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Which oral antifungal is best for toenail onychomycosis?
Terbinafine, 250 mg taken daily for 12 weeks, is the best regimen for toenail onychomycosis due to better clinical and mycologic cure rates, tolerability, and cost effectiveness (strength of recommendation [SOR]: A, meta-analyses).
This expensive treatment is not always a high priority
José E. Rodríguez, MD
Florida State University College of Medicine, Tallahassee
In my practice of mostly uninsured patients, onychomycosis treatment is not a high priority. The recommended drug, terbinafine, is costly and not available as a generic. Since this is primarily a cosmetic problem, we usually don’t treat it in my population. In the rare case that someone is willing to pay out of pocket, however, I will now use terbinafine, based on this review. At one of my practices, itraconazole was available at a reduced price, but that discount is outweighed by the superior safety profile of terbinafine.
Evidence summary
Fungal infections of the nail (onychomycosis) are often treated for relief of local symptoms and cosmetic reasons. Griseofulvin, fluconazole, itraconazole, and terbinafine have all been used orally.
A meta-analysis comparing the efficacy of terbinafine (Lamisil), pulse-dosed and continuous-dosed itraconazole (Sporanox), fluconazole (Diflucan), and griseofulvin showed mycological cure rates of varying degrees for each treatment (TABLE).1 Another meta-analysis of 6 studies comparing terbinafine with itraconazole reported odds ratios ranging from 1.8 (95% confidence interval [CI], 1.1–2.8) to 2.9 (95% CI, 1.9–4.1), indicating an 80% to 190% increased likelihood of clinical cure with terbinafine compared with itraconazole.2
Lower relapse rates with terbinafine
Longer-term mycologic cure and clinical relapse rates have also been reported. A 5-year blinded prospective study found long-term mycologic cures of 46% for terbinafine vs 13% for itraconazole (number needed to treat [NNT]=4.3). This study also showed a lower clinical relapse for terbinafine (21% vs 48%; NNT=3.7).3 A cost-efficacy analysis of terbinafine, itraconazole, and griseofulvin found terbinafine to be the most cost-effective (TABLE).4
A randomized, double-blind, controlled trial compared daily terbinafine with pulse-dose terbinafine.5 Daily terbinafine (250 mg for 3 months) had a 70.9% mycologic cure, while pulse-dose terbinafine (500 mg daily for 1 week per month for 3 months) had only a 58.7% mycologic cure (relative risk [RR]=1.21 [95% CI, 1.02–1.43]; NNT=8.2). There was no significant difference in tolerability of the regimens.
Terbinafine is well-tolerated by most patients. A telephone survey after treatment with daily terbinafine or pulse-dose itraconazole reported greater ease and convenience, and higher overall satisfaction with continuous terbinafine vs pulse-dose itraconazole.6
A multicenter trial of diabetic patients with onychomycosis (mean±SD age, 55.7±11.7 years) revealed that terbinafine had comparable efficacy and caused no hypoglycemic reactions in this group, who were being treated with insulin or oral hypoglycemics.7 The terbinafine prescribing information suggests not using the drug for patients with chronic or active liver disease and recommends checking a pretreatment AST and ALT.8
TABLE
Efficacy and cost of treating toenail onychomycosis1,4
| TREATMENT | MYCOLOGICAL CURE RATES | COST PER CURE* |
|---|---|---|
| Terbinafine (continuous) | 76% (± 3%) | $ 645 |
| Itraconazole (pulse-dose) | 63% (± 7%) | $ 856 |
| Itraconazole (continuous) | 59% (± 5%) | $ 1845 |
| Griseofulvin | 60% (± 6%) | $ 2722 |
| Fluconazole | 48% (± 5%) | Not reported |
| * Cost includes drug, monitoring, and office visits (in 1996 dollars). | ||
Recommendations from others
Guidelines from the British Association of Dermatologists point out that terbinafine is superior to itraconazole, and consider it a first-line treatment because it has a better cure rate and lower relapse rate.9 UpToDate suggests oral terbinafine as initial treatment for onychomycosis at a dose of 250 mg daily for 12 weeks.10
1. Gupta AK, Ryder JE, Johnson AM. Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosis. Br J Dermatology 2004;150:537-544.
2. Krob AH, Fleischer AB, Jr, D’Agostino R, Jr, Feldman SR. Terbinafine is more effective than itraconazole in treating toenail onychomycosis: results from a meta-analysis of randomized controlled trials. J Cutan Med Surg 2003;7:306-311.
3. Sigurgeirsson B, Olafsson JH, Steinsson JB, Paul C, Billstein S, Evans EG. Long-term effectiveness of treatment vs itraconazole in onychomycosis: a 5-year blinded prospective follow-up study. Arch Dermatology 2002;138:353-357.
4. Angello JT, Voytovich RM, Jan SA. A cost/efficacy analysis of oral antifungals indicated for the treatment of onychomycosis: griseofulvin, itraconazole, and terbinafine. Am J Manag Care 1997;3:442-450.
5. Warshaw EM, Fett DD, Bloomfield HE, et al. Pulse versus continuous terbinafine for onychomycosis: a randomized, double blind, controlled trial. J Am Acad Dermatol 2005;53:578-584
6. Warshaw EM, Bowman T, Bodman MA, Kim JJ, Silva S, Mathias SD. Satisfaction with onychomycosis treatment. Pulse versus continuous dosing. J Am Podiatr Med Assoc 2003;93:373-379.
7. Farkas B, Paul C, Dobozy A, Hunyadi J, Horvath A, Fekete G. Terbinafine (Lamasil) treatment of toenail onychomycosis in patients with insulin-dependent and non-insulin-dependent diabetes mellitus: a multicentre trial. Br J Dermatology 2002;146:254-260
8. Physicians’; Desk Reference. 61st ed. Montvale, NJ: Thomson PDR; 2007.
9. Roberts DT, Taylor WD, Boyle J. For the British Association of Dermatologists. Guidelines for treatment of onychomycosis. Br J Dermatol 2003;148:402-410.
10. Goldstein AO, Goldstein BG. Onychomycosis. UpToDate [database online]. Updated April 3, 2006. Available at: www.uptodate.com. Accessed on August 4, 2006.
Terbinafine, 250 mg taken daily for 12 weeks, is the best regimen for toenail onychomycosis due to better clinical and mycologic cure rates, tolerability, and cost effectiveness (strength of recommendation [SOR]: A, meta-analyses).
This expensive treatment is not always a high priority
José E. Rodríguez, MD
Florida State University College of Medicine, Tallahassee
In my practice of mostly uninsured patients, onychomycosis treatment is not a high priority. The recommended drug, terbinafine, is costly and not available as a generic. Since this is primarily a cosmetic problem, we usually don’t treat it in my population. In the rare case that someone is willing to pay out of pocket, however, I will now use terbinafine, based on this review. At one of my practices, itraconazole was available at a reduced price, but that discount is outweighed by the superior safety profile of terbinafine.
Evidence summary
Fungal infections of the nail (onychomycosis) are often treated for relief of local symptoms and cosmetic reasons. Griseofulvin, fluconazole, itraconazole, and terbinafine have all been used orally.
A meta-analysis comparing the efficacy of terbinafine (Lamisil), pulse-dosed and continuous-dosed itraconazole (Sporanox), fluconazole (Diflucan), and griseofulvin showed mycological cure rates of varying degrees for each treatment (TABLE).1 Another meta-analysis of 6 studies comparing terbinafine with itraconazole reported odds ratios ranging from 1.8 (95% confidence interval [CI], 1.1–2.8) to 2.9 (95% CI, 1.9–4.1), indicating an 80% to 190% increased likelihood of clinical cure with terbinafine compared with itraconazole.2
Lower relapse rates with terbinafine
Longer-term mycologic cure and clinical relapse rates have also been reported. A 5-year blinded prospective study found long-term mycologic cures of 46% for terbinafine vs 13% for itraconazole (number needed to treat [NNT]=4.3). This study also showed a lower clinical relapse for terbinafine (21% vs 48%; NNT=3.7).3 A cost-efficacy analysis of terbinafine, itraconazole, and griseofulvin found terbinafine to be the most cost-effective (TABLE).4
A randomized, double-blind, controlled trial compared daily terbinafine with pulse-dose terbinafine.5 Daily terbinafine (250 mg for 3 months) had a 70.9% mycologic cure, while pulse-dose terbinafine (500 mg daily for 1 week per month for 3 months) had only a 58.7% mycologic cure (relative risk [RR]=1.21 [95% CI, 1.02–1.43]; NNT=8.2). There was no significant difference in tolerability of the regimens.
Terbinafine is well-tolerated by most patients. A telephone survey after treatment with daily terbinafine or pulse-dose itraconazole reported greater ease and convenience, and higher overall satisfaction with continuous terbinafine vs pulse-dose itraconazole.6
A multicenter trial of diabetic patients with onychomycosis (mean±SD age, 55.7±11.7 years) revealed that terbinafine had comparable efficacy and caused no hypoglycemic reactions in this group, who were being treated with insulin or oral hypoglycemics.7 The terbinafine prescribing information suggests not using the drug for patients with chronic or active liver disease and recommends checking a pretreatment AST and ALT.8
TABLE
Efficacy and cost of treating toenail onychomycosis1,4
| TREATMENT | MYCOLOGICAL CURE RATES | COST PER CURE* |
|---|---|---|
| Terbinafine (continuous) | 76% (± 3%) | $ 645 |
| Itraconazole (pulse-dose) | 63% (± 7%) | $ 856 |
| Itraconazole (continuous) | 59% (± 5%) | $ 1845 |
| Griseofulvin | 60% (± 6%) | $ 2722 |
| Fluconazole | 48% (± 5%) | Not reported |
| * Cost includes drug, monitoring, and office visits (in 1996 dollars). | ||
Recommendations from others
Guidelines from the British Association of Dermatologists point out that terbinafine is superior to itraconazole, and consider it a first-line treatment because it has a better cure rate and lower relapse rate.9 UpToDate suggests oral terbinafine as initial treatment for onychomycosis at a dose of 250 mg daily for 12 weeks.10
Terbinafine, 250 mg taken daily for 12 weeks, is the best regimen for toenail onychomycosis due to better clinical and mycologic cure rates, tolerability, and cost effectiveness (strength of recommendation [SOR]: A, meta-analyses).
This expensive treatment is not always a high priority
José E. Rodríguez, MD
Florida State University College of Medicine, Tallahassee
In my practice of mostly uninsured patients, onychomycosis treatment is not a high priority. The recommended drug, terbinafine, is costly and not available as a generic. Since this is primarily a cosmetic problem, we usually don’t treat it in my population. In the rare case that someone is willing to pay out of pocket, however, I will now use terbinafine, based on this review. At one of my practices, itraconazole was available at a reduced price, but that discount is outweighed by the superior safety profile of terbinafine.
Evidence summary
Fungal infections of the nail (onychomycosis) are often treated for relief of local symptoms and cosmetic reasons. Griseofulvin, fluconazole, itraconazole, and terbinafine have all been used orally.
A meta-analysis comparing the efficacy of terbinafine (Lamisil), pulse-dosed and continuous-dosed itraconazole (Sporanox), fluconazole (Diflucan), and griseofulvin showed mycological cure rates of varying degrees for each treatment (TABLE).1 Another meta-analysis of 6 studies comparing terbinafine with itraconazole reported odds ratios ranging from 1.8 (95% confidence interval [CI], 1.1–2.8) to 2.9 (95% CI, 1.9–4.1), indicating an 80% to 190% increased likelihood of clinical cure with terbinafine compared with itraconazole.2
Lower relapse rates with terbinafine
Longer-term mycologic cure and clinical relapse rates have also been reported. A 5-year blinded prospective study found long-term mycologic cures of 46% for terbinafine vs 13% for itraconazole (number needed to treat [NNT]=4.3). This study also showed a lower clinical relapse for terbinafine (21% vs 48%; NNT=3.7).3 A cost-efficacy analysis of terbinafine, itraconazole, and griseofulvin found terbinafine to be the most cost-effective (TABLE).4
A randomized, double-blind, controlled trial compared daily terbinafine with pulse-dose terbinafine.5 Daily terbinafine (250 mg for 3 months) had a 70.9% mycologic cure, while pulse-dose terbinafine (500 mg daily for 1 week per month for 3 months) had only a 58.7% mycologic cure (relative risk [RR]=1.21 [95% CI, 1.02–1.43]; NNT=8.2). There was no significant difference in tolerability of the regimens.
Terbinafine is well-tolerated by most patients. A telephone survey after treatment with daily terbinafine or pulse-dose itraconazole reported greater ease and convenience, and higher overall satisfaction with continuous terbinafine vs pulse-dose itraconazole.6
A multicenter trial of diabetic patients with onychomycosis (mean±SD age, 55.7±11.7 years) revealed that terbinafine had comparable efficacy and caused no hypoglycemic reactions in this group, who were being treated with insulin or oral hypoglycemics.7 The terbinafine prescribing information suggests not using the drug for patients with chronic or active liver disease and recommends checking a pretreatment AST and ALT.8
TABLE
Efficacy and cost of treating toenail onychomycosis1,4
| TREATMENT | MYCOLOGICAL CURE RATES | COST PER CURE* |
|---|---|---|
| Terbinafine (continuous) | 76% (± 3%) | $ 645 |
| Itraconazole (pulse-dose) | 63% (± 7%) | $ 856 |
| Itraconazole (continuous) | 59% (± 5%) | $ 1845 |
| Griseofulvin | 60% (± 6%) | $ 2722 |
| Fluconazole | 48% (± 5%) | Not reported |
| * Cost includes drug, monitoring, and office visits (in 1996 dollars). | ||
Recommendations from others
Guidelines from the British Association of Dermatologists point out that terbinafine is superior to itraconazole, and consider it a first-line treatment because it has a better cure rate and lower relapse rate.9 UpToDate suggests oral terbinafine as initial treatment for onychomycosis at a dose of 250 mg daily for 12 weeks.10
1. Gupta AK, Ryder JE, Johnson AM. Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosis. Br J Dermatology 2004;150:537-544.
2. Krob AH, Fleischer AB, Jr, D’Agostino R, Jr, Feldman SR. Terbinafine is more effective than itraconazole in treating toenail onychomycosis: results from a meta-analysis of randomized controlled trials. J Cutan Med Surg 2003;7:306-311.
3. Sigurgeirsson B, Olafsson JH, Steinsson JB, Paul C, Billstein S, Evans EG. Long-term effectiveness of treatment vs itraconazole in onychomycosis: a 5-year blinded prospective follow-up study. Arch Dermatology 2002;138:353-357.
4. Angello JT, Voytovich RM, Jan SA. A cost/efficacy analysis of oral antifungals indicated for the treatment of onychomycosis: griseofulvin, itraconazole, and terbinafine. Am J Manag Care 1997;3:442-450.
5. Warshaw EM, Fett DD, Bloomfield HE, et al. Pulse versus continuous terbinafine for onychomycosis: a randomized, double blind, controlled trial. J Am Acad Dermatol 2005;53:578-584
6. Warshaw EM, Bowman T, Bodman MA, Kim JJ, Silva S, Mathias SD. Satisfaction with onychomycosis treatment. Pulse versus continuous dosing. J Am Podiatr Med Assoc 2003;93:373-379.
7. Farkas B, Paul C, Dobozy A, Hunyadi J, Horvath A, Fekete G. Terbinafine (Lamasil) treatment of toenail onychomycosis in patients with insulin-dependent and non-insulin-dependent diabetes mellitus: a multicentre trial. Br J Dermatology 2002;146:254-260
8. Physicians’; Desk Reference. 61st ed. Montvale, NJ: Thomson PDR; 2007.
9. Roberts DT, Taylor WD, Boyle J. For the British Association of Dermatologists. Guidelines for treatment of onychomycosis. Br J Dermatol 2003;148:402-410.
10. Goldstein AO, Goldstein BG. Onychomycosis. UpToDate [database online]. Updated April 3, 2006. Available at: www.uptodate.com. Accessed on August 4, 2006.
1. Gupta AK, Ryder JE, Johnson AM. Cumulative meta-analysis of systemic antifungal agents for the treatment of onychomycosis. Br J Dermatology 2004;150:537-544.
2. Krob AH, Fleischer AB, Jr, D’Agostino R, Jr, Feldman SR. Terbinafine is more effective than itraconazole in treating toenail onychomycosis: results from a meta-analysis of randomized controlled trials. J Cutan Med Surg 2003;7:306-311.
3. Sigurgeirsson B, Olafsson JH, Steinsson JB, Paul C, Billstein S, Evans EG. Long-term effectiveness of treatment vs itraconazole in onychomycosis: a 5-year blinded prospective follow-up study. Arch Dermatology 2002;138:353-357.
4. Angello JT, Voytovich RM, Jan SA. A cost/efficacy analysis of oral antifungals indicated for the treatment of onychomycosis: griseofulvin, itraconazole, and terbinafine. Am J Manag Care 1997;3:442-450.
5. Warshaw EM, Fett DD, Bloomfield HE, et al. Pulse versus continuous terbinafine for onychomycosis: a randomized, double blind, controlled trial. J Am Acad Dermatol 2005;53:578-584
6. Warshaw EM, Bowman T, Bodman MA, Kim JJ, Silva S, Mathias SD. Satisfaction with onychomycosis treatment. Pulse versus continuous dosing. J Am Podiatr Med Assoc 2003;93:373-379.
7. Farkas B, Paul C, Dobozy A, Hunyadi J, Horvath A, Fekete G. Terbinafine (Lamasil) treatment of toenail onychomycosis in patients with insulin-dependent and non-insulin-dependent diabetes mellitus: a multicentre trial. Br J Dermatology 2002;146:254-260
8. Physicians’; Desk Reference. 61st ed. Montvale, NJ: Thomson PDR; 2007.
9. Roberts DT, Taylor WD, Boyle J. For the British Association of Dermatologists. Guidelines for treatment of onychomycosis. Br J Dermatol 2003;148:402-410.
10. Goldstein AO, Goldstein BG. Onychomycosis. UpToDate [database online]. Updated April 3, 2006. Available at: www.uptodate.com. Accessed on August 4, 2006.
Evidence-based answers from the Family Physicians Inquiries Network
Is DEET safe for children?
Reported evidence suggests that DEET use is safe for children older than 2 months, with only very rare incidence of major adverse effects (strength of recommendation [SOR]: C). Typically, a topical concentration between 10% and 30% should be used (SOR: C). Increasing DEET concentration does not improve protection, but does increase the duration of action (SOR: A).
Evidence summary
The increasing prevalence of mosquito-borne diseases, including West Nile virus, has raised concerns about safe and effective forms of prevention. For decades, parents have used the insect repellent DEET (N,N-diethyl-metatoluamide), but questions remain regarding adverse effects, including seizures, particularly when used in children.
Two large case series suggested that the risk of DEET is low. The first collected poison control center reports during the 1980s. The report concluded that DEET exposure rarely led to adverse effects and that the route of administration (ie, ingestion) was more closely linked to toxicity than age or gender.1 There were 5 major adverse reactions reported from 9086 exposures to DEET (0.05%); these included hypotension, hypotonic reaction, and syncope, and 1 death (a suicide ingestion).
The second series, also collected from poison control centers, included roughly 21,000 reports of DEET exposures during the 1990s. The authors concluded that the risk of toxicity was low and that there was no clear dose-dependent relationship between exposure and extent of severity of neurologic manifestations.2 This report found a rate of major adverse reactions (0.1%) from DEET that was similar to the first case series. The major reactions reported included hypotension, seizures, respiratory distress, and 2 deaths (0.01%). When limiting the data to infants and children only, there were 10 major events among 17,252 reported exposures (0.06%), and no deaths. Although infants and children accounted for 83.1% of all reported exposures, the majority of the serious outcomes (including the deaths) occurred in adults. About half of all those exposed reportedly had no ill effects, the other half had minor effects (transient effects that resolved without treatment). Only 4% experienced moderate effects (non–life threatening problem, but one that would likely require treatment). There were no data presented on the overall size of the exposed population, eg, users of DEET in the US.
Two recent narrative reviews also concluded that DEET toxicity is rare in children. The first review found that DEET posed essentially no risk in children.3 The second review was sponsored by SC Johnson and Company, the makers of OFF! brand insect repellent. It assessed animal studies, epidemiologic data, and case reports, and supported the safety of DEET in children.4
A theoretical risk is that DEET toxicity could be enhanced by coapplication with other agents. Some studies have uncovered dangerous interactions with military and industrial chemicals, but such exposures are unlikely in most children. The most practical concern regards sun-screen. One study reported that use of sun-screen increased the penetration of DEET.5 However, since the poison control center studies indicated that toxicity did not occur in a dose-dependent manner; the clinical significance of increased penetration is not clear.1,2
Increasing the concentration of DEET does not improve protection but does provide longer duration. Concentrations of 6.65% protect for about 2 hours while 23.8% DEET can last about 5 hours.6 By understanding this relationship, parents can apply lowest concentration necessary to provide the protection needed.
Recommendations from others
The American Academy of Pediatrics recommends avoiding DEET in children under 2 months of age. For all other children, it advises using DEET with a concentration between 10% and 30%.7
Counsel parents to take 3 steps to prevent bites—avoid, cover up, and repel
Paul Crawford, MD
USAF-Eglin Family Practice Residency, Eglin Air Force Base, Fla
The emergence of West Nile virus has heightened awareness of mosquitoes, and I often field questions about how to protect children from bites. I counsel parents to take 3 steps to prevent bites—avoid, cover up, and repel. Mosquitoes are active at dawn and dusk, so staying indoors during these times is protective. Covering up with long sleeves, pants, and socks protects from most bites. Lastly, DEET repellent protects exposed areas from mosquitoes. Lotions make it easier to apply DEET to children. Commonly, parents express fear of DEET due to media reports. This review will help me ease their fears.
1. Veltri JC, Osimitz TG, Bradford DC, Page BC. Retrospective analysis of calls to poison control centers resulting from exposure to the insect repellent N,N-diethyl-m-toluamide (DEET) from 1985–1989. J Toxicol Clin Toxicol 1994;32:1-16.
2. Bell JW, Veltri JC, Page BC. Human exposures to N,N-diethyl-m-toluamide insect repellents reported to the American Association of Poison Control Centers 1993–1997. Int J Toxicol 2002;21:341-352.
3. Koren G, Matsui D, Bailey B. DEET-based insect repellents: safety implications for children and pregnant and lactating women. CMAJ 2003;169:209-212.Erratum in: CMAJ 2003;169:283.
4. Osimitz TG, Murphy JV. Neurological effects associated with use of the insect repellent N,N-diethyl-m-toluamide (DEET). J Toxicol Clin Toxicol 1997;35:443-445.
5. Ross EA, Savage KA, Utley LJ, Tebbett IR. Insect repellent interactions: sunscreens enhance DEET (N,N-diethyl-m-toluamide) absorption. Drug Metab Dispos 2004;32:783-785.
6. Fradin MS, Day JF. Comparative efficacy of insect repellents against mosquito bites. N Engl J Med 2002;347:13-18.
7. American Academy of Pediatrics. West Nile virus information. Available at: www.aap.org/family/wnv-jun03.htm. Accessed on April 8, 2005.
Reported evidence suggests that DEET use is safe for children older than 2 months, with only very rare incidence of major adverse effects (strength of recommendation [SOR]: C). Typically, a topical concentration between 10% and 30% should be used (SOR: C). Increasing DEET concentration does not improve protection, but does increase the duration of action (SOR: A).
Evidence summary
The increasing prevalence of mosquito-borne diseases, including West Nile virus, has raised concerns about safe and effective forms of prevention. For decades, parents have used the insect repellent DEET (N,N-diethyl-metatoluamide), but questions remain regarding adverse effects, including seizures, particularly when used in children.
Two large case series suggested that the risk of DEET is low. The first collected poison control center reports during the 1980s. The report concluded that DEET exposure rarely led to adverse effects and that the route of administration (ie, ingestion) was more closely linked to toxicity than age or gender.1 There were 5 major adverse reactions reported from 9086 exposures to DEET (0.05%); these included hypotension, hypotonic reaction, and syncope, and 1 death (a suicide ingestion).
The second series, also collected from poison control centers, included roughly 21,000 reports of DEET exposures during the 1990s. The authors concluded that the risk of toxicity was low and that there was no clear dose-dependent relationship between exposure and extent of severity of neurologic manifestations.2 This report found a rate of major adverse reactions (0.1%) from DEET that was similar to the first case series. The major reactions reported included hypotension, seizures, respiratory distress, and 2 deaths (0.01%). When limiting the data to infants and children only, there were 10 major events among 17,252 reported exposures (0.06%), and no deaths. Although infants and children accounted for 83.1% of all reported exposures, the majority of the serious outcomes (including the deaths) occurred in adults. About half of all those exposed reportedly had no ill effects, the other half had minor effects (transient effects that resolved without treatment). Only 4% experienced moderate effects (non–life threatening problem, but one that would likely require treatment). There were no data presented on the overall size of the exposed population, eg, users of DEET in the US.
Two recent narrative reviews also concluded that DEET toxicity is rare in children. The first review found that DEET posed essentially no risk in children.3 The second review was sponsored by SC Johnson and Company, the makers of OFF! brand insect repellent. It assessed animal studies, epidemiologic data, and case reports, and supported the safety of DEET in children.4
A theoretical risk is that DEET toxicity could be enhanced by coapplication with other agents. Some studies have uncovered dangerous interactions with military and industrial chemicals, but such exposures are unlikely in most children. The most practical concern regards sun-screen. One study reported that use of sun-screen increased the penetration of DEET.5 However, since the poison control center studies indicated that toxicity did not occur in a dose-dependent manner; the clinical significance of increased penetration is not clear.1,2
Increasing the concentration of DEET does not improve protection but does provide longer duration. Concentrations of 6.65% protect for about 2 hours while 23.8% DEET can last about 5 hours.6 By understanding this relationship, parents can apply lowest concentration necessary to provide the protection needed.
Recommendations from others
The American Academy of Pediatrics recommends avoiding DEET in children under 2 months of age. For all other children, it advises using DEET with a concentration between 10% and 30%.7
Counsel parents to take 3 steps to prevent bites—avoid, cover up, and repel
Paul Crawford, MD
USAF-Eglin Family Practice Residency, Eglin Air Force Base, Fla
The emergence of West Nile virus has heightened awareness of mosquitoes, and I often field questions about how to protect children from bites. I counsel parents to take 3 steps to prevent bites—avoid, cover up, and repel. Mosquitoes are active at dawn and dusk, so staying indoors during these times is protective. Covering up with long sleeves, pants, and socks protects from most bites. Lastly, DEET repellent protects exposed areas from mosquitoes. Lotions make it easier to apply DEET to children. Commonly, parents express fear of DEET due to media reports. This review will help me ease their fears.
Reported evidence suggests that DEET use is safe for children older than 2 months, with only very rare incidence of major adverse effects (strength of recommendation [SOR]: C). Typically, a topical concentration between 10% and 30% should be used (SOR: C). Increasing DEET concentration does not improve protection, but does increase the duration of action (SOR: A).
Evidence summary
The increasing prevalence of mosquito-borne diseases, including West Nile virus, has raised concerns about safe and effective forms of prevention. For decades, parents have used the insect repellent DEET (N,N-diethyl-metatoluamide), but questions remain regarding adverse effects, including seizures, particularly when used in children.
Two large case series suggested that the risk of DEET is low. The first collected poison control center reports during the 1980s. The report concluded that DEET exposure rarely led to adverse effects and that the route of administration (ie, ingestion) was more closely linked to toxicity than age or gender.1 There were 5 major adverse reactions reported from 9086 exposures to DEET (0.05%); these included hypotension, hypotonic reaction, and syncope, and 1 death (a suicide ingestion).
The second series, also collected from poison control centers, included roughly 21,000 reports of DEET exposures during the 1990s. The authors concluded that the risk of toxicity was low and that there was no clear dose-dependent relationship between exposure and extent of severity of neurologic manifestations.2 This report found a rate of major adverse reactions (0.1%) from DEET that was similar to the first case series. The major reactions reported included hypotension, seizures, respiratory distress, and 2 deaths (0.01%). When limiting the data to infants and children only, there were 10 major events among 17,252 reported exposures (0.06%), and no deaths. Although infants and children accounted for 83.1% of all reported exposures, the majority of the serious outcomes (including the deaths) occurred in adults. About half of all those exposed reportedly had no ill effects, the other half had minor effects (transient effects that resolved without treatment). Only 4% experienced moderate effects (non–life threatening problem, but one that would likely require treatment). There were no data presented on the overall size of the exposed population, eg, users of DEET in the US.
Two recent narrative reviews also concluded that DEET toxicity is rare in children. The first review found that DEET posed essentially no risk in children.3 The second review was sponsored by SC Johnson and Company, the makers of OFF! brand insect repellent. It assessed animal studies, epidemiologic data, and case reports, and supported the safety of DEET in children.4
A theoretical risk is that DEET toxicity could be enhanced by coapplication with other agents. Some studies have uncovered dangerous interactions with military and industrial chemicals, but such exposures are unlikely in most children. The most practical concern regards sun-screen. One study reported that use of sun-screen increased the penetration of DEET.5 However, since the poison control center studies indicated that toxicity did not occur in a dose-dependent manner; the clinical significance of increased penetration is not clear.1,2
Increasing the concentration of DEET does not improve protection but does provide longer duration. Concentrations of 6.65% protect for about 2 hours while 23.8% DEET can last about 5 hours.6 By understanding this relationship, parents can apply lowest concentration necessary to provide the protection needed.
Recommendations from others
The American Academy of Pediatrics recommends avoiding DEET in children under 2 months of age. For all other children, it advises using DEET with a concentration between 10% and 30%.7
Counsel parents to take 3 steps to prevent bites—avoid, cover up, and repel
Paul Crawford, MD
USAF-Eglin Family Practice Residency, Eglin Air Force Base, Fla
The emergence of West Nile virus has heightened awareness of mosquitoes, and I often field questions about how to protect children from bites. I counsel parents to take 3 steps to prevent bites—avoid, cover up, and repel. Mosquitoes are active at dawn and dusk, so staying indoors during these times is protective. Covering up with long sleeves, pants, and socks protects from most bites. Lastly, DEET repellent protects exposed areas from mosquitoes. Lotions make it easier to apply DEET to children. Commonly, parents express fear of DEET due to media reports. This review will help me ease their fears.
1. Veltri JC, Osimitz TG, Bradford DC, Page BC. Retrospective analysis of calls to poison control centers resulting from exposure to the insect repellent N,N-diethyl-m-toluamide (DEET) from 1985–1989. J Toxicol Clin Toxicol 1994;32:1-16.
2. Bell JW, Veltri JC, Page BC. Human exposures to N,N-diethyl-m-toluamide insect repellents reported to the American Association of Poison Control Centers 1993–1997. Int J Toxicol 2002;21:341-352.
3. Koren G, Matsui D, Bailey B. DEET-based insect repellents: safety implications for children and pregnant and lactating women. CMAJ 2003;169:209-212.Erratum in: CMAJ 2003;169:283.
4. Osimitz TG, Murphy JV. Neurological effects associated with use of the insect repellent N,N-diethyl-m-toluamide (DEET). J Toxicol Clin Toxicol 1997;35:443-445.
5. Ross EA, Savage KA, Utley LJ, Tebbett IR. Insect repellent interactions: sunscreens enhance DEET (N,N-diethyl-m-toluamide) absorption. Drug Metab Dispos 2004;32:783-785.
6. Fradin MS, Day JF. Comparative efficacy of insect repellents against mosquito bites. N Engl J Med 2002;347:13-18.
7. American Academy of Pediatrics. West Nile virus information. Available at: www.aap.org/family/wnv-jun03.htm. Accessed on April 8, 2005.
1. Veltri JC, Osimitz TG, Bradford DC, Page BC. Retrospective analysis of calls to poison control centers resulting from exposure to the insect repellent N,N-diethyl-m-toluamide (DEET) from 1985–1989. J Toxicol Clin Toxicol 1994;32:1-16.
2. Bell JW, Veltri JC, Page BC. Human exposures to N,N-diethyl-m-toluamide insect repellents reported to the American Association of Poison Control Centers 1993–1997. Int J Toxicol 2002;21:341-352.
3. Koren G, Matsui D, Bailey B. DEET-based insect repellents: safety implications for children and pregnant and lactating women. CMAJ 2003;169:209-212.Erratum in: CMAJ 2003;169:283.
4. Osimitz TG, Murphy JV. Neurological effects associated with use of the insect repellent N,N-diethyl-m-toluamide (DEET). J Toxicol Clin Toxicol 1997;35:443-445.
5. Ross EA, Savage KA, Utley LJ, Tebbett IR. Insect repellent interactions: sunscreens enhance DEET (N,N-diethyl-m-toluamide) absorption. Drug Metab Dispos 2004;32:783-785.
6. Fradin MS, Day JF. Comparative efficacy of insect repellents against mosquito bites. N Engl J Med 2002;347:13-18.
7. American Academy of Pediatrics. West Nile virus information. Available at: www.aap.org/family/wnv-jun03.htm. Accessed on April 8, 2005.
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