and dangerous due to the higher risk of overdose. Woolf has argued that adding capsaicin into the capsules would be a safe way to deter abuse. A person taking the capsule in the prescribed way (i.e., swallowing it whole) would suffer no ill effects from the additive. However, a person crushing it would expose the irritant. Anyone then swallowing it, snorting it, or injecting it would be exposed to the full power of the chemical. "Imagine snorting an extract of 50 jalapeño peppers and you get the idea," Woolf said in an interview with the Harvard University Gazette. As of 2006, Woolf's proposal is still in the preliminary stages of development and the additive has not yet entered the production stage.

Pest deterrent

Capsaicin is also used to deter pests. A common example is the use of ground-up or crushed dried chilli pods in birdseed to deter squirrels, since birds are unaffected by capsaicin. Insects are also unaffected.

Mechanism of action

The burning and painful sensations associated with capsaicin result from its chemical interaction with sensory neurons. Capsaicin, as a member of the vanilloid family, binds to a receptor called the vanilloid receptor subtype 1 (VR1). First cloned in 1997, VR1 is an ion channel-type receptor. VR1, which can also be stimulated with heat and physical abrasion, permits cations to pass through the cell membrane and into the cell when activated. The resulting "depolarization" of the neuron stimulates it to signal the brain. By binding to the VR1 receptor, the capsaicin molecule produces the same effect that excessive heat or abrasive damage would cause, explaining why the spiciness of capsaicin is described as a burning sensation.

The VR1 ion channel has subsequently been shown to be a member of the superfamily of TRP ion channels, and as such is now referred to as TRPV1. There are a number of different TRP ion channels that have been shown to be sensitive to different ranges of temperature and probably are responsible for our range of temperature sensation. Thus, capsaicin does not actually cause a chemical burn, or indeed any damage to tissue at all; it causes only the sensation of one.

Toxicity

Acute health effects

Capsaicin is a highly irritant material requiring proper protective goggles, respirators, and proper hazmat handling procedures. It is hazardous in cases of skin contact (irritant, sensitizer), of eye contact (irritant), of ingestion, of inhalation (lung irritant, lung sensitizer). Severe over-exposure can result in death. Painful exposures to capsaicin-containing peppers are among the most common plant-related exposures presented to poison centers. They cause burning or stinging pain to the skin, and if ingested in large amounts by adults or small amounts by children, can produce nausea, vomiting, abdominal pain, and burning diarrhea. Eye exposure produces intense tearing, pain, conjunctivitis, and blepharospasm.

Treatment after exposure

The primary treatment is removal from exposure. Contaminated clothing should be removed and placed in airtight bags to prevent secondary exposure. Skin irrigation with copious cold water is used for significant dermal exposures. Symptomatic treatments, such as topical ophthalmic anesthetics, nebulized bronchodilators, or oral antihistamines and corticosteroids, are indicated as appropriate in more severely affected victims. Capsaicin-induced dermatitis has been treated variably with immersion in water or oil, vinegar, bleach, lidocaine gel, and topical antacid suspensions. Cold water produces earlier symptomatic relief, but oil immersion has longer-lasting benefit.

Effects of dietary consumption

The effects of ingestion of small quantities has given different experimental results. One study showed no mucosal erosions or other abnormalities after eating ground jalapeño peppers. Whereas another showed mucosal microbleeding and even one case of grossly visible gastric bleeding after eating red and black peppers. This study also showed "no spice was significantly different from aspirin in any parameter studied." Other studies have shown an association between chronic consumption of capsaicin-rich foods and stomach cancer, yet one such study was not adjusted to any other factors in diet. Another of the said studies also showed a similar risk to stomach cancer with higher consumption of rice.

References

• Dray A (1992) "Mechanism of action of capsaicin-like molecules on sensory neurons" Life Sci 51(23):1759-65
• Garnanez RJ, McKee LH (2001) "Temporal effectiveness of sugar solutions on mouth burn by capsaicin" IFT Annual Meeting 2001
• Henkin R (1991) '"Cooling the burn from hot peppers" JAMA 266(19):2766
• Nasrawi CW, Pangborn RM (1990) "Temporal effectiveness of mouth-rinsing on capsaicin mouth-burn" Physiol Behav 47(4):617-23
• Tewksbury JJ, Nabhan GP (2001) "Seed dispersal: Directed deterrence by capsaicin in chillies" Nature 412, 403-404 (26 July 2001), doi: 10.1038/35086653
• Michael L. Kirifides1, Michael P. Kurnellas1, Larry Clark2 and Bruce P. Bryant1, "Calcium responses of chicken trigeminal ganglion neurons to methyl

anthranilate and capsaicin" The Journal of Experimental Biology 207, 715-722 Published by The Company of Biologists 2004

• Tarantula Venom, Chilli Peppers Have Same "Bite," Study Finds http://news.nationalgeographic.com/news/2006/11/061108-tarantula-venom.html

See also

• Piperine, the active piquant chemical in black pepper
• Allyl isothiocyanate, the active piquant chemical in mustard, radishes, horseradish, and wasabi
• Allicin, the active piquant flavor chemical in uncooked garlic and onions (see those articles for discussion of other chemicals in them relating to pungency, and eye irritation)
• Naga Jolokia pepper, the world's most capsaicin-rich fruit

External links

• EPA Capsaicin Reregistration Eligibility Decision Fact Sheet
• Capsaicin and Its Therapeutic Potential
• Molecule of the Month
• European Commission, opinion of the Scientific Committee on Food on capsaicin.
• An online article on popular capsaicin applications by Dave DeWitt
• A WikiHow article on How to Cool Chilli Pepper Burns.
• The Straight Dope staff report: Are birds immune to hot pepper, enabling them to eat vast amounts and spread the seeds?