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Diethyltoluamide (Topical)


VA CLASSIFICATION
Primary: DE900

Commonly used brand name(s): Backwoods Cutter; Cutter Pleasant Protection; Deep Woods OFF!; Deep Woods OFF! For Sportsmen; Muskol; OFF!; OFF! For Maximum Protection; OFF! Skintastic; OFF! Skintastic For Children; OFF! Skintastic For Kids; Ultra Muskol.

Other commonly used names are
DEET {01} {02} and m-DET {02}
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Insect repellent (topical){02}{04}

Indications

Accepted

Infections transmitted by bites of insects (prophylaxis) or
Infestations by insects or other arthropods (prophylaxis)—Diethyltoluamide is an insect repellent indicated for the topical prevention of infections transmitted by bites of insects or infestations by insects or other arthropods. {01} {02} {04} {20} Diethyltoluamide is effective against mosquitoes, biting flies (gnats, sandflies, deer flies, stable flies, black flies), ticks, harvest mites, and fleas. {01} {02} {04}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    191.27 {15}

Mechanism of action/Effect:

Unknown. {21}

Absorption:

Diethyltoluamide is absorbed through the skin. In one study, approximately 17% of diethyltoluamide was absorbed into the systemic circulation following topical application of 4 mcg per square centimeter of body surface (mcg/cm 2) on intact skin (ventral surface of the forearm) of 4 human volunteers. {02} {03} In another study using a 50% solution of diethyltoluamide, approximately 50% was absorbed within 6 hours following topical application of 1 mL of the solution. {01} {05} {09} Factors that may affect the degree of systemic absorption and the risk of toxicity of diethyltoluamide are: the quantity of insect repellent applied, the concentration of diethyltoluamide in the repellent, applying the repellent to broken or abraded skin or onto skin folds, frequency of application, and the use of occlusive covering over the area where the repellent was applied. {01} {13}

Variable penetration of diethyltoluamide into the skin, ranging from 9 to 56% of a topically applied dose, has been reported. It has been postulated that a reservoir depot effect and subsequent slow release of diethyltoluamide into the systemic circulation occur, {02} which may help explain the central nervous system (CNS) and dermatologic effects seen after continuous and repetitive use. {05}

Biotransformation:

Hepatic—Undergoes oxidation of benzylic moiety to produce m-carboxyl- N,N diethylbenzoylamide and hydroxylation of the sidechain to produce the glucuronide of N hydroxyethyl- N-ethyl- m-toluamide. {02}

Time to peak concentration:

If absorption occurs, peak plasma concentrations are achieved in 1 hour. {01} {05}

Elimination:
    Renal— {01} {02} {03} {05}Approximately 50% of the absorbed dose of diethyltoluamide is eliminated in the urine over 5 days following topical application. {01} {02} {03}


Precautions to Consider

Carcinogenicity/Tumorigenicity/Mutagenicity

Animal studies with diethyltoluamide have shown no carcinogenic, tumorigenic, or mutagenic effects. {02}

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans.

Studies in rats have shown that diethyltoluamide crosses the placenta. Residual diethyltoluamide was observed for 3 months after birth in the body tissues of offspring of female rats that had been administered repeatedly 1000 mg per kg of body weight of the repellent. {02} One animal study reported embryotoxic effects. However, this has not been confirmed by other studies. {02}

Breast-feeding

It is not known whether diethyltoluamide is distributed into breast milk. However, problems in humans have not been documented. {21}

Pediatrics

Diethyltoluamide should be used with caution in children. Because of their increased surface-area-to-body-mass ratio, children may be at increased risk for toxicity due to greater skin absorption. {01} Low-concentration products should be used {01} {06} {12} and applied sparingly. {01} {04}


Geriatrics


No information is available on the relationship of age to the effects of diethyltoluamide in geriatric patients.

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).


Risk-benefit should be considered when the following medical problem exists
Sensitivity to diethyltoluamide{21}


Side/Adverse Effects

Note: The amount and the concentration of diethyltoluamide are major factors that affect the degree of risks for the development of toxicity. Toxicity may result from administration of large doses or from chronic exposure leading to accumulation of this product. (See also Absorption section.) The time to onset of symptoms of toxicity usually ranges from 30 to 60 minutes after exposure. Symptoms of toxicity due to chronic exposure may occur days, weeks, or months after use of diethyltoluamide is begun. {01}

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
Incidence rare
    
Cardiovascular toxicity specifically
bradycardia and{01} (slow heartbeat), hypotension{01} (low blood pressure; unusual tiredness or weakness)
    
CNS toxicity{01}{07} including
ataxia (clumsiness or unsteadiness), clonic jerking movement (uncontrolled jerking movement), coma (loss of consciousness), confusion (mood or mental changes), insomnia (trouble in sleeping), muscle cramping
psychosis{01}{05}
seizures{01}{06}
slurred speech and
tremors{01}
    
dermatologic/allergic reactions{01}{08}{11} such as
anaphylaxis{01} (changes in facial skin color; skin rash; hives; itching; fast or irregular breathing; puffiness or swelling of the eyelids or around the eyes; shortness of breath; troubled breathing; tightness in chest; wheezing), bullous skin eruptions {01}(skin blisters), contact urticaria and{09}{10} (skin rash{01}{07}; hives{01}{07}; itching), erythema {01}(reddening of skin)

Note: Cardiovascular, CNS, and dermatologic toxicities are more likely to occur with prolonged or excessive use.
Anaphylaxis may include anaphylactic shock with sudden, severe decrease in blood pressure and collapse






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

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

Before using this product
»   Conditions affecting use, especially:
Sensitivity to diethyltoluamide





Use in children—Increased risk of toxicity because of greater skin absorption; using low-concentration products of diethyltoluamide and applying sparingly to exposed skin {01} {04} {06} {12}


Proper use of this product {01} {02} {03} {04} {12}
» Diethyltoluamide is for external use only.

Reading directions on the label prior to use

» Using low-concentration products (containing less than 30% of diethyltoluamide) {22} and applying sparingly to exposed area(s) of skin; one application of a low-concentration product lasts about 4 to 8 hours

» If applying product on face, keeping diethyltoluamide away from eyes, lips, or inside of nose; if it accidentally gets into eyes or onto lips or inside of nose, immediately flushing with water and checking with physician if irritation, especially of the eyes, persists; if using aerosol or spray dosage forms, applying carefully to face with hands

» Not applying to wounds or irritated or broken skin because of increased absorption; applying sparingly onto skin folds because of increased risk of irritation

Wearing long sleeves and long pants when possible and applying diethyltoluamide to clothing; not applying under clothing; washing treated clothing after use or when protection is no longer needed

» Not using products containing alcohol, which is flammable, near fire or open flame or while smoking; not smoking or exposing treated skin to fire until repellent has completely dried; keeping treated clothing away from fire, open flame, or smoking

Not keeping diethyltoluamide on skin any longer than necessary; washing skin with soap and water after use

Not using on or near furniture, plastics, watch crystals, leather, or painted or varnished surfaces, including automobiles, to avoid damage to these materials

Proper administration

For liquid or lotion dosage forms
Applying enough diethyltoluamide to cover exposed skin, rubbing in gently, and allowing to dry

For topical aerosol or topical spray dosage forms
Holding container 6 to 8 inches from skin or clothing; spraying in a slow, sweeping motion just enough diethyltoluamide to cover exposed skin; spreading evenly with hands to moisten all exposed skin and allowing to dry

For towelettes dosage form
Wiping the towelette over exposed skin and allowing diethyltoluamide to dry

» Proper dosing

» Proper storage

Precautions while using this product
Not breathing in diethyltoluamide {01} {04} {12}

Not applying diethyltoluamide to hands of young children; taking precautions to prevent children from transferring diethyltoluamide to their eyes or mouth; not applying under diapers of infants; discouraging infants from licking area of application {12}

» Washing treated skin and checking with physician if side effects seem to have occurred after application; taking product container with you to physician {04}


Side/adverse effects
Signs and symptoms of potential side effects, especially cardiovascular toxicity, CNS toxicity, and dermatologic/allergic reactions {01} {07} {08} {11}


General Dosing Information
Diethyltoluamide is for external use only. {04}

Application of insect repellent containing high concentrations of diethyltoluamide should be avoided because it carries an increased risk of adverse reactions. Use of lower-concentration products (containing less than 30% of diethyltoluamide) {22} is reported to be equally effective. {01} {12}

Diethyltoluamide should be applied sparingly. Prolonged and excessive use should be avoided. One application using a low-concentration product usually lasts about 4 to 8 hours. The concentration of diethyltoluamide in a product is directly proportional to its duration of action. However, saturation does not increase efficacy. {01} {22}

Diethyltoluamide should not be applied to wounds or irritated or broken skin, because of increased absorption. It should be applied sparingly onto skin folds because the natural occlusive mechanism of skin folds may increase the risk of irritation. Contact with the eyes, lips, or inside of the nose also should be avoided. {04} {12}

It is advisable to apply this product to clothing rather than skin, if possible, to minimize skin exposure to diethyltoluamide. {12}

Diethyltoluamide should be applied sparingly to children because they may be at increased risk of toxicity due to greater skin absorption. Use of a lower-concentration product is also recommended for children. {01} {04} {06} {12}

Diethyltoluamide should not be kept on the skin any longer than necessary. When protection is no longer needed, treated skin should be washed with soap and water. {12}

For treatment of adverse effects
Recommended treatment consists of the following

   • Washing treated skin with soap and water. {04} {06} {12}
   • Symptomatic and supportive treatment. {19}


Topical Dosage Forms

DIETHYLTOLUAMIDE LIQUID

Usual adult and adolescent dose
Insect repellent (topical)
Topical, sparingly to exposed area(s) of skin. Reapply when necessary. {12}


Usual pediatric dose
See Usual adult and adolescent dose. {12}

Strength(s) usually available
U.S.—


100% (OTC) [OFF! For Maximum Protection{01}{14}]

Canada—


100% (OTC) [OFF! For Maximum Protection{14}]

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.

Auxiliary labeling:
   • For external use only.
   • Keep out of reach of children.


DIETHYLTOLUAMIDE LOTION

Usual adult and adolescent dose
See Diethyltoluamide Liquid. {12}

Usual pediatric dose
See Diethyltoluamide Liquid. {12}

Strength(s) usually available
U.S.—


7.5% (OTC) [OFF! Skintastic{01}{14}]


100% (OTC) [Muskol{16}]

Canada—


7.5% (OTC) [OFF! Skintastic{01}{14}]


25% (OTC) [Muskol{24}]

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.

Auxiliary labeling:
   • For external use only.
   • Keep out of reach of children.


DIETHYLTOLUAMIDE TOPICAL AEROSOL

Usual adult and adolescent dose
Insect repellent (topical)
Topical, spray on or apply sparingly to exposed area(s) of skin, or spray onto clothing. Reapply when necessary. {12}


Usual pediatric dose
See Usual adult and adolescent dose. {12}

Strength(s) usually available
U.S.—


15% (OTC) [OFF!{17}]


23% (OTC) [Backwoods Cutter{23}]


25% (OTC) [Muskol{16}]


30% (OTC) [Deep Woods OFF!{01}{14}]


40% (OTC) [Deep Woods OFF! For Sportsmen{14}] [Ultra Muskol{14}{16}{18}]

Canada—


15% (OTC) [Muskol{24}]


25% (OTC) [Muskol{24}]


30% (OTC) [Deep Woods OFF!{14}]

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 or excessive heat.

Auxiliary labeling:
   • For external use only.
   • Keep out of reach of children.


Caution:
Flammable.


DIETHYLTOLUAMIDE TOPICAL SPRAY SOLUTION

Usual adult and adolescent dose
See Diethyltoluamide Topical Aerosol. {04} {12}

Usual pediatric dose
See Diethyltoluamide Topical Aerosol. {04} {12}

Strength(s) usually available
U.S.—


5% (OTC) [OFF! Skintastic For Kids{14}]


6.5% (OTC) [OFF! Skintastic{14}]


10% (OTC) [Cutter Pleasant Protection{23}]


15% (OTC) [OFF!{01}{14}{17}]


25% (OTC) [Deep Woods OFF!{01}{04}{14}{16}]


100% (OTC) [Muskol{16}{18}]

Canada—


7.5% (OTC) [OFF! Skintastic{14}]


15% (OTC) [OFF!{14}]


25% (OTC) [Deep Woods OFF!{14}]


100% (OTC) [Muskol{24}]

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 or excessive heat.

Auxiliary labeling:
   • For external use only.
   • Keep out of reach of children.


Caution:
Flammable.


DIETHYLTOLUAMIDE TOWELETTES

Usual adult and adolescent dose
Insect repellent (topical)
Topical, as towelette to exposed area(s) of skin. Reapply when necessary. {12}


Usual pediatric dose
See Usual adult and adolescent dose. {12}

Strength(s) usually available
U.S.—


7.5% (OTC) [OFF! Skintastic For Children{14}]

Canada—
Not commercially available. {14}

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

Auxiliary labeling:
   • For external use only.
   • Keep out of reach of children.



Developed: 06/23/1995



References
  1. Clem JR, Havemann DF, Raebel MA. Insect repellent (N,N-Diethyl-m-toluamide) cardiovascular toxicity in an adult. Ann Pharmacother 1993; 27: 289-93.
  1. Robbins PJ, Cherniack MG. Review of the biodistribution and toxicity of the insect repellent N,N-diethyl-m-toluamide (DEET). J Toxicol Environ Health 1986; 18: 503-25.
  1. Feldmann RJ, Maibach HI. Absorption of some organic compounds through the skin in man. J Invest Dermatol 1970; 54(5): 399-404.
  1. Deep Woods OFF! label (S. C. Johnson and Son, Inc.—US), Rec 3/95.
  1. Snyder JW, Poe RO, Stubbins JF, et al. Acute manic pyschosis following the dermal application of N,N-diethyl-m-toluamide (DEET) in an adult. Clin Toxicol 1986; 24(5): 429-39.
  1. Lipscomb JW, Kramer JE, Leikin JB. Seizure following brief exposure to the insect repellent N,N-Diethyl-m-Toluamide. Ann Emerg Med 1992; 21(3): 315-7.
  1. Roland EK, Jan JE, Rigg JM. Toxic encephalopathy in a child after brief exposure to insect repellents. Can Med Assoc J 1985; 132(2): 155-6.
  1. Amichai B, Lazarov A, Halevy S. Contact dermatitis from diethyltoluamide. Contact Dermatitis 1994; 30(3): 188.
  1. von Mayenburg J, Rakoski J. Contact urticaria to diethyltoluamide. Contact Dermatitis 1983; 9(2): 171.
  1. Maibach HI, Johnson HL. Contact urticaria syndrome. Arch Dermatol 1975. 111(6): 726-30.
  1. Reuveni H, Yagupsky P. Diethyltoluamide-containing insect repellent. Adverse effects in worldwide use. Arch Dermatol 1982; 118(8): 582-3.
  1. Anonymous. Seizures temporarily associated with use of DEET insect repellent—New York and Connecticut (From MMWR). Arch Dermatol 1989; 125(12): 1619-20.
  1. Goldfrank LR, Flomenbaum NE, Lewis NA, et al. Goldfrank's toxicologic emergencies. 5th ed. Norwalk, CT: Appleton & Lange, 1994: 157-8.
  1. Personal communication, 5/11/95.
  1. Fleeger CA, editor. USP dictionary of USAN and international drug names 1995. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1994: 214-5.
  1. Red book 1994. Montvale, NJ: Medical Economics Data, 1994: 495, 593.
  1. Red book 1993. Montvale, NJ: Medical Economics Data, 1993: 413.
  1. Personal communication, 4/5/95.
  1. Arena JM, Drew RH, editors. Poisoning. 5th ed. Springfield, Ill: Charles C. Thomas, 1986: 251.
  1. Panel comment, 4/95.
  1. Reviewers' consensus on monograph revision of 4/95.
  1. Panel comment, 5/95.
  1. Personal communication, 5/24/95.
  1. Personal communication, 5/24/95.
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