J Am Board Fam Pract: first published as 10.3122/jabfm.12.3.236 on 1 May 1999. Downloaded from

STEPPED CARE: AN EVIDENCE-BASED APPROACH TO DRUG THERAPY Pharmacotherapy of Tinea Capitis

Mary E. Temple, PharmD, Milap C. Nahata, PharmD, and Katalin I. Koranyi, MD

Editors' Note: This month we continue the new feature­ dans do. We will avoid making conclusions that are not sup­ STEPped Care: An Evidence-BasedApproach to Drug Ther­ ported by POEMs. Nevertheless, POEMs should be incorpo­ apy. These articles are designed to provide concise answers to rated into clinical practice. The rest is up to the reader. Blend­ the drog therapy questions that family physicians encounter in ing POEMs with rational thought, clinical experience, and their daily practice. The format ofthe feature will folhw the importantly, patient preferences can be the essence ofthe art mnemonic STEP: safety (an analysis ofadverse effects that ofmedicine. patients and providers care about), tolerability (pooled drop­ We hope you will find these new articles useful and easy to out rates from large clinical trials), effectiveness (how well the read. Your comments and suggestions are wekome. You may drogs work and in what patient population[sj), and price contact the editors through the editorial office ofJABFP or on (costs ofdrog, but also cost-effectiveness oftherapy). 1 Hence, the Internet (http://clinic.isu.edu/drogsteps/intro.html). the name STEPped Care. We hope the articles provide you with useful information that Since the informatics pioneers at McMaster University can be applied in everyday practice, and we look forward to introduced evidence-based medicine,2 Slawson and col­ your feedback. leagues3,4 have brought it to mainstream family medicine ed­ ucation and practice. This feature is designed to further the Rex W. Force, PhannD, STEPped Care Feature Editor mission ofsearchingfor the troth in medical practice. Authors John P. Geyman, MD, Editor will provide information in a stroctured format that allows Journal ofthe American Board ofFamily Practice the readers to get to the meat ofa therapeutic issue in a way References that can help physicians (and patients) make informed deci­ 1. Shaughnessy AF, Slawson DC, Bennett)H. Separating the wheat from the chaff: identifying fallacies in pharmaceutical sions. The articles will discourage the use ofdisease-oriented promotion.) Gen Intern Mea 1994;9:563-8. evidence (DOE) to make treatment decisions. Examples of 2. Evidence-based medicine: a new approach to teaching the DOEr include blood pressure hwering, decreases in hemoglobin practice of medicine. Evidence-Based Medicine Working Group.)AMA 1992;268:2420-5. A Ie, and SO on. We will include studies that are POEMs-pa­ 3. Slawson DC, Shaughnessy AF, Bennett )H. Becoming a tient-oriented evidence that matters (myocardial infarctions, medical information master: feeling good about not know­ ing everything.) Fam Pract 1994;38:505-13. pain, strokes, mortality, etc)-with the goal ofoffering our 4. Shaughnessy AF, Slawson DC, Bennett)H. Becoming an in­ http://www.jabfm.org/ patients the most practical, appropriate, and scientifically sub­ formation master: a guidebook to the medical information stantiated therapies. Number needed to treat to observe benefit jungle.) Fam Pract 1994;39:489-99. 5. Laupacis A. Sackett DL, Roberts RS. An assessment of clini­ in a single patient will also be included as a way ofdefining cally: useful measures of the consequences of treatment. N advantages in terms that are relatively easy to understand. ),6 Engl) Med 1988;318:1728-33. 6. Wtffen P), Moore RA. Demonstrating effectiveness-the At times this effort will be frustrating. Even as vast as the concept of numbers-needed-to-treat. J Clin Pharm Ther biomedical literature is, it does not always support what clini- 1996;21:23-7. on 27 September 2021 by guest. Protected copyright.

Tinea capitis, or ringworm of the scalp, is the capitis is transmitted by humans (anthropophilic) most common dermatophyte infection in pedi­ or is acquired from animals (zoophilic). Trichophy­ atric populations throughout the world. 1-4 In the ton tonsurans and Microsporum audouinii are associ­ United States, 3 to 8 percent of the population can ated with anthropophilic infections, and Microspo­ be affected. 5-7 Additionally, 34 percent of house­ rum canis is associated with zoophilic infections.9•IO hold contacts of children with tinea capitis are In the United States T tonsurans has replaced asymptomatic carriers of the infection.8 Tinea M audouinii as the most common pathogen, and it causes up to 96 percent of tinea capitis infec­ tions. II Generally, Trichophyton infections are Submitted, revised, 3 February 1999. equally distributed between boys and girls and From the College of Pharmacy (MET, MCN) the Depart­ ment of Pediatrics, College of Medicine (MCN, KIK), and affect far more African-Americans than whites. Children's Hospital (MET, MCN, KIK), The Ohio State The infection is rare in adults and adolescents University, Columbus. Address reprints requests to Milap C. Nahata, PharmD, College of Pharmacy, The Ohio State Uni­ (who have reached puberty), although they can versity, 500 West 12th Ave, Columbus, OH 43210. be carriers. The rarity of infection is most likely

236 JABFP May-June 1999 Vol. 12 No.3 J Am Board Fam Pract: first published as 10.3122/jabfm.12.3.236 on 1 May 1999. Downloaded from

attributed to the fungistatic activity of short- and approach. The STEP approach involves: safety long-chain fatty acids found in the sebum of (analysis of adverse events most concerning to pa­ these individuals.3.5.7 tients and physicians), tolerability (pooled drop­ Although griseofulvin is the only agent ap­ out rates from large clinical trials), effectiveness proved for the treatment of tinea capitis by the (the efficacy of medications and what patient pop­ Food and Drug Administration, (FDA) a variety ulations benefit most), and price (cost of drug, but of other systemic and topical agents, including ke­ also cost effectiveness of therapy). toconazole, itraconazole, fluconazole, terbinafine, corticosteroids, and selenium sulfide, are also be­ Safety and Tolerability ing used. Griseofulvin is fungistatic and acts by in­ Treatment of tinea capitis usually requires ex­ terfering with fungal nucleic acid synthesis. 12 Ke­ tended therapy with medications that can cause toconazole, itraconazole, and fluconazole are all adverse reactions in some patients. In a 12-week fungistatic and inhibit the biosynthesis of fungal randomized double-blind study, 79 patients (most ergosterol. 13 Terbinafine is the only systemic were African-Americans) were given griseofulvin agent that is fungicidal at low concentrations and microsize (n - 46) or ketoconazole (n - 33).16 Al­ acts by inhibiting squalene epoxide and thus er­ though 6 percent of patients taking griseofulvin gosterol biosynthesis.14 developed mild elevations in aspartate amino­ Adjunctive agents used in the treatment of transferase, these elevations were not of clinical tinea capitis include corticosteroids and selenium importance as patients continued on therapy. Two sulfide. Corticosteroids are used to alter the host patients (6 percent) in the ketoconazole group and immune-mediated responses in patients with 3 (6.5 percent) in the griseofulvin group withdrew complicated tinea capitis, whereas selenium sul­ for unknown reasons. An additional patient on ke­ fide is used as a topical sporicidal agent. 15 toconazole withdrew from the study because of The focus of tinea capitis literature has been nausea. largely disease oriented. Most studies have evalu­ A 6-week double-blind study comparing keto­ ated the microbiologic response to certain agents conazole (n - 24) with griseofulvin microsize (n - using disease-oriented evidence as surrogates. 23) in 47 children with dermatophyte infections There are some studies, however, that can provide found a twofold increase in serum alanine and as­ POEMs (patient-oriented evidence that matters, partate aminotransferase concentrations after 3

eg, compliance rates and clinical cure, such as hair weeks of treatment in 1 patient on griseofulvin; http://www.jabfm.org/ regrowth, decreased inflammation, and relapse however, concentrations returned to normal in rates) for comparative purposes. 16-30 subsequent visits. No adverse events were re­ ported in the ketoconazole group.17 Methods In a double-blind, randomized study of 35 pa­ MEDLINE and Metacrawler search engines en­ tients given ultramicronized griseofulvin (n - 17) compassing January 1966 through July 1998 were or itraconazole (n - 18), 12 percent of patients tak­ on 27 September 2021 by guest. Protected copyright. used to obtain clinical trials and general informa­ ing griseofulvin discontinued therapy because of tion regarding the treatment of tinea capitis. severe nausea, vomiting, and abdominal pain.ls Search terms included "tinea capitis," "griseoful­ These symptoms resolved after stopping griseo­ vin," "ketoconazole," "itraconazole," "flucona­ fulvin. Although no adverse events were noted zole," "terbinafine," "selenium," "corticosteroids," with itraconazole, 1 patient dropped out for an "antifungal," "trichophyton," and "microsporum." unstated reason. The searches were limited to human clinical trials, Although headache and gastrointestinal dis­ pediatric patients, and review articles published in tress are the most commonly reported adverse ef­ English language journals. Randomized, con­ fects of griseofulvin, rare cases of systemic lupus, trolled studies were included for review if they had myositis, and toxic epidermal necrolysis have been POEMs (eg, decreased clinic visits, inflammation, reported. 17.19 Ketoconazole has caused serious he­ alopecia, and recurrences). patotoxicity, adrenal insufficiency, myopathy, and This article will delineate the role and outline dermatologic eruptions. Whereas the latter three the paradigm for rational use of various antifun­ adverse effects have been associated with doses gals used to treat tinea capitis by using the STEP used in tinea capitis, hepatotoxicity has not. I 7 Nei-

Pharmacotherapy of Tinea Capitis 237 J Am Board Fam Pract: first published as 10.3122/jabfm.12.3.236 on 1 May 1999. Downloaded from

ther fluconazole nor itraconazole has been associ­ conazole, griseofulvin). Although this disease-ori­ ated with hepatotoxicity in pediatric patients ented evidence exists, it does not provide informa­ treated for tinea capitis. 13 tion about clinical cure and relapse rates. A 6-week study of efficacy and safety of POEMs are available in a double-blind ran­ terbinafine 125 mg/d in 12 children found 4 pa­ domized comparison of micronized griseofulvin tients with mild transient adverse effects including and ketoconazole. 16 This study consisted of urban anorexia (17 percent), and mild stomach upset (17 African-American children aged 2 to 16 years. percent).20 A comparative duration- and weight­ Outcomes included disease-oriented evidence based study of terbinafine given for 1, 2 or 4 weeks (fungal culture results) and POEMs (clinical signs had 20 of 161 patients experiencing adverse ef­ and symptoms). Of the 79 patients who were en­ fects. Increased hepatic enzyme levels (40 percent) rolled, 46 received griseofulvin (10 - 20 mglkg/d) and eosinophilia (25 percent) were the most com­ and 33 received ketoconazole (3.3 - 6.6 mglkg/d). mon adverse effects, followed by elevated triglyc­ All patients taking griseofulvin had significandy eride levels (20 percent), leukocytosis (10 percent), improved outcomes including hair regrowth and and headache (5 percent).21 reductions in scaling, crusting, erythema, and in­ The major pharmacokinetic drug interactions flammation. Six patients taking ketoconazole (18 with the antifungal medications in the treatment percent) remained symptomatic and had positive of tinea capitis either involve factors affecting gas­ mycologic cultures after 12 weeks of therapy, trointestinal absorption or drug metabolism. The while no patients taking griseofulvin failed treat­ azoles (ketoconazole, itraconazole, and flucona­ ment after 12 weeks. Nevertheless, mycologic zole) inhibit cytochrome P-450 3A4 and 2C9, and cure rates were not statistically different between thus impair the metabolism of drugs, leading to the two groups (P< 0.10). toxic concentrations of concurrendy administered An 8-week study of micronized griseofulvin drugs in some patients. Drugs including astemi­ compared with ketoconazole in 63 children (75 zole, cisapride, midazolam, triazolam, and terfena­ percent with T tonsurans) with tinea capitis sup­ dine are well documented to have serious interac­ ported these results.24 Most of these patients (89 tions with the azoles, especially ketoconazole and percent) were African-American, female (55 per­ itraconazole.22 Griseofulvin is an enzyme inducer cent), and had a median lesion duration of 5.7 and thus has caused therapeutic failure with agents weeks before receiving treatment. Patients were such as oral contraceptives. Terbinafine is exten­ randomly assigned to receive ketoconazole 5 http://www.jabfm.org/ sively metabolized and can interact with other mglkg/d (n - 28) or griseofulvin 15 mglkg/d (n- drugs; however, it has been poorly studied. Cime­ 35). Treatment continued until lesions resolved tidine inhibits the metabolism of terbinafine and and microscopic examination of the hair was neg­ thus increases its concentrations. Terbinafine can ative. The median duration of treatment was 108 inhibit the metabolism of certain agents such as days in those given ketoconazole and 60 days in 23

nortriptyline. Absorption of griseofulvin, itra­ those given griseofulvin. Children were examined on 27 September 2021 by guest. Protected copyright. conazole, and ketoconazole is increased with a at 2-week intervals for fungal cultures, new hair meal. Increased gastric pH reduces absorption of growth, time to complete scalp clearing, inflam­ itraconazole and ketoconazole.3 As a result, agents mation, and scaling. POEMs included sterile cul­ such as proton pump inhibitors, and H2 antago­ tures: 92 percent and 59 percent of patients given nists should be used with caution because they in­ griseofulvin and ketoconazole, respectively, had crease gastric pH. sterile cultures at final follow-up. Based on these data, 3 patients would need to Effectiveness be treated with griseofulvin to prevent one treat­ Trichophyton tonsurans ment failure in a ketoconazole-treated group. Disease-oriented evidence suggests agents that Also, even though mean time for beginning new concentrate in the sebum (terbinafine, itracona­ hair growth was not significandy different be­ zole, fluconazole) are more likely to achieve tween the groups, a significandy longer time was higher cure rates (both clinical and microbiologic) required for complete clearing of lesions for those and might require shorter duration of treatment patients receiving ketoconazole than those on than those concentrating in eccrine sweat (keto- griseofulvin (P < 0.01). Three patients (11 per-

238 JABFP May-June 1999 Vol. 12 No.3 J Am Board Fam Pract: first published as 10.3122/jabfm.12.3.236 on 1 May 1999. Downloaded from cent) taking ketoconazole had persistent symp­ and compliance was presumably high, although toms at 6 months and needed griseofulvin treat­ no specific percentages were provided. ment before clinical symptoms resolved. Two pa­ Itraconazole has also been shown to be effective tients on ketoconazole relapsed 4 weeks after in treating tinea capitis both in daily dosing and completing treatment and 1 on griseofulvin re­ pulse dosing, although the data supporting its effi­ lapsed 4 months after completing treatment. cacy are not strong. To date, no randomized trials Whereas the data seem to suggest that griseoful­ exist comparing itraconazole with other antifungal vin is effective in treating tinea capitis, results of agents for treating Ttonsurans. 25,28 Whereas some these controlled trials might be questioned by the studies of itraconazole show clinical efficacy, pa­ results found in retrospective studies. Neverthe­ tient response is questionable. In a study of 2 5 pe­ less, one must be skeptical of these studies, as diatric patients with confirmed tinea capitis, after 4 many of them involved a majority of Mrican­ weeks of itraconazole, 100 mg daily, along with a American male children, whose tinea capitis is shampoo containing selenium sulfide, only 10 pa­ known to be more difficult to treat.25 ,26 tients were successfully cured as defined by nega­ Preliminary noncomparable data suggest that tive cultures and clinical improvement. The other terbinafine might be useful,21,27 A randomized 15 children required further treatment. After 2- double-blind study of 161 patients compared vari­ week evaluations for 2 months, 14 remained cul­ ous lengths of treatment of terbinafine. Oral ture positive, and 1 was clinically worse at week 8. terbinafine taken for 1, 2, or 4 weeks showed my­ Although this study was small, it does suggest that cologic cure rates of 88 percent, 62 percent, and more than 50 percent of patients might not re­ 100 percent, respectively, among 24 patients with spond to 100 mg of itraconazole given daily for 4 T tonsurans (not statistically different). Mycologic weeks.29 Consequently, conflicting results regard­ and clinical cure rates were not significantly dif­ ing itraconazole efficacy indicate a need for further ferent between the groups. randomized controlled studies to provide sound A noncomparative study of terbinafine in 13 pa­ POEMs in treating tinea capitis. tients with tinea capitis, 7 of whom had T tonsurans Intralesional corticosteroid injections have infection, reviewed the effects of patients receiving been used as adjunctive therapy in patients with terbinafine pulse therapy in which 1 week of taking complicated tinea capitis. POEMs for this prac­ the medication was followed by a 2-week period tice, however, are not supported by randomized, off the medication.27 Pulse therapy involves the use controlled clinical trials. 15 A study of 30 children http://www.jabfm.org/ of a medication for a specific period, then a period with complicated tinea capitis randomized each without medicine, followed by a period in which patient to receive either griseofulvin alone or the medicine is again administrated. Pulse therapy griseofulvin with intralesional triamcinolone 2.5 can increase compliance and decrease costs and ad­ mg. No significant differences between groups in verse effects associated with continued administra­ time to negative cultures, onset of new hair tion. The disadvantages of pulse therapy in tinea growth, or time to scalp clearing were evident. on 27 September 2021 by guest. Protected copyright. capitis have not been proved, but they could in­ Although the treatment of tinea capitis requires clude decreased effectiveness compared with stan­ systemic therapy, adjunctive topical therapy has dard therapies. If patients did not respond to the been found to be effective in decreasing spread of week of pulse therapy, a second I-week course of infectious spores to other persons.31 ,32 A variety of terbinafine followed by a 3-week off period be­ topical agents are currently available as adjunctive tween the second and third pulses of treatment was therapy; however, selenium sulfide seems to be administered. most commonly used. Selenium sulfide is available Doses based on weight of each child were de­ in a 1 percent shampoo and 2.5 percent lotion. termined as follows: greater than 40 kg, 250 mg/d; Some important evidence exists: 54 patients with T 20 to 40 kg, 125 mg/d; less than 20 kg, 62.5 mg/d. tonsurans receiving griseofulvin 15 mglkg/d were Twelve of 13 patients were clinically and mycolog­ randomized to receive either the 2.5 percent lotion ically cured. Patients with moderate to severe in­ or 1 percent selenium sulfide shampoo or a bland fection required three courses of pulse therapy, nonmedicated shampoo. Patients were observed at and those with mild infection required one to two 2-week intervals until they were clinically and my­ courses. The patient acceptance of pulse therapy cologically cured. The selenium sulfide products

Phannacotherapy of Tinea Capitis 239 J Am Board Fam Pract: first published as 10.3122/jabfm.12.3.236 on 1 May 1999. Downloaded from Table 1. Costs Associated with Treating TInea Capitis in a 30-kg Child.

Medication Dosing Regimen Average Wholesale Price ($)

Griseofulvin 15 mglkg/d for 6 - 8 wk 169.72 - 226.30 Ketoconazole 100 - 200 mg/d for 6 wk 67.62 - 135.24 Itraconazole pulse therapy* 5 mglkg/d for 1 - 3 wk 68.04 - 204.12 Itraconazole 100 mg/d for 4 - 6 wk 181.04 - 272.16 Fluconazole 6 mglkg/d for 20 d 88.95 Terbinafine pulse therapy 125 mg/d for 1 - 3 wk 23.17 - 69.51 Terbinafine 125 mg/d for 4 - 6 wk 92.68 - 139.02 Prednisone 10 mg 30 mg/d for 1 wk 1.97 Selenium sulfide 2.5% lotion 120 mL. Applied 3 times a wk 4.07 Selenium sulfide 1 % shampoo 210 mL Applied 3 times a wk 4.57

From Drug Topics Red Book 1998. 34 *Pulse therapy involves medication use for specific period (ie, 2 weeks) followed by no therapy for I week of no therapy; then another week of medication use.

were statistically superior to the nonmedicated mycologic cure. Complete mycologic cure did oc­ shampoo for time required to eliminate shedding cur in 9 of 22 patients and 16 of 22 patients at the and viable spores. When the two different sele­ 4- and 8-week posttreatment evaluations, respec­ nium products were compared, however, no differ­ tively. No POEM literature was found for keto­ ence was noted. conazole, fluconazole, or selenium sulfide with re­ gard to Microsporum species. Microsporum (canis or audouin#) Although Microsporum species are not prominent Price in the United States, they still cause tinea capitis The average wholesale price of each antifungal in some patients. Two studies with POEMs were regimen as supported by both disease-oriented ev­ available. A double-blind randomized study com­ idence and POEMs of cure is displayed in Table pared itraconazole 100 mg (n - 17) with griseoful­ 1.34 These costs are based on the treatment of a vin 500 mg (n - 17) in pediatric patients aged 2 to 30-kg child with tinea capitis. Although no phar­ http://www.jabfm.org/ 11 years. Clinical and mycologic examinations macoeconomic studies have been conducted com­ were performed during treatment at 0, 2, 4 and 6 paring various agents used to treat tinea capitis, it weeks and 2, 4, and 8 weeks after completing is apparent that griseofulvin would be the most treatment. Clinical evaluation included degrees of costly agent supported by POEMs for treating scaling, erythema, and inflammation. In each tinea capitis. Although ketoconazole is less expen­ group of patients, 15 (88 percent) were clinically sive than griseofulvin, it might also cause more ad­ cured at the 8-week posttreatment evaluation. verse effects. Other agents listed in Table 1, in­ on 27 September 2021 by guest. Protected copyright. Both patient groups had 10 percent, 40 percent, cluding itraconazole and terbinafine, do not have and 60 percent reductions in clinical symptoms at strong comparative POEMs to support their use; 2, 4 and 6 weeks of treatment, respectively. IS however, they could be less costly than griseoful­ Although terbinafine therapy has resulted in vin. Finally, it should be noted that costs of treat­ important POEMs in efficacy against T tonsurans, ment failures, transportation for clinic visits, lost only disease-oriented evidence is available, and wages, monitoring laboratory data, and managing data are not so compelling with Microsporum adverse drug reactions are not included in Table 1. species. A study of 22 children with dry noninflam­ matory tinea capitis (aged 2 to 9 years, race unspec­ Summary ified) given terbinafine once daily for 6 weeks An overview of STEPped care is presented in (doses based on weight: 62.5 mg/d ifless than 20 Table 2. Current literature suggests that griseoful­ kg, 125 mg/d if20 to 40 kg, 250 mg/d if more than vin continues to be effective in most patients with 40 kg) evaluated mycologic cure rates. 33 At the end tinea capitis. Ketoconazole is no more effective of treatment, none of the 22 patients had complete than griseofulvin and causes more adverse events

240 JABFP May-June 1999 Vol. 12 No.3 J Am Board Fam Pract: first published as 10.3122/jabfm.12.3.236 on 1 May 1999. Downloaded from

Table 2. Drug STEPs Overview. 8. Vargo K, Cohen BA. Prevalence of undetected tinea capitis in household members of children with dis­ Safety and Mild adverse effects are associated with ease. Pediatrics 1993;92:155-7. tolerability griseofulvin, ketoconazole, terbinafine and itraconazole. \Vhile ketoconazole is associ­ 9. Macura AB. Dermatophyte infections. Int] Derma­ ated with adrenal insufficiency, myopathy toI1993;32:313-23. and urticaria in adults with treat tinea 10. Odom R. Pathophysiology of dermatophyte infec­ capitis, none of these adverse events were tions.] Am Acad DermatoI1993;28(5 Pt 1):S2-S7. noted in the pediatric studies. Although clinically si~ficant drug interactions are 11. Bronson DM, Desai DR, Barsky S, Foley SM. An common WIth ketoconazole and itracona­ epidemic of infection with Trichophyton tmlsUrans re­ zole, their prevalence was not apparent in vealed in a 20-year survey of fungal infections in the pediatric studies Chicago.] AmAcad DermatoI1983;8:322-30. Effectiveness Griseofulvin continues to be effective as a first-line drug in many patients. Terbinafine 12. Blank H. Antifungal and other effects of griseoful­ and itraconazole may be used in unrespon­ vin. Am] Med 1965;39:831-8. sive cases. Terbinafine and itraconazole are 13. Cross]T ]r, Hickerson SL, Yamauchi T. Antifungal effective in pulse and traditional doses; however, strong comparative clinical trial drugs. Pediatr Rev 1995;16:123-9. data supporting their use are scarce 14. Gupta AK, Shear NH. Terbinafine: an update.] Am Price Griseofulvin is the most costly agent suP:' Acad Dermatol 1997;37:979-88. ported by POEM for treating tinea capitis. 15. Ginsburg CM, Gan VN, Petruska M. Randomized Other antifungal agents are less costly; however, strong clinical data are lacking to controlled trial of intralesional corticosteroid and support their use griseofulvin vs griseofulvin alone for treatment of Summary Griseofulvin continues to be the agent of kerion. Pediatr Infect Dis] 1987 ;6: 1084-7 . choice. Randomized controlled trials need 16. Tanz RR, Hebert AA, Esterly NB. Treating tinea to be done to determine the role of other capitis: should ketoconarole replace griseofulvin? ] antifungal agents Pediatr 1988;112:987-91. 17. Martinez-Roig A, Torres-Rodriguez]M, Bart1ett­ Coma A. Double blind study of ketoconazole and and drug interactions. No POEMs exist for flu­ griseofulvin in dermatophytoses. Pediatr Infect Dis] conawle. Itraconawle and terbinafine are promis­ 1988;7:37-40. ing agents. Randomized comparative studies with 18. Lopez-Gomez S, Del-Palacio A, Van Cutsem ], griseofulvin and other antifungal agents are re­ Soledad-Cuetara M, Iglesias L, Rodriguez-Noriega quired to clarify their role in treating tinea capitis A. Itraconazole versus griseofulvin in the treatment caused by T tonsurans infection. Finally, adjunctive of tinea capitis: a double-blind randomized study in

children. Int] DermatoI1994;33(10):743-7. http://www.jabfm.org/ 1 percent selenium sulfide therapy is as effective as 19. Knasmuller S, Parzefall W, Helma C, Kassie F, 2.5 percent selenium sulfide lotion when used in Ecker S, Schulte-Hermann R. Toxic effects of grise­ combination with syStemic antifungal agents. ofulvin: disease models, mechanisms, and risk assess­ ment. Crit Rev Toxicol 1997;27:495-537. References 20. Nejjam F, Zagula M, Cabiac MD, Guessous N, 1. Rosenthal]R. Pediatric fungal infections from head Humbert H, Lakhdar H. Pilot study of terbinafine to toe: what's new? Curr Opin Pediatr 1994;64:435- in children suffering from tinea capitis: evaluation of on 27 September 2021 by guest. Protected copyright. 41. efficacy, safety, and pharmacokinetics. Br] Dermatol 2. Frieden I], Howard R. Tinea capitis: epidemiology, 1995;132:98-105. diagnosis, treatment, and control.] Am Acad Der­ 21. Haroon TS, Hussain I, Aman S,]ahangir M, Kazmi matoI1994;31(3 Pt 2):S42-6. AH, Sami AR, et al. A randomized double-blind 3. al-Fouzan AS, Nanda A. Dermatophytosis of chil­ comparative study of terbinafine for 1, 2, and 4 dren in Kuwait. Pediatr DermatoI1992;9:27 -30. weeks in tinea capitis. Br] DermatoI1996; 13 5 :86-8. 4. Venugopal PV; Venugopal Tv. Tinea capitis in 22. Katz HI. Possible drug interactions in oral treat­ Saudi Arabia. Int] DermatoI1993;32:39-4O. ment of onychomycosis.] Am Podiatr Med Assoc 5. Sharma V, Hall]C, Knapp]F, Sarai S, Galloway D, 1997;87:571-4. Babel DE. Scalp colonization by Trichophyton ton­ 23. van der Kuy PH, Hooymans PM. Nortriptyline in­ surans in an urban pediatric clinic. Asymptomatic toxication induced by terbinafine. BM] 1998;316: carrier state? Arch DermatoI1988;124:1511-3. 441. 6 Terreni AA. Tinea capitis survey in Charleston, Sc. 24. Gao VN, Petruska M, Ginsburg CM. Epidemiology Arch DermatoI1961;83:88-91. and treatment of tinea capitis: ketoconazole vs. 7. Bocobo F, Eadie GA, Miedler L]. Epidemiologic griseofulvin. Pediatr Infect Dis] 1987;6:46-9. study of tinea capitis caused by T tonsurans and M 25. Greer DL. Treatment of tinea capitis with itracona­ audouinii. Public Health Rep 1965;80:891-8. role.] Am Acad DermatoI1996;35:637-8.

Pharmacotherapy of Tinea Capitis 241 J Am Board Fam Pract: first published as 10.3122/jabfm.12.3.236 on 1 May 1999. Downloaded from

26. Abdel-Rahman SM, Nahata MC, Powell DA. Re­ 30. Nichter L, Thomas DM, Atkinson], Reinisch]F, sponse to initial griseofulvin therapy in pediatric pa­ Sloan GM. Scalp infections in black children: think tients with tinea capitis. Ann Pharmacother 1997;31: kerion. Plastic Reconstruct Surg 1981 ;80: 717 -9. 406-10. 31. Allen HB, Honig P], Leyden]], McGinley K]. Sele­ 27. Gupta AK, Adam P. Terbinafine pulse therapy is ef­ nium sulfide: adjunctive therapy for tinea capitis. Pe­ fective in tinea capitis. Pediatr Dermatol 1998; 15: diatrics 1982:69:81-3. 56-8. 32. Givens TG, Murray MM, Baker Re. Comparison 28. Gupta AK, Alexis ME, Raboobee N, Hofstader SL, of 1% and 2.5% selenium sulfide in the treatment of Lynde Cw, Adam P, et al. Itraconazole pulse ther­ tinea capitis. Arch Pediatr Adolesc Med 1995; 149: apy is effective in the treatment of tinea capitis in 808-11. children: an open multicentre study. Br] Dermatol 33. Dragos V, Lunder M. Lack of efficacy of 6-week 1997;13 7 :251-4. treatment with oral terbinafine for tinea capitis due 29. Abdel-Rahman SM, Powell DA, Nahata Me. Effi­ to Microsporum canis in children. Pediatr Dermatol cacy of itraconazole in children with Trichophyton 1997; 14:46-8. tonsurans tinea capitis.] Am Acad Dermatol 1998; 34. Drug topics red book 1998. Montvale, NJ: Medical 38:443-6. Economics, 1998. http://www.jabfm.org/ on 27 September 2021 by guest. Protected copyright.

242 JABFP May-]une 1999 Vol. 12 No.3